Longitudinal changes in serum HBV DNA levels and predictors of progression during the natural course of HBeAg‐negative chronic hepatitis B virus infection

Abstract

We evaluated the longitudinal changes of viraemia and predictors of progression in a prospectively followed cohort of 150 untreated patients with HBeAg-negative chronic hepatitis B virus (HBV) infection. According to the first year of follow-up, 85 patients were classified into inactive carrier state and 65 into chronic hepatitis B (CHB). Serum HBV DNA levels were determined at baseline in all patients, at year-1 in carriers or last pretherapy visit in CHB patients and during alanine aminotransferase (ALT) elevations in carriers progressing to CHB. HBV DNA levels at any occasion were > or =80, > or =2000 or > or =20 000 IU/mL in 81%, 23% or 0% of carriers and 100%, 95% or 83% of CHB patients. The cumulative progression rate from carrier to CHB was 11%, 16%, 24% at 2-, 3-, 4 years and was independently associated with higher baseline ALT (always within traditional normal range) and baseline HBV DNA > or =2000 or > or =5000 IU/mL. In 12 carriers progressed to CHB, HBV DNA increased by >1 log(10) IU/mL. During 7.5 months of median follow-up, HBV DNA change > or =1 log(10) IU/mL was observed in 49% of CHB patients. In conclusion, serum HBV DNA levels are detectable in the majority of inactive HBV carriers exceeding 2000 IU/mL in only 23% and 20 000 IU/mL in none of them. Carriers have approximately 15% 3-year risk of progression to CHB, which is associated with higher baseline ALT and viraemia > or =2000-5000 IU/mL, and thus should be closely followed. Approximately 20% of HBeAg-negative CHB patients have HBV DNA <20 000 IU/mL with fluctuations >1 log(10) occurring in many of them.

Follow-up and indications for liver biopsy in HBeAg-negative chronic hepatitis B virus infection with persistently normal ALT: A systematic review

“…An initial follow-up of at least 1 year is supported by the finding of mild histological lesions in HBeAg-negative patients with truly PNALT during the first year [12,13]. Since the risk of developing abnormal ALT in HBeAg-negative patients with normal baseline ALT has been reported to be higher during the first year (15-20%) [12,14] and declines after 3 years of follow-up [9,14,15], frequent monitoring during the first 1-3 years is critical in determining whether a patient has PNALT. Besides the frequency of determinations and duration of follow-up, definition of PNALT should include standardized criteria for the upper limit of normal (ULN) of ALT.…”

“…Instead, we recommend lifelong monitoring with more frequent testing during the first 3 years. Patients with high baseline viremia levels have higher risk of subsequent exacerbation [14,29]. These patients may benefit from non-invasive assessment of liver fibrosis.…”

Current practice of chronic hepatitis B treatment in Southern Italy

“…In fact, under treatment of chronic hepatitis cases limits the effectiveness of efficacious drugs currently available for treatment of chronic hepatitis. However, it should be considered that a limited period of observation cannot be exhaustive to take appropriate decision regarding timing and type of treatment as changes or fluctuation of viral load over time may occur [7]. It may explain why in some chronic hepatitis cases therapy was not provided during the study period.…”

EASL clinical practice guidelines on the management of chronic hepatitis B: The need for liver biopsy

“…It is widely accepted that liver biopsy is not required in such patients with HBV DNA <2000 IU/ml [1,3,4], while HBeAg-negative patients with HBV DNA >2000 IU/ml appear to represent a controversial group. According to studies from our group and from France, 18-25% of HBeAg-negative chronic HBV patients with persistently normal ALT have HBV DNA >2000 IU/ml (<20,000 IU/ml in the vast majority of them) [5,6], but histological lesions justifying therapeutic intervention are rather rarely present in such cases [6,7]. In fact, even when a liver biopsy showed changes fulfilling the histological criteria for therapeutic intervention (Pmoderate necroinflammation and/or moderate fibrosis), this was almost always due to the presence of moderate fibrosis accompanied by minimal necroinflammation [6,7].…”