Abnormal Liver Function Tests

Red flags

• Suspected cirrhosis — low platelets, ascites, splenomegaly
• Decompensated liver disease — jaundice, coagulopathy (INR >1.5), hepatic encephalopathy, ascites, or suspected variceal bleeding
• Suspected primary or secondary liver cancer — liver lesion(s) on ultrasound or elevated alpha-fetoprotein (AFP)

Background

The degree of LFT elevation does not always correlate with disease severity — mild increases may be clinically insignificant, or cirrhosis may be present with normal LFTs. The most common cause of mildly abnormal LFTs is steatotic liver disease (SLD) — the terms MAFLD/MASLD have replaced NAFLD (see fatty-liver-nash.md).

Recognised patterns:

Pattern	Tests	Suggests
Hepatocellular	↑ALT, ↑AST	Hepatocyte injury
Cholestatic	↑ALP, ↑GGT	Biliary obstruction
Impaired synthetic function	↑bilirubin, ↑INR/PT, ↓albumin	Advanced liver disease
Portal hypertension	↓platelets → pancytopenia (advanced)	Cirrhosis

Assessment

1. History — possible causes of liver injury

• Metabolic (SLD) risk factors: diabetes/metabolic syndrome, dyslipidaemia, obesity.
• Infections: intercurrent CMV/EBV; viral hepatitis (ask about overseas travel, transfusions, tattoos, unprotected sex, past IV drug use); cholecystitis/cholangitis.
• Cancer — primary or metastatic.
• Medications (including OTC/complementary) — common culprits: amoxicillin/ clavulanate, flucloxacillin, erythromycin, co-trimoxazole, tetracyclines, quinolones, nitrofurantoin, isoniazid, minocycline; sodium valproate, phenytoin, carbamazepine; azathioprine, paracetamol, statins, methotrexate; black cohosh, Chinese herbal medicines, germander, kava, noni juice, pennyroyal, usnic acid, green tea extract, weight-loss/bodybuilding supplements. Consult LiverTox for up-to-date medication-specific information.
• Excess alcohol (also increases toxicity of other hepatotoxic medications) or illicit drug/prescribed medication misuse.
• Systemic/inherited conditions: autoimmune hepatitis (bimodal age 10–20 and 45–75yrs, more common in females, often but not always with other autoimmune disease — diagnosis via elevated transaminases/IgG/autoantibodies [ANA, SMA, anti-LKM1] + biopsy + exclusion of other causes); coeliac disease; Wilson’s disease; haemochromatosis; alpha-1-antitrypsin deficiency.

2. Clinical features

• Acute hepatitis: fever, abdominal pain/anorexia/nausea/vomiting, jaundice/dark urine/pale faeces, enlarged tender liver/spleen, urticaria and joint pains (particularly hepatitis A/B).
• Cirrhosis: spider naevi, jaundice, leukonychia, palmar erythema, gynaecomastia, muscle wasting, liver enlargement or a shrunken/hardened liver, ascites — see liver-cirrhosis-and-failure.md.
• Acute liver failure: rapid hepatic function decline with jaundice + hepatic encephalopathy + coagulopathy (INR >1.5).

3. Review prior LFTs to establish whether this is new, worsening, or previously unrecognised.

4. Investigations

• Repeat LFTs: immediately if 2–5× ULN or a sudden unexplained rise; in 4 weeks if a transient cause is suspected or the rise is modest (<2× ULN).
• Baseline synthetic-function tests: FBC (low platelets → portal hypertension; pancytopenia if severe), EUC (low albumin → impaired synthetic function), INR/PT.
• Abdominal ultrasound if significantly abnormal enzymes — suspicious lesions raise primary liver cancer/metastases.
• Further tests guided by the pattern (below).

Isolated abnormalities

• Isolated raised GGT: seldom reflects significant liver disease — most commonly excess alcohol or enzyme-inducing medications (anticonvulsants); only significant with other elevated LFTs.
• Isolated raised ALP: usually a bone disorder (Paget’s, primary/metastatic bone malignancy, hyperparathyroidism, osteomalacia) — also physiological in childhood growth, pregnancy (3rd trimester), or after fatty meals. Investigate with calcium/phosphate/vitamin D/PTH ± bone scan if suspected.
• Isolated raised bilirubin: if anaemic, investigate for haemolysis. Otherwise likely Gilbert’s syndrome (3–8% of the population, fluctuating unconjugated bilirubin rarely >85µmol/L, no health implications, no special precautions needed — bilirubin may rise when unwell/stressed/drinking, without adverse outcome).

Predominant patterns

Predominantly raised ALP + GGT (cholestatic): arrange urgent abdominal ultrasound. Causes — biliary dilation (CBD stones, pancreatic cancer/ cholangiocarcinoma, benign/inflammatory strictures including chronic pancreatitis or PSC); infiltration (malignant or benign e.g. amyloidosis, sarcoidosis); intrahepatic cholestasis (drug hepatotoxicity — flucloxacillin and clavulanic acid are common causes even weeks after the medication has finished; COCP; pregnancy; small-duct PSC; primary biliary cholangitis — middle-aged women, test antimitochondrial antibodies [AMA] if suspected).

