By Liz Highleyman

Not all patients with chronic hepatitis B virus (HBV) require treatment, only those with progressive liver disease. Liver biopsy has been considered the "gold standard" for assessing liver damage, but researchers have explored numerous biomarkers or predictive factors that might help patients avoid the discomfort and expense of repeated biopsies.

LIVER BIOPSY

At the recent 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008), Greek researchers described a study to evaluate the severity of liver histology in hepatitis B "e" antigen (HBeAg) negative chronic hepatitis B patients with HBV DNA < 20,000 IU/mL.

The optimal HBV DNA level for differentiating patients with active HBeAg negative chronic hepatitis B and inactive HBV carriers remains uncertain, the investigators noted as background. Though expert opinion varies, liver biopsy is typically recommended for patients with HBV DNA > 2000 IU/mL (down from a previous threshold of 20,000 IU/mL).

Between September 2001 and December 2007, liver biopsies were performed for 140 HBeAg negative patients. Participants were stratified according to ALT elevation and HBV viral load at the time of biopsy:

• Group A2: HBV DNA 80-1999 IU/mL and elevated ALT (above the upper limit of normal on at least 2 occasions) (n = 42);

• Group A1: HBV DNA 2000-19,999 IU/mL and elevated ALT (n = 63);

• Group B: HBV DNA 2000-19,999 IU/mL but persistently normal ALT (n = 35).

Patients with HBV DNA < 2,000 IU/mL and persistently normal ALT did not undergo biopsies.

Liver histology was evaluated by a single pathologist using the Ishak scoring system. A grading score of 7 or higher and/or stage of 2 or higher was considered and indication for treatment.

Results

• There was no significant difference in characteristic between Group A1 and A2, except the patients with higher viral load had a trend toward worse fibrosis (stage 2.8 vs 2.2) and more frequent severe fibrosis/cirrhosis (37% vs. 19% with stage 4-6).

• Group A and Group B patients did not differ with regard to age, sex, body mass index, alcohol use, or HBV DNA levels, but they had higher ALT (as per study protocol), worse grading scores (6.1 vs 2.9; P < 0.001), and a higher stage (2.6 vs 1.0; P < 0.001).

• 70% of patients in Group A were considered to have a histological indication for treatment (A1 75%; A2 62%), compared with just 17% in Group B.

• Among Group B participants, those deemed to have an indication for treatment were due to stage 2 fibrosis, without active necroinflammation (grading score 2-4 in all 6 patients).

Based on these findings, the researchers concluded, "there are no substantial differences" between HBeAg negative chronic hepatitis B patients with elevated ALT and HBV DNA < 2000 or 2000-20,000 IU/mL.

The recommended that liver biopsies should be done for all HBeAg negative patients with elevated ALT, regardless of HBV viremia, since histological lesions are present in the majority of such individuals, even if HBV DNA is below 2000 IU/mL.

In contrast, they continued, immediate liver biopsy is not required for HBeAg negative patients with persistently normal ALT and HBV DNA levels of 2000-20,000 IU/mL, since minimal liver damage is found in the majority of such individuals, and fewer than 20% may have moderate fibrosis without active necroinflammation.

12/9/08

Reference
GV Papatheodoridis, EK Manesis, S Manolakopoulos, and others. Is Liver Biopsy Required for All Patients (pts) with HBeAg-negative (HBeAg-) Chronic HBV Infection and HBV DNA <20,000 IU/mL? 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008). San Francisco. October 31-November 4, 2008. Abstract 117. Abstract 840.