Differentials
Common
Hepatitis C
History
blood/body fluid exposure (e.g., history of drug use, blood transfusion)
Exam
other features of decompensated cirrhosis (e.g., jaundice, asterixis, confusion, altered consciousness, or coma); extrahepatic manifestations (e.g., vasculitis, renal complications, porphyria cutanea tarda).
1st investigation
- hepatitis C serology:
positive
- polymerase chain reaction for hepatitis C RNA:
positive
- hepatitis C genotype:
genotype 1-6
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Other investigations
- liver biopsy:
fibrosis and inflammation
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Alcohol-related liver disease
History
history of excessive drinking, jaundice, abdominal discomfort, nausea
Exam
jaundice, tender hepatomegaly, hepatic bruit, spider angiomas, palmar erythema, signs of hepatic encephalopathy
1st investigation
- serum gamma glutamyl transferase:
elevated
- hepatic profile:
elevated bilirubin, elevation of aspartate aminotransferase more than alanine aminotransferase
Other investigations
- prothrombin time:
prolonged
- albumin:
low
- ultrasound:
changes in reflectivity of liver parenchyma due to hepatitis
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Congestive heart failure
History
exertional dyspnea, fatigue limiting exercise tolerance, leg swelling, abdominal swelling, hypertension, diabetes, valvular heart disease, smoker, family history of sudden cardiac death, myocardial infarction, stroke, peripheral arterial disease, history of chest pain, cardiac interventions
Exam
peripheral edema, rales, dyspnea, jugular venous distention, cool extremities, narrow pulse pressure, pleural effusions
1st investigation
- brain natriuretic peptide (BNP)/N-terminal prohormone BNP:
elevated
More - ECG:
left ventricular hypertrophy (LVH)
- chest x-ray:
cardiomegaly, pleural effusions, fluid in horizontal fissure
- ascitic fluid total protein concentration:
≥2.5 g/dL
Other investigations
- echocardiogram with Doppler:
may have low left ventricular ejection fraction, LVH valvular function abnormalities, left ventricular dilatation
Nephrotic syndrome
History
abdominal distension/discomfort/pain, limb swelling, eye swelling, hypertension, history of oliguria
Exam
edema (orbital, scrotal, labial, or peripheral), abdominal distension, hypertension, hypovolemic episodes, orthostatic hypotension, tachycardia, peripheral vasoconstriction
1st investigation
- urinalysis:
heavy proteinuria
Other investigations
- serum albumin:
low
- serum cholesterol:
high
Pancreatitis
History
acute onset abdominal pain radiating to the back; nausea, vomiting
Exam
epigastric abdominal tenderness
1st investigation
Other investigations
- abdominal ultrasound:
may see ascites, gallstones, dilated common bile duct, and enlarged pancreas
More - CT scan of abdomen with oral and intravenous contrast:
may show pancreatic inflammation, peripancreatic stranding, calcifications, or fluid collections; confirms or excludes gallstones
More - magnetic imaging/magnetic resonance cholangiopancreatography (MRI/MRCP):
findings may include stones, tumors, diffuse or segmental enlargement of the pancreas with irregular contour and obliteration of the peripancreatic fat, necrosis, or pseudocysts
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Metabolic dysfunction-associated steatotic liver disease
History
often asymptomatic, may be obese, history of diabetes mellitus, hypertension, high triglyceride level, low HDL cholesterol, cardiac disease, sleep apnea; dull right upper quadrant discomfort
Exam
hypertension, acanthosis nigricans, striae, central obesity, jaundice; end-stage diagnosis: may have muscle wasting, gynecomastia, palmar erythema, spider angiomata, petechiae, scratch marks, 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 tests:
may be normal or elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST), bilirubin elevated in decompensated disease, alkaline phosphatase may be elevated up to twice the upper limit of normal
More - prothrombin time/INR:
may be normal; cirrhosis: may be elevated
- CBC:
initially normal; thrombocytopenia often occurs with cirrhosis
- metabolic panel:
abnormal
More - lipid panel:
elevated total cholesterol, LDL, triglyceride; low HDL
More - abdominal ultrasound:
hypoechoic areas (ovoid, round, or linear) within a hyperechoic (bright) liver; perihilar sparing frequently seen
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Other investigations
- abdominal CT scan with contrast:
low liver attenuation; no mass effect or contour deformation, intrahepatic vessels follow normal course through fatty lesions, without deformity
More - abdominal MRI:
T1-weighted images: areas of fatty infiltration with increased signal intensity
More - liver biopsy:
demonstrates macrovesicular steatosis, occasional Mallory hyaline bodies, balloon cells, lobular inflammation, perisinusoidal fibrosis
More - simple liver test-based algorithms:
risk stratification of patients by severity of fibrosis
More - transient elastography:
decreased liver elasticity; may show fibrosis/cirrhosis/advanced fibrosis
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Uncommon
Hepatitis B
History
perinatal exposure, sexual transmission (multiple sexual partners, men who have sex with men), injection drug use, living in or travel to a highly endemic region, incarceration, or a family history of HBV infection, chronic liver disease, and/or hepatocellular carcinoma.
