Chronic HBV infection with persistently normal ALT b. not to treat

Abstract

Chronic hepatitis B (CHB) is a lifelong, progressive and potentially fatal disease if not properly treated. Fortunately, successful therapy with antiviral agents resulted in sustained improvements in virologic, biochemical, histologic features of disease and clinical outcome. Although the recent development of a new and potent anti-hepatitis B virus (HBV) agents may offer many therapeutic options against HBV, there are still unsolved issues and areas for the optimal antiviral therapy. The various clinical courses and different status of the diseases, the variable response to antiviral agents, and the lack of long-term outcome of antiviral treatment contribute to the difficulties in establishment of ideal guidelines, particularly in some special patient groups [1]. It is very important to establish optimal guidelines for whom to treat and when to start, as well as how to treat in Asian patients with CHB. An individual patient’s alanine aminotransferase (ALT) level is an important factor in the decision to initiate the treatment of CHB because the elevated ALT levels indicate immune-mediated inflammation to eliminate HBV-infected hepatocytes and a higher rate of hepatitis B virus e antigen (HBeAg) seroconversion [1–3]. However, up to 40–50% of all HBeAg-positive patients may have normal ALT levels for prolonged periods [4]. The primary goal of treatment for CHB is to induce sustained suppression of HBV replication and to prevent progression of disease. APASL guidelines recommended that HBeAg-positive patients with HBV DNA levels of ≥20,000 IU/ml (≥105 copies/ml) and elevated ALT levels should be considered for treatment. However, the following issues remain unsettled: Should patients with an ALT level of less than two times upper limit of normal (ULN) be treated, and if so when and how? At that time, APASL guidelines recommended that patients with persistently normal or minimally elevated ALT should not be treated except in cirrhotic patients, but need adequate follow-up [1]. The newer therapeutic options have been shown to offer clinical benefits over lamivudine and may represent better therapeutic choices. Emerging evidence suggests that the more appropriate HBV DNA threshold for the treatment of HBeAg-negative patients is ≥2,000 IU/ml (≥104 copies/ml) [2, 3]. This review discusses the key issues and current challenges in the management of chronic HBV infection with persistently normal ALT (PNALT), which is usually defined as ALT remaining normal for at least 2 years in periodic biochemical examinations, to treat or not to treat [5].