Epidemiologic and virologic characteristics of hepatitis B virus genotype B having the recombination with genotype C

BACKGROUND & AIMS: Hepatitis B virus (HBV) isolates of genotype B (HBV/B) with or without the recombination with genotype C over the precore region plus core gene have been reported. METHODS: All the 41 HBV/B isolates having the recombination with genotype C (HBV/Ba) possessed the nucleotide 1838 of A in contrast to that of G in all 29 of those without the recombination (HBV/Bj). Taking advantage of this single nucleotide polymorphism, a restriction fragment length polymorphism method was developed that distinguished HBV/Ba from HBV/Bj. RESULTS: HBV/Bj was detected in 90 of the 97 (93%) carriers of HBV/B from Japan, whereas HBV/Ba occurred in all 177 carriers of HBV/B from other countries (China, 20; Hong Kong, 45; Taiwan, 32; Thailand, 30; Vietnam, 30; and the United States, 20 [all of an Asian ethnicity]). In a case-control study, hepatitis B e antigen (HBeAg) and the double mutation in the core promoter (T1762/A1764) were significantly more frequent in 80 carriers each of HBV/Ba than HBV/Bj (35% vs. 18%, P < 0.05 and 33% vs. 15%, P < 0.05, respectively). Differences in the prevalence of HBeAg were more conspicuous between the carriers of HBV/Bj and HBV/Ba older than 30 years (5 of 66 or 8% vs. 16 of 62 or 26%, P < 0.01). CONCLUSIONS: HBV/B having the recombination with genotype C is frequent in Asia, except in Japan, and HBeAg is more prevalent in carriers of HBV/Ba than HBV/Bj.     

Immunology of hepatitis C virus infections

The immune response in patients chronically infected with HCV plays a unique role during the infection because of its potential to contribute not only to viral clearance and, in some cases, protective immunity, but also to liver injury. A detailed understanding of the immunological mechanisms involved in persistence to HCV is essential to fully appreciate the complexity of the disease. In recent years, enormous progress has been made to characterize the dysfunctional natural killer cells and T cells during the chronic phase of infection. This information is important to further optimize treatment strategies based on the strengthening antiviral and immunomodulatory activities in patients chronically infected with HCV.     

Hepatitis B virus and hepatitis C virus infections in children

PURPOSE OF REVIEW: To analyse the most relevant recent information on efficacy, duration and coverage of anti-hepatitis B virus vaccination; correlates of mother-to-child hepatitis C virus transmission; the natural history and outcomes of hepatitis B and C virus infections in children; the efficacy and safety of specific therapies. RECENT FINDINGS: Insufficient hepatitis B virus vaccine coverage and incomplete or delayed vaccine cycles need improvement in many countries. Hepatitis B virus mutants may explain some fulminant hepatitis in perinatally infected infants and vaccine failures. No interventions to prevent vertical hepatitis C virus transmission have been identified. Spontaneous clearance of hepatitis B is lower in children than in adults, while the rates appear to be similar for hepatitis C. The disease progression is slower for both infections in childhood. Several studies support the efficacy and safety of interferons and lamivudine in chronic hepatitis B or of interferons and ribavirin in chronic hepatitis C in children, but the optimal therapy remains unclear. SUMMARY: There are doubts as to the long-term persistence of anti-hepatitis B immunization in low-endemicity areas. Routine hepatitis C virus testing in pregnancy is not recommended as there are no available prophylactic measures. Although hepatitis B and C virus infections are usually asymptomatic or with mild manifestations in childhood, concerns around their long-term clinical impact suggest the need for early treatment. Children should preferably be treated in the context of targeted trials for a better understanding of the efficacy and tolerance of drugs currently used in adults.     

Challenge of managing hepatitis B virus and hepatitis C virus infections in resource-limited settings

The global burden of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and coinfection represents a major public health concern, particularly in resource-limited settings. Elimination of HCV by 2030 has become foreseeable, with effective direct-acting antiviral oral therapies and the availability of affordable generics in low-and-middle-income countries (LMICs). However, access to oral nucleos(t)ide therapy for HBV remains critical and is limited outside the existing global HIV program platforms despite affordable prices. Prevention of mother-to-child transmission of HBV through scaling up of birth dose implementation in LMICs is essential to achieve the 2030 elimination goal. Most individuals living with HBV and/or HCV in resource-limited settings are unaware of their infection, and with improved access to medications, the most significant barrier remains access to affordable diagnostics and preventive strategies. The coronavirus disease 2019 pandemic interrupted hepatitis elimination programs, albeit offered opportunities for improved diagnostic capacities and raised political awareness of the critical need for strengthening health care services and universal health coverage. This review underpins the HBV and HCV management challenges in resource-limited settings, highlighting the current status and suggested future elimination strategies in some of these countries. Global efforts should continue to improve awareness and political commitment. Financial resources should be secured to access and implement comprehensive strategies for diagnosis and linkage to care in resource-constrained settings to fulfill the 2030 elimination goal.     

