Interferon alfa for chronic hepatitis B infection: increased efficacy of prolonged treatment. The European Concerted Action on Viral Hepatitis (EUROHEP).

Interferon alfa (IFN-alpha) is the primary treatment for chronic hepatitis B. The standard duration of IFN-alpha therapy is considered 16 weeks; however, the optimal treatment length is still poorly defined. We evaluated the efficacy and acceptability of prolonged IFN-alpha treatment in patients with chronic hepatitis B. To investigate whether treatment prolongation could enhance the rate of hepatitis B e antigen (HBeAg) seroconversion, we conducted a prospective, controlled, multicenter trial in which all patients were treated with a standard regimen of 10 million units IFN-alpha 3 times per week over 16 weeks. Patients who were still HBeAg-positive after 16 weeks of therapy were randomized to prolongation of the identical regimen up to 32 weeks (prolonged therapy) or discontinuation of treatment (standard therapy). Among the 162 patients who entered the study, 27 (17%) were HBeAg-negative after the first 16 weeks of treatment, and 118 were randomized to standard or prolonged therapy. After randomization, a response (HBeAg seroconversion and sustained hepatitis B virus [HBV]-DNA negativity) was observed in 7 of the 57 (12%) patients assigned to standard therapy versus 17 of the 61 (28%) patients assigned to prolonged therapy (P =.04). A low level of viral replication after 16 weeks of treatment, as indicated by serum HBV-DNA values under 10 pg/mL, was found to be the only independent predictor of response (52% vs. 0%; P <.001) during prolonged therapy. The prolonged IFN-alpha schedule was well tolerated in the large majority of patients. In chronic hepatitis B, prolongation of IFN-alpha therapy up to 32 weeks is superior to a standard course of 16 weeks. Those patients who exhibit a low level of viral replication at the end of the standard regimen benefit most from prolonged treatment.     

Chronic hepatitis C: interferon retreatment of relapsers. A meta-analysis of individual patient data. European Concerted Action on Viral Hepatitis (EUROHEP).

Relapse after interferon (IFN) therapy for chronic hepatitis C virus (HCV) infection occurs in 50% of patients after the initial response. The benefit of retreatment with IFN alone has not been assessed in large controlled studies. To assess the effectiveness and the tolerability of IFN retreatment and to identify the optimal second course regimen, we performed a meta-analysis of individual patient's data on a set of 549 patients (mean age 43.8 years; 12.2 SD, men: 65%) who had an end-of-treatment biochemical response to a first IFN course and then relapsed. Retreatment was started within 24 months after the end of the first course. Biochemical end-of-treatment responses (ETR) and sustained responses (SR) were observed in 405 of 549 (73.8%; 95% confidence interval [CI] 70.1-77.5) and in 124 of 549 (22.6%; CI 19.1-26.1) patients, respectively. One hundred seventy-five of 404 patients (43.3%; CI 38.6-48.2) developed an end-of-treatment, biochemical, and virological response when retreated. A biochemical and virological SR to retreatment occurred in 73 of 494 (14.8%; CI 11.7-18) patients. Thirty-two patients (5. 8%; CI 3.5-7.8) stopped retreatment for adverse effects. Biochemical and virological SR was predicted independently by logistic regression analysis using a negative HCV RNA at the end of the first cycle of IFN (P =.01) and by retreatment with a high IFN dose (P =. 03). Age, cirrhosis, genotype, and gamma-glutamyl transferase levels before retreatment were not significant by multivariate analysis. The excellent tolerability of IFN monotherapy retreatment makes it an option for patients who transiently cleared HCV-RNA during their first IFN course. Patients should be retreated with a high IFN dose regardless of the strength of the dose received during the previous course of treatment.     

European collaborative study on factors influencing outcome after liver transplantation for hepatitis C. European Concerted Action on Viral Hepatitis (EUROHEP) Group.