Exam
may be normal or may have palmar erythema and spider angiomata, with or without signs of portal hypertension including jaundice, splenomegaly and asterixis
1st investigation
- hepatitis B serology:
positive
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Other investigations
- hepatitis B DNA:
positive
- liver biopsy:
presence of liver fibrosis and inflammation
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Primary biliary cholangitis
History
positive family history of either primary biliary cholangitis (PBC) itself or of other autoimmune disease; pruritus, fatigue
Exam
may be normal in early stages; spider nevi, skin excoriations, melanin pigmentation in the skin, xanthelasmas, xanthomas (uncommon), hepatomegaly, splenomegaly, jaundice, muscle wasting, edema
1st investigation
Other investigations
- antinuclear antibody immunofluorescence:
staining pattern either antinuclear rim (indicates reaction with nuclear pore complex) or multiple nuclear dots (indicates reaction with Sp100 protein), or both
More - serum immunoglobulin:
polyclonal elevation of IgM and IgG
More - liver biopsy:
bile duct lesions (biliary ductular cell disruption within inflamed portal tracts) and granulomata formation; later disease stages: bile duct loss (ductopenia) with progressive biliary fibrosis; a more inflammatory pattern with interface hepatitis can be seen in a minority of patients
More - transient elastography:
identifies and quantifies liver fibrosis
Autoimmune hepatitis
History
fatigue, arthralgia, polymyalgia, history of thyroid disease, rheumatoid arthritis, or ulcerative colitis
Exam
jaundice, right upper quadrant pain
1st investigation
Other investigations
- liver biopsy:
periportal lesion or interface hepatitis (a portal mononuclear and plasma cell infiltrate)
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Hemochromatosis
History
fatigue, skin pigmentation, diabetes (polyuria, polydipsia), sexual dysfunction, family history of liver disease, joint pain
Exam
signs of cardiac failure (rales, peripheral edema, jugular venous distension), arrhythmias, arthritis, hepatomegaly
1st investigation
- transferrin saturation:
>50% in men; >45% in women
Other investigations
- HFE mutation analysis:
C282Y mutation homozygosity (p.Cys282Tyr); less commonly compound heterozygosity (C282Y/H63D) and rare mutations
- MRI liver:
liver to muscle signal intensity <0.88
More - liver biopsy:
excessive iron deposition
Wilson disease
History
family history of liver disease or neurologic disease
Exam
Kayser-Fleischer ring, jaundice, dystonia, tremors, psychoses, may present in liver failure
1st investigation
- slit lamp:
detection of Kayser-Fleischer rings
- serum ceruloplasmin:
level of <5 mg/dL (<50 mg/L) strongly suggests Wilson disease but further testing is required to make the diagnosis
More - 24-hour urinary copper:
>100 micrograms (>40 micrograms may suggest Wilson disease and require further investigation)
- nonceruloplasmin-bound copper concentration:
elevated
Other investigations
- liver biopsy:
liver copper >250 micrograms/g
Constrictive pericarditis
History
history of open heart surgery, mantle chest radiation, tuberculous pericarditis, chest pain
Exam
pericardial rub, fever, jugular venous distention, hepatomegaly, pulsus paradoxus
1st investigation
- chest x-ray:
pleural effusion or pericardial calcification
- echocardiogram:
thickened pericardium, abnormal ventricular diastolic filling
- abdominal ultrasound with Doppler:
dilated portal vein, ascites, decreased cephalad flow or retrograde flow in portal vein on Doppler, nodular contour liver (not sensitive)
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Other investigations
- cardiac catheterization:
decrease in initial wedge left ventricular pressure gradient during first beat of inspiration, enhanced ventricular interaction causing discordance of left and right ventricular pressures
Budd-Chiari syndrome
History
jaundice, abdominal pain, nausea/vomiting, history of hereditary or acquired hypercoagulable states, myeloproliferative disorders, polycythemia vera, or inherited or acquired thrombophilia
Exam
jaundice, hepatomegaly, splenomegaly, absent hepatojugular reflex, dilated abdominal veins, dilated venous collaterals in the flanks and over the back, pedal edema
1st investigation
- Doppler ultrasound:
centrilobular liver necrosis
Other investigations
- MRI:
hepatic venous thrombosis
- hepatic venography:
spiderweb pattern, possible thrombus in inferior vena cava
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Chronic renal failure
History
abdominal distension/discomfort, limb swelling, eye swelling, hypertension
Exam
edema (orbital, scrotal, labial, or peripheral), abdominal distension, hypertension, oliguria
