Table 1.

Differential diagnosis of cirrhosis, excluding alcoholic cirrhosis¹

Diseases	Diagnostic studies	Liver biopsy
Wilson’s disease	Serum ceruloplasmin < 20 mg/dL; 24-h urine copper excretion > 100 μg/24 h; slit-lamp ophthalmologic examination for Kayser-Fleischer rings	Steatosis; glycogenated nuclei in hepatocytes; focal hepatocellular necrosis, fibrosis, and ultimately, cirrhosis, usually macronodular[34]; copper retention in hepatocytes; hepatic copper concentration > 250 μg/g dry weight
Hemochromatosis	Serum transferrin-iron saturation > 45%; serum ferritin typically > 1000 μg/L; genotyping for detection of HFE mutations: C282Y and H63D; non-contrast CT of liver demonstrates attenuation values of > 70 HU[36]	Grade 4 stainable iron in hepatocytes, with periportal distribution and sparing of Kupffer cells; hepatic iron concentration > 80 μmol/g dry weight; hepatic iron index > 1.9
Hepatitis C	Anti-HCV; HCV RNA in patients who test positive for HCV antibody	Triad of histological findings with acute infection: lymphoid aggregates in portal tracts, epithelial damage of small bile ducts, and prominent microvesicular and macrovesicular steatosis; chronic infection: periportal necrosis, intralobular necrosis, portal inflammation, and fibrosis; no characteristic pathognomonic features
Chronic hepatitis B	HBsAg; serum level of HBV DNA > 2000-20000 IU/mL	Acute infection: lobular disarray, ballooning degeneration, numerous apoptotic (Councilman) bodies, Kupffer cell activation, and lymphocyte-predominant lobular and portal inflammation; chronic infection: varying degree of predominantly lymphocytic portal inflammation with interface hepatitis and spotty lobular inflammation[34]; presence of HBcAg staining in the liver
Autoimmune hepatitis	Antinuclear antibody (ANA); smooth muscle antibody (SMA); antibodies to liver and kidney microsomes (anti-LKM1); anti-soluble liver antigen (anti-SLA); asialoglycoprotein receptor antibodies	Interface hepatitis at junction of portal region and liver lobule; lobular hepatitis with lymphocytoplasmacytic infiltration; intrahepatic bile ducts generally appear normal
α1-antitrypsin deficiency	Serum α1-antitrypsin genotype or phenotype (homozygous PiZZ or heterozygous PiSZ phenotype)	Giant-cell hepatitis with multinucleated giant cells; lobular disarray; cellular and canalicular cholestasis; neoductular proliferation; bridging hepatic fibrosis; PAS-positive and diastase-resistant cytoplasmic granules in periportal hepatocytes
Primary biliary cirrhosis	Antimitochondrial antibodies (AMA) ≥ 1: 80 titer; ANA, with immunofluorescence typically revealing speckled, homogeneous, nuclear dot, centromere, or rim-like patterns	Focal and segmental nonsuppurative cholangitis; “florid duct lesion”: bile duct surrounded by intense lymphocytic or granulomatous infiltrate with basal integrity of the bile duct breached by individual lymphocytes; granulomas in close proximity to bile duct; bile ductular proliferation (cholangioles or pseudoducts) along periphery of portal tract
Non alcoholic fatty liver disease	Diagnosis of exclusion, correlated with: metabolic syndrome: diabetes mellitus, hypertension, hyperlipidemia, abdominal obesity with waist circumference > 102 cm for men and > 88 cm for women; obesity (BMI ≥ 30 kg/m2); obstructive sleep apnea; sedentary lifestyle	Macrovesicular steatosis; early hepatocyte inflammation, predominantly neutrophilic; late nondescript fibrosis and cirrhosis

¹Patients may have more than one disease contributing to cirrhosis (e.g., alcoholism and iron overload, or alcoholism and hepatitis C). HFE: Human hemochromatosis protein; CT: Computed tomography; HU: Hounsfield units; HCV: Hepatitis C virus; HBsAg: Hepatitis B surface antigen; HBV: Hepatitis B virus; DNA: Deoxyribonucleic acid; HBcAg: Hepatitis B core antigen; PAS: Periodic acid-Schiff; BMI: Body mass index.