Differentials

Common

Alcoholic liver disease

History

10-12 years of heavy alcohol consumption (>40-80 g/day for men and 20-40 g/day for women), abdominal pain, pruritus, generalised malaise, weight loss, fatigue, anorexia, cachexia, pale stool, dark urine, melaena, or haematemesis

Exam

generalised wasting, gynaecomastia, altered mental status, asterixis or altered deep tendon reflexes, ecchymosis or petechiae, spider angioma, thenar eminence loss, palmar erythema, caput medusae, ascites, hepatosplenomegaly or small liver, pleural effusion, right heart failure, positive rectal examination (blood)

1st investigation
  • serum liver function tests:

    aspartate aminotransferase (AST) and alanine aminotransferase (ALT) rarely >200 U/L; raised serum bilirubin; low albumin

  • AST:ALT ratio:

    more than 2:1 in alcoholic liver disease, reflecting lower ALT activity in these patients[100]

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  • prothrombin time (PT)/INR:

    elevated

    More
  • FBC:

    low platelet count; high WBC count

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  • urea:

    elevated

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  • CAGE score:

    >2

    More
  • Alcohol Use Disorders Identification Test (AUDIT)-C score:

    >5

    More
  • abdominal ultrasound:

    usually hyperechoic due to fatty infiltration, may describe mixed echogenicity; possibly nodular liver in cirrhotic patients with evidence of portal hypertension, splenomegaly, and ascites

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Other investigations
  • upper gastrointestinal endoscopy:

    varices

  • chest x-ray:

    may show consolidation

    More
  • urine culture:

    may be positive

    More
  • blood culture:

    may be positive

    More
  • culture of ascitic fluid:

    may be positive

    More

Choledocholithiasis

History

right upper quadrant (RUQ) pain, aggravated by meals, fever

Exam

RUQ abdominal tenderness, fever (in cholecystitis)

1st investigation
  • serum liver function tests:

    high direct bilirubin, gamma glutamyl transferase, and alkaline phosphatase

  • prothrombin time/INR:

    usually normal or mildly increased due to reduced vitamin K absorption

  • FBC:

    elevated white blood cell count

  • abdominal ultrasound:

    intra- and extrahepatic biliary tree dilatation with/without stone(s) in the common bile duct

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Other investigations
  • serum cholesterol:

    may be increased

  • magnetic resonance cholangiopancreatography (MRCP):

    stone(s) in the bile duct

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  • endoscopic ultrasound:

    stone(s) in the bile duct

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  • CT:

    partially calcified biliary calculi; complications such as cholangitis, cholecystitis, pancreatitis

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  • endoscopic retrograde cholangiopancreatography (ERCP):

    stone(s) in the bile duct

    More

Hepatitis A

History

may be history of risk factors (e.g., travel to endemic part of the world, close contact with known infected person, known food-borne outbreak), anorexia, nausea, vomiting, diarrhoea, abdominal pain, weight loss

Exam

abdominal tenderness, tender hepatosplenomegaly, lymphadenopathy, jaundice; fulminant infection: worsening jaundice, ascites, signs of encephalopathy (e.g., memory, attention, and concentration deficits, confusion, asterixis, nystagmus, clonus, rigidity, coma)

1st investigation
  • serum liver function tests:

    high direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma glutamyl transferase

  • serum IgM anti-hepatitis A virus:

    positive

  • prothrombin time/INR:

    may be increased

  • FBC:

    low or normal platelet count

Other investigations

    Hepatitis B

    History

    may be history of risk factor (e.g., travel to endemic part of the world, high-risk sexual history, intravenous drug use), may have minimal or no symptoms, may have lethargy, nausea, vomiting, abdominal pain; acute presentation (uncommon): worsening jaundice and lethargy, confusion; chronic infection with late complications: pruritus, abdominal swelling, haematemesis, melaena, confusion, lethargy, weight loss, weakness, bruising