Predominantly raised AST/ALT (hepatocellular): ALT is more specific/sensitive for liver damage than AST. If AST alone is raised, consider a non-liver (skeletal muscle) cause. AST:ALT ratio ≥2 suggests alcohol, especially with raised GGT/MCV. Causes: hepatitis (especially alcoholic), drug-induced liver injury, cirrhosis (suspect if AST:ALT ratio >1); rarer causes — Wilson disease, autoimmune hepatitis, alpha-1-antitrypsin deficiency. Rhabdomyolysis (↑CK) can mimic hepatitis with markedly raised AST/ALT.

Asymptomatic patient with raised ALT/AST:

• <3× ULN: repeat in 1–3 months; investigate further only if it persists.
• >3× ULN: investigate — abdominal ultrasound (if not done), hepatitis serology (HBsAg, HBsAb, HBcAb, HCV IgG), iron studies, and (if relevant) Hepatitis A IgM/CMV IgM/EBV IgM for acute self-limiting hepatitis. May need referral for liver biopsy.

5. Pregnancy with abnormal LFTs

Consider: acute viral hepatitis; cholelithiasis in pregnancy; intrahepatic cholestasis of pregnancy (second half of pregnancy, pruritus of palms/soles, elevated LFTs); hyperemesis gravidarum (severe cases); HELLP syndrome (haemolysis, elevated LFTs, low platelets — near term, usually with pre-eclampsia); acute fatty liver of pregnancy (late 3rd trimester, life-threatening).

Non-hepatic causes (if the cause remains uncertain)

• Hepatic congestion in heart failure.
• Thyroid disease (check TSH).
• Coeliac disease — mildly elevated transaminases can occur in undiagnosed patients; check anti-tTG + serum IgA; transaminases normalise on a gluten-free diet.
• Muscle disease (↑CK) — polymyositis, heavy exercise, inherited myopathy.

Management

Emergency assessment if:

• Acute liver failure (encephalopathy + severe derangement, especially INR >1.5 or bilirubin >60).
• Suspected/known cirrhosis with acute decompensation (encephalopathy, GI bleeding, new-onset ascites — especially with pain, fever, or other systemic symptoms).
• Sepsis.

Urgent gastroenterology referral if:

• Abnormal LFTs and any of: bilirubin >34; albumin <35; INR >1.7 and/or platelets outside normal range with known/suspected liver disease (excluding unconjugated hyperbilirubinaemia); new symptoms (nausea, anorexia) or ≥5% unexplained weight loss in 1 month (≥10% in 6 months); ALT >200 for more than a month.
• New abnormal liver function in a pregnant patient.
• Liver lesion suspicious for malignancy on radiology, or a new liver lesion (excluding simple cysts) with known chronic liver disease.
• Raised AFP with known chronic liver disease.

Non-urgent gastroenterology referral if:

• Liver disease treatment needed beyond primary-care scope (viral hepatitis, haemochromatosis, autoimmune liver disease, PSC, Wilson’s disease).
• Abnormal LFTs with a negative liver screen, regardless of severity/degree of prior work-up.

General management

• Suspected drug/alcohol cause: consider stopping/reducing the substance and repeat the specific test in 6–8 weeks — normalisation implicates the cause.
• Minor elevation (usually <1.5× ULN), asymptomatic: review history/risk factors, address potential causes (lifestyle, alcohol reduction), consider more than one cause, retest in 3 months.
• If a specific liver disease is identified, manage per the relevant page: viral-hepatitis.md, liver-cirrhosis-and-failure.md, fatty-liver-nash.md, haemochromatosis.md.

Worked examples (interpreting the pattern)

These illustrative cases (AST/ALT/bilirubin/GGT/ALP/albumin/globulin) show how the patterns above combine in practice — globulin is elevated in inflammatory conditions (chronic active hepatitis, primary biliary cholangitis, sclerosing cholangitis, chronic drug injury) and is a useful first thing to check alongside albumin when the picture is unclear.

Case	AST	ALT	Bili	GGT	ALP	Alb	Glob	Pattern
Viral hepatitis	2300	2750	137	87	155(n)	42(n)	35(n)	Hepatocellular
Alcoholic hepatitis	365	260	225	350	250	27	38	Mixed, AST>ALT
Primary biliary cholangitis	65	85	45	680	845	25	45(h)	Cholestatic, ↑globulin
Autoimmune hepatitis	256	350	86	120	255	23	58(h)	Hepatocellular, ↑globulin
Fatty liver disease	65	85	12	150	125	38	28	Mild, non-specific
Complete biliary obstruction	65	56	550	450	550	45	32	Cholestatic
Partial biliary obstruction	65	56	350	950	550	42	32	Cholestatic (GGT/ALP > bili)