1st investigation
- serum BUN and creatinine:
elevated
Other investigations
- renal ultrasound:
usually small kidneys
Protein-losing enteropathy
History
diarrhea, edema (peripheral, periorbital, scrotal, or labial)
Exam
orbital edema, scrotal edema, labial edema
1st investigation
- serum albumin:
low
Other investigations
- stool alpha 1 antitrypsin:
high
Peritoneal carcinomatosis
History
history of underlying gastrointestinal, lung, or breast malignancy or malignant melanoma
Exam
periumbilical lymph nodes, positive stool occult blood (gastrointestinal cancer), hepatic bruits (hepatocellular carcinoma)
1st investigation
- cytology of centrifuged peritoneal fluid:
may show malignant cells
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Other investigations
- abdominal CT:
peritoneal carcinomatosis or abdominal mass lesion
- organ-targeted biopsy:
presence of malignancy
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Myxedema
History
cold intolerance, fatigue, hoarse voice, constipation
Exam
dry skin, hair loss, bradycardia
1st investigation
- serum thyroid-stimulating hormone:
elevated
More - serum free T4:
low
Other investigations
Schistosomiasis
History
history of foreign travel (Egypt, sub-Saharan Africa, Brazil, Venezuela, China, Indonesia, Philippines), contact with fresh water, acute fever, headache,right upper quadrant pain, myalgias, bloody diarrhea, chronic hypogastric pain, left iliac fossa pain, diarrhea alternating with constipation, fecal blood, seizures, hematuria, dysuria, renal colic
Exam
hepatomegaly, splenomegaly
1st investigation
- stool or urine microscopy:
eggs visualized
More - schistosomal serology:
may be positive
Other investigations
Systemic lupus erythematosus
History
arthritis, fatigue, fever (absence of infection), anxiety, depression, skin rash, Raynaud phenomenon
Exam
butterfly rash, arthritis, hepatomegaly, splenomegaly, peripheral neuropathy
1st investigation
- antinuclear antibodies (ANA):
positive
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Other investigations
- anti-double-stranded DNA antibodies:
positive
- anti-Smith antibodies:
positive
Fulminant hepatic failure
History
history of cirrhosis, chronic liver disease, confusion, slurred speech, irritability
Exam
pronounced confusion, incoherent speech, somnolent but rousable, coma, seizures
1st investigation
Other investigations
- blood ammonia:
high
- serum glucose:
low
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Hepatic metastases
History
history of underlying cancer, loss of appetite, weight loss, and cachexia
Exam
nodular liver, may have jaundice
1st investigation
- CT:
hepatic metastases
Other investigations
- liver biopsy:
malignant histology
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Tuberculous peritonitis
History
history of tuberculosis, may have low-grade fever, fatigue, and abdominal pain
Exam
abdominal tenderness or mass, fever, thickened mesentery on abdominal palpation
1st investigation
Other investigations
- peritoneoscopy:
caseating granulomas with acid-fast bacilli in tuberculosis
More - abdominal CT:
thickened mesentery and peritoneal disease
Chylous ascites
History
history of abdominal trauma, neoplasms, abdominal surgery
Exam
lymphadenopathy, abdominal distension, dullness on flank percussion
1st investigation
- triglyceride level, ascitic fluid:
>110 mg/dL
Other investigations
Urogenital surgical trauma
History
history of recent abdominal surgery or trauma
Exam
decreased urine output
1st investigation
- abdominal CT:
may show trauma to the bladder or other areas of urogenital system
Other investigations
Bile ascites
History
history of biliary surgery, abdominal trauma or cholecystitis; abdominal pain, vomiting
Exam
abdominal distention, tenderness, and ileus
1st investigation
- radionuclide imaging of the hepatobiliary tract:
bile leak may be seen
Other investigations
- ascitic fluid bilirubin:
high
Ovarian tumors
History
abdominal pain and distension, vaginal bleeding, irregular menses
Exam
ovarian or pelvic mass
1st investigation
- transvaginal pelvic ultrasound with Doppler:
presence of solid, complex, septated, multiloculated mass; high blood flow
- CA-125:
may be elevated (>35 units/mL)
More - paracentesis:
cytology may be positive for malignant cells
Other investigations
Tricuspid regurgitation
History
history of rheumatic fever, decreased exercise intolerance
Exam
pansystolic murmur, jugular venous distension, peripheral edema
1st investigation
- chest x-ray:
cardiomegaly
Other investigations
- echocardiogram:
dilated right ventricle, delay in closure of tricuspid valve
- cardiac catheterization:
increased right atrium and right ventricular end diastolic pressure
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