    Exam

    acute infection: usually normal, but may have jaundice, tender hepatomegaly, and if severe: signs of encephalopathy (e.g., memory, attention, and concentration deficits, confusion, asterixis, nystagmus, clonus, rigidity, coma); chronic infection: may have jaundice, muscle wasting, gynaecomastia, palmar erythema, spider angiomata, petechiae, ascites, distended abdominal veins, hepatosplenomegaly, signs of encephalopathy

    1st investigation
    • serum liver function tests:

      high direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma glutamyl transferase

    • prothrombin time/INR:

      may be increased

    • FBC:

      low or normal platelet count

    • serum hepatitis B surface antigen (HBsAg):

      positive - appears 2-10 weeks after exposure to hepatitis B virus (HBV); in self-limiting acute HBV infection, HBsAg usually becomes undetectable after 4-6 months of infection; persistence of HBsAg for >6 months implies chronic HBV infection[101]

    • serum anti-hepatitis B core antigen (anti-HBc) IgM:

      positive - appears within weeks of acute infection and remains detectable for 4-8 months; during the window period (several weeks to months) after the disappearance of HBsAg and before the appearance of anti-HBs, detection of IgM anti-HBc may be the only way to make the diagnosis of acute HBV infection

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    • serum hepatitis B e antigen (HBeAg):

      positive

      More
    • hepatitis B virus DNA:

      elevated

    Other investigations
    • abdominal ultrasound:

      cirrhosis; hepatocellular carcinoma

    Hepatitis C

    History

    may be history of risk factors, (e.g., intravenous drug use, blood transfusion before 1992 in the US, high-risk sexual history); acute infection: usually asymptomatic, may be fatigue, jaundice; chronic infection: may be asymptomatic, but possible symptoms related to cirrhosis and its complications, such as pruritus, abdominal swelling, haematemesis, melaena, confusion, lethargy, weight loss, weakness, bruising

    Exam

    early disease: normal examination; late disease with chronic infection: may be jaundice, muscle wasting, gynaecomastia, palmar erythema, spider angiomata, petechiae, ascites, distended abdominal veins, hepatosplenomegaly, signs of encephalopathy (e.g., memory, attention, and concentration deficits, confusion, asterixis, nystagmus, clonus, rigidity, coma)

    1st investigation
    • serum liver function tests:

      high direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma glutamyl transferase

    • prothrombin time/INR:

      may be increased

    • FBC:

      low or normal platelet count

    • anti-hepatitis C antibody:

      positive; negative antibodies do not rule out hepatitis C virus infection in acute infection or in severely immunocompromised patients

    • nucleic acid amplification test:

      positive; detects viraemia in early infection

    Other investigations
    • abdominal ultrasound:

      may show cirrhosis and evidence of portal hypertension

    Drug-induced liver injury

    History

    over 100 drugs implicated, right upper quadrant pain, pruritus, generalised malaise, weight loss, fatigue, anorexia, pale stool, dark urine; risk factors for drug-induced liver injury include age, female sex, African-American race, alcohol consumption, pregnancy, and chronic liver disease[27]

    Exam

    tender hepatosplenomegaly, lymphadenopathy

    1st investigation
    • serum liver function tests:

      high total bilirubin, alanine aminotransferase, and aspartate aminotransferase

    • prothrombin time/INR:

      increased

    • FBC:

      low or normal platelet count, high white blood cell count

    • abdominal ultrasound:

      non-specific findings

    • serum paracetamol:

      elevated if overdose, may be normal in staggered overdose

    Other investigations

      Ascending cholangitis

      History

      chills, pain, pale stools, dark urine, pruritus, generalised malaise, weight loss, fatigue, anorexia

      Exam

      Charcot's triad: fever, right upper quadrant tenderness, jaundice

      1st investigation
      • serum liver function tests:

        high direct bilirubin, gamma glutamyl transferase, and alkaline phosphatase

      • prothrombin time/INR:

        may be increased

      • FBC:

        elevated white blood cell count

      • CRP:

        elevated

      • abdominal ultrasound:

        biliary dilatation and stone(s) in bile duct

      Other investigations
      • magnetic resonance cholangiopancreatography:

        stone(s) in the bile duct

      • endoscopic ultrasound:

        stone(s) in the bile duct

      • endoscopic retrograde cholangiopancreatography:

        bile duct obstruction; pus draining from the biliary tree

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      Pancreatic carcinoma

      History

      often asymptomatic until late disease, depression, weight loss, early satiety, new-onset diabetes, abdominal pain, pruritus, generalised malaise, fatigue, anorexia, pale stool, dark urine

