Differentials
Alcohol-related liver disease
SIGNS / SYMPTOMS
No specific differentiating signs or symptoms.
Quantification of alcohol intake. Varying levels of significant alcohol intake have been suggested, from 70 g/week to 294 g/week.[3][8][40][41]
INVESTIGATIONS
aspartate aminotransferase (AST):alanine aminotransferase (ALT) ratio typically >2 in alcohol-related liver disease.
Cryptogenic cirrhosis
SIGNS / SYMPTOMS
No specific differentiating signs or symptoms.
INVESTIGATIONS
Diagnosed by exclusion of all other forms of chronic liver disease and histology, which is non-diagnostic for any particular disease entity. Circumstantial evidence indicates that metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) is the likely aetiology in a significant number of patients labelled with cryptogenic cirrhosis - that is, burned-out MASH.[65] Other causes of cryptogenic cirrhosis include undiagnosed or burned-out autoimmune hepatitis, 'unknown' viral (non-A, non-B, non-C) hepatitis, and occult alcoholism.
Autoimmune hepatitis
SIGNS / SYMPTOMS
No specific differentiating signs or symptoms.
INVESTIGATIONS
Circulating autoantibodies, hyperglobulinaemia, and inflammatory changes on liver histology.
Hepatitis B
SIGNS / SYMPTOMS
High-risk behaviour (unprotected sex with multiple partners, intravenous drug use, tattoos), blood transfusions prior to 1992, needlestick injury, or from endemic areas (Asia, Africa, Middle East, Eastern Europe, Amazon, Alaska). No specific differentiating signs or symptoms.
INVESTIGATIONS
HBsAg, HBsAb, HBcAb, HBeAg, HBeAb, and HBV DNA may be positive.
Hepatitis C
SIGNS / SYMPTOMS
High-risk behaviour (unprotected sex with multiple partners, intravenous drug use, tattoos), blood transfusions prior to 1992, needlestick injury, or from endemic areas (Asia, Africa, Middle-East, Eastern Europe, Amazon, Alaska). No specific differentiating signs or symptoms.
INVESTIGATIONS
hepatitis C virus (HCV) Ab, HCV polymerase chain reaction may be positive.
Haemochromatosis (HFE)
SIGNS / SYMPTOMS
Usually presents in midlife. Symptoms include fatigue, joint pains, new-onset diabetes, decreased libido, cardiac arrhythmias, and heart failure.
INVESTIGATIONS
Iron studies indicate elevated ferritin and percent iron saturation, HFE genetic testing is positive, and iron quantification on histology is elevated.
Primary biliary cholangitis
SIGNS / SYMPTOMS
Women comprise 75% to 90% of patients with the disease. Most common presenting symptoms are fatigue, pruritus, and abdominal pain.
INVESTIGATIONS
Significant elevations in alkaline phosphatase, gamma-glutamyl transferase, and immunoglobulin levels (mainly IgM) are usually the most prominent findings. A positive anti-mitochondrial antibody is found in 90% to 95% of patients and has a specificity of 98%.[66]
Primary sclerosing cholangitis
SIGNS / SYMPTOMS
A chronic liver disease caused by progressive inflammation and scarring of the bile ducts of the liver. Associated with inflammatory bowel disease (namely, ulcerative colitis) in 70% of cases.
INVESTIGATIONS
Cholangiogram (endoscopic retrograde cholangiopancreatography or magnetic resonance cholangiopancreatography); elevated alkaline phosphatase and gamma-glutamyl transferase; 80% of patients will have positive peripheral anti-neutrophilic cytoplasmic antibody.
Wilson's disease
SIGNS / SYMPTOMS
Autosomal recessive genetic disorder in which copper accumulates in tissues; results in neurological or psychiatric symptoms and liver disease. Wilson's disease manifests as liver disease in children and adolescents, peaking at ages 10 to 13 years, and as neuropsychiatric illness in young adults aged 19 to 20 years. Characterised by presence of Kayser-Fleischer rings on slit-lamp examination.
INVESTIGATIONS
Diagnosis is confirmed by low serum ceruloplasmin, elevated urinary copper excretion, and elevated hepatic copper content.
One of the few chronic liver diseases that can present as acute liver failure.
Alpha-1 antitrypsin (A1AT) deficiency
SIGNS / SYMPTOMS
A genetic disorder caused by defective production of A1AT, leading to decreased A1AT activity in the blood and lungs, and deposition of excessive abnormal A1AT protein in liver cells. Most commonly presents as neonatal jaundice.
INVESTIGATIONS
The diagnosis is confirmed by liver biopsy, which shows eosinophilic, periodic acid Schiff-positive, diastase-resistant globules in the endoplasmic reticulum, or periportal hepatocytes.
Drug-induced liver injury
SIGNS / SYMPTOMS
Often idiosyncratic. History of increase in aminotransferases after starting medication, which normalises after discontinuation.
INVESTIGATIONS
Peripheral eosinophilia in some cases; histology is sometimes helpful.
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