BACKGROUND & AIMS: Liver transplantation for hepatitis C virus (HCV)-related liver disease is characterized by frequent graft infection by HCV. The prognosis and risk factors for morbidity and mortality in this condition were determined. METHODS: A retrospective study of 652 consecutive anti-HCV-positive patients undergoing liver transplantation between 1984 and 1995 in 15 European centers was conducted; 102 patients coinfected with hepatitis B virus (HBV) received immunoglobulin prophylaxis for antibody to hepatitis B surface antigen. RESULTS: Overall, 5-year survival was 72%. Five-year actuarial rates of hepatitis and cirrhosis were 80% and 10%. Genotypes 1b, 1a, and 2 were detected in 214 (80%), 24 (9%), and 24 (9%) of 268 patients analyzed. The only discriminant factor for patient or graft survival was hepatocellular carcinoma as primary indication. Independent risk factors for recurrent hepatitis included the absence of HBV coinfection before transplantation (relative risk [RR], 1.7; 95% confidence interval [CI], 1.2-2.6; P = 0.005), genotype 1b (RR, 2; 95% CI, 1.3-2.9; P = 0.01), and age > 49 years (RR, 1.4; 95% CI, 1.1-1.8; P = 0.01). CONCLUSIONS: The results of transplantation for HCV-related disease are compromised by a significant risk of cirrhosis, although 5-year survival is satisfactory. Genotype 1b, age, and absence of pretransplantation coinfection by HBV are risk factors for recurrent HCV.     

Hepatitis B surface antigen: association with sustained response to peginterferon alfa-2a in hepatitis B e antigen-positive patients

Purpose

Patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, who achieve HBeAg seroconversion 6 months after completing 48 weeks of peginterferon alfa-2a therapy, have an increased chance of clearing hepatitis B surface antigen (HBsAg) during long-term treatment-free follow-up. This analysis aimed to determine whether HBsAg quantification during treatment could be used to identify posttreatment response.

Methods

Patients (n = 399) treated with peginterferon alfa-2a (180 μg/week) alone or in combination with lamivudine (100 mg/day) for 48 weeks during a large, randomized study were included in this retrospective analysis. Receiver-operating characteristic analyses were used to identify baseline and on-treatment HBsAg levels associated with response (HBeAg seroconversion 6 months posttreatment).

Results

Baseline HBsAg levels were lower in patients achieving posttreatment response than in nonresponders (3.97 and 4.21 IU/mL, respectively, p = 0.039). Two baseline HBsAg cutoff levels (5,000 and 50,000 IU/mL) provided a positive predictive value of 42% and a negative predictive value of 77%. HBsAg decline was significantly greater during and posttreatment in responders than in nonresponders (p < 0.0001). HBeAg seroconversion rates 6 months posttreatment were significantly higher in patients with HBsAg < 1,500 IU/mL at weeks 12 and 24 (56.7 and 54.4%, respectively) versus patients with HBsAg 1,500–20,000 IU/mL (32.3 and 26.1%, respectively) or HBsAg < 20,000 IU/mL (16.3 and 15.4%, respectively) (all p < 0.0001 and <0.0001).

Conclusions

HBsAg levels at baseline strongly associated with posttreatment response were not identified. Low HBsAg levels during peginterferon alfa-2a therapy were associated with high rates of posttreatment response. On-treatment HBsAg quantification may, therefore, help guide patient management in the future.     

重组干扰素α-2a,α-2b治疗慢性乙型肝炎疗效比较

探讨不同亚型α干扰素（IFNα-2α，IFNα-2b）治疗慢性乙型肝炎的疗效差异。110例慢性乙型肝炎（CHB）患者被随机分为IFNα-2α，治疗组（52例）和IFNα-2b治疗组（58例）。IFNα-2α治疗组采用IFNα-2a（因特芬）每日3MU肌注，IFNα-2b治疗组采用IFNα-2b（隆化诺）每日3MU肌注，30天后改隔日3MU肌注，疗程6月。观察两组用药3月，6月后血清ALT昨常率，HBeAg阴转率，HBV－DNA阴转率和治疗反应率。ALT复常率两组无明显差异（P＞0．05）。HBeAg阴转率：IFNα－2b治疗组（51.7%,67.2%)，明显优于IFNα－2a治疗组（32.7%,44.2%)，两组差异明显（P＜0．05）。HBV DNA阴转率：6月后IFNα－2b治疗组（58．6％），明显优于IFNα-2α治疗组（34．6％），两组差异明显（P＜0．05）。治疗后完全反应率：IFNα－2b治疗组（46．6％） ，明显优于IFNα-2α治疗组（21．2％），两组间有极显著差异（P＜0．01）。干扰素α-2b亚型治疗慢性乙型肝炎疗效明显优于干扰素α-2α，亚型。     

Efficacy of a Chinese herbal formula on hepatitis B e antigen-positive chronic hepatitis B patients