      Exam

      positive Courvoisier's law/sign, palpable gallbladder, ill-appearing, cachectic

      1st investigation
      • serum liver function tests:

        high direct bilirubin, alkaline phosphatase, and gamma glutamyl transferase

      • prothrombin time/INR:

        may be increased

      • FBC:

        low or normal platelet count, Hb, and haematocrit

      • abdominal ultrasound:

        pancreatic mass and dilated common bile duct ± pancreatic duct dilatation

      Other investigations
      • CT:

        pancreatic mass and dilated bile duct ± pancreatic duct dilatation

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      • fluorodeoxyglucose-positron emission tomography/CT (FDG‑PET/CT):

        increased FDG activity of pancreatic lesion

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      • linear endoscopic ultrasound:

        pancreatic mass

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      • endoscopic retrograde cholangiopancreatography (ERCP):

        bile duct and pancreatic duct strictures

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      Liver metastases

      History

      history of malignancy (colorectal, breast, lung, lymphoma); weight loss, fatigue, abdominal swelling

      Exam

      jaundice, hepatomegaly, ascites, cachexia, signs of other malignancies

      1st investigation
      • serum liver function tests:

        raised transaminases suggest hepatocyte destruction; raised alkaline phosphatase and gamma glutamyl transferase suggest cholestasis caused by external compression of the biliary tree

      • prothrombin time/INR:

        may be increased

      • abdominal ultrasound:

        identifies metastases and biliary duct dilatation

      Other investigations
      • CT chest, abdomen, pelvis:

        identifies extent of intra-abdominal tumour, and may identify primary malignancy if not already known

      Haemolytic anaemia

      History

      fever or chills, family history of haemolytic disorders, abdominal pain, pruritus, generalised malaise, weight loss, fatigue, anorexia, dark urine

      Exam

      new onset of pallor, splenomegaly

      1st investigation
      • serum liver function tests:

        high indirect bilirubin with normal or minimally elevated aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase

      • FBC:

        low Hb

      • direct/indirect bilirubin:

        elevated indirect bilirubin

      • abdominal ultrasound:

        non-specific

      Other investigations
      • LDH:

        elevated

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      • haptoglobin:

        decreased

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      • peripheral blood smear:

        sickle cells, schistocytes, or target cells

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      • reticulocyte count:

        elevated

      • serum direct antiglobulin test (Coombs' test):

        positive

        More
      • serum indirect antiglobulin test (Coombs' test):

        may detect drug-induced autoantibodies

      Decompensated cirrhosis

      History

      known chronic liver disease; recent infection may precipitate decompensation; may report haematemesis or melaena

      Exam

      jaundice, ascites; stigmata of chronic liver disease including generalised wasting, gynaecomastia, ecchymosis or petechiae, spider angioma, thenar eminence loss, palmar erythema, caput medusae; signs of hepatic encephalopathy including shortened attention span, confusion, impaired addition or subtraction, disorientation in time and/or space, dyspraxia, asterixis, hyperreflexia, nystagmus, clonus, and rigidity; melaena

      1st investigation
      • serum liver function tests:

        elevated bilirubin; variable derangement of alanine aminotransferase, aspartate aminotransferase and/or alkaline phosphatase

      • prothrombin time/INR:

        elevated (>1.5)

