Antiviral treatment for chronic hepatitis B infection in renal transplant recipients

Abstract

Chronic infection with hepatitis B virus (HBV) leads to adverse clinical outcomes in renal transplant recipients (RTRs) because of increased hepatic complications. The use of oral nucleos(t)ide analogs (NAs) has brought the management of HBV infection in RTRs to a new paradigm. Lamivudine (LAM) can effectively suppress HBV DNA levels, normalize liver biochemistry, and significantly improve short- and long-term patient survival in HBsAg-positive RTRs. However, it has the burden of high drug resistance. The prevention and management of drug-resistant HBV infection in RTRs has emerged as an important clinical issue. In treatment-naïve hepatitis B surface antigen (HBsAg)-positive RTRs, ETV has demonstrated high efficacy, low resistance rates, and favorable tolerability. Entecavir can also significantly improve transaminasemia in LAM-resistant patients, although the virological response is relatively modest in comparison to the virological response in treatment-naïve patients. Adefovir (ADV) and tenofovir (TDF) are viable options for LAM-resistant HBV infection in RTR; however, their use in patients with moderate to severe allograft dysfunction entails a balance between the potential risk and benefit, the appropriate dose adjustment, and allograft function monitoring for nephrotoxicity. The long-term patient survival of HBsAg-positive RTRs has significantly improved with the progress in these effective antiviral treatments, and is approaching the survival rate of their HBsAg-negative counterparts. Many efficacious options of first-line and rescue therapies are available, but the choice of NA in HBsAg-positive RTR should take into consideration antiviral potency, drug resistance pattern, renal allograft function, and the cost and availability of drugs in different localities. 乙型肝炎病毒 (HBV) 慢性感染所導致的肝臟併發症，並不利於腎臟移植接受者 (RTR) 的預後，因此口服核苷/核苷酸類似物 (NA) 療法佔有重要的角色。對於 HBsAg 陽性的腎臟移植接受者，lamivudine (LAM) 一方面可有效抑制 HBV DNA 的水平及促進肝臟生化的正常化，同時更能顯著改善病人的短期和長期存活率；然而與之相關的抗藥性仍然居高不下。事實上，RTR 間抗藥性 HBV 感染的預防與處置已成為一個重大的臨床課題。在初治的 HBsAg 陽性 RTR 之間，entecavir (ETV) 的功效已獲得證實，兼具低抗藥性與良好耐受性。在 LAM 抗藥病人間，ETV 可明顯改善肝酵素上升，雖然病毒學反應稍低於初治病人之間。誠然，對於已出現 LAM 抗藥性 HBV 感染的 RTR，adefovir (ADV) 或 tenofovir (TDF) 均為可行用藥，然而基於腎臟毒性問題，在植入腎臟呈中至重度功能障礙的患者間，其使用必須加倍謹慎，並在有需要時作出適當的劑量調整及腎功能監測。隨著有效抗病毒療法的實施，HBsAg 陽性 RTR 的長期存活已取得明顯改善，並接近 HBsAg 陰性患者的存活水平。在目前已有多種第一線與救援用藥可供 HBsAg 陽性 RTR 應用之下，NA 的選擇因素應包括抗病毒效力、抗藥狀況、對植入腎臟的影響、藥物價格、供應是否充足等。