Use of virologic assays in the diagnosis and management of hepatitis C virus infection

This article discusses the use of virologic assays in the diagnosis and management of hepatitis C virus (HCV) infection. The use of virologic tests has become essential in the management of HCV infection to diagnose HCV infection, guide treatment decisions, and assess the virologic response to antiviral therapy. The continuing development of test systems accompanied by new antiviral drugs and novel therapeutic approaches should lead to an optimization of the treatment of HCV infection.     

Role of macrophages and monocytes in hepatitis C virus infections

A number of studies conducted over many years have shown that hepatitis C virus(HCV)can infect a variety of cell types.In vivo infection of monocytes,macrophages,and dendritic cells by HCV has been frequently shown by a number of researchers.These studies have demonstrated replication of HCV by detecting the presence of both negative genomic strands and a variety of non-structural HCV proteins in infected cells.In addition,analyses of genome sequences have also shown that different cell types can harbor different HCV variants.Investigators have also done preliminary studies of which cellular genes are affected by HCV infection,but there have not yet been a sufficient number of these studies to understand the effects of infection on these cells.Analyses of in vitro HCV replication have shown that monocytes,macrophages and dendritic cells can be infected by HCV from patient sera or plasma.These studies suggest that entry and cellular locations may vary between different cell types.Some studies suggest that macrophages may preferentially allow HCV genotype 1 to replicate,but macrophages do not appear to select particular hypervariable regions.Overall,these studies agree with a model where monocytes and macrophages act as an amplification system,in which these cells are infected and show few cytopathic effects,but continuously produce HCV.This allows them to produce virus over an extended time and allows its spread to other cell types.     

HBsAg-negative hepatitis B virus infections in hepatitis C virus-associated hepatocellular carcinoma

This study was conducted to evaluate reports that hepatitis B virus (HBV) DNA sequences can be found in the serum and/or tumour tissue from some hepatocellular carcinoma (HCC) patients who have no detectable hepatitis B surface antigen (HBsAg) in their sera. Such HBV infections would be highly atypical, because prospective studies have shown a clear succession of specific serologic markers during and after most HBV infections. As most HBsAg-negative HCC patients in Japan have hepatitis C virus (HCV) infections, the present study was conducted to determine whether some of these patients actually have unrecognized HBV infections. Thirty newly diagnosed HCC patients from Kurume, Japan, with antibody to the hepatitis C virus (anti-HCV) were studied. None of the 30 had HBsAg detectable in their serum. Of 22 for whom test results for antibodies to the hepatitis B core antigen (anti-HBc) and antibodies to HBsAg (anti-HBs) were available, 14 (64%) had anti-HBc and anti-HBs, four (18%) had anti-HBc alone, and four (18%) had no HBV markers. Nested polymerase chain reaction was used to detect the HBV surface (S), core (C), polymerase (P) and core promoter gene sequences in the HCC tissues and in the adjacent nontumorous liver tissues. HBV DNA was detected in HCC and/or adjacent nontumorous liver in 22 of 30 (73%) patients [detected in both HCC and nontumorous liver in 19/30 patients (63%)]. Among the 22 patients with detectable HBV DNA, more than one HBV gene was detected in 10 (46%). Among the four patients whose sera were negative for all HBV markers, three had HBV DNA in either HCC and nontumorous liver (two cases) or only in the nontumorous liver (one case); HBV DNA could not be detected in tissues from the fourth patient. In 18 of 21 (86%) patients with detectable HBV core promoter sequences, mutations at both nucleotides 1762 (A-GT) and 1764 (G-A) in the core promoter region were found. No deletions were detected in the core promoter gene region of the type reported to be associated with some cases of HBsAg-negative HBV infection. Thus, HBV DNA was detectable in 22 (73%) HBsAg-negative, anti-HCV-positive HCCs, including three (10%) who were also negative for anti-HBc and anti-HBs. HBV mutations at both nucleotides 1762 (A-GT) and 1764 (G-A) in the core promoter region were found in the majority of cases, mutations that have previously been reported in HBV that is integrated in HCC DNA. In serologic surveys to determine etiologic associations of HCC, patients such as those in this study would have been incorrectly designated as having 'HCV-associated HCC,' whereas the data in this study suggest that HBV could have played a role in the development of their HCCs.     

Role of interferons in the treatment of hepatitis B and hepatitis C virus infections

BACKGROUND: Since the discovery of hepatitis C (HCV), the efficacy of treatment has significantly progressed using standard mono-therapy: with Interferon alpha (IFN) during six months we obtained approximately 10% sustained response and currently with the association of pegylated IFN and Ribavirin a 55% sustained response was achieved. CURRENT POSITION AND MAJOR POINTS: HCV infection continues to present therapeutic problems which have not entirely been solved, mainly related to clinical and biological tolerance, and non-responders. Moreover, the care of patients with extra-hepatic localization, cirrhotic patients, as well as therapeutic problems of co-infected HIV-HCV patients. As regards hepatitis B (HBV) new effective treatments against this virus have appeared, IFN then nucleoside analogs, some of which are available in France (i.e. lamivudine, adefovir, dipovoxil). The main objective of chronic hepatitis B treatment is to obtain the complete inhibition of the HBV virus by Hbe-antigen antibody seroconversion which would therefore significantly increase patient survival. In this article the advantages and disadvantages of the different treatments are assessed. FUTURE PERSPECTIVES: Despite the considerable and rapid progress obtained in the therapeutic treatment of infection due to HCV and HBV a number of unknown factors remain, which warrants further trials, in particular to evaluate the efficacy as well as the tolerance of the antiviral agent association.     