      • FBC:

        thrombocytopenia

      • urea:

        elevated following an upper gastrointestinal bleed

      • CRP:

        elevated in infection

      • full metabolic profile:

        hyponatraemia; abnormal calcium, phosphorus, or magnesium levels; hypoglycaemia

      • culture of ascitic fluid:

        may be positive

        More
      • blood culture:

        may be positive

        More
      • chest x-ray:

        may show pneumonia or pleural effusion

        More
      • urine culture:

        may be positive

        More
      • ultrasound:

        ascites, splenomegaly

      Other investigations
      • CT:

        may demonstrate hepatocellular carcinoma

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      • echocardiogram:

        normal

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      • upper gastrointestinal endoscopy:

        may detect variceal bleed

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      Acute liver failure

      History

      abdominal discomfort, nausea, vomiting, anorexia; relatives may report personality changes; may be history of paracetamol overdose or other drug ingestion, risk factors for viral hepatitis, history of shock (predisposes to ischaemic hepatitis); may be past medical history of hypercoagulable state (Budd-Chiari syndrome); may be a family history of Wilson's disease

      Exam

      hepatomegaly and right upper quadrant tenderness may be present; signs of hepatic encephalopathy include shortened attention span, confusion, impaired addition or subtraction, disorientation in time and/or space, dyspraxia, asterixis, hyperreflexia, nystagmus, clonus, and rigidity; stigmata of chronic liver disease are absent

      1st investigation
      • prothrombin time/INR:

        elevated (>1.5)

      • serum liver function tests:

        hyperbilirubinaemia, elevated liver enzymes

      • basic metabolic panel:

        may be elevated urea and creatinine, metabolic derangements

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      • FBC:

        leukocytosis, anaemia, thrombocytopenia

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      • arterial blood gas:

        metabolic acidosis

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      • paracetamol level:

        may be elevated; however, low paracetamol levels do not exclude paracetamol hepatotoxicity

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      Other investigations
      • viral hepatitis serologies:

        may be positive

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      • autoimmune hepatitis markers:

        may be positive

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      • pregnancy test:

        may be positive

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      • chest x-ray:

        possible aspiration pneumonia

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      • abdominal ultrasound with Doppler:

        hepatic vessel thrombosis, loss of hepatic venous signal, and reverse flow in the portal vein in Budd-Chiari syndrome; hepatomegaly, splenomegaly, hepatic surface nodularity

      • work-up for Wilson's disease:

        low serum ceruloplasmin; elevated serum copper; elevated 24-hour urinary copper excretion, Kayser-Fleischer rings present on slit-lamp ophthalmological examination

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      • CT scan of head:

        cerebral oedema, haemorrhage

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      Acute-on-chronic liver failure

      History

      history of acute hepatic insult in a patient with chronic liver disease (e.g., sepsis, active alcohol misuse); jaundice, ascites, abdominal discomfort, nausea, vomiting, anorexia; relatives may report personality changes; may be signs of variceal bleeding (e.g., haematemesis, melaena)

      Exam

      jaundice, ascites; stigmata of chronic liver disease including generalised wasting, gynaecomastia, ecchymosis or petechiae, spider angioma, thenar eminence loss, palmar erythema, caput medusae; signs of hepatic encephalopathy including shortened attention span, confusion, impaired addition or subtraction, disorientation in time and/or space, dyspraxia, asterixis, hyperreflexia, nystagmus, clonus, and rigidity

      1st investigation
      • prothrombin time/INR:

        elevated (>1.5)

      • serum liver function tests:

        hyperbilirubinaemia, elevated liver enzymes

      • FBC:

        elevated white cell count

      • CRP:

        elevated

      • serum electrolytes, urea, and creatinine:

        elevated urea and creatinine; hyponatraemia

      Other investigations
      • paracetamol level:

        may be elevated

        More
      • upper gastrointestinal endoscopy:

        may detect variceal bleed

        More
      • culture of ascitic fluid:

        may be positive

        More
      • blood culture:

        may be positive

        More
      • urine culture:

        may be positive

        More
      • chest x-ray:

        may show consolidation

        More

      Uncommon

      Gilbert's syndrome

      History

      young adult, more common in males, often asymptomatic or non-specific symptoms (abdominal cramps, fatigue, malaise)

