Effects of pegylated interferon-α based therapies on functional cure and the risk of hepatocellular carcinoma development in patients with chronic hepatitis B

Chronic hepatitis B virus (HBV) infection continues to pose a serious global health threat and a significant socio-economic burden in many areas of the world. Almost all current clinical practice guidelines on the management of chronic hepatitis B (CHB) infection recommend that eligible patients pursue the optimal treatment endpoint, which is defined as HBsAg loss with or without anti-HBs seroconversion. This review describes the effects of various regimens containing pegylated interferon (peg-IFN)-alpha on functional cure and the outcome of hepatocellular carcinoma (HCC) in patients with CHB. Peg-IFN-alpha monotherapy is a treatment option recommended by local and international clinical practice guidelines to help more CHB patients achieve a sustained off-treatment virological response, which is particularly appropriate for relatively young patients who demand a finite treatment approach. Peg-IFN-alpha add-on or sequential therapy in patients who have achieved a suppressed viral load after nucleos(t)ide analog (NA) therapy may offer further benefits on HBeAg seroconversion and HBsAg decline, although the effects of de novo combination therapy with peg-IFN-alpha and NAs on long-term outcomes remain unclear. Evaluation of baseline and on-treatment predictors is useful for selecting the patients who are likely to achieve additional benefits. Furthermore, some recent studies have shown that peg-IFN-alpha-based therapy results in better prevention of HBV-related hepatocellular carcinoma (HCC), especially in high-risk patients.