Prospective controlled study of post-transfusion hepatitis after cardiac surgery in a large referral hospital in India.

We studied the risk of post-transfusion hepatitis (PTH) in recipients of blood collected from voluntary donors screened for HBsAg. Two hundred and fifty patients without any previous history of liver disease or transfusion were followed up for 12 months subsequent to cardiac surgery. Thirty-five of them had closed-heart surgery without receiving transfusion and served as controls. The remaining 215 patients received single-point transfusions (mean 4 +/- 2.4 units). None of the controls and 15 (6.9%) blood recipients developed PTH. Three (20%) patients had hepatitis-B-virus-induced hepatitis while the remainder (80%) had non A, non B (NANB) hepatitis. The number of units of blood transfused and surrogate markers for development of PTH (donor alanine aminotransferase, anti-HBc and anti-HBs antibody) were not associated with the occurrence of PTH (p greater than 0.05). Nine (60%) of the 15 patients developing PTH were asymptomatic. All the patients recovered from the PTH, except one who died of fulminant hepatitis. At the end of 1 year of follow-up, none of the patients had evidence of chronic hepatitis. Only three (25%) of the patients with NANB-PTH developed anti-hepatitis C virus (HCV) antibody during the follow-up. We conclude that the incidence of PTH in India is similar to other parts of the world and NANB virus was the major cause of the PTH. The absence of chronicity and lack of seroconversion to anti-HCV antibody in the majority of the patients after 1 year of follow-up may suggest the possibility of a NANB virus other than HCV as the major cause of PTH in India.     

Transmission of viral hepatitis by blood and blood derivatives: current risks, past heritage

For more than 40 years in the history of transfusion medicine, transmission of viral hepatitis from infected donors to recipients has been a frequent and serious adverse effect of the administration of blood components and plasma derivatives. This epidemic is now over, at least in developed and resource-rich countries. Hence, the attention of clinicians and investigators now focuses mainly on the measures to reduce the residual risk, on the possible emergence of novel or undiscovered agents causing post-transfusion hepatitis, and on the long-term outcome of patients who became infected more than ten years ago. The present article reviews these issues.     

Anti-hepatitis a virus seroprevalence and seroconversion in a cohort of patients with chronic viral hepatitis

BACKGROUND: Patients with chronic hepatitis C infected by hepatitis A virus have a substantial risk of fulminant hepatitis or death, while the course of hepatitis A virus is uncomplicated in most subjects with chronic hepatitis B. AIM: To evaluate the prevalence of anti-hepatitis A virus antibodies and the incidence of hepatitis A virus seroconversion in a nationwide sample of 530 patients with chronic hepatitis B and/or hepatitis C infection initially susceptible to this infection after a follow-up of some years. RESULTS: The overall anti-hepatitis A virus prevalence was 85.7%, with no difference between males and females. By the age of 50 years, almost all patients were found to have been exposed to hepatitis A virus. After a mean follow-up period of 76 months the overall anti-hepatitis A virus seroconversion rate in the 76 initially susceptible individuals was 1.2 per 100 person/years. However, it was 0.3 per 100 person/years in those hepatitis B surface antigen positive but 3.36 per 100 person/years in those anti-hepatitis C virus positive. None of the seroconverters was affected by a clinically evident disease or showed deterioration of underlying chronic liver disease. CONCLUSIONS: The present study shows that Italian patients >50 years of age with chronic liver disease have already been exposed to hepatitis A virus suggesting that anti-hepatitis A virus screening is not advisable in these subjects.     