      Exam

      normal other than icterus

      1st investigation
      • serum liver function tests:

        high indirect bilirubin; normal alkaline phosphatase

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      • prothrombin time/INR:

        normal

      • FBC:

        normal

      Other investigations
      • blood smear:

        normal

      • reticulocyte count:

        normal

      Hepatitis E

      History

      may be history of risk factors (e.g., travel to Southeast Asia, northern and central Africa, India, and Central America), exposure to pigs or undercooked pork; more common in middle-aged/older men; anorexia, nausea and vomiting, diarrhoea, abdominal pain, pruritus, myalgia, neurological symptoms (5% of patients); pregnancy is associated with more florid disease; patients with pre-existing liver disease have a high risk of decompensation and a 70% mortality

      Exam

      may be normal; abdominal tenderness, tender hepatosplenomegaly, lymphadenopathy, jaundice, ascites, signs of encephalopathy (e.g., memory, attention, and concentration deficits, confusion, asterixis, nystagmus, clonus, rigidity, coma)

      1st investigation
      • serum liver function tests:

        high direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma glutamyl transferase

      • prothrombin time/INR:

        may be increased

      • abdominal ultrasound:

        nonspecific

      Other investigations
      • serum anti-hepatitis E virus IgM antibodies:

        positive

        More
      • hepatitis E virus polymerase chain reaction:

        positive

      Hepatitis D

      History

      may be history of risk factors (e.g., infection with hepatitis B virus, high-risk sexual history, intravenous drug use), minimal or no symptoms; acute presentation (uncommon): jaundice, lethargy, confusion; chronic infection with late complications: itching, abdominal swelling, haematemesis, melaena, confusion, lethargy, weight loss, weakness, bruising

      Exam

      usually normal, but if severe acute infection may be jaundice, tender hepatomegaly, signs of encephalopathy (e.g., memory, attention, and concentration deficits, confusion, asterixis, nystagmus, clonus, rigidity, coma); chronic, late infection: may be jaundice, muscle wasting, gynaecomastia, palmar erythema, spider angiomata, petechiae, ascites, distended abdominal veins, hepatosplenomegaly, signs of encephalopathy

      1st investigation
      • serum liver function tests:

        high direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma glutamyl transferase

      • prothrombin time/INR:

        may be increased

      • FBC:

        low or normal platelet count

      • abdominal ultrasound:

        nonspecific

      Other investigations
      • serum IgM anti-hepatitis D virus:

        positive

      • serum total (IgM and IgG) anti-hepatitis D virus antibodies:

        positive

      • serum hepatitis B surface antigen (HBsAg):

        positive

      • serum anti-hepatitis B core antigen antibody:

        positive

      • serum hepatitis B e antigen (HBeAg):

        positive

        More

      Leptospirosis

      History

      history of direct or indirect contact with urine of infected animals or contaminated water; acute phase symptoms include fever, rigors, headache, calf muscle tenderness, abdominal pain, diarrhoea, nausea vomiting, asthenia, anorexia, and photophobia; immune phase symptoms occur 5 to 7 days later and include severe eye pain, headache, photophobia, pulmonary symptoms (cough, dyspnoea, chest pain, haemoptysis), palpitations, muscle tenderness, and mental status changes

      Exam

      acute/initial phase: high fever (up to 40℃ [104°F]), rigors, hypotension, tachycardia, lymphadenopathy, calf muscle tenderness; immune phase: consolidation secondary to pulmonary haemorrhage, crackles and wheeze secondary to pulmonary oedema; arrhythmias, nuchal rigidity, delirium, weakness and paralysis, mental status changes, focal neurological deficit; both phases: hepatosplenomegaly, abdominal tenderness, jaundice, bilateral conjunctival suffusion

      1st investigation
      • FBC:

        high WBC count; low platelet count; anaemia

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      • serum liver function tests:

        markedly elevated conjugated bilirubin levels, elevated aminotransferases or alkaline phosphatase