BACKGROUND No guideline recommends antiviral therapy for hepatitis B e antigen(HBe Ag)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus(HBV) DNA viral load.AIM To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV infection.METHODS In total,395 patients(30–65 years old) with confirmed HBe Ag-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 wk.Endpoints to evaluate therapeutic efficacy included:(1) HBV DNA levels decreased to less than 4 log10 IU/m L at weeks 48 and 96;and(2) HBe Ag clearance and seroconversion rates at weeks 48 and 96.RESULTS HBV DNA levels ≤ 4 log10 IU/m L were 10.05% at week 48 and 18.59% at week 96 in the treatment group.The HBe Ag clearance and conversion rates were 8.54% and 8.04% at week 48 and 16.08% and 14.57% at week 96,respectively.However,HBV DNA levels ≤ 4 log10 IU/m L were 2.55% and 2.55% at weeks 48 and 96,respectively,and the HBe Ag clearance rates were 3.06% and 5.61% at weeks 48 and 96,respectively,in the control group.The quantitative hepatitis B surface antigen and HBe Ag levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 12 and 24 were strong predictors of HBe Ag clearance.CONCLUSION High rates of HBV DNA reduction,HBe Ag clearance and seroconversion could be achieved with Chinese herbal formula treatments,and the treatments were relatively safe for HBe Ag-positive chronic hepatitis B-infected patients with persistently normal alanine aminotransferase.The ability of the compound to modulate host immune function probably contributed to this effect.     

恩替卡韦对核苷初治HBeAg阳性慢性乙型肝炎患者的疗效

目的:探讨恩替卡韦对核苷初治HBeAg阳性慢性乙型肝炎患者的疗效.方法:101例慢性乙型肝炎患者被随机分配到恩替卡韦(ETV)组和阿德福韦酯(ADV)组,分别给予0.5 mg/d恩替卡韦和10 mg/d阿德福韦酯治疗.疗效的主要观测指标有:血清HBVDNA水平,HBeAg转阴或丙氨酸氨基转移酶(ALT)复常.结果:48 wk时,ETV组与ADV组HBV DNA均下降,且>103copies/mL的比率有统计学差异(95.83% vs 60.38%,P<0.001);ALT复常率2组亦有显著差别(52.08% vs 28.30%,P=0.015);2组均无HBeAg转阴;不良事件发生率分别为77.08%与71.69%p=0.536),两组差异没有统计学意义.结论:在核苷初治HBeAg阳性慢性乙型肝炎的治疗中,恩替卡韦比阿德福韦酯有更强的病毒学与生物化学应答率,但HBeAg转阴率不高,还需进一步观测.     

聚乙二醇化干扰素治疗乙型肝炎病毒e抗原阳性慢性乙型肝炎患者乙型肝炎病毒表面抗原消失的相关因素

目的 探讨聚乙二醇化干扰素（PEG-IFN α-2a）治疗HBeAg阳性慢性乙型肝炎(CHB)患者过程中预测HBsAg消失的相关因素。方法 对72例HBeAg阳性CHB患者,应用PEG-IFN α-2a 180 μg,每周1次,共48周。每3个月检测ALT、AST及HBV DNA、HBeAg和H BsAg定量,对48周治疗结束时HBsAg消失与基线、12周、24周的HBV DNA、HBeAg和HBsAg定量的相关关系进行分析。计数资料行Fisher精确检验及受试者工作特征(ROC)曲线分析。结果65例HBeAg阳性CHB患者完成本研究,其中7例HBsAg消失。48周时HBsAg的消失与治疗12周时H BeAg水平有关（Fisher确切概率法,P=0.023）,与治疗24周时HBeAg水平高度相关 （Fisher确切概率法,P=0.004）,与12周或24周时HBsAg＜250 IU/mL相关(Fisher确切概率法,P=0.001,P=0.002)。与12周时HBV DNA阴转相关（Fisher确切概率法,P=0.039）,而与24周时HBV DNA是否阴转无关（Fisher确切概率法,P= 0.130）。经ROC曲线分析显示,12周、24周HBsAg及24周HBeAg曲线下面积(AUC)分别为0.8584(P=0.0021)、0.9606(P=0.001)及0.8350(P=0.040)。结论 联合应用24周HBeAg和HBsAg定量水平可能是预测48周疗程结束时是否发生HBsAg消失的有效指标。     

Mycophenolate mofetil in combination with recombinant interferon alfa-2a in interferon-nonresponder patients with chronic hepatitis C