输血后丙型肝炎病毒感染的血清病毒定量研究

目的 研究血清丙型肝炎病毒（ＨＣＶ）含量与ＨＣＶ致病的关系及ＨＣＶ含量与抗－ＨＣＶ和丙氨酸转氨酶（ＡＬＴ）的相关性。方法 以逆转录－聚合酶链反应（ＲＴ－ＰＣＲ）法对ＨＣＶ感染的受血及相关供血系列血清进行ＨＣＶ ＲＮＡ定量分析,同时检测ＡＬＴ与抗－ＨＣＶ。结果 致输血后ＨＣＶ感染的供血中,ＨＣＶ ＲＮＡ平均含量为１０＾８．６拷贝／Ｌ,抗－ＨＣＶ及ＡＬＴ的异常检出率随ＨＣＶ ＲＮＡ滴度升高而增加。结论     

A cross-sectional study on HGV infection in a rural population

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Prevalence of hepatitis C virus antibodies in chronic liver disease and hepatocellular carcinoma patients in India

The prevalence of antibodies to hepatitis C virus (HCV) was investigated in 129 patients with chronic liver disease (85 with chronic active hepatitis and 44 with cirrhosis) and 53 patients with hepatocellular carcinoma. The commercially available second generation anti-HCV enzyme immunoassay kit was used. Antibodies to hepatitis C virus were detected in 16.2% of the patients with chronic liver disease and in 15.1% with hepatocellular carcinoma. Of the HCV positive patients in all groups 51.7% were positive for hepatitis B virus (HBV) markers indicating present or past infection. Prevalence of HBV markers in all the three groups (CAH, cirrhosis and HCC) was higher as compared with anti-HCV prevalence. These results suggest that HCV infection may not be a major cause of chronic liver disease and hepatocellular carcinoma in India and indicate the presence of other aetiological agents.     

HBsAg阴性的慢性乙型和丙型重叠感染肝炎患者临床研究

为探讨HBsAg阴性的慢性乙型重叠丙型肝炎患者HBV -DNA水平及临床特征 ,采用PCR -微板核酸杂交 -ELISA法对 2 0 3例HBVM一项 /一项以上阳性的慢性丙型肝炎患者进行HBV -DNA定量及HCV -RNA基因分型检测 ,并分析患者性别、年龄以及肝功能等临床特征。HBsAg阴性及HBsAg阳性慢性丙型肝炎患者在性别、年龄分布上无差异 ;但血清ALT及总胆红素水平在HBsAg阳性者较高。Ⅱ / 1b型HCV感染在HBsAg阴性者中的比例高于HBsAg阳性者 (P <0 0 5 )。HBsAg阴性慢性丙肝患者HBV -DNA阳性率及HBV水平均低于HBsAg阳性患者。HBsAg阴性的慢性丙肝患者中 ,抗HBc单独阳性者HBV -DNA阳性率最高 ,但HBV -DNA水平无显著性差异。Ⅱ /1b型HCV感染在HBV -DNA阴性患者中的出现频率较高 ,与HBV -DNA阳性患者相比差异有显著性。因此 ,临床上对于那些肝功能损害严重 ,同时有抗HBc阳性或Ⅱ / 1b型HCV感染 ,尤其是HCV -RNA阴性而肝功能仍有持续损害的患者要及时行HBV -DNA检测 ,以除外HBV活动的可能     

Long-term follow up of chronic hepatitis C patients after alpha-interferon treatment: a functional study