      • CRP:

        elevated

      • serum electrolytes, urea, and creatinine:

        elevated urea and creatinine; hypokalaemia

      • blood culture:

        positive after 1 week to 4 months

        More
      • enzyme-linked immunosorbent assay (ELISA):

        positive during immune phase

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      • urinalysis:

        mild proteinuria; pyuria; haematuria; hyaline or granular casts

      Other investigations
      • microscopic agglutination test (MAT):

        fourfold increase between acute and convalescent sera is diagnostic

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      • PCR:

        positive for leptospiral DNA

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      Immunoglobulin G4 (IgG4) cholangiopathy

      History

      epigastric and abdominal pain, jaundice, weight loss; typically men aged 50-60 years; may give history of new onset diabetes mellitus or diarrhoea associated with pancreatic insufficiency

      Exam

      epigastric tenderness, jaundice; may have lymphadenopathy, bibasal crepitation related to multisystemic manifestation

      1st investigation
      • serum liver function tests:

        high direct bilirubin, gamma glutamyl transferase, and alkaline phosphatase; mildly elevated aspartate aminotransferase and alanine aminotransferase

      • serum IgG4 level:

        ≥1.35 g/L (≥135 mg/dL)

      • abdominal ultrasound or CT scan:

        biliary dilatation with simultaneous intra- and extrahepatic duct dilatation

      Other investigations
      • magnetic resonance cholangiopancreatography:

        simultaneous strictures and radiological evidence of associated pancreatitis

      • endoscopic ultrasound:

        useful in obtaining tissue for histology; may reveal vascular involvement of the splenic, portal, and superior mesenteric veins

      • endoscopic retrograde cholangiopancreatography (ERCP):

        bile duct obstruction; pus draining from the biliary tree

        More

      Cholangiocarcinoma

      History

      pruritus, generalised malaise, weight loss, fatigue, anorexia, pale stool, dark urine

      Exam

      usually normal; cachectic

      1st investigation
      • serum liver function tests:

        high direct bilirubin, alkaline phosphatase, and gamma glutamyl transferase

      • prothrombin time/INR:

        may be increased

      • FBC:

        low or normal platelet count, Hb, and haematocrit

      • abdominal ultrasound:

        diagnosis suspected when intrahepatic ducts are dilated; intrahepatic cholangiocarcinoma may be seen as a mass lesion

      • abdominal CT or MRI:

        intrahepatic mass lesion, dilated intrahepatic ducts, and localised lymphadenopathy may be seen

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      Other investigations
      • endoscopic ultrasound:

        biliary dilation (intra- and extrahepatic) with extrahepatic mass causing obstruction/stricture

        More
      • magnetic resonance cholangiopancreatography:

        biliary stricture

      • endoscopic retrograde cholangiopancreatography (ERCP):

        biliary stricture

        More

      Hepatocellular carcinoma (HCC)

      History

      history of cirrhosis or chronic hepatitis B infection, jaundice, weight loss, right upper quadrant pain, abdominal distension

      Exam

      jaundice, hepatomegaly, cachexia, splenomegaly

      1st investigation
      • serum liver function tests:

        elevated aminotransferases, alkaline phosphatase, and bilirubin; low albumin

      • FBC:

        low platelet count is indicative of portal hypertension resulting from cirrhosis

      • prothrombin time/INR:

        normal or elevated

      • alpha fetoprotein (AFP):

        AFP level is elevated in 60% of patients with HCC, typically those with the most advanced disease; mild elevations may occur in patients with chronic hepatitis but not HCC[105]

      • ultrasound of liver:

        poorly defined margins and coarse, irregular internal echoes

      Other investigations
      • anti-hepatitis B core antigen (HBc) IgG:

        positive in chronic infection

      • anti-hepatitis C virus IgG:

        positive in chronic infection

      • CT scan of abdomen with contrast:

        hypervascular pattern; highly specific for HCC

      Post-operative stricture

      History

      gallbladder or bile duct surgery, abdominal pain, pruritus, fatigue, anorexia, pale stool, dark urine

