Table 1

Diagnostic criteria agreed for each liver disease or stage of liver disease

DiagnosisDiagnostic criteriaManagement
Primary biliary cholangitisIncreased alkaline phosphatase, positive AMAReferral 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 positiveRefer to HBV services
HaemochromatosisBoth ferritin and transferrin saturation increased above local normal rangesReferral for genetic confirmation and venesection.
Wilson’s diseaseCaeruloplasmin abnormal (<0.47 g/L) (only performed on aged less than 55 years)Referral to secondary care
Alpha 1 antitrypsin (A1AT) deficiencyLow level A1AT (<0.9 g/L)Referral to secondary care
NAFLD simple steatosisALT 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 fibrosisAbove 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 fibrosisAbove 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 scoreLiver 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 phosphataseNormal GGT, tests above normalUnlikely 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 syndromeIsolated elevated bilirubinIf 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 reactionNone 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 presentationsNone of the above positiveIn 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.