AIM: To evaluate the long-term functional outcome of chronic hepatitis C (CHC) patients treated with interferon (IFN) therapy. METHODS: Thirty-six patients with CHC were followed up for a mean of 36 months (+/- 19, SD) after a course of IFN therapy. Biochemical, virological (qualitative hepatitis C virus (HCV)-RNA and HCV genotype), and functional (monoethylglycinexylidide (MEGX) test) evaluations were carried out at the time of liver biopsy. Patients were divided into long-term responders (LTR), relapsers (RR), or non-responders (NR) according to IFN therapy outcome. At the end of follow up, patients were non-invasively re-evaluated by means of biochemistry, qualitative HCV-RNA, MEGX test, and liver ultrasonography. RESULTS: A significant decrease in MEGX values was observed in all patients. However, when patients were examined according to treatment outcome, only NR and RR showed a significant decrease in liver function as compared to pretreatment levels (MEGX30, 80.5 +/- 26.8-62.9 +/- 24.2 ng/mL, P< 0.01; MEGX60, 72.9 +/- 18.1-60.5 +/- 19.7 ng/mL, P< 0.05; MEGXAUC, 3,816 +/- 1,243-3,095 +/- 1,205 ng/mL per h, P< 0.05). On the contrary, LTR patients showed no significant modifications in MEGX values at each sampling time (MEGX,5, 72.9 +/- 31.4-70.3 +/- 29.7 ng/mL; MEGX30, 84.0 +/- 27.6-71.5 +/- 21.8 ng/ mL; MEGX60, 69.5 +/- 26.8-63.2 +/- 14.4 ng/mL; MEGXAUC 4028 +/- 1,378-3,620 +/- 1,041 ng/mL per h). At the end of follow up, LTR patients showed normal liver biochemistry and negativity of serum HCV-RNA, while NR and RR patients showed a significant decrease in platelets. CONCLUSIONS: In CHC patients long-term response to IFN therapy, besides favoring positive clinical and virologic long-term outcome, results in maintaining preserved liver function. Furthermore, IFN therapy seems to determine a decrease in the rate of functional disease progression, even in NR and RR. The MEGX test may be considered as a useful tool for performing serial follow up of CHC patients.     

Ribavirin monotherapy in patients with chronic hepatitis C: a retrospective study of 95 patients

Ribavirin is a purine nucleoside that inhibits the replication of a variety of RNA viruses and was shown to have a transient efficacy in chronic hepatitis C during short-term therapy. We have analysed retrospectively its efficacy in 95 patients with liver biopsy-proven chronic hepatitis C. Patients received oral ribavirin (600–1200mg daily) for a mean duration of 11 months. Alanine aminotransferase (ALT) levels returned to normal values in 38 patients (40%) and decreased by more than 50% in 20 other patients (21%). HCV RNA clearance from serum was observed in seven patients (8%). The biochemical response rate was higher in patients with chronic hepatitis (54%) than in those with cirrhosis (24%) ( P =0.003). Clearance of HCV RNA was observed in 10% of the patients with chronic hepatitis vs 4% of the patients with cirrhosis. In non-responders to interferon (IFN) therapy, ALT levels returned to normal values in 11 (26%) and HCV RNA became negative in one (2%), as compared to 48% and 3%, respectively, in those contraindicated for IFN. In 17 patients in whom paired liver biopsy specimens were available, the histology activity index (HAI) improved in 12. Therapy was generally well tolerated although 11 patients had to stop therapy because of side-effects, which were more common in cirrhotic patients. In conclusion, our results suggest that long-term administration of ribavirin is well tolerated and may be beneficial in controlling the progression of chronic hepatitis C. This may represent an alternative therapy in patients who have contraindications for interferon therapy or as a palliative approach in non-responders to IFN.     

Comparing the safety,tolerability and quality of life in patients with chronic hepatitis B vs chronic hepatitis C treated with peginterferon alpha‐2a

Background/Aims: Hepatitis B and C viruses (HBV and HCV) are two clinically distinct but related diseases. Pooled data from five studies of peginterferon alpha‐2a in patients with chronic HCV infection (CHC) were compared with two studies of the drug in patients with chronic HBV infection (CHB). Method: The HBV studies included both hepatitis B e antigen (HBeAg)‐positive (n=271) and HBeAg‐negative (n=177) patients; 791 patients took part in the HCV trials. In all studies, patients were treated with 180 μg peginterferon alpha‐2a monotherapy once weekly for 48 weeks. The number of adverse events (AEs), discontinuations and dose modifications were documented. Health‐related quality of life (HRQL) was assessed using the Short‐Form 36 questionnaire. Safety was assessed throughout the treatment period. A 24‐week treatment‐free follow‐up period was also included. Results: Differences (HBV vs HCV) were observed in the incidence of AEs (88–89 vs 96–100%), serious AEs (4–5 vs 7–16%) and treatment withdrawals (6–8 vs 17–33%). The frequency of depression‐related events was lower in CHB patients (4 vs 22%, P<0.001), as was the impact of treatment on HRQL. Conclusions: The safety and tolerability of peginterferon alpha‐2a in patients with CHB compares favourably with that observed in CHC patients, with a lower incidence of common interferon‐related AEs and a significantly lower incidence of depression.     