BACKGROUND/AIMS: Since ribavirin was able to improve the antiviral efficacy of interferon alfa in patients with chronic hepatitis C, several other adjuncts have been studied. It has been shown that mycophenolate mofetil (MMF) is a more potent inhibitor of the inosine 5'-monophosphate-dehydrogenase (IMPDH) than ribavirin. The present study is a pilot study evaluating the efficacy and safety of combination therapy with interferon alfa-2a and MMF in interferon alfa nonresponder patients. METHODS: Thirty-eight adult patients with chronic hepatitis C who did not respond to a previous interferon alfa monotherapy were enrolled to receive 6 million units of interferon alfa-2a tiw in combination with MMF (1 week 500 mg/day, 1 week 1000 mg/day, 22 weeks 2000 mg/day). RESULTS: An interim analysis of 29 patients after 12 weeks of therapy showed that only one patient had negative hepatitis C virus-RNA at this time point. There was no significant reduction of the viral load during therapy. Due to inefficacy the study was discontinued. CONCLUSIONS: Combination therapy of interferon alfa-2a and MMF is ineffective in improving virological response rates in nonresponder patients with chronic hepatitis C. These data suggest that inhibition of the IMPDH seems not to be the major mechanism of ribavirin in enhancing the antiviral effect of interferon alfa in chronic hepatitis C.     

干扰素治疗慢性乙型肝炎时e抗原血清学转换的相关因素

目的探讨HBeAg阳性慢性乙型肝炎在聚乙二醇干扰素α-2a（PEG-IFN α-2a）治疗过程中HBeAg血清学转换和病毒学应答的相关因素，HBeAg血清学转换与HBV DNA应答的相关性。方法患者采用PEG-IFNα-2a每次180μg，皮下注射，每周1次，共治疗48周，治疗结束后随访24周。用Abbott公司生产的第三代HBV血清学检测试剂和AXSYM自动酶标检测仪检测血清HBeAg、抗-HBe，实时荧光定量PCR检测HBVDNA载量，分析不同治疗阶段和随访结束的病毒学应答率（HBV DNA〈1．0×10^5拷贝／ml），HBeAg血清转换率及变化规律和影响病毒学应答和HBeAg血清转换的因素。结果治疗12周和随访结束时HBeAg血清转换组和非转换组的ALT水平比较，差异有统计学意义。病毒学应答无论在治疗期还是随访结束时，应答组与非应答组之间的ALT水平差异均有统计学意义。HBeAg血清学转换与非转换组之间的HBV DNA载量之间在治疗12周、治疗结束和随访结束时，差异无统计学意义。治疗期间病毒学应答与非应答组的HBV DNA载量之间的差异有统计学意义，但持续病毒学应答与HBV DNA载量无显著相关性。治疗12、24周和48周获得病毒学应答组的HBeAg血清转换率分别为43．8％、21．4％和18．9％。治疗12、24周和48周时病毒学应答组，在随访结束时的HBeAg的血清转换率分别为42．9％、33．3％和27．6％。多因素分析显示，治疗72周的HBeAg血清转换与治疗结束时的HBV DNA阴转显著相关（OR=2．15，95．0％CI=1．744-2．664，P〈0．01）。结论治疗12周和持续HBeAg血清学转换以及病毒学应答均与ALT基线水平相关，HBeAg血清学转换与基础HBV DNA载量无关，但与治疗过程中病毒学应答相关。     

Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B. The European Concerted Action on Viral Hepatitis (Eurohep)

BACKGROUND: The effect of hepatitis delta virus (HDV) infection on the clinical course of cirrhosis type B is poorly defined. AIMS: To investigate the impact of HDV status on morbidity and mortality in cirrhosis type B. PATIENTS/METHODS: Retrospective cohort study of 200 Western European patients with compensated cirrhosis type B followed for a median period of 6.6 years. RESULTS: At diagnosis, 20% of patients had antibodies to HDV (anti-HDV); median age was lower in anti-HDV positive cirrhotics (34 v 48 years respectively). Kaplan-Meier five year probability of hepatocellular carcinoma (HCC) was 6, 10, and 9% in anti-HDV positive/HBeAg negative, anti-HDV negative/HBeAg negative, and anti-HDV negative/HBeAg positive cirrhotics respectively; the corresponding figures for decompensation were 22, 16, and 19% and for survival they were 92, 89, and 83% respectively. Cox regression analysis identified age, albumin concentration, gamma-globulin concentration, and HDV status as significant independent prognostic variables. After adjustment for clinical and serological differences at baseline, the risk (95% confidence interval) for HCC, decompensation, and mortality was increased by a factor of 3.2 (1.0 to 10), 2.2 (0.8 to 5.7), and 2.0 (0.7 to 5.7) respectively in anti-HDV positive relative to HDV negative cirrhotic patients. The adjusted estimated five year risk for HCC was 13, 4, and 2% for anti-HDV positive/HBeAg negative, anti-HDV negative/HBeAg negative, and anti-HDV negative/HBeAg positive cirrhotics respectively; the corresponding figures for decompensation were 18, 8, and 14% and for survival 90, 95, and 93% respectively. CONCLUSIONS: HDV infection increases the risk for HCC threefold and for mortality twofold in patients with cirrhosis type B.     

