The prevalence of occult hepatitis B in chronic hepatitis C patients treated with interferon-based antiviral therapy

Background and study aims

Occult hepatitis B infection (OBI) is known to be mostly prevalent in chronic hepatitis C (CHC) patients and OBI reactivation might be life-threatening in patients undergoing interferon (IFN)-free direct acting antiviral (DAA) therapy. As previous studies have revealed a relationship between OBI and non-response to IFN-based antiviral therapy, the aim of the current study was to determine if there was a higher prevalence of OBI in IFN non-responders than responders.

Hepatitis C virus genotypes among patients with thalassemia and inherited bleeding disorders in Markazi province, Iran

Hepatitis C virus (HCV) genotypes, multiple genotypes infection and HCV seroprevalence were investigated among 98 thalassemia patients and 76 haemophiliacs in Markazi province, Iran. HCV antibody was detected in 5 (5.1%) of the first group and 33 (43.4%) of the latter. Risk factors associated with anti-HCV antibody were also determined. Anti-HCV positivity in thalassemiacs were related to the number of blood transfusion units, splenectomy and duration of thalassemia. Analysis of risk factors in haemophiliacs revealed that seropositivity was significantly associated with duration of transfusion (P =0.009) and severity of disease (P = 0.000). The prevalence of HCV antibody in thalassemia subjects dropped from 8.1% to 0% after implementation of anti-HCV screening (1996). It was found that higher prevalence of HCV antibody in haemophiliacs (43.4%) compared with thalassemia patients (5.1%) correlated with clotting factor concentrates. Of the 34 seropositive haemophilia patients, HCV RNA was detected in 23 (67.7%). HCV genotype distribution was one in 50%, three in 18.2%, two in 4.54% and mixed in 27.3% (1 + 2 in 9.1%, 1 + 3 in 4.54%, 1 + 4 in 9.2% and 2 + 3a in 4.54%) cases. Among the five anti-HCV-positive thalassemiacs, two (40%) were positive for HCV RNA and one sample was found to be subtype 3a. This study confirms that multitransfused patients in Markazi province had similar genotype distribution as those previously reported form some other regions of Iran. Considering the possibilities of HCV mixed genotype among patients with haemophilia and thalassemia, accuracy and precision should be highly concerned in the detection of genotypes and their subsequent treatment.     

PCR直接法检测HBsAg阴性肝病的价值

目的研究ＨＢｓＡｇ阴性肝病患者和自然人群中乙肝病毒（ＨＢＶ）携带者。方法采用ＤＮＡＰＣＲ直接法测定急、慢性肝炎，肝硬变和单项ＡＬＴ增高者共２３１例ＨＢｓＡｇ阴性患者中ＨＢＶＤＮＡ，２４０例ＨＢＶ标志阴性的自然人群对照。结果检出率在患者组和对照组分别为３３．７％（７８／２３１）和１１．５％（２８／２４０），Ｐ＜０．０１。单项ＡＬＴ增高组最高，达６６．７％（１０／１５），其他依次为慢肝组（ＣＨ）４１．９％（１３／３１）、肝硬变组（ＬＣ）３０．７％（５２／１６９）和急肝组１８．７％（３／１０）。单项ＡＬＴ增高组与ＬＣ、急肝组有显著差异（Ｐ＜０．０１）。结论在ＨＢｓＡｇ阴性的肝病患者和自然人群中均有ＨＢＶ携带者     

Interferon and lamivudine vs. interferon for hepatitis B e antigen-positive hepatitis B treatment: meta-analysis of randomized controlled trials.