Vaccines and immunotherapies against hepatitis B and hepatitis C viruses

Summary.  Both hepatitis B and hepatitis C viruses (HBV and HCV) cause chronic infections worldwide that are associated with development of liver diseases ranging from mild liver inflammation to hepatocellular carcinomas. While efficient preventive vaccines are available for HBV, efforts are ongoing to develop one in case of HCV. Yet, both infections share the fact that therapeutic agents available to treat already established infections are yet poorly efficient, toxic or associated with development of resistance. Thus, novel immune-based therapies are actively being developed to complement or replace standard antiviral treatments. Among those, development of therapeutic vaccines represents a major effort. Peptide-, recombinant protein- or viral vector-based vaccines have been engineered and tested at preclinical and clinical levels. Means to adjuvant these vaccines are being pursued, including approaches based on combining vaccines of different nature. This review will outline major advances in the field of both HBV and HCV therapeutic vaccine development with a particular focus on candidates presented at the 12th International Symposium on Viral Hepatitis and Liver Disease (July 2006, Paris, France).     

双环醇治疗慢性乙型肝炎的临床研究

初步探讨双环醇治疗慢性乙型肝炎的保肝、抗病毒效果 ,并比较双环醇对不同基因型的乙肝患者的疗效。选取 33例慢性乙型肝炎患者 ,口服双环醇 2 5mg每日 3次 ,6个月。治疗前测乙型肝炎病毒基因型 ,治疗结束后分析不同基因型乙肝患者ALT、AST、HBeAg、HBVDNA变化。复常率ALT2 1例 (6 3 6 % ) ,AST15例 (4 5 5 % ) ,转阴率HBeAg :11例 (33 3% ) ,HBVDNA :9例 (2 7 3% )。B型和C型抗病毒总有效率分别是 5例 (4 1 7% )、8例 (4 0 0 % )。双环醇治疗慢性乙型肝炎有较好的保护肝细胞抑制乙肝病毒的效果。基因型B型和C型患者对双环醇疗效比较无显著差异     

Current risks of viral hepatitis from blood transfusions

The incidence of transfusion-associated hepatitis in the United States has fallen dramatically since the late 1960s. Where once the risks were so great that as many as one in three transfused patients contracted hepatitis, now they are infinitesimal. Many factors share responsibility for this accomplishment; however, two stand above the rest: (i) improved donor selection and screening criteria, especially elimination of paid blood donations; and (ii) major advances in testing for viral hepatitis carriers. Currently, four tests are used for the prevention of transfusion-associated hepatitis: (i) hepatitis B surface antigen; (ii) hepatitis C virus antibody; (iii) hepatitis B core antibody; and (iv) alanine aminotransferase. The first two tests are largely responsible for the current low risks of transfusion-associated hepatitis due to hepatitis B virus and hepatitis C virus of 1 in 63000 and 1 in 125000, per unit, respectively. To further reduce the risks of transfusion-associated hepatitis will require the enhanced sensitivity provided by nucleic acid amplification techniques (e.g. polymerase chain reaction). Currently, however, no such tests are licensed and practical, automated, or inexpensive enough for individual blood donor screening. We have made such great strides in the prevention of transfusion-transmitted hepatitis that background rates of viral hepatitis now greatly exceed the risk of transmission via transfusion. For this reason, while it may still be reasonable to consider a transfusion as a possible cause for hepatitis, it is imperative that many other possibilities (e.g., iatrogenic and other risk factors) be ruled out.     