慢性丙型肝炎干扰素治疗后复发患者的干扰素再治疗

目的探讨干扰素(IFN)治疗后复发的慢性丙型肝炎患者对IFN再治疗的应答情况及影响因素。方法对聚乙二醇化干扰素(PEG-IFN)α-2a与重组人干扰素(CIFN)α-2a治疗中国慢性丙型肝炎患者疗效与安全性的随机、开放、多中心对照研究中的6O例干扰素治疗后复发患者的再治疗进行回顾性研究。其中PEG-IFN α-2a组35例和CIFN α-2a组25例,以持续病毒学应答(SVR)作为疗效的主要评价指标,分析HCV RNA载量、基因型、药物种类对IFN疗效的影响。结果 60例复发患者用IFN再治疗后,55．00％取得治疗结束时的病毒学应答(ETVR),35．00％取得SVR;其中PEG-IFN α-2a组74.29％取得ETVR,显著高于CIFN α-2a组(28．00％),P<0．01; PEG-IFN α-2a组45．71％取得SVR,高于CIFN α-2a组(20．00％), P>0．05;病毒载量高、低组间的ETVR、SVR的差异无统计学意义;对于HCV基因1型感染患者,PEG- IFN α-2a的ETVR(75．00％)和SVR(45．83％)均显著高于CIFN α-2a组(分别为22．22％和11．11％), P相似文献   

A pilot study of extended duration peginterferon alfa-2a for patients with hepatitis B e antigen-negative chronic hepatitis B

OBJECTIVES: Forty-eight weeks of peginterferon alfa-2a is the approved regimen for chronic hepatitis B (CHB). Standard interferon is more effective for hepatitis B e antigen (HBeAg)-negative CHB when given for longer than 1 yr. This study evaluated peginterferon alfa-2a for 60 wk, alone or in combination with lamivudine. METHODS: Thirteen patients with HBeAg-negative CHB received peginterferon alfa-2a (180 microg/week) for 60 wk or peginterferon alfa-2a (180 microg/week) for 12 wk followed by 48 wk of peginterferon alfa-2a plus lamivudine. The primary end point, sustained virologic response (SVR), was defined as a reduction in hepatitis B virus deoxyribonucleic acid (HBV DNA) of >or=2 log10 copies/mL and HBV DNA<20,000 copies/mL at 24 wk of follow-up (week 84). Hepatitis B surface antigen (HBsAg) concentrations were analyzed and compared to changes in HBV DNA. RESULTS: SVR was achieved by 9/13 patients (69%). At week 84, HBV DNA was undetectable by polymerase chain reaction in 5/13 (38%) patients, and 3 additional patients had a sustained 2-3 log reduction in HBV DNA. Five patients demonstrated a >90% decrease in HBsAg concentration at week 60, including 3 with undetectable HBV DNA at week 84 and a fourth who met criteria for SVR. CONCLUSIONS: Sixty weeks of peginterferon alfa-2a with or without lamivudine resulted in a higher rate of SVR compared to historical controls with HBeAg-negative CHB treated with 48 wk of pegylated interferon. Larger studies are necessary to assess if longer duration therapy is more effective than the standard regimen and results in a greater decline in HBsAg concentration.     

