Treatment of HBsAg-positive chronic active hepatitis with human fibroblast interferon

Two patients with HBsAg positive chronic active hepatitis have been treated with human fibroblast interferon 10(7) units daily for two weeks. Before treatment, both patients had high levels of hepatitis B surface antigen, core antibody, and DNA-binding antibody in the blood and one patient had a fourfold rise in serum AST. During treatment there was a striking fall in the core antibody titre and also in the DNA-binding antibody, which has been maintained for several months subsequently; in one patient the initially high AST level fell to normal. No significant adverse effects occurred, and these observations should encourage further trials of fibroblasts interferon in hepatitis B.     

Effectiveness of combined plasma exchange treatment in fulminant viral hepatitis

The plasma exchange is an effective measure in the treatment of acute liver failure. The authors report their own first experiences in this field in the management of fulminant viral hepatitis. Four out of 7 treated patients survived. So, the survival rate was augmented from 25 per cent in a control group of 8 patients without plasma exchange to 57.1 per cent. Other necessary therapeutic measures are high energetic nutrition, branched chained amino acids, stimulation of liver cell regeneration, correction of coagulation alterations, and intensive care. The success depends on coma stage in the beginning of treatment. Patients with signs of praecoma should be admitted to specialized centers. The number of such centers should be limited because of the necessary experiences and the high costs of combined plasma exchange treatment of this rare hepatitis complication.     

Anti-alpha interferon antibodies after alpha interferon treatment in patients with chronic viral hepatitis

Thirty-five patients with chronic viral hepatitis (B, D or non A, non B), treated with alpha interferon were evaluated by a highly sensitive enzyme immunoassay for the presence of alpha interferon neutralizing antibodies before and after three months of treatment. Although 4 subjects (11.4%) became immunized against alpha interferon, treatment with the drug was successful in inhibiting viral replication in 3 of them. We conclude that the appearance of anti alpha interferon antibodies does not affect the effectiveness of the drug, and is therefore not worth monitoring.     

干扰素治疗病毒性肝炎的研究进展

半个世纪以来,Isaacs等20多位学者在干扰素（IFN）的发现和发展中作出了重要贡献：发现了IFN及其亚型;阐明了IFN基因全序列;克隆并表达了人IFN-α蛋白和IFN-β蛋白,成为可用于治疗的重组基因产品;深入研究了IFN在免疫调控、抗病毒的分子机制及其在信号通路中的作用;IFN剂型的修饰及制备,改变了药动学,延长了半减期,不仅使用更方便,而且增强了疗效。目前,聚乙二醇IFN已广泛应用于病毒性肝炎、肿瘤等疾病的治疗。     

Interferon and cyclosporin A in the treatment of fulminant viral hepatitis

The prognosis of fulminant hepatitis due to non-A, non-B virus infection and acute reactivation of hepatitis B virus in HB carriers is generally poor, and the treatment of choice in Western countries is recognized as liver transplantation. In countries such as Japan where liver transplantation is not readily available, however, these intractable types of fulminant hepatitis have to be treated medically. Based on the assumption that persistent replication of causal viruses and enhanced host immune responses, especially cellular immunity, to eradicate the viruses are the key mechanism in progressive liver cell destruction and the poor prognosis, we attempted a combination treatment with interferon and cyclosporin A for these types of fulminant viral hepatitis. Subjects in the present study consisted of 1 patient with acute severe hepatitis without coma and 13 patients with coma (13 with fulminant hepatic failure) due to non-A, non-B virus and acute reactivation of hepatitis B virus. The patients were given interferon-beta, 300 × 10⁴U daily, and cyclosporin A, at an initial dose of 3 mg/kg, with tapering. Fourteen patients with coma received artificial liver support that we devised. The patient with acute severe hepatitis survived, showing histologically remarkable liver regeneration. Eight of the 14 patients with hepatic coma, all of whom were indications for liver transplantation according to the criteria of the King's College group, survived. Decreased transaminase level, increased liver volume, and histological liver regeneration were observed in all the survivors. The combination of interferon and cyclosporin A is worth attempting in fulminant hepatitis caused by non-A, non-B virus and acute reactivation of hepatitis B virus in HB carriers.     

Portal hypertension in fulminant viral hepatitis.

