Primary Sclerosing Cholangitis (Clinical)

Overview

Definition

Primary sclerosing cholangitis Primary Sclerosing Cholangitis Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis ( PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis) is a liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease characterized by intrahepatic and extrahepatic bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans, forming multifocal Multifocal Retinoblastoma bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct strictures.^[8,14] It is important to differentiate PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis from:^[5,8,9,14]

• Small-duct PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis: normal bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy ducts noted on cholangiography, but cholestatic features and histology similar to PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis
• Secondary sclerosing cholangitis (SSC): also characterized by multifocal Multifocal Retinoblastoma biliary strictures, but has identifiable causes (e.g., cholangiocarcinoma Cholangiocarcinoma A malignant tumor arising from the epithelium of the bile ducts. Rare Malignant Liver Tumors, biliary trauma or infection)

Epidemiology

• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency is approximately 6.3 cases per 100,000^[6]
• Higher rate in Scandinavian countries ^[6,16]
• 70% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are men.^[5,16]
• Age at diagnosis is around 30–40 years.^[6]
• Predominantly seen in nonsmokers^[5]

Etiology

The cause of primary sclerosing cholangitis Primary Sclerosing Cholangitis Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis ( PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis) is unknown, but the disease is associated with:

• Inflammatory bowel disease (IBD):^[2,8,14]
  • Approximately 80% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Ulcerative colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis > Crohn’s disease
• Genetic predisposition:
  • PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis is increased among 1st-degree relatives of affected individuals.
  • Increased prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of:^[6]
    • HLA-B8 HLA-B8 A specific hla-b surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the hla-b*08 allele family. Primary Sclerosing Cholangitis
    • HLA-DR3
    • HLA-Drw52a
• Ischemic damage to the biliary ducts
• Bacterial infection leading to chronic or recurrent cholangitis

Pathophysiology

• Environmental insult in susceptible individuals → cholangiocyte activation → cytokine production → perpetual inflammatory response^[6,7,9,13]
• Chronic periductal inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation leads to:^[15]
  • Cholangiocyte damage → peribiliary gland proliferation (accessory glands containing biliary stem cells) 
  • Portal myofibroblast activation → periductal fibrosis Periductal Fibrosis Primary Sclerosing Cholangitis (“ onion skin Onion Skin Primary Sclerosing Cholangitis”) → biliary strictures and interlobular duct Interlobular Duct Primary Sclerosing Cholangitis loss
  • Hepatic stellate cell Hepatic stellate cell Perisinusoidal cells of the liver, located in the space of disse between hepatocytes and sinusoidal endothelial cells. Primary Sclerosing Cholangitis activation → hepatic fibrosis Hepatic fibrosis Autosomal Recessive Polycystic Kidney Disease (ARPKD) → cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
  • Potential malignant transformation Transformation Change brought about to an organism’s genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell’s genome. Bacteriology of cholangiocytes Cholangiocytes Primary Sclerosing Cholangitis

Clinical Presentation

Though many patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are asymptomatic, others may present with:^[2,8,10,16]

• Insidious onset of:
  • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
  • Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema)
  • Jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice (later in the course)
• Later development of:
  • Hepatomegaly
  • Splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly 
  • Cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
• Evidence of biliary obstruction (approximately 75% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship):
  • Acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis (15%–20% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship):
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever 
    • Right upper quadrant Right upper quadrant Anterior Abdominal Wall: Anatomy abdominal pain Abdominal Pain Acute Abdomen 
  • Gallstones Gallstones Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis
  • Choledocholithiasis Choledocholithiasis Presence or formation of gallstones in the common bile duct. Cholelithiasis
• Associated IBD:
  • Chronic diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • Colicky abdominal pain Abdominal Pain Acute Abdomen
  • Tenesmus
• PSC-autoimmune hepatitis ( AIH AIH Autoimmune hepatitis (AIH) is a rare form of chronic liver disease in which the immune system attacks the liver causing inflammation. It predominantly affects women. Clinical presentation ranges from asymptomatic cases to patients that present with symptoms of acute liver failure (jaundice, right upper quadrant pain). Autoimmune Hepatitis) overlap syndrome:^[8,9]
  • More often seen in children or young adults
  • Clinical, histologic, and biochemical findings of AIH AIH Autoimmune hepatitis (AIH) is a rare form of chronic liver disease in which the immune system attacks the liver causing inflammation. It predominantly affects women. Clinical presentation ranges from asymptomatic cases to patients that present with symptoms of acute liver failure (jaundice, right upper quadrant pain). Autoimmune Hepatitis + cholangiographic findings of PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis

Diagnosis

Arriving at the diagnosis of PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis requires a cholestatic picture (evidenced by lab tests), characteristic multifocal Multifocal Retinoblastoma bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct strictures, and segmental dilatations (on imaging) and exclusion of secondary causes. Guideline details are available here (AASLD, ACG, British Society of Gastroenterology, EASLD).

Laboratory testing 

Laboratory testing is usually the 1st step in the workup, and findings may include:

• Evidence of cholestasis:^[5]
  • ↑ Alkaline phosphatase Alkaline Phosphatase An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. Osteosarcoma (most common lab abnormality)^[8,16]
  • ↑ Gamma-glutamyltransferase Gamma-glutamyltransferase An enzyme, sometimes called ggt, with a key role in the synthesis and degradation of glutathione; (GSH, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid. Liver Function Tests ( GGT GGT An enzyme, sometimes called ggt, with a key role in the synthesis and degradation of glutathione; (gsh, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid. Alcoholic Liver Disease)
  • ↑ Conjugated bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism (can be normal at the time of diagnosis)^[8]
• Aspartate Aspartate One of the non-essential amino acids commonly occurring in the l-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. Synthesis of Nonessential Amino Acids aminotransferase ( AST AST Enzymes of the transferase class that catalyze the conversion of l-aspartate and 2-ketoglutarate to oxaloacetate and l-glutamate. Liver Function Tests) and alanine Alanine A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. Synthesis of Nonessential Amino Acids aminotransferase ( ALT ALT An enzyme that catalyzes the conversion of l-alanine and 2-oxoglutarate to pyruvate and l-glutamate. Liver Function Tests) may be slightly ↑ (typically < 300 IU/L).
  • ↑ AST AST Enzymes of the transferase class that catalyze the conversion of l-aspartate and 2-ketoglutarate to oxaloacetate and l-glutamate. Liver Function Tests/ ALT ALT An enzyme that catalyzes the conversion of l-alanine and 2-oxoglutarate to pyruvate and l-glutamate. Liver Function Tests levels (> 5x the upper limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation) or PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis in < 25 years of age, add workup for AIH AIH Autoimmune hepatitis (AIH) is a rare form of chronic liver disease in which the immune system attacks the liver causing inflammation. It predominantly affects women. Clinical presentation ranges from asymptomatic cases to patients that present with symptoms of acute liver failure (jaundice, right upper quadrant pain). Autoimmune Hepatitis.^[5]
  • Additional tests for AIH AIH Autoimmune hepatitis (AIH) is a rare form of chronic liver disease in which the immune system attacks the liver causing inflammation. It predominantly affects women. Clinical presentation ranges from asymptomatic cases to patients that present with symptoms of acute liver failure (jaundice, right upper quadrant pain). Autoimmune Hepatitis would include characteristic antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions (e.g., smooth muscle antibody) and liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma.^[10]
• Additional testing:^[8]
  • Antimitochondrial antibodies Antimitochondrial Antibodies Primary Biliary Cholangitis (AMAs) are negative (testing helps to rule out primary biliary cholangitis Primary Biliary Cholangitis Primary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis. Primary Biliary Cholangitis).
  • Immunoglobulin G4 (IgG4) level (to rule out IgG4-associated cholangitis, which is a distinct type responsive to corticosteroids Corticosteroids Chorioretinitis)
  • Perinuclear anti-neutrophil cytoplasmic antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions ( P-ANCA p-ANCA Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis) are positive in about 75% of cases (not specific to PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis).^[5,9,16]
  • Immunoglobulin M ( IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions) levels may be ↑.^[5]