Management of hepatitis C virus infections in intravenous drug users

Intravenous drug use is a major route of hepatitis C virus (HCV) transmission. In Belgium, more than 70% of the intravenous drug users (IVDUs) are HCV seropositive. In the past, medical treatment of HCV-positive IVDUs has been controversial. However, current studies support that the anti-HCV therapy of IVDUs should be the same as in other HCV-infected patients. In prison populations, HCV screening and therapy has to be performed. Patients should be counseled about the benefits of alcohol abstinence, should be educated about safer injection techniques to avoid reinfection, and should be vaccinated to avoid hepatitis A or B co-infections. Treatment of HCV infections should not be withheld from patient populations with complicated social problems. Physicians should rather develop individual treatment and follow-up plans in order to optimize compliance in IVDUs.     

血液透析患者乙、丙型肝炎感染的状况

目的研究血液透析患者乙、丙型肝炎感染状况及感染途径。方法对４９例维持性血液透析患者用套式逆转录聚合酶链反应方法（ＲＴＰＣＲ）检测了乙型肝炎病毒脱氧核糖核酸（ＨＢＶＤＮＡ）及丙型肝炎病毒核糖核酸（ＨＣＶＲＮＡ），用第二代酶联免疫吸附法（ＥＬＩＳＡ）检测丙型肝炎抗体、乙型肝炎标志物（ＨＢＶＭ）。结果透析患者乙型肝炎感染率５３．１％，丙型肝炎感染率６９．４％。输血组乙、丙型肝炎感染率大于未输血组；透析程２４个月以上者丙型肝炎感染率大于透析１２个月以内者（Ｐ＜００５）。ｌｏｇｉｓｔｉｃ多元回归分析显示，透析年限的增加是丙型肝炎感染的主要因素，提示透析程的危险度大于输血危险度。２０份血站提供的血制品有３份ＨＣＶＲＮＡ阳性，２０份复用透析器经消毒处理后检测出２份ＨＣＶＲＮＡ阳性，９例工作人员ＨＣＶＲＮＡ及ＨＢＶＤＮＡ均阴性。结论加强透析室的管理及工作人员的防护，减少输血及透析器的复用，对减少透析中乙、丙型肝炎感染至关重要     

Blood exposures and hepatitis C virus infections among emergency responders

BACKGROUND: Blood exposures in the workplace may put first responders, a group which includes firefighters, emergency medical technicians, and paramedics, at increased risk for hepatitis C virus (HCV) infection. To determine the prevalence of antibody to HCV (anti-HCV) and risk factors for infection among first responders, we analyzed data from prevalence surveys conducted among first responders in Atlanta, Ga, in 1991; Connecticut in 1992; and Philadelphia, Pa, in 1999. METHODS: Serum or blood samples from participants of the 3 surveys were tested for anti-HCV. Prevalence of anti-HCV was compared with that in the general US population and among participants by occupational (Atlanta) and nonoccupational (Atlanta and Philadelphia) risk factors for infection. RESULTS: Prevalence of anti-HCV among the 2946 participants of the 3 surveys ranged from 1.3% to 3.6% and was no different than among appropriate referent groups in the general US population. First responders in Atlanta reported high rates of skin exposures to blood (174 per 100 person-years) but few mucosal or needle-stick exposures (1 and 0 per 100 person-years, respectively) during the 6 months prior to the survey. Hepatitis C virus infection was not associated with a history of skin exposures to blood (prevalence ratio [PR], 1.1; 95% confidence interval [CI], 0.3-4.2), and HCV prevalence did not increase with longer duration (>10 years) of employment (PR, 1.1; 95% CI, 0.3-4.3). Nonoccupational risk factors associated with HCV infection included history of a sexually transmitted disease (PR, 7.4; 95% CI, 1.6-35.3) among Atlanta participants and histories of illegal drug use (PR, 4.4; 95% CI, 2.6-7.2) and blood transfusion before 1992 (PR, 1.9; 95% CI, 1.1-3.3) among Philadelphia participants. CONCLUSIONS: First responders are exposed to blood in the workplace, and standard precautions should be rigorously implemented. Although risk for HCV infection related to percutaneous or mucosal exposures could not be accurately assessed, the low prevalence of HCV infection indicates that routine HCV testing of first responders as an occupational group is not warranted. Testing should routinely be offered to those requiring postexposure management and those with a history of nonoccupational risk factors indicating an increased risk for infection.