The gradient between wedged and free hepatic venous pressures were measured in 10 unselected adult patients suffering from fulminant viral hepatitis. The gradient was increased in all the studied patients, ranging from 0.9 to 2.1 kPa; this finding indicates that portal hypertension was present in all these cases. Ascites was present in all the five patients having a gradient about 1.5 kPa and affected only two of the five patients having a gradient below 1.5 kPa; this observation suggests that portal hypertension plays a role in the mechanism of ascites in fulminant viral hepatitis. Portal hypertension in fulminant viral hepatitis is likely to be the consequence of an intrahepatic block due to massive necrosis of the liver cells.     

干扰素治疗慢性病毒性肝炎的疗效预测

目前临床用于治疗慢性肝炎的有普通干扰素和聚乙二醇干扰素,影响其抗病毒疗效的因素比较复杂.下面就干扰素治疗慢性乙型肝炎和慢性丙型肝炎疗效预测因素进行综述.一、干扰素治疗慢性乙型肝炎的疗效预测干扰素治疗慢性乙型肝炎的优势为有限疗程和相对较高的HBeAg和HBsAg的血清学转换率.由于干扰素较核苷类抗HBV药物不良反应明显,且影响疗效的因素较多,有必要对其疗效进行预测,以获得最大效益价格比.     

An etiological study on fulminant viral hepatitis]

Viral markers were studied in 79 cases of viral hepatitis with hepatic failure. The results were shown as follows: 8 cases were positive for anti-HAV IgM (10.12%); 76 cases positive for HBsAg or anti-HBc IgM (96.20%) and 41 cases positive for anti-HCV antibodies (51.89%). Among those with anti-HCV positive, 35 cases were co-infected with HBV, 5 cases with HAV and/or HCV, only one was infected with HCV alone 2 cases were HD-Ag positive (2.52%) and one not identified (1.27%). With the reference of clinical findings, patients co-infected with HBV/HCV or anti-HBc IgM positive were more critical and usually entail higher mortality. In cases with HCV co-infections, the positive HBV replication markers seems to be reduced. Hepatic failure without HBV replicative markers had a high rate of hepatic coma as well as poor outcome.     

Evaluation of viral replication in children with chronic hepatitis B with and without interferon treatment

BACKGROUND: In chronic infection with hepatitis virus B the fact that HBeAg becomes negative does not always mean suppression of viral replication. METHOD: HBV replication was assessed in 74 patients with chronic hepatitis or viral B cirrhosis, in whom diagnosis was made according to clinical, biological, and histological criteria. The patients were divided into two groups: group I (36 patients with interferon- therapy, 3 million U/m 2/ dose, 3 doses/week over a period of 4-6 months) and group II (control group of 38 patients who did not undergo interferon therapy). After a follow up period of 6 years in which patients underwent clinical, biochemical and serologic monitorization, HBV DNA was detected by the hybridization method on solid medium. RESULTS: During evolution the levels of transaminases became normal in both groups. The HBe Ag/Ab seroconversion rate at the end of the interferon therapy was 52.8% and the spontaneous HBe Ag/Ab seroconversion rate was 72.7% in group II after an average evolution of 6 years. HBs Ag/Ab seroconversion was not detected in any patient. Assessment of viral replication by HBV DNA testing at the end of the follow up period showed higher levels as compared to the HBeAg testing (69.4% vs. 25% in group I, 55.2% vs. 7.9% in group II). The absence of viral replication (HBV DNA negative) had similar rates in both groups (30.6% in group I vs. 44.8% in group II, p>0.9) and HBV DNA titers in the two groups were not significantly different at the end of the follow up period. In both groups, HBV DNA titers were significantly higher in patients with positive HBeAg. The concordance between the two viral markers was 100%. CONCLUSION: Because of the fluctuating evolution, long-term follow up and monitorization (including HBV DNA testing) of patients with chronic hepatitis B and of inactive HBsAg carriers are necessary.     

人工肝支持系统治疗慢性重型肝炎的临床研究

目的探讨利用普通血液透析机进行人工肝(血浆置换联合血液透析)治疗慢性重型肝炎的临床疗效。方法对68例慢性重型肝炎进行186次人工肝支持治疗,观察治疗前、后临床症状的变化,血生化肝、肾功能指标的变化,预后情况及不良反应。结果全部病例均出现精神状态好转,肝性脑病程度减轻,乏力、腹胀减轻,食欲改善,尿量增加,全身水肿减轻;肝功能指标有明显改善:TBIL、ALT、AST、TBA、BUN、Cr、NH3均明显降低,ALB、PA 均明显提高(P<0.001～<0.05)。早、中期患者存活率明显高于晚期患者,两者比较有显差异(P<0.001)。结论利用普通血液透析机进行人工肝(血浆置换联合血液透析)治疗慢性重型肝炎操作方便,治疗安全、有效;人工肝治疗时应掌握时机,早期治疗。     