      Exam

      often normal examination

      1st investigation
      • serum liver function tests:

        high direct bilirubin, alkaline phosphatase, and gamma glutamyl transferase

      • prothrombin time/INR:

        may be increased

      • FBC:

        low or normal platelet count, Hb, and haematocrit

      • abdominal ultrasound:

        non-specific

      • magnetic resonance cholangiopancreatography:

        biliary stricture

      Other investigations
      • endoscopic retrograde cholangiopancreatography (ERCP):

        biliary stricture

        More

      Primary sclerosing cholangitis

      History

      often asymptomatic, history of ulcerative colitis or Crohn's disease may be present; chills, night sweats, abdominal pain suggest infection; pruritus, generalised malaise, weight loss, fatigue, anorexia, pale stool, dark urine

      Exam

      usually normal, skin excoriations may be present

      1st investigation
      • serum liver function tests:

        high direct bilirubin, alkaline phosphatase, and gamma glutamyl transferase

      • prothrombin time/INR:

        may be increased

      • FBC:

        low or normal platelet count

        More
      • abdominal ultrasound:

        non-specific

        More
      • magnetic resonance cholangiopancreatography (MRCP):

        biliary strictures

        More
      Other investigations
      • endoscopic retrograde cholangiopancreatography (ERCP):

        biliary strictures

        More

      Primary biliary cholangitis

      History

      female, pruritus, fatigue, generalised malaise, weight loss, anorexia, pale stool, dark urine, keratoconjunctivitis, xerostomia

      Exam

      xanthelasma, hepatosplenomegaly, right upper quadrant pain, fatty subcutaneous deposits

      1st investigation
      • serum liver function tests:

        high direct bilirubin, alkaline phosphatase, and gamma glutamyl transferase

      • serum anti-mitochondrial antibody:

        positive

        More
      • serum cholesterol:

        usually elevated

        More
      • ultrasound:

        normal or cirrhosis

        More
      Other investigations
      • magnetic resonance cholangiopancreatography (MRCP):

        normal

        More

      Wilson's disease

      History

      family history may be positive; symptoms emerging in childhood, adolescence, or early adulthood; tremor, slurred speech, abdominal pain, pruritus, generalised malaise, weakness, weight loss, anorexia, pale stools, dark urine, irritability, depression, easy bruising

      Exam

      Kayser-Fleischer rings, parkinsonian-like tremor, rigidity, clumsy gait, poor balance, impaired coordination, abnormal postures, repetitive movements, bradykinesia (tongue, lips, and jaw), dysarthria, dysphonia (hoarse voice), inappropriate and uncontrollable grinning (risus sardonicus), drooling, hypermelanotic pigmentation, bruises, signs of dementia and/or psychosis, jaundice, hepatosplenomegaly

      1st investigation
      • serum liver tests:

        may be normal, elevated aspartate aminotransferase, alanine aminotransferase, direct bilirubin; alkaline phosphatase normal or below normal; alkaline phosphatase (ALP): bilirubin ratio of <4 has a high sensitivity and specificity for diagnosing acute liver failure secondary to Wilson's disease[104]

      • prothrombin time/INR:

        may be increased

      • FBC:

        may be normal; cirrhosis: low platelet count

      • abdominal ultrasound:

        non-specific

      • serum ceruloplasmin:

        decreased

        More
      • 24-hour urinary copper excretion:

        elevated

        More
      • slit-lamp ophthalmological examination:

        Kayser-Fleischer rings present in Wilson disease

      Other investigations
      • serum copper:

        usually decreased, occasionally normal or elevated

        More
      • liver biopsy with copper concentration:

        elevated copper

        More
      • genetic testing:

        positive (pattern of di- and trinucleotide repeats around ATP7B)

        More

      Hereditary haemochromatosis

      History

      asymptomatic or found after screening in patients with a positive family history; jaundice occurs in decompensated disease with established cirrhosis; rarely, patients present with symptoms of diabetes

      Exam

      usually normal; gynaecomastia, ascites, altered mental state, cachectic; in decompensated disease signs of chronic liver disease plus associated arthropathy

      1st investigation
      • serum liver function tests:

        high direct bilirubin, alkaline phosphatase, and gamma glutamyl transferase

      • prothrombin time/INR:

        may be increased

      • FBC:

        low or normal platelet count

      • serum iron, serum total iron binding capacity (TIBC), serum ferritin:

        high iron, low TIBC, high ferritin

      • serum transferrin saturation:

