Diagnosis | Diagnostic criteria | Management |
Primary biliary cholangitis | Increased alkaline phosphatase, positive AMA | Referral to secondary care |
Autoimmune hepatitis (AIH) | ALT increased, positive ANA Positive ASMA >1:80. | Referral to secondary care |
Hepatitis C virus infection (HCV) | HCV antibody positive. Perform PCR or HCV Ag by local preference. | Referral for HCV treatment, if HCV PCR of HCV Ag positive. |
Hepatitis B infection (HBV) | HBsAg positive | Refer to HBV services |
Haemochromatosis | Both ferritin and transferrin saturation increased above local normal ranges | Referral for genetic confirmation and venesection. |
Wilson’s disease | Caeruloplasmin abnormal (<0.47 g/L) (only performed on aged less than 55 years) | Referral to secondary care |
Alpha 1 antitrypsin (A1AT) deficiency | Low level A1AT (<0.9 g/L) | Referral to secondary care |
NAFLD simple steatosis | ALT and/or GGT elevated, all above tests normal, alcohol intake less than 14 units* per week. NAFLD fibrosis score low (<−1.455) | Primary care, screen for diabetes, address cardiovascular risk factors, perform abdominal ultrasound if no abnormality other than increased echogenicity, then manage repeat NAFLD fibrosis score annually |
NAFLD-NASH with significant fibrosis | Above tests normal drink less than 14 units per week. NAFLD fibrosis score high or indeterminate (>−1.455) | Refer secondary care for assessment of liver fibrosis. |
ARLD with no/minimal fibrosis | Above tests normal (1+ ASMA allowed), drinking in excess of 14 units per week AST/ALT ratio (<0.8), APRI score (<0.5) or FIB4 (1.45) all low | Management in primary care, advise abstinence and perform alcohol brief intervention. Onward referral to alcohol problems services depending on local guidelines. |
ARLD with indeterminate or high fibrosis score | Liver screen tests negative (1+ ASMA allowed), drinking in excess of 14. AST/ALT ratio (>1.0), APRI (>0.5) score or FIB4 (>1.45) elevated or abnormal bilirubin albumin or clotting. | Refer to secondary care for staging |
Isolated elevated alkaline phosphatase | Normal GGT, tests above normal | Unlikely to be liver disease. Consider systemic disease causing abnormality (eg pregnancy, fractures, Paget’s disease, growing child). In primary care, consider abdominal U/S |
Gilbert’s syndrome | Isolated elevated bilirubin | If less than 45 µmol/L in non-fasting/dieting state. Reassurance in primary care. If >45 µmol/L, check for haemolysis and genetic testing for Gilbert’s syndrome. If both negative, consider referral. |
Drug reaction | None of the above criteria is fulfilled, check if prescribed potentially hepatotoxic drug in the 3 months preceding first abnormal LFT. Can check using www.livertox.nlm.nih.gov. | In clear drug-induced liver injury stop drug and repeat LFTs. Normalisation over 6–8 weeks confirms diagnosis. NB elevations less than 5× ULN occurring with initiation of statins is common and safe, not requiring stopping of the drug. |
Other diseases or atypical presentations | None of the above positive | In primary care consider requesting abdominal U/S. Consider systemic disease-causing abnormal LFTs. Repeat LFTs in 3 months; if abnormality persists, in the absence of explanation, consider referral depending on the clinical context of the patient and risk scores for age-standardised mortality. |
↵*Unit of alcohol is 10 mL (8 g) of pure alcohol.
ALT, alanine transaminase; AMA, antimitochondrial antibody; ANA, anti nuclear antibody; ARLD, alcohol-related liver disease; ASMA, anti smooth muscle antibody; AST, aspartate transminase; GGT, gamma glutamyltransferase; HBsAg, hepatitis B surface antigen; HCV, hepatitis C virus; HCV Ag, hepatitis C virus antigen; LFT, liver function test; NAFLD, non-alcoholic fatty liver disease; NASH, non alcoholic fatty liver disease; PCR, polymerase chain reaction; U/s, ultrasound.