Evaluation of nursing care during treatment of viral hepatitis C by interferon

OBJECTIVE: Interferon alpha treatment requires parenteral administration and some patients receive injections from nurses. The aim of this study was to evaluate the role of nursing care during ambulatory treatment of hepatitis C by interferon alpha. METHODS: A questionnaire was sent by mail to all nurses who practice ambulatory care in the Val de Marne region (n =545). RESULTS: One hundred fourteen questionnaires were returned (return rate: 20%). Among these nurses, only 42 (37%) were caring for at least 1 patient for the treatment of hepatitis C by interferon. In the 16 months before the survey, these 42 nurses had cared for 135 patients. The nurses cared for the patients throughout the entire treatment in 81% and only to teach them in 19% of cases. The time spent for each injection was 12 min 48 sec, 2 min 42 sec for the injection itself, 3 min 54 sec to answer to patient's questions, 3 min 30 sec for psychological support, and 2 min 48 sec for unspecific time. In relation to hepatitis C and interferon treatment, 74% and 64% of the nurses felt that patients asked questions they did not ask their physician. Seventy seven of the nurses felt they were did not have enough training to answer the questions. Psychological support for the patient was noted as important or very important by 38 % of nurses. CONCLUSIONS: The role of nurses during interferon treatment is not limited to injecting the drug. Advice and psychological support takes up most of the time spent with patients. Specific training and better collaboration with the physician who prescribes the treatment are needed.     

干扰素治疗慢性丙型肝炎的持续应答与复发相关因素的研究

目的 探讨丙型肝炎病毒（HCV）基因型、RNA含量与肝组织炎症活动的相关性，慢性丙型肝炎患者经干扰素治疗后复发的相关因素。方法 对慢性丙型肝炎患者的血清进行丙氨酸氨基转移酶（ALT）检测，采用Cobas Amplicor Monnitour Test．version 2．0试剂进行HCVRNA定量和Simmonds酶切分型方法进行HCV基因分型检测。对聚乙二醇化干扰素α-2a（PEG—IFN α-2a）与干扰素α-2a治疗24周结束时，取得病毒学应答的慢性丙型肝炎患者进行24周随访观察，对临床特征、病毒学特征、治疗药物等因素与复发的相关性进行分析。结果 208例丙型肝炎患者基础HCVRNA含量与ALT水平无相关性（r=0．093，P〉0．05），HCV基因1型与非基因1型之间ALT的水平差异无统计学意义，HCV基因型与RNA含量无相关性；在治疗结束取得病毒学应答的119例患者中，随访24周持续应答者61例（51．3％），复发58例（48．7％）。患者的性别、年龄、HCV感染途径、既往干扰素治疗史、天冬氨酸氨基转移酶／ALT比值、血小板计数和血清基础HCV载量等因素均与复发率无显著相关性。基因1型患者复发率（54．5％）显著高于非1型（32．1％）（x^2=4．265，P=0．039）。PEG-IFNα-2a组复发率（47．0％）低于IFNα-2a组（52．8％），但差异无统计学意义。结论 病毒基因型与慢性丙型肝炎干扰素治疗后的病毒复发显著相关。     

Recombinant alpha 2c-interferon therapy in fulminant viral hepatitis

Recombinant alpha 2c-interferon was administered to 12 consecutive patients with fulminant viral hepatitis. The disease was caused by coinfection by HBV and HDV in seven patients, by HDV superinfection of a chronic HBV carrier in two, by HBV alone in two and by HAV in one. Eight patients were drug addicts. Interferon administration was initiated shortly after the onset of hepatic encephalopathy and no patient was in grade IV coma at the beginning of therapy. Ten patients died and only two survived. One of the survivors was an asymptomatic HBV carrier superinfected by HDV in whom treatment with interferon for 3 months did not prevent the development of chronic delta infection and liver cirrhosis. These results show that alpha 2c-interferon does not have significant therapeutic value in fulminant viral hepatitis, particularly if it is caused by HDV.     

干扰素在病毒性肝炎治疗中的地位及前景

近年来,病毒性肝炎的抗病毒治疗,不论是乙型肝炎还丙型肝炎均己取得很大进展.就乙型肝炎而言,近来己有6种核苷(酸)类药物用于临床,但是各国的治疗指南中仍采用干扰素作为抗病毒治疗的一线药物.