Long-Term suppression of hepatitis B e antigen-negative chronic hepatitis B by 24-month interferon therapy

Abstract

To assess whether extended treatment with interferon improves the outcome of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B, 101 consecutive patients were treated with 6 MU of interferon alfa 2b 3 times weekly for 24 months. During the 68-month study, 30 patients (30%) had a sustained response (i.e., normal serum transaminase levels and undetectable hepatitis B virus DNA by non-polymerase chain reaction [PCR] assays), and 15 cleared serum surface antigen. Twenty-five nonresponders, 16 relapsers, and 30 who discontinued treatment were considered treatment failures. Multivariate analysis predicted a sustained response for young age (odds ratio, 0.94; 95% confidence interval, 0.89-0.99; P ‫؍‬ .041) and high pretreatment serum levels of immunoglobulin M (IgM) anti-hepatitis B core antigen (HBc) (odds ratio, 4.52; 95% confidence interval, 1.63-12.5; P ‫؍‬ .004). Liver disease progressed in none of the sustained responders but in 16 with treatment failure (0% vs. 22%, P ‫؍‬ .002); hepatocellular carcinoma (HCC) developed with similar frequency in both groups (7%). Overall, estimated 8-year complication-free survival was longer for the 30 sustained responders than the 71 patients with treatment failure (90% vs. 60%, P < .001), but 8-year patient survival was similar in the 2 groups (100% and 90%). Short complicationfree survival was predicted by failure to respond to interferon (hazard ratio, 7.8; 95% confidence interval, 1.8-34.0; P ‫؍‬ .006) and high scores for liver fibrosis (hazard ratio, 1.71; 95% confidence interval, 1.17-2.50; P ‫؍‬ .005). In conclusion, 24 months of treatment with interferon alfa 2b led to sustained disease suppression in a significant proportion of patients with HBeAg-negative chronic hepatitis B. (HEPATOLOGY 2003;37:756-763.)

Early serum HBsAg drop: A strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patients

“…In this respect, the slow continuing decline of serum HBsAg observed in relapsers is perhaps similar to what we see in hepatitis C, where therapy extended to 72 weeks clearly reduces the relapse rate in a subset of patients. It is of note that prolongation of treatment has been tested with conventional interferon 15 and recently with PEG-IFN in a small pilot HBeAg-negative study. 8 Larger studies are therefore needed to validate this concept and to verify if measurement of HBsAg can be useful in determining to the duration of treatment in HBeAg-negative patients with PEG-IFN.…”

Outcome of hepatitis B e antigen-negative chronic hepatitis B on long-term nucleos(t)ide analog therapy starting with lamivudine

“…[8][9][10][11] In particular in HBeAg-negative CHB, interferon-alfa (IFN␣), the first available effective therapeutic option in CHB, is the agent offering the higher chances for sustained-off therapy response ranging between 18% and 30%. [10][11][12][13] Conversely, both lamivudine and ADV, 2 oral, safe, and well-tolerated drugs, are mainly considered and used as agents for long-term therapy in an effort to maintain on-therapy remission and prevent progression of liver disease, which currently represents the most realistic therapeutic option for most HBeAg-negative CHB patients. 11,14,15 Lamivudine, which was the first agent used as longterm maintenance therapy in HBeAg-negative CHB since the late 1990s, is associated with high initial on-therapy remission rates, but with progressively increasing rates of viral resistance usually followed by biochemical breakthrough phenomena.…”

HBsAg-guided extension of Peg-IFN therapy in HBeAg-negative responders

“…Extension of conventional IFN from 1 to 2 years leads to higher rates of sustained virological response (SVR) due to reduced rates of post treatment relapse (17)(18)(19). This was recently confirmed also for Peg-IFN therapy (9,20).…”