Hoofnagle J H
Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Adv Intern Med. 1994;39:241-75.
Viral hepatitis comprises five different diseases caused by five different viral agents: hepatitis A, B, C, D, and E virus. All five forms can cause acute hepatitis, only hepatitis B, C and D can cause chronic hepatitis. Alpha interferon has been shown to be effective in inducing sustained remissions in all three forms of chronic viral hepatitis. Its efficacy in acute viral hepatitis has not been documented, although preliminary results suggest that interferon may decrease the chronicity rate of acute hepatitis C. In chronic hepatitis B, alpha interferon therapy with 5 mu daily or 10 mu three time weekly for 16 weeks will induce a long-term remission in disease with loss of HBV DNA and HBeAg from serum in 25% to 40% of patients and ultimately, a loss of HBsAg in approximately half of the responders. Patients likely to respond are those with high initial serum aminotransferases and low levels of HBV DNA. In chronic hepatitis C, therapy with 3 to 5 mu of alpha interferon 3 times weekly for 24 to 48 weeks will induce a temporary remission in disease with loss of HCV RNA from serum, fall of aminotransferases into the normal range and improvement in liver histology in 50% of patients and a sustained remission persisting after therapy is stopped in 25% of patients. Patients with a short duration of disease and without cirrhosis are the most likely to respond. Unfortunately, there are no completely reliable means of predicting which patients are likely to respond to interferon and which of these will have a lasting response. In chronic hepatitis D, a prolonged course of alpha interferon given in doses of 3 to 5 mu daily or 9 to 10 mu three times weekly results in remission in disease as marked by loss of HDV RNA from blood and fall of aminotransferases into the normal range in up to 50% of patients. Unfortunately, this response is rarely sustained after treatment unless HBsAg becomes negative, which occurs in only a small number of patients. Despite the benefits of alpha interferon therapy in many patients with chronic viral hepatitis, several shortcomings of this therapy are evident: less than 50% of patients respond, side effects can be problematical, and some patients are not appropriate for therapy. Thus, interferon is not indicated for patients with advanced cirrhosis or for those who are severely immunosuppressed. Alpha interferon is an important first step in therapy for chronic viral hepatitis, but further approaches are needed to increase its efficacy and safety.
甲型、乙型、丙型、丁型和戊型肝炎病毒。所有五种类型均可引起急性肝炎，只有乙型、丙型和丁型肝炎可导致慢性肝炎。已证明α干扰素对所有三种慢性病毒性肝炎的持续缓解有效。其在急性病毒性肝炎中的疗效尚无文献记载，尽管初步结果表明干扰素可能降低急性丙型肝炎的慢性化率。在慢性乙型肝炎中，每天500万单位或每周三次1000万单位的α干扰素治疗16周，将使25%至40%的患者疾病长期缓解，血清中HBV DNA和HBeAg消失，最终，约一半的应答者HBsAg消失。可能有反应的患者是那些初始血清转氨酶高且HBV DNA水平低的患者。在慢性丙型肝炎中，每周三次使用3至500万单位的α干扰素治疗24至48周，将使50%的患者疾病暂时缓解，血清中HCV RNA消失，转氨酶降至正常范围，肝脏组织学改善，25%的患者在治疗停止后持续缓解。病程短且无肝硬化的患者最有可能有反应。不幸的是，没有完全可靠的方法来预测哪些患者可能对干扰素产生反应以及哪些患者会有持久反应。在慢性丁型肝炎中，每天给予3至500万单位或每周三次9至1000万单位的α干扰素长期治疗，可使高达50%的患者疾病缓解，表现为血液中HDV RNA消失和转氨酶降至正常范围。不幸的是，除非HBsAg转阴，这种反应在治疗后很少持续，而只有少数患者会出现HBsAg转阴。尽管α干扰素治疗对许多慢性病毒性肝炎患者有益，但这种治疗的几个缺点很明显：不到50%的患者有反应，副作用可能成问题，而且一些患者不适合治疗。因此，干扰素不适用于晚期肝硬化患者或严重免疫抑制患者。α干扰素是慢性病毒性肝炎治疗的重要第一步，但需要进一步的方法来提高其疗效和安全性。