        >45%

      Other investigations
      • genetic test for haemochromatosis:

        positive for haemochromatosis gene mutation

      • liver biopsy:

        increased iron stores

        More

      Alpha-1 antitrypsin deficiency

      History

      family history of liver disease, abdominal pain, pruritus, generalised malaise, weight loss, fatigue, anorexia, emphysema

      Exam

      jaundice, asterixis, hepatomegaly, ascites; wheeze and/or chest hyper-inflation if emphysema is present

      1st investigation
      • serum liver function tests:

        high direct bilirubin, aspartate aminotransferase, and alanine aminotransferase and alkaline phosphatase

      • prothrombin time/INR:

        may be increased

      • FBC:

        low or normal platelet count

      • alpha-1 antitrypsin (AAT) serum level:

        <20 micromol/L (<108.7 mg/dL)

      Other investigations
      • phenotyping:

        characteristic AAT-variant proteins

        More
      • genotyping:

        presence of the alleles encoding the AAT-variant proteins

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      Parasitic infections

      History

      travel to endemic areas, abdominal pain, pruritus, generalised malaise, weight loss, fatigue, anorexia, pale stool, dark urine

      Exam

      cachexia, muscle wasting, tender abdomen, hepatomegaly

      1st investigation
      • stool for ova and parasites:

        positive

        More
      • serum liver function tests:

        high direct bilirubin, alkaline phosphatase, and gamma glutamyl transferase

      • prothrombin time/international normalised ratio:

        may be increased

      • FBC:

        low or normal platelet count

      • CRP:

        may be elevated

      • abdominal ultrasound:

        Ascaris lumbricoides: long, linear, echogenic structures; 4 lines sign or non-shadowing echogenic strips with central tube; Entamoeba histolytica liver abscess

      • Giemsa-stained thick and thin blood smears:

        Plasmodium falciparum trophozoites in infected erythrocytes

      Other investigations
      • cholangiography:

        Clonorchis sinensis: multiple saccular dilatations of intrahepatic bile ducts; periportal fibrosis

      • magnetic resonance cholangiopancreatography:

        parasite visualised in the bile duct

      • endoscopic retrograde cholangiopancreatography:

        parasite visualised in the bile duct

        More

      AIDS cholangiopathy

      History

      abdominal pain, pruritus, generalised malaise, weight loss, fatigue, anorexia, pale stool, dark urine, high-risk sexual activity (many partners, unprotected intercourse, intercourse with HIV-infected), HIV-positive, diarrhoea

      Exam

      cachexia, right upper quadrant and epigastric pain, fever

      1st investigation
      • serum liver function tests:

        high direct bilirubin, alkaline phosphatase, and gamma glutamyl transferase

      • prothrombin time/INR:

        may be increased

      • FBC:

        low or normal platelet count

      • abdominal ultrasound:

        non-specific

      Other investigations
      • endoscopic retrograde cholangiopancreatography:

        papillary stenosis and/or biliary strictures

      Heart failure

      History

      dyspnoea, paroxysmal nocturnal dyspnoea, orthopnoea, ascites; may be history of chest pain associated with myocardial infarction in ischaemic hepatitis; risk factors for heart failure (e.g., previous myocardial infarction, diabetes mellitus, hypertension, valvular heart disease, atrial fibrillation)

      Exam

      jaundice, hepatomegaly, ascites, hepatojugular reflux, cardiomegaly, elevated jugular venous pressure, third heart sound gallop rhythm, rales, signs of pleural effusion, peripheral oedema

      1st investigation
      • serum liver function tests:

        elevated bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase

        More
      • serum troponin:

        may be elevated

      • electrocardiogram:

        may show atrial fibrillation or left bundle branch block

      • chest x-ray:

        may show increased cardio-thoracic ratio and/or bilateral pleural effusions

      • echocardiogram:

        left ventricular impairment; may show valvular heart disease

      Other investigations

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