Lamivudine and 24 weeks of lamivudine/interferon combination therapy for hepatitis B e antigen-positive chronic hepatitis B in interferon nonresponders

BACKGROUND/AIMS: Lamivudine is effective in treatment-naive patients with chronic hepatitis B, but its role in interferon nonresponders has not been described. We assessed lamivudine treatment, with or without added interferon, in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had failed interferon therapy previously. METHODS: Patients were randomized to lamivudine (100 mg) or placebo for 52 weeks or to a 24-week regimen of lamivudine plus interferon. Primary treatment comparisons were at week 52, with a 16-week posttreatment follow-up period. Measurements included histology (primary endpoint), HBeAg response, normalization of alanine aminotransferase, reduction of hepatitis B virus (HBV) DNA, and safety. RESULTS: Among 238 patients, histologic response was significantly more common in patients treated with lamivudine (52 versus placebo 25%, P=0.002) or the combination regimen (32%, P=0.01). HBeAg loss was also more common with lamivudine (33 versus 13 versus 21%), as were virologic and alanine aminotransferase responses. Among 28 subjects with HBeAg loss/seroconversion, 71% had durable responses 16 weeks posttreatment. CONCLUSIONS: Lamivudine for 52 weeks is as effective in interferon nonresponders as in previously reported treatment-naive patients; however, a combination of lamivudine for 24 weeks and interferon for 16 weeks was not effective in this population.     

Viral factors correlate with hepatitis B e antigen seroconverson in patients with chronic hepatitis B.

BACKGROUND/AIMS: Seroconversion (SC) from hepatitis B envelope antigen (HBeAg) to anti-HBe usually indicates lower viral loads, resolved hepatitis activity and improved long-term outcomes. However, the role of viral factors in the development of SC remains largely unknown. We thus comprehensively studied these factors in 25 patients with sustained HBeAg SC and seven control patients with sustained loss of HBeAg. METHODS: We determined viral factors in serum samples obtained 1 year before, 6 months before, 3 months before, at the time of, 6 months after and 1 year after HBeAg SC or HBeAg loss. Precore A1896 and basal core promoter T1762/A1764 mutants were determined by polymerase chain reaction (PCR)-based assays. Serum HBV levels were determined by a real-time PCR assay. RESULTS: We found that decline of serum viral load, frequently accompanied by hepatitis exacerbation, occurred within 1 year before HBeAg SC. The proportions of precore and BCP mutations also increased gradually throughout the process of HBeAg SC. The virologic features were similar between HBeAg SC group and HBeAg loss group. Before HBeAg SC or loss, genotype B patients had higher serum viral loads and lower proportions of BCP mutation compared with genotype C patients. CONCLUSION: Our findings suggested that viral factors correlate with the development of sustained HBeAg SC or loss.     

乙型肝炎e抗原阴性和阳性慢性乙型肝炎患者临床转归的回顾性分析

目的 随访HBeAg阴性和HBeAg阳性慢性乙型肝炎的临床转归，为比较两者的预后提供佐证。方法 采用回顾性分析，随访6～18年，平均（11．8±4．1）年，经肝穿刺病理组织学诊断，HBeAg阴性65例、HBeAg阳性118例慢性乙型肝炎患者的临床转归。统计学处理采用t检验和Х^2检验。结果 HBeAg阴性慢性乙型肝炎患者累计发展为肝硬化7例，占10．8％，肝癌4例，占6．2％，死亡8例，占12．3％；HBeAg阳性慢性乙型肝炎患者累计发展为肝硬化15例，占12．7％，肝癌8例，占6．8％，死亡12例，占10．2％。两组相比，肝硬化、肝癌和死亡的发生率差异均无统计学意义（均P〉0．05）。结论 HBeAg阴性和HBeAg阳性慢性乙型肝炎患者的远期临床转归差异无统计学意义。     

Anti-viral effect of recombinant interferon alfa-2a on hepatitis C virus

Anti-viral effect of interferon alfa-2a on hepatitis C virus was evaluated by detecting hepatitis C virus ribonucleic acid (HCV RNA) in 40 patients who had received enrolled in the double-blind controlled trial of short-term (8 weeks) interferon and also in six patients who had received long-term (1 year) interferon treatment. Among the 20 patients who received short-term interferon treatment, reduction of HCV RNA was observed in 5 of 12 patients who showed the reduction of alanine aminotransferase (ALT) levels. In contrast, reduction of HCV RNA level was not observed in any of 20 patients who received the placebo. Among ten patients (six long-term and four short-term treatment) who were available for long-term follow-up, five showed the complete normalization and two showed reduction of ALT levels to less than 50 IU/1 for 1 year after the end of treatment. HCV RNA turned negative and remained negative 1 year after the end of treatment in four of these seven patients. Thus, the anti-viral effect of interferon on HCV was confirmed by detecting the HCV RNA. The clinical effect of interferon on type C hepatitis was considered to be brought about by the decrease or disappearance of the virus.