Predominantly Raised ALT

 

 

Introduction

• Abnormal LFTs have often not been investigated adequately- Many patients present with end stage liver disease without a previous diagnosis of liver disease were noted to have previous abnormal liver tests.
   
• Mild rises should not be overlooked– the extent of liver blood test abnormality is not a guide to clinical significance (e.g. chronic Hep C with a lower ALT may be worse than acute Hep A with an ALT>1000).
   
• Patients should be considered for investigation irrespective on the abnormality- Do not overlook mild rises and consider patients for investigation if no obvious cause regardless of the duration or level of the abnormality.
   
• However, the majority of adults with abnormal LFTs will be identified to have metabolic associated steatotic liver disease (MASLD, previously known as non-alcoholic fatty liver disease or NAFLD) or alcohol-related liver disease (ARLD). Most simply require reinforcement of lifestyle advice and ongoing assessment in primary care.

 

 

Red flags

• Synthetic failure – jaundice, low albumin, ascites, prolonged INR, encephalopathy
   
• Features of malignancy –
  • weight loss and marked cholestasis
  • weight loss >60yrs with any of:diarrhoea, back pain, abdominal pain, nausea or vomiting, constipation, new onset diabetes
  • Jaundice in patient >40years
• ALT >300 iu/l
   
• Dilatation of common bile duct on ultrasound or liver/gallbladder/pancreatic mass lesions

 

 

Key Features of Assessment

(In patients > 80 years oldor with significant frailty use clinical judgement to avoid unnecessary investigation)

 

In addition to usual assessment check for:

• Contributing conditions – diabetes, viral hepatitis, autoimmune disease, cancer, coeliac, haemochromatosis, IBD (risk of primary sclerosing cholangitis or autoimmune hepatitis)
• Excessive alcohol or recreational drug use
• Pregnancy
• Medications– esp. statins, anticonvulsants, antibiotics (particularly flucloxacillin, erythromycin, doxycycline or co-amoxiclav), paracetamol.
• Herbal treatments – black cohosh, weight loss/bodybuilding supplements, Chinese herbal medicines, green tea extract, turmeric.

 

 

Investigations

Consider causes and further investigations depending on the type of abnormality:

Management

1] If ALT >300: refer A&G and arrange investigations as per flowchart including viral screen (Hep. A, B, C & E, CMV & EBV)

 

2] If ALT < 300 iu/l

• Provide lifestyle as appropriate (decrease alcohol, weight reduction if raised BMI
• Follow NAFLD/ARLD pathway if clinical concern or abnormal Fib 4 score/NAFLD score.
• If no clinical cause (drug induced/intercurrent illness/NAFLD/ARLD) for abnormal LFT then further investigate as per flowchart.
• If liver screen normal – repeat LFTs in 3/12 (consider earlier if ALT>150), then refer if persistently raised

 

3) For All - Review medications:

• Recent statins, antibiotics, NSAIDs; STOP any drugs known to be associated with drug-induced liver injury.
• If there is a temporal relationship between a new medication and LFT changes, consider drug-induced liver injury and discontinuation medication. Repeat LFTs after 1-3 months.

 

NAFLD (MASLD) /fatty liver: If USS liver shows fatty liver or raised AST:ALT ratio (with high BMI) See NAFLD guidelines( note raised AST:ALT ratio is not relevant for patients with a normal BMI)

 

Alcohol-related Liver Disease:

See RMS Suspected Alcoholic Liver Disease

 

Raised Ferritin: (>200Mcg/L female, >300mcg/L male)

• Exclude common causes – alcoholism, inflammation, metabolic syndrome/fatty liver, acute liver injury, malignancy.
• Check FBC and iron saturation
• If transferrin saturation >45% with raised ferritin – request HFE gene on ICE
• See Genetic Haemochromatosis Clinical Guideline

(Genetic haemochromatosis is a common condition, affecting around 1 in 150 people, characterised by iron overload. The majority of patients with genetic haemochromatosis are homozygotes for the C282Y polymorphism. Early treatment with venesection is effective in preventing irreversible complications and improving mortality.)

 

Autoimmune liver disease/hepatitis:

• Positive SMA/ANA: autoantibodies occur in about 8% of population.
• Not significant if normal LFTS
• Significant if raised serum IgG (16 g/l) and/or raised ALT

 

 

Advice and Guidance

Please send advice and guidance requests via e-RS to: http://rms.cornwall.nhs.uk/primary_care_clinical_referral_criteria/rms/primary_care_clinical_referral_criteria/gastro/rcht_hepatology_advice_and_guidance

 

 

Referral

Acutely Unwell  (e.g. sepsis, severe encephalopathy, severe ascites restricting movement and breathing, GI bleeding.) - Admit via Acute GP (Mon-Fri 8am-6pm, Sat-Sun 9am-6pm) or via the on-call Medical SpR outside of these hours.

 

Suspected cancer – Fast trackUSC Upper GI Cancer

• >40 years old with jaundice
   
• Abnormal CT or ultrasound scan consistent with pancreatic, liver, or gallbladder cancer

• Patient older than 60 years with weight loss and any of: diarrhoea, back pain, abdominal pain, nausea or vomiting, constipation, new onset diabetes

 

ALT>300 and asymptomatic:(if symptomatic admit/refer  depending on symptoms)

• Refer hepatology A&G

 

↑ALT + ↑Bilirubin:

• Refer urgent hepatology

 

Jaundiced patients:

• Painless jaundice - Arrange FBC, LFTs, INR and USS and refer urgently to the Rapid Access Jaundice clinic.
• Painful jaundice +/- sepsis – admit general surgery

 

Symptomatic liver disease (ascites/encephalopathy):

Urgent Hepatology referral or urgent admission (particularly if unwell or gastrointestinal bleeding)

 

Pregnant with abnormal LFTs: refer to Maternity Day Assessment unit via on-call O&G SpR

 

Viral Hepatitis:

• Hepatitis C infection (HCV)  - HCV antibody positive – check hepatitis C PCR, HIV/HBV serology
  • If positive HCV PCR - refer routine hepatology
  • If negativeHCV PCR- repeat 3/12 later and if still negative, reassure patient infection has cleared, no (referral)
• Hepatitis B infection (HBV)
  • HbsAg positive – referral routine hepatology with HIV/HCV serology
• Hepatitis A or E, CMV, EBV: If ↑ALT and LFTs not improving by 6/52 refer urgent hepatology

 

Autoimmune hepatitis (AIH):

• ↑ALT + positive autoantibodies (SMA/ANA/LKM) + ↑IgG: refer urgent hepatology or A&G

 

Wilson's disease

• Abnormally low caeruloplasmin  - refer hepatology

 

Alpha - 1 -antitrypsin deficiency

• If < 0.7 g/l – refer hepatology
• If 0.7 to 0.9g/l – A&G hepatology

 

Raised ferritin with suspected haemochromatosis:

• If HFE gene +ve (homozygous only)– refer routine hepatology
• If HFE gene not present/heterozygous – refer hepatology A&G if needed

 

 

 

For East-facing Cornwall practices. Please see South & West Devon DRSS Referral Guidelines

 

 

Supporting Information

For professionals:

• Gut – Guidelines on the Management of Abnormal Liver Blood Tests
• Health Technology Assessment – Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS): A Prospective Cohort Study
• RCGP e-learning abnormal LFTS

 

For patients:

• Patient UK – Abnormal Liver Function Tests

 

 

 

Page Review Information

 

Review date	June 2024
Next review date	June 2026
Speciality Lead GP	Dr Madeleine Attridge (Hepatology lead GP)
Contributors	Dr Hyder Hussaini (Consultant Hepatologist RCHT) Anna Barton (Principal Clinical Biochemist)