Disparity of basal and therapeutically activated interferon signalling in constraining hepatitis E virus infection

Hepatitis E virus (HEV) represents one of the foremost causes of acute hepatitis globally. Although there is no proven medication for hepatitis E, pegylated interferon‐α (IFN‐α) has been used as off‐label drug for treating HEV. However, the efficacy and molecular mechanisms of how IFN signalling interacts with HEV remain undefined. As IFN‐α has been approved for treating chronic hepatitis C (HCV) for decades and the role of interferon signalling has been well studied in HCV infection, this study aimed to comprehensively investigate virus–host interactions in HEV infection with focusing on the IFN signalling, in comparison with HCV infection. A comprehensive screen of human cytokines and chemokines revealed that IFN‐α was the sole humoral factor inhibiting HEV replication. IFN‐α treatment exerted a rapid and potent antiviral activity against HCV, whereas it had moderate and delayed anti‐HEV effects in vitro and in patients. Surprisingly, blocking the basal IFN pathway by inhibiting JAK1 to phosphorylate STAT1 has resulted in drastic facilitation of HEV, but not HCV infection. Gene silencing of the key components of JAK‐STAT cascade of the IFN signalling, including JAK1, STAT1 and interferon regulatory factor 9 (IRF9), stimulated HEV infection. In conclusion, compared to HCV, HEV is less sensitive to IFN treatment. In contrast, the basal IFN cascade could effectively restrict HEV infection. This bears significant implications in management of HEV patients and future therapeutic development.     

A virological perspective on the need for vaccination

Superinfecton of chronic carriers of hepatitis B virus (HBV) or hepatitis C virus (HCV) with hepatitis A virus (HAV) is often associated with more severe liver disease than infection with HAV alone. Superinfection commonly causes markers of HBV and HCV replication to fall to significantly lower levels. The pathogenesis of acute liver damage characteristic of viral hepatitis is thought to be mediated by host cytotoxic T-lymphocytes (CTLs) directed against virus-infected hepatocytes. It has been proposed that the more aggressive liver disease observed in individuals infected with HAV in addition to chronic HBV/HCV is a result of the induction of interferon (IFN)-alpha during acute HAV infection. This accounts for the antiviral effect on the active markers of HBV/HCV replication, and the enhanced CTL response against HBV/HCV-infected hepatocytes. Alternatively, HAV may indirectly stimulate the T helper 1 (Th1)-type cytokine responses, such as interleukin (IL)-2, IFN-gamma and tumour necrosis factor (TNF)-alpha, which directly promote the antiviral CTL response. Clearance of HBV infection, and possible HAV and HCV, is associated with a specific CTL response, while viral persistence in chronic HBV and HCV infection has been attributed to an imbalance in the Th1-Th2 arms of the immune response. Vaccination against hepatitis A should be considered for patients with chronic HBV/HCV infection, to minimize the risk of exacerbating underlying liver disease.     

Suppression of hepatitis B virus replication mediated by hepatitis A‐induced cytokine production

Abstract: Background: Acute hepatitis A virus (HAV) infection can cause severe hepatitis especially in patients with underlying chronic liver disease. In patients with pre‐existing chronic hepatitis B (HBV) acute HAV infection can suppress HBV replication. The exact mechanism of HBV suppression during acute HAV infection is still a subject of debate. One mechanism may be the production of HAV infection‐induced cytokines leading to suppression of HBV replication and viral clearance. Aim: To evaluate cytokine production and HBV‐specific lympho‐proliferative responses (LPR) during acute HAV infection in a patient with chronic HBV infection‐clearing markers of active HBV replication. Design: Early detection of a case of acute HAV infection in an HBeAg‐positive, HBV DNA‐positive chronic HBV patient treated with lamivudine. Results: At the time of HAV infection a sharp peak in the gamma‐interferon (IFN‐γ) level occurred just before the rise in serum transaminase activity. This was subsequently followed by a decrease in HBV DNA and HBeAg below the limit of detection of the assay. However the HBV‐specific T‐cell response was not modified. After resolution of the acute HAV infection and withdrawal of antiviral therapy HBV replication relapsed. Conclusion: The sharp rise in IFN‐γ production mediated by the acute HAV infection may be pivotal in the suppression of HBV replication in chronic hepatitis B.     

Analysis of serum α‐fetoprotein concentration in patients with viral hepatitis

OBJECTIVE: To investigate serum α‐fetoprotein (AFP) concentrations in patients with viral hepatitis. METHODS: Serum concentrations of total bilirubin (TB), alanine aminotransferase (ALT), aspartate amino­transferase (AST), albumin, globulin, AFP and viral markers were determined in 310 patients with pathologically proven viral hepatitis. The relation between the concentration of AFP and clinical manifestation, pathology, family history of liver malignant disease and virus type was studied. RESULTS: Serum AFP concentrations were elevated in 115 of the 310 patients (37.1%). According to the pathological diagnosis, the lowest positive rate of AFP was in acute hepatitis (11.7%), the highest was in chronic severe hepatitis (66.7%), the second highest in liver cirrhosis (57.5%), and chronic hepatitis was intermediate (34.2%). If the diagnosis was based on the clinical manifestation, the highest positive rate was found in chronic severe hepatitis, the lowest in chronic hepatitis, and acute hepatitis was intermediate. The positive rate of serum AFP by virus type was 35.5% for hepatitis B (HBV), superinfected with HAV or with HEV was 62.8%, and with HCV was 27.3%. Only one in six patients with HCV infection and none with simple HAV or HEV infection were positive for AFP. In patients with a family history of liver cancer, the positive rate of AFP was higher than in those without such a history (57.9%vs 38.2%; P = 0.75). CONCLUSIONS: The results indicate that AFP positivity is not uncommon in patients with viral hepatitis and if the patient has an elevated concentration, it is highly likely to be HBV infection or HBV super­infected with HAV or HEV.     

Risks associated with hepatitis A and hepatitis B in patients with hepatitis C.

Individuals with hepatitis C virus (HCV) are at risk for acquiring hepatitis A virus (HAV) or hepatitis B virus (HBV) because of shared risk factors. A number of organizations recommend vaccination against HAV and HBV for patients with HCV. The rationale for vaccinating these patients is to prevent hepatic superinfections. Acute HAV superinfection causes more severe disease, acute hepatic failure, and higher fatality rates in patients with underlying chronic liver disease, specifically chronic HBV infection and chronic HCV infection. Available data, although limited, suggest that HBV coinfection with HAV and HCV causes more severe hepatic injury than infection with HAV or HCV alone. At standard doses, hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild-to-moderate hepatitis C or chronic liver disease. