Does a patient have to remain with transaminitis (elevated liver enzymes) without treatment?

Management of Transaminitis

Patients with transaminitis (elevated liver enzymes) do not have to remain untreated, as specific management is recommended based on the cause and severity of the elevation.

Evaluation and Classification of Transaminitis

• Transaminitis is graded based on elevation of AST/ALT levels: Grade 1 (>ULN to 3.0× ULN), Grade 2 (>3.0 to 5.0× ULN), Grade 3 (>5.0 to 20× ULN), and Grade 4 (>20× ULN) 1
• Modest elevations of hepatic transaminases (ALT/AST) are not uncommon in the pretreatment liver function tests of tuberculosis patients 2
• Initial evaluation should include assessment for metabolic syndrome risk factors, medication review, viral hepatitis testing, and alcohol history 1

Management Based on Severity

• For Grade 1 transaminitis (mild elevation <3× ULN), close monitoring without specific treatment is recommended, with monitoring labs 1-2 times weekly 1
• If the AST/ALT are two or more times normal, liver function should be monitored weekly for two weeks, then two weekly until normal 2
• If the AST/ALT is under two times normal, liver function should be repeated at two weeks. If transaminase levels have fallen, further repeat tests are only required for symptoms 2
• For Grade 2 transaminitis, discontinue potential hepatotoxic medications if medically feasible and increase monitoring frequency 1

Management Based on Etiology

Autoimmune Hepatitis

• All patients with active autoimmune hepatitis should be treated to prevent progression of liver disease 2
• Predniso(lo)ne as initial therapy followed by the addition of azathioprine after two weeks is the first-line treatment of autoimmune hepatitis 2
• Treatment should be continued for at least three years and for at least two years following complete normalization of transaminases and IgG 2
• Only a small minority of patients stay in remission without maintenance therapy 2

Drug-Induced Liver Injury

• If the AST/ALT level rises to five times normal or the bilirubin level rises, hepatotoxic medications (e.g., rifampicin, isoniazid, and pyrazinamide) should be stopped 2
• If the patient is not unwell and the form of tuberculosis is non-infectious, no treatment needs to be given until liver function returns to normal 2
• Once liver function is normal, challenge dosages of the original drugs can be reintroduced sequentially with daily monitoring 2

Viral Hepatitis

• For chronic hepatitis B with elevated transaminases, antiviral therapy may be indicated 3
• Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy 3

Special Considerations

• Patients with decompensated liver disease may be at higher risk for lactic acidosis and should be monitored closely when on nucleoside analogue inhibitors 3
• Treatment should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity 3
• A relapse of autoimmune hepatitis is frequent (50–90%) after drug withdrawal and typically occurs in the first 12 months after stopping treatment 2
• Patients with multiple relapses of autoimmune hepatitis were shown to experience more side effects and have adverse outcomes, suggesting long-term maintenance treatment is advisable 2

Monitoring and Follow-up

• Regular monitoring after treatment withdrawal is essential, and surveillance should continue lifelong for autoimmune hepatitis 2
• For mild transaminitis without known chronic liver disease, regular monitoring of liver function is not required unless symptoms develop (fever, malaise, vomiting, jaundice, or unexplained deterioration) 2
• For patients with known chronic liver disease, regular monitoring of liver function (weekly for two weeks then two weekly for the first two months) is required 2

When to Consider Referral

• If transaminase levels remain elevated for six months or more despite appropriate management 4, 5
• For patients with acute severe transaminitis (>20× ULN) as this may indicate serious conditions like ischemic hepatitis, which has significantly higher mortality 6
• For patients with sub-optimal response despite reconfirmation of diagnosis and adherence to treatment 2