Can liver function tests (LFTs) be normal in patients with hepatitis?

Can LFTs Be Normal with Hepatitis?

Yes, liver function tests can absolutely be normal in patients with hepatitis, and this represents a critical diagnostic pitfall that can lead to missed cases of significant liver disease with serious long-term consequences.

The Evidence for Normal LFTs in Hepatitis

Hepatitis C

• Approximately 50% of patients with chronic hepatitis C who are both anti-HCV and PCR positive will have completely normal transaminase values 1.
• Despite normal LFTs, these viraemic patients should never be considered "healthy carriers" as the majority will have histological liver disease with or without cirrhosis 1.
• The 2018 Gut guidelines specifically illustrate this danger: a patient with hepatitis C can have ALT within the normal reference interval, yet if not investigated and diagnosed, faces substantial risk of progressing to end-stage liver disease 1.

Hepatitis B

• Patients with chronic hepatitis B may have normal standard ALT values, but current treatment guidelines recognize that ALT >30 U/L in males and >19 U/L in females should be considered significant 1.
• This reflects that the current upper limit of normal for ALT may be too high, likely because patients with occult NAFLD were included when generating normal ranges 1.

Histological Evidence Despite Normal LFTs

• In one study, 11% of patients with chronic active hepatitis or active cirrhosis had normal ALT levels 1.
• In another study, more than 50% of patients with chronic active hepatitis, chronic persistent hepatitis, or cirrhosis had normal ALT levels 1.
• Liver biopsy studies consistently show that patients with normal transaminases often have evidence of significant liver disease on histology 1.

Critical Clinical Implications

Why This Matters for Mortality and Morbidity

• The extent of liver blood test abnormality is not necessarily a guide to clinical significance 1.
• Prognosis is determined by diagnosis and clinical context, not by the magnitude of LFT derangement 1.
• Hepatitis C, alcohol-related liver disease, and NAFLD—the most common causes of chronic liver disease—are frequently associated with only mild or moderate liver blood test abnormalities 1.
• Patients continue to present with undiagnosed end-stage liver disease that might have been preventable by earlier diagnosis 1.

The Screening Limitation

• Routine liver tests to screen for chronic HCV infection are of limited value because about 50% of infected patients will have normal transaminases 1.
• The American Gastroenterological Association notes that LFTs used in isolation are neither specific diagnostic tools nor effective exclusion tools for significant liver disease 2.
• Normal LFTs do not exclude liver disease: liver disease develops silently and tests may be normal until complications of liver failure or portal hypertension develop 2.

Recommended Clinical Approach

When to Test for Viral Hepatitis Regardless of LFTs

• A key early test is serology for viral hepatitis in high-risk groups, as liver blood tests can be normal in this setting 1.
• High-risk groups include 1:
  • People who inject drugs
  • Migrants from high-prevalence areas
  • Prisoners
  • Those with country of origin or parental exposure risk factors

Monitoring Patients with Normal LFTs

• The value of monitoring transaminases is limited, with levels fluctuating from normal to abnormal over time 1.
• Anti-HCV positive patients who are PCR negative with normal ALT levels should be followed up annually until the natural history is better known 1.
• Liver biopsy may be recommended if there is return of viraemia or flare up of liver enzymes 1.

Assessment Beyond Standard LFTs

• Liver biopsy is recommended for patients found to be viraemic, whether or not liver function tests are abnormal 1.
• Results of routine liver tests correlate poorly with both necroinflammatory and fibrosis scores found on liver biopsy 1.
• Many patients with significant liver fibrosis may have liver enzymes in the normal reference range and normal synthetic function 1.

Common Pitfalls to Avoid

• Never assume normal LFTs exclude hepatitis or significant liver disease 1, 2.
• Do not rely on the magnitude of LFT abnormality to determine clinical significance—a patient with hepatitis A can have ALT >1000 U/L and recover completely, while a patient with hepatitis C with normal ALT can progress to end-stage liver disease if undiagnosed 1.
• Do not wait for LFTs to become abnormal before testing high-risk patients for viral hepatitis—test based on risk factors, not LFT results 1.
• Recognize that normalized liver blood tests do not necessarily imply absence or resolution of disease in chronic conditions like HCV and NAFLD 1.