Managing the Challenges of Long-Term Anti-viral Therapy
Qin Ning MD & PhD
National Medical Center for Major Public Health Events, & Department and Institute of Infectious Disease, Tongji Hospital, Wuhan China
Chronic hepatitis B virus (HBV) infection is still among the major public health challenges worldwide. Long-term treatment with potent and safe nucleolus(t)ide analogs (NAs) can reduce hepatocellular carcinoma (HCC) and cirrhosis-related complications through profound viral suppression. However, indefnite therapy raises several crucial issues with pros and cons. First, because seroclearance of hepatitis B surface (HBsAg) as functional cure with NAs is rare achievable, a finite therapy including sequential/combination immune modulations such as pegylated interferon therapy may provide an opportunity to facilitate HBsAg seroclearance by the restoration of exhausted immune cells with close monitoring the side effects. Secondly, a low level viriemia often occurs with risk of viral resistance and disease progression (e.g., decompensation, fibrosis progression, HCC, or liver-related mortality). So far, the APASL criteria to stop NA treatment is undetectable HBV DNA levels with normalization of ALT; however, this criterion for cessation of treatment is associated with various incidence rates of virological/clinical relapse with a certain of them develop to severe hepatitis flare or even liver failure and more than 40% of NA-stoppers eventually receive retreatment. Thererfore, a very intensive follow-up strategy and identifcation of low-risk patients for virological/clinical relapse by different biomarkers are the keys to stop the NA treatment safely. Several viral and host factors have been reviewed for their potential roles in predicting clinical relapse. Finally, the recent APASL guidance on stopping nucleos(t)ide analogues
has proposed rules to stop NA and the subsequent follow-up strategy to achieve a better prognosis after stopping NA. In general, for both HBeAg-positive and HBeAg-negative patients who have stopped treatment, these measurements should be done every 1–3 months at the minimum until 12 months.