AIMS: To compare interferon monotherapy with its combination with lamivudine for hepatitis B e antigen (HBeAg)-positive hepatitis B treatment. METHODS: Two independent researchers identified pertinent randomized controlled trials. The trials were evaluated for methodological quality and heterogeneity. Rates of sustained virological and biochemical responses, and HBeAg clearance and seroconversion were used as primary efficacy measures. Quantitative meta-analyses were conducted to assess differences between groups for conventional and pegylated interferon, and overall. RESULTS: Greater sustained virological, biochemical and seroconversion rates were observed with addition of lamivudine to conventional [odds ratio (OR)=3.1, 95% confidence intervals (CI) (1.7-5.5), P<0.0001, OR=1.8, 95% CI (1.2-2.7), P=0.007 and OR=1.8, 95% CI (1.1-2.8), P=0.01 respectively], although not pegylated [OR=1.1, 95% CI (0.5-2.3), P=0.8, OR=1.0, 95% CI (0.7-1.3), P=0.94, and OR=0.9, 95% CI (0.6-1.2), P=0.34 respectively] interferon-alpha, with no significant affect on HBeAg clearance rates [OR=1.6, 95% CI (0.9-2.7), P=0.09, and OR=0.8, 95% CI (0.6-1.1), P=0.26 respectively]. Excluding virological response (P<0.001), pegylated interferon monotherapy and conventional interferon and lamivudine combination therapy were similarly efficacious (P>0.05), with the former studied in harder to treat patients, as evidenced by the superior virological response observed with conventional as compared with pegylated interferon monotherapy (P<0.0001). CONCLUSION: In comparable populations, pegylated interferon monotherapy is likely to be equally or more efficacious than conventional interferon and lamivudine combination therapy, thus constituting the treatment of choice, with no added benefit with lamivudine addition. However, when conventional interferon is used, its combination with lamivudine should be considered.     

Epidemiology of hepatitis D virus (delta) infection in Yugoslavia

ABSTRACT— In 614 HBsAg-positive Yugoslavian patients, radioimmunoassay testing for anti-delta showed the presence of this antibody in serum in 11.2%. Of the patients, 213 belonged to a risk group (i.v. drug users, hemophiliacs, hemodialysed patients and patients with posttransfusion hepatitis); a significant number of these patients (63; 29.6%) were found to have anti-delta. A second group was composed of 401 HBsAg-positive patients from the general population (patients with acute hepatitis B, with fulminant hepatitis B and patients with chronic HBV infection); delta infection was found only in six (1.5%). Immunohistochemical methods failed to demonstrate the delta antigen in the livers of 73 patients with chronic HBV infection. Testing the liver of 36 patients with fulminant hepatitis B for delta antigen demonstrated this reactivity in only one (2.8%) liver sample. Delta antigen was also found in the liver of a female patient who underwent biopsy in 1972. The results of this study suggest the HDV is not endemic in Yugoslavia; however, it is frequently found in patients at risk of blood exposure, primarily i.v. drug users.     

复方鳖甲软肝片治疗慢性乙型肝炎早期肝硬化的临床研究

慢性乙型肝炎患者由于体内乙型肝炎病毒的持续复制，造成肝细胞反复的炎症损伤，诱发大量炎症细胞因子的产生，激活肝脏中的贮脂细胞转化为成纤维母细胞，成纤维母细胞产生大量纤维结缔组织．最终导致肝脏正常结构丧失，形成肝硬化。肝脏纤维化的增生性变化在肝硬化的形成中起着重要的作用，故早期肝硬化的治疗具有十分重要的意义。本文对复方鳖甲软肝片治疗慢性乙型肝炎早期肝硬化的疗效及安全性进行了以下的临床研究。     

Viusid, a nutritional supplement, in combination with interferon alpha-2b and ribavirin in patients with chronic hepatitis C.

BACKGROUND: The pathogenesis of chronic hepatitis C (CHC) is associated to severe oxidative stress that leads to necro-inflammation and progression of fibrosis. Previous trials suggested that antioxidative therapy may have a beneficial effect. We evaluated the efficacy and safety of Viusid in combination with interferon alpha-2b (IFN alpha-2b) and ribavirin in patients with CHC. METHODS: We randomly assigned 100 patients, between October 2002 and December 2004, in two arms: IFN alpha-2b (5 MU on alternate days), ribavirin at a dose of 13 mg/kg daily and Viusid (three sachets daily) vs. IFN alpha-2b (5 MU on alternate days) and ribavirin at a dose of 13 mg/kg daily. Subjects were treated for 48 weeks and then followed for an additional 24 weeks. The primary end point was the histologic response (reduction of at least two points without fibrosis worsening in the total score on the Histological Activity Index). RESULTS: A significantly high proportion of patients who received combined therapy plus Viusid had a histologic response better than those patients who received IFN alpha-2b and ribavirin (57% vs. 37%, P=0.03). The patients with virologic response achieved the highest percentages of histologic response, irrespective of assigned treatment. Among non-responders, the highest reduction in the mean change from baseline score for necro-inflammatory activity (NA) and fibrosis (F) was reported in patients treated with Viusid [NA, -1.50 (Viusid), -1.20 (without Viusid); F, -0.31 (Viusid), 0.00 (without Viusid)]. Sustained normalization of serum alanine aminotransferase concentration was highest in the Viusid group compared with standard therapy (67% vs. 41%, P=0.009). The overall safety profile was similar in both groups, but interestingly, the anemia was less intense in the group with Viusid (P=0.04). CONCLUSIONS: Our results suggest that triple therapy with Viusid, IFN alpha-2b and ribavirin was well tolerated and may have a beneficial effect on histologic and biochemical variables. The intensity of anemia is reduced in patients treated with Viusid.     

HBV 1762／1764联合突变的研究

目的探讨乙肝病毒C基因启动子区1 762/1764联合突变的临床意义.方法随机选择HBV DNA、HBeAg阳性和HBV DNA、HBeAg阴性的慢性乙型肝炎患者各50例.用实时荧光定量PCR法,对两组患者进行HBV 1 762/1764双变异及HBV DNA定量测定.结果HBV 1 762/1764变异阳性率在HBeAg阳性组为24.0%,在HBeAg阴性组为70.0%,两组比较差异有显著性意义(P＜0.01);HBV DNA含量,HBV 1 762/1764突变者显著高于HBV 1 762/1764未突变者(P＜0.01).结论HBV 1 762/1764联合突变可能抑制HBeAg表达和导致HBV复制增强.     

A Randomized, Controlled Study of Thymosin-α1 Therapy in Patients with Anti-HBe, HBV-DNA-Positive Chronic Hepatitis B

No consistently effective therapy is yet available for the treatment of chronic HBsAg, anti-HBe, HBV-DNA-positive hepatitis. A multicenter trial has shown that the response rates are not significantly different when patients with anti-HBe-positive hepatitis are treated with six-month course of thymosin-₁ or of interferon-. However, since among these patients, interferon's real efficacy is still debated, with sustained biochemical response achieved in only a few of the treated patients, we conducted this controlled study to investigate the safety and efficacy of thymosin-₁ as compared with no treatment. Forty-four chronic hepatitis B virus (HBV) carriers, who were anti-HBe- and HBV-DNA-positive, were randomized, with stratification for the presence of cirrhosis at baseline liver biopsy, to receive either thymosin-₁ at a dose of 900 g/m² twice a week for six months or no treatment. At entry, both groups of patients were comparable for sex, age, liver histology, ALT, IgM anti-HBc, and HBV-DNA levels. Forty-two patients were followed-up for 20 months (median; range 12–32 months) after completion of therapy: one dropped out, and one developed hepatocellular carcinoma at six months. Thymosin-₁ treatment had no side effects. Six months after the end of the therapy, HBV-DNA was negative and ALT had normalized in 14% of treated cases and in 4.5% of control group, while IgM anti-HBc was negative (<0.200) in 14% of the treated patients and in 4.5% of the controls. Among the treated patients, the median ALT levels stayed significantly lower compared to the pretreatment values during the treatment period and six months of follow-up. During the first year, there were six flares of hepatitis in the control group and five among the treated patients (P = NS), yielding a per year average of 0.3 and 0.23 flares per patient, respectively. Among the treated patients, median IgM anti-HBc levels were low with respect to baseline values 4–10 months after treatment started. None became HBsAg negative. In conclusion, these results indicate that, in anti-HBe, HBV-DNA-positive chronic hepatitis B, thymosin-₁ therapy alone does not increase the response rate, but may contribute to reduce the immune-mediated liver cell necrosis as indirectly assessed by ALT and IgM anti-HBc levels.