Imaging

• Ultrasonography (US):^[8]
  • Not diagnostic
  • Usually performed during the initial workup to exclude biliary obstruction
  • Thickening of the wall of the common bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy and hepatic ducts are potential findings.
• Magnetic resonance cholangiopancreatography Magnetic resonance cholangiopancreatography Non-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities. Primary Sclerosing Cholangitis ( MRCP MRCP Non-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities. Primary Sclerosing Cholangitis): 
  • Investigation of choice^{[5, 8, 9, 14]}
    • Noninvasive
    • No risk of pancreatitis Pancreatitis Inflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis. Acute Pancreatitis
    • Lower cost
    • No radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma
  • Findings:^{[5,8,9,14,16]}
    • Stricturing and dilation of intrahepatic and/or extrahepatic bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy ducts
    • Appears as “beading” (diagnostic for PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis)
    • In about 45% of cases, a dominant stricture Stricture Primary Sclerosing Cholangitis (stenotic common bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct ≤ 1.5 mm in diameter or hepatic duct ≤ 1 mm in diameter) is found.^[14]
    • When a dominant stricture Stricture Primary Sclerosing Cholangitis is present → rule out cholangiocarcinoma Cholangiocarcinoma A malignant tumor arising from the epithelium of the bile ducts. Rare Malignant Liver Tumors (needs brush cytology and/or endoscopic biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma)^[8]
• Endoscopic retrograde cholangiopancreatography Endoscopic Retrograde Cholangiopancreatography Fiberoptic endoscopy designed for duodenal observation and cannulation of Vater’s ampulla, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (Vater) papillotomy may be performed during this procedure. Primary Sclerosing Cholangitis ( ERCP ERCP Fiberoptic endoscopy designed for duodenal observation and cannulation of vater’s ampulla, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (vater) papillotomy may be performed during this procedure. Primary Sclerosing Cholangitis): 
  • 2nd choice for diagnosis in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who cannot undergo MRCP MRCP Non-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities. Primary Sclerosing Cholangitis ( patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with implanted devices, such as a pacemaker Pacemaker A device designed to stimulate, by electric impulses, contraction of the heart muscles. It may be temporary (external) or permanent (internal or internal-external). Bradyarrhythmias)^[8]
    • Invasive
    • Carries risk of bacterial cholangitis and pancreatitis Pancreatitis Inflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis. Acute Pancreatitis^{[8, 16]}
  • Unlike MRCP MRCP Non-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities. Primary Sclerosing Cholangitis, ERCP ERCP Fiberoptic endoscopy designed for duodenal observation and cannulation of vater’s ampulla, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (vater) papillotomy may be performed during this procedure. Primary Sclerosing Cholangitis allows:
    • Brush cytology or biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma
    • Therapeutic intervention (in cases of obstruction)
  • Similar findings to MRCP MRCP Non-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities. Primary Sclerosing Cholangitis

Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma

• Rarely required for the diagnosis^[5,8,16]
• Will show:^[5,8,9]
  • Peribiliary duct proliferation
  • Periductal fibrosis Periductal Fibrosis Primary Sclerosing Cholangitis (“ onion skin Onion Skin Primary Sclerosing Cholangitis”): a characteristic histopathologic finding, though not seen frequently
  • Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
  • Loss of bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy ducts
  • Potential biliary cirrhosis Biliary cirrhosis Fibrosis of the hepatic parenchyma due to obstruction of bile flow (cholestasis) in the intrahepatic or extrahepatic bile ducts. Primary biliary cholangitis involves the destruction of small intrahepatic bile ducts and decreased bile secretion. Secondary biliary cholangitis is produced by prolonged obstruction of large intrahepatic or extrahepatic bile ducts from a variety of causes. Cystic Fibrosis
• Indications:
  • Presentation has overlap features with autoimmune hepatitis Autoimmune hepatitis Autoimmune hepatitis (AIH) is a rare form of chronic liver disease in which the immune system attacks the liver causing inflammation. It predominantly affects women. Clinical presentation ranges from asymptomatic cases to patients that present with symptoms of acute liver failure (jaundice, right upper quadrant pain). Autoimmune Hepatitis.^[5,8]
  • Small-duct PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis is suspected.
  • A dominant stricture Stricture Primary Sclerosing Cholangitis (suspect cholangiocarcinoma Cholangiocarcinoma A malignant tumor arising from the epithelium of the bile ducts. Rare Malignant Liver Tumors) is noted.^[8,9]
• Stages:^[16]
  • Stage 1 Stage 1 Trypanosoma brucei/African trypanosomiasis: Cholangitis or portal hepatitis 
  • Stage 2: Periportal fibrosis Periportal Fibrosis Schistosoma/Schistosomiasis or periportal hepatitis
  • Stage 3: Septal fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans, bridging necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage or both
  • Stage 4: Biliary cirrhosis Biliary cirrhosis Fibrosis of the hepatic parenchyma due to obstruction of bile flow (cholestasis) in the intrahepatic or extrahepatic bile ducts. Primary biliary cholangitis involves the destruction of small intrahepatic bile ducts and decreased bile secretion. Secondary biliary cholangitis is produced by prolonged obstruction of large intrahepatic or extrahepatic bile ducts from a variety of causes. Cystic Fibrosis

Complications and Management

Complications

Primary sclerosing cholangitis Primary Sclerosing Cholangitis Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis is a progressive and chronic disease that causes inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation in the bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy ducts, which can lead to several complications:

• Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema):^[5,8]
  • Leads to dermatologic complications
  • Debilitating; contributes to a poor quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life
• Biliary cirrhosis Biliary cirrhosis Fibrosis of the hepatic parenchyma due to obstruction of bile flow (cholestasis) in the intrahepatic or extrahepatic bile ducts. Primary biliary cholangitis involves the destruction of small intrahepatic bile ducts and decreased bile secretion. Secondary biliary cholangitis is produced by prolonged obstruction of large intrahepatic or extrahepatic bile ducts from a variety of causes. Cystic Fibrosis → portal hypertension Portal hypertension Portal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension:
  • Varices
    • Platelet count: predicts presence of varices^[8]
    • Platelet count < 150 × 10³/dL indicates advanced disease and is associated with a higher risk of varices.^[5]
  • Ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites
  • Hepatic encephalopathy Encephalopathy Hyper-IgM Syndrome
• ↑ Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of malignancy Malignancy Hemothorax:
  • Cholangiocarcinoma Cholangiocarcinoma A malignant tumor arising from the epithelium of the bile ducts. Rare Malignant Liver Tumors:
    • Risk is at least 100 times higher in PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis.^[5] 
    • Risk factors include ↑ bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism, ulcerative colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis with colorectal cancer Colorectal cancer Colorectal cancer (CRC) is the 2nd leading cause of cancer-related deaths in the United States. Colorectal cancer is a heterogeneous disease that arises from genetic and epigenetic abnormalities, with influence from environmental factors. Colorectal Cancer, variceal bleeding, proctocolectomy, ↑ duration of IBD, and polymorphisms of the NKG2D gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics.^[8]
    •  Cancer antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination 19-9 ( CA CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts) 19-9): associated biomarker^[8]
  • Colorectal adenocarcinoma Colorectal adenocarcinoma Lynch syndrome:
    • ↑ Risk in PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis and IBD^[8]
    • Exposure of colonic mucosa to toxic bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance → may lead to carcinogenesis Carcinogenesis The origin, production or development of cancer through genotypic and phenotypic changes which upset the normal balance between cell proliferation and cell death. Carcinogenesis generally requires a constellation of steps, which may occur quickly or over a period of many years. Carcinogenesis^[5] 
    • PSC-associated colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy cancer, commonly found in the proximal colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy^[5]
  • Gallbladder cancer Gallbladder Cancer Cholecystectomy:
    • Gallbladder polyps Gallbladder Polyps Cholecystectomy also develop, and those reaching > 8 mm have increased risk for malignancy Malignancy Hemothorax.^[5]
    • Gallbladder Gallbladder The gallbladder is a pear-shaped sac, located directly beneath the liver, that sits on top of the superior part of the duodenum. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Gallbladder and Biliary Tract: Anatomy masses/polyps in PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis were found to be malignant in 40%–60% of cases.^[8,12]
  • Hepatocellular carcinoma Hepatocellular carcinoma Hepatocellular carcinoma (HCC) typically arises in a chronically diseased or cirrhotic liver and is the most common primary liver cancer. Diagnosis may include ultrasound, CT, MRI, biopsy (if inconclusive imaging), and/or biomarkers. Hepatocellular Carcinoma (HCC) and Liver Metastases: low risk compared to above cancers^[11]
• Cholelithiasis Cholelithiasis Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis, choledocholithiasis Choledocholithiasis Presence or formation of gallstones in the common bile duct. Cholelithiasis, and acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis
  • Gallstones Gallstones Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis are seen in about 25% of cases.^[5] 
  • Stagnant bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy (especially in dominant strictures) can lead to bacterial colonization Colonization Bacteriology and cholangitis.^[8]
• Fat-soluble vitamin Fat-soluble Vitamin Fat-soluble vitamins are absorbed and stored in adipose tissue (fat) and the liver. These vitamins can be released from storage and used when necessary. The 4 important fat-soluble vitamins are A, D, E, and K. Fat-soluble Vitamins and their Deficiencies deficiencies (A, D, E, K):
  • Rare, generally seen in advanced disease
  • Due to ↓ secretion Secretion Coagulation Studies of conjugated bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance
• Osteopenia Osteopenia Osteoporosis or osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis: Mechanism is unclear.
  • Osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis: 4%–10%^[8]
  • Metabolic bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types disease is ↑ with IBD, higher age, and lower body mass index Body mass index An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity.^[5]