Low serum level of hepatitis B core-related antigen indicates unlikely reactivation of hepatitis after cessation of lamivudine therapy

Aim: The clinical significance of hepatitis B virus (HBV) core-related antigen (HBcrAg) in predicting the reactivation of hepatitis after halting lamivudine administration was analyzed. Methods: A total of 34 patients with chronic hepatitis B were enrolled. Lamivudine was administered for at least 6 months before cessation, and reactivation of hepatitis was defined as elevation of alanine aminotransferase levels to more than 80 IU/L within 12 months of cessation. Results: In total, 20 (59%) patients experienced hepatitis reactivation. Although concentrations of HBV DNA and HBcrAg in serum did not differ between the two groups of patients at the onset of lamivudine administration, HBcrAg serum levels were significantly higher (P = 0.009) in the reactivation patients (median 4.9, 25-75% range 4.7- 5.9 log unit/mL) than the non-reactivation patients (median 3.2, 25-75% range <3.0-4.5 log unit/mL) post-lamivudine treatment. The concentration of HBV DNA did not differ between the two groups (median <3.7, 25-75% range <3.7-<3.7 log copy/mL in the reactivation group vs. median <3.7, 25-75% range <3.7-<3.7 log copy/mL in the non- reactivation group). Receiver operating characteristic analysis of HBcrAg concentration showed an area under the curve of 0.764 in predicting patients without reactivation of hepatitis. Conclusion: HBcrAg can be a useful marker to identify patients who are not at risk of reactivation of severe hepatitis after discontinuation of lamivudine administration.     

Detection of hepatocellular carcinoma after interferon therapy for chronic hepatitis C: Clinical study of 26 cases

The clinical findings in 26 patients in whom hepatocellular carcinoma (HCC) was detected after the start of interferon (IFN) therapy for chronic hepatitis C were analysed. Histological study before IFN therapy showed that 34.6% of patients were categorized as stage 3 (septal fibrosis with architectural distortion; the 0–4 scale) and 80.8% demonstrated at least some evidence of septal fibrosis or more advanced features. The AFP levels examined before IFN therapy were more than 20 ng/mL in 13 patients (84.6% of those studied). One of 26 patients had a complete response to IFN therapy, while six of 26 patients had only a partial response. HCC was detected within 1 year after the start of IFN therapy in 76.9% of patients. Thus, the possibility of the early occurrence of HCC or its existence at the time of therapy should be seriously considered when IFN therapy is contemplated. Patients with stage 3 or 3–4 histology may already have a small undetectable HCC before IFN therapy. Thus, for this reason, every patient treated with IFN should be examined at short regular intervals for the development of HCC during and after IFN therapy.     

Prevalence of hepatitis C virus infection in thalassemia and haemodialysis patients in north Iran-Rasht

Hepatitis C virus (HCV) seroprevalence and risk factors in north Iran were investigated in 105 thalassemia sufferers, 93 haemodialysis patients and 5976 blood donors by second generation ELISA. Our study showed that haemodialysis patients and thalassemia sufferers were at higher risk of having HCV infection; the prevalence being 55.9% and 63.8% respectively in comparison to the prevalence of blood donors (0.5%). A confirmatory immunoblotting was employed using HCV-positive cases (54 thalassemia sufferers and 19 blood donors). The result showed that 92.6% of samples of the first group and 10.5% of the latter were positive. Thus, it can be suggested that ELISA in low-risk cases may produce considerable false positives. In HCV-positive patients with thalassemia, the incidence of HCV among different age groups and genders was similar but a strong correlation in respect to the number of blood transfusion (P=0.008) was observed. In HCV-positive haemodialysis patients, it was found that there was no correlation with liver function tests (alanine aminotransferase and aspartate aminotransferase: ALT and AST), but a significant correlation was observed in respect to the duration of dialysis(P=0.000) and the number of units transfused (P=0.000). Consequently, it still seems blood transfusion is the main factor for increasing the incidence of HCV in thalassemia sufferers and haemodialysis patients.