Hoofnagle J H
Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md., USA.
Digestion. 1998 Aug;59(5):563-78. doi: 10.1159/000007532.
Worldwide viral hepatitis is the most common cause of jaundice, chronic liver disease cirrhosis and hepatocellular carcinoma. While important advances have been made in prevention of viral hepatitis, therapy of this disease remains unsatisfactory. There are no specific therapies of proven benefit for acute hepatitis, although use of alpha-interferon during the acute phase of hepatitis C may result in a decrease in the rate of chronicity. For chronic viral hepatitis, alpha-interferon has been widely used, but is expensive, poorly tolerated and limited in effectiveness. New antiviral agents and use of combinations of antivirals are now being evaluated and promise to provide a therapy that is effective in the majority of patients. The currently recommended therapy of chronic hepatitis B is a 4- to 6-month course of alpha-interferon in doses of 5-10 million units three times a week; a regimen that results in sustained clearance of hepatitis B virus (HBV) DNA and hepatitis B e antigen (HBeAg) from serum in approximately one-third and a loss of hepatitis B surface antigen (HBsAg) in one-tenth of patients. Long-term follow-up of patients who respond to interferon treatment with clearance of HBeAg indicate that the majority ultimately clear HBsAg as well and have continued remission in the liver disease, although low levels of HBV DNA can commonly be detected in liver tissue. Better therapies of hepatitis B are needed. Recently, several oral 'second-generation' nucleoside analogues have been developed that have potent activity against HBV. The best studied is lamivudine (3-thiacytidine) which results in marked inhibition of HBV DNA levels and improvement in serum aminotransferases and hepatic histology in the majority of patients. When stopped, however, most patients relapse and the shortcomings of long-term therapy have been the development of viral resistance in up to one-quarter of patients within a year and a higher percentage with more prolonged therapy. Future approaches of therapy of promise for hepatitis B are combinations of lamivudine with interferon and other antiviral nucleoside analogues. The currently recommended therapy of chronic hepatitis C is a 12- to 18-month course of alpha interferon in doses of 3 million units three times a week: a regimen that results in sustained clearance of hepatitis C virus (HCV) RNA in approximately 20% of patients. Sustained responses have been associated with marked improvements in hepatic histology and long-term studies indicate that the majority of patients remain free of virus in serum and liver, suggesting a 'cure' of infection. Responses to interferon correlate to some degree with clinical and virological features, including young age, absence of hepatic fibrosis, low levels of HCV RNA in serum and HCV genotypes 2 and 3. (ABSTRACT TRUNCATED)
在全球范围内，病毒性肝炎是黄疸、慢性肝病、肝硬化及肝细胞癌最常见的病因。尽管在病毒性肝炎的预防方面已取得重要进展，但该疾病的治疗仍不尽人意。对于急性肝炎，尚无经证实有效的特异性疗法，不过在丙型肝炎急性期使用α干扰素可能会降低慢性化率。对于慢性病毒性肝炎，α干扰素已被广泛应用，但其价格昂贵、耐受性差且疗效有限。新型抗病毒药物以及抗病毒药物联合使用正在进行评估，有望为大多数患者提供有效的治疗方法。目前推荐的慢性乙型肝炎治疗方案是给予4至6个月疗程的α干扰素，剂量为每周三次，每次500万至1000万单位；该方案可使约三分之一的患者血清中的乙肝病毒（HBV）DNA和乙肝e抗原（HBeAg）持续清除，十分之一的患者乙肝表面抗原（HBsAg）消失。对干扰素治疗有反应且HBeAg清除的患者进行长期随访表明，大多数患者最终也能清除HBsAg，肝病持续缓解，尽管在肝组织中通常可检测到低水平的HBV DNA。仍需要更好的乙型肝炎治疗方法。最近，已研发出几种对HBV具有强效活性的口服“第二代”核苷类似物。研究最多的是拉米夫定（3 - 硫代胞苷），它能显著抑制大多数患者的HBV DNA水平，并改善血清转氨酶及肝脏组织学。然而，停药后大多数患者会复发，长期治疗的缺点是一年内高达四分之一的患者会出现病毒耐药，治疗时间延长时耐药比例更高。未来有望用于乙型肝炎治疗的方法是拉米夫定与干扰素及其他抗病毒核苷类似物联合使用。目前推荐的慢性丙型肝炎治疗方案是给予12至18个月疗程的α干扰素，剂量为每周三次，每次300万单位：该方案可使约20%的患者丙肝病毒（HCV）RNA持续清除。持续应答与肝脏组织学的显著改善相关，长期研究表明大多数患者血清和肝脏中无病毒，提示感染得到“治愈”。对干扰素的应答在一定程度上与临床及病毒学特征相关，包括年轻、无肝纤维化、血清中HCV RNA水平低以及HCV基因2型和3型。