Management

Specific recommendations may vary depending on practice location. To review guideline details, information can be accessed at AASLD, ACG, British Society of Gastroenterology, EASLD.

Medical management (no proven medical therapy to prevent progression of PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis): 

• Ursodeoxycholic acid Ursodeoxycholic acid An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic. Primary Biliary Cholangitis:^[5,16]
  • Currently not recommended as routine therapy^{[8, 9]}
  • Improves biochemical tests but provides no definite benefit in terms of need for transplantation
  • Does not improve survival
• Other immunosuppressive and anti-inflammatory agents have not shown a benefit.^[5]
• Therapy for other associated conditions:
  • Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema):^[5,9]
    • Cholestyramine Cholestyramine A strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium cl(-) anion. Lipid Control Drugs 4–16 g/day is 1st-line therapy.
    • Rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis 150–300 mg twice a day and naltrexone Naltrexone Derivative of noroxymorphone that is the n-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. Opioid Analgesics (up to 50 mg/day) are 2nd-line options.
  • PSC-AIH overlap syndrome: Corticosteroids Corticosteroids Chorioretinitis and immunosuppressive agents are recommended.^[8]
  • IgG4-associated cholangitis: Corticosteroids Corticosteroids Chorioretinitis may be given.^[9]
  • Bacterial cholangitis:^[8]
    • Antibiotics are recommended.
    • When bacterial cholangitis becomes recurrent, prophylactic antibiotics are given.

ERCP ERCP Fiberoptic endoscopy designed for duodenal observation and cannulation of vater’s ampulla, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (vater) papillotomy may be performed during this procedure. Primary Sclerosing Cholangitis (endoscopic management):

• Duct dilation and stenting for biliary strictures:
  • Goal: relieve biliary obstruction (as this eventually leads to jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice, pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema), worsening biochemical test results, and liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy decompensation)
  • Balloon dilatation (with or without stenting) recommended in dominant stricture Stricture Primary Sclerosing Cholangitis, pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema), or cholangitis^[5,8]
  • In unsuccessful endoscopic treatment of dominant strictures, consider percutaneous approach (carries higher morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status).^[8]
  • Antibiotics are given prior to procedure to prevent cholangitis ( quinolones Quinolones A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or nalidixic acid. Fluoroquinolones or cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins have been used).^[5,9]
• Complications of therapeutic endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) include:^[8]
  • Cholangitis
  • Pancreatitis Pancreatitis Inflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis. Acute Pancreatitis
  • Hemorrhage
  • Biliary tract Biliary tract Bile is secreted by hepatocytes into thin channels called canaliculi. These canaliculi lead into slightly larger interlobular bile ductules, which are part of the portal triads at the “corners” of hepatic lobules. The bile leaves the liver via the right and left hepatic ducts, which join together to form the common hepatic duct. Gallbladder and Biliary Tract: Anatomy perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis
• Screening Screening Preoperative Care for cholangiocarcinoma Cholangiocarcinoma A malignant tumor arising from the epithelium of the bile ducts. Rare Malignant Liver Tumors:
  • Cholangiocarcinoma Cholangiocarcinoma A malignant tumor arising from the epithelium of the bile ducts. Rare Malignant Liver Tumors develops in about 15% of cases.^[8]
  • Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma is performed when a dominant stricture Stricture Primary Sclerosing Cholangitis is noted.^[5,8,9]

Liver transplantation Liver transplantation The transference of a part of or an entire liver from one human or animal to another. Hepatocellular Carcinoma (HCC) and Liver Metastases: 

• The only definitive treatment
• Indications:
  • Recurrent acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis^[8]
  • End-stage liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease complications (intractable ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites, hepatic encephalopathy Encephalopathy Hyper-IgM Syndrome, esophageal varices)
  • Refer when Model for End-stage Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy Disease (MELD) score > 14^[5]  or UKELD score > 48^[9] 
  • Cholangiocarcinoma Cholangiocarcinoma A malignant tumor arising from the epithelium of the bile ducts. Rare Malignant Liver Tumors^[8]
  • Intractable pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema)^[8]
• Outcome:^[5,8,16]
  • 5-year survival rate: 85%
  • Disease recurrence rate: 20%–25% (in 5‒10 years) 
  • Retransplantation rate higher in PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis than in other liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy diseases

Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy surveillance Surveillance Developmental Milestones and Normal Growth:

• Serum liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy tests ( alkaline phosphatase Alkaline Phosphatase An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. Osteosarcoma ( ALP ALP An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. Osteosarcoma), bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism, albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests, aminotransferases), platelet count, PT/INR every 6–12 months^[14]
• Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy elastography (or serum fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans tests) every 2–3 years^[8,14] 

Additional procedures:

• Screen for varices: upper endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) is recommended in those with platelet count < 150 x 10³/dL (due to risk of varices).^[5]
• In PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis with gallbladder polyps Gallbladder Polyps Cholecystectomy (which has increased risk of gallbladder cancer Gallbladder Cancer Cholecystectomy), recommendations vary:
  • European and American Association for the Study of Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy diseases: Perform cholecystectomy Cholecystectomy Cholecystectomy is a surgical procedure performed with the goal of resecting and extracting the gallbladder. It is one of the most common abdominal surgeries performed in the Western world. Cholecystectomy is performed for symptomatic cholelithiasis, cholecystitis, gallbladder polyps > 0.5 cm, porcelain gallbladder, choledocholithiasis and gallstone pancreatitis, and rarely, for gallbladder cancer. Cholecystectomy regardless of size.^[8,13] 
  • American College of Gastroenterology: Perform cholecystectomy Cholecystectomy Cholecystectomy is a surgical procedure performed with the goal of resecting and extracting the gallbladder. It is one of the most common abdominal surgeries performed in the Western world. Cholecystectomy is performed for symptomatic cholelithiasis, cholecystitis, gallbladder polyps > 0.5 cm, porcelain gallbladder, choledocholithiasis and gallstone pancreatitis, and rarely, for gallbladder cancer. Cholecystectomy if > 8 mm.^[5]

Cancer screening Screening Preoperative Care:

• Gallbladder cancer Gallbladder Cancer Cholecystectomy and cholangiocarcinoma Cholangiocarcinoma A malignant tumor arising from the epithelium of the bile ducts. Rare Malignant Liver Tumors:^[5,8]
  • Serial imaging (US, abdominal computed tomography (CT), or MRI with MRCP MRCP Non-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities. Primary Sclerosing Cholangitis) every 6–12 months
  • Periodic CA CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts) 19-9
• Colorectal cancer Colorectal cancer Colorectal cancer (CRC) is the 2nd leading cause of cancer-related deaths in the United States. Colorectal cancer is a heterogeneous disease that arises from genetic and epigenetic abnormalities, with influence from environmental factors. Colorectal Cancer:
  • Colonoscopy Colonoscopy Endoscopic examination, therapy or surgery of the luminal surface of the colon. Colorectal Cancer Screening with biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma is recommended at the time of diagnosis of PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis and annually for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with IBD^[5,8,9]
• Hepatocellular carcinoma Hepatocellular carcinoma Hepatocellular carcinoma (HCC) typically arises in a chronically diseased or cirrhotic liver and is the most common primary liver cancer. Diagnosis may include ultrasound, CT, MRI, biopsy (if inconclusive imaging), and/or biomarkers. Hepatocellular Carcinoma (HCC) and Liver Metastases:^[9]
  • Performed in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
  • Abdominal US and alpha-fetoprotein Alpha-fetoprotein The first alpha-globulins to appear in mammalian sera during fetal development and the dominant serum proteins in early embryonic life. Hepatocellular Carcinoma (HCC) and Liver Metastases ( AFP AFP The first alpha-globulins to appear in mammalian sera during fetal development and the dominant serum proteins in early embryonic life. Hepatocellular Carcinoma (HCC) and Liver Metastases) every 6 months

General health maintenance:

• Screening Screening Preoperative Care and treatment for osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis^[5,8]
  • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types density test is recommended on diagnosis of PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis, with retesting every 2‒4 years.
  • Bisphosphonate therapy (e.g., alendronate Alendronate A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis. Bisphosphonates) + calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes and vitamin D Vitamin D A vitamin that includes both cholecalciferols and ergocalciferols, which have the common effect of preventing or curing rickets in animals. It can also be viewed as a hormone since it can be formed in skin by action of ultraviolet rays upon the precursors, 7-dehydrocholesterol and ergosterol, and acts on vitamin D receptors to regulate calcium in opposition to parathyroid hormone. Fat-soluble Vitamins and their Deficiencies for those with osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis.
  • In patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis and esophageal varices, parenteral bisphosphonate is recommended (as oral forms can ↑ ulcers).^[5]
• Screening Screening Preoperative Care and supplementation for fat-soluble vitamin Fat-soluble Vitamin Fat-soluble vitamins are absorbed and stored in adipose tissue (fat) and the liver. These vitamins can be released from storage and used when necessary. The 4 important fat-soluble vitamins are A, D, E, and K. Fat-soluble Vitamins and their Deficiencies deficiencies in advanced disease^[5,9]

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

• Median survival (without liver transplantation Liver transplantation The transference of a part of or an entire liver from one human or animal to another. Hepatocellular Carcinoma (HCC) and Liver Metastases) is 10–12 years.^[6,16]
• Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas is worse in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with concurrent IBD.^[2]
• Major factors that affect survival: liver failure Liver failure Severe inability of the liver to perform its normal metabolic functions, as evidenced by severe jaundice and abnormal serum levels of ammonia; bilirubin; alkaline phosphatase; aspartate aminotransferase; lactate dehydrogenases; and albumin/globulin ratio. Autoimmune Hepatitis and cholangiocarcinoma Cholangiocarcinoma A malignant tumor arising from the epithelium of the bile ducts. Rare Malignant Liver Tumors^[16]

Differential Diagnosis

Primary sclerosing cholangitis Primary Sclerosing Cholangitis Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis should be differentiated from primary biliary cholangitis Primary Biliary Cholangitis Primary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis. Primary Biliary Cholangitis ( PBC PBC Primary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis. Primary Biliary Cholangitis), because the 2 conditions are similar in presentation:

• PBC PBC Primary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis. Primary Biliary Cholangitis: autoimmune destruction of the intrahepatic bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy ducts. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are typically women, and may present with pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema), fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, and evidence of cholestasis or cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis. Diagnosis is made with elevated liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes, AMAs, and liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma, which will differentiate PBC PBC Primary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis. Primary Biliary Cholangitis from PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis. Management includes ursodeoxycholic acid Ursodeoxycholic acid An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic. Primary Biliary Cholangitis, vitamin supplementation, and liver transplantation Liver transplantation The transference of a part of or an entire liver from one human or animal to another. Hepatocellular Carcinoma (HCC) and Liver Metastases for advanced disease.
• Bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct obstruction: an obstruction of the biliary system that may be due to gallstones Gallstones Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis, malignancy Malignancy Hemothorax, or trauma. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with acute jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice and right upper abdominal pain Abdominal Pain Acute Abdomen. Diagnosis will show elevated liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes, and imaging (US or MRCP MRCP Non-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities. Primary Sclerosing Cholangitis) will differentiate bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct obstruction from PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis. Treatment is based on the etiology. 
• Autoimmune hepatitis Autoimmune hepatitis Autoimmune hepatitis (AIH) is a rare form of chronic liver disease in which the immune system attacks the liver causing inflammation. It predominantly affects women. Clinical presentation ranges from asymptomatic cases to patients that present with symptoms of acute liver failure (jaundice, right upper quadrant pain). Autoimmune Hepatitis: an autoimmune disease causing chronic inflammation Chronic Inflammation Inflammation of the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy. The clinical presentation ranges from asymptomatic, to symptoms of acute liver failure Liver failure Severe inability of the liver to perform its normal metabolic functions, as evidenced by severe jaundice and abnormal serum levels of ammonia; bilirubin; alkaline phosphatase; aspartate aminotransferase; lactate dehydrogenases; and albumin/globulin ratio. Autoimmune Hepatitis. Serum anti-smooth muscle antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions and liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma will determine the diagnosis and differentiate autoimmune hepatitis Autoimmune hepatitis Autoimmune hepatitis (AIH) is a rare form of chronic liver disease in which the immune system attacks the liver causing inflammation. It predominantly affects women. Clinical presentation ranges from asymptomatic cases to patients that present with symptoms of acute liver failure (jaundice, right upper quadrant pain). Autoimmune Hepatitis from PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis. Treatment is with corticosteroids Corticosteroids Chorioretinitis and azathioprine Azathioprine An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the fourth annual report on carcinogens, this substance has been listed as a known carcinogen. Immunosuppressants. With early treatment, the prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas is favorable.
• Acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis: a life-threatening condition characterized by fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice, and abdominal pain Abdominal Pain Acute Abdomen that develops as a result of stasis and infection of the biliary tract Biliary tract Bile is secreted by hepatocytes into thin channels called canaliculi. These canaliculi lead into slightly larger interlobular bile ductules, which are part of the portal triads at the “corners” of hepatic lobules. The bile leaves the liver via the right and left hepatic ducts, which join together to form the common hepatic duct. Gallbladder and Biliary Tract: Anatomy. Biliary strictures from PSC PSC Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis may precipitate acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis. The diagnosis is confirmed with elevated liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy tests, leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus, and an US showing dilation of the common bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct or gallstones Gallstones Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis. Treatment includes hemodynamic stabilization, broad-spectrum Broad-Spectrum Fluoroquinolones antibiotics, urgent biliary drainage, and cholecystectomy Cholecystectomy Cholecystectomy is a surgical procedure performed with the goal of resecting and extracting the gallbladder. It is one of the most common abdominal surgeries performed in the Western world. Cholecystectomy is performed for symptomatic cholelithiasis, cholecystitis, gallbladder polyps > 0.5 cm, porcelain gallbladder, choledocholithiasis and gallstone pancreatitis, and rarely, for gallbladder cancer. Cholecystectomy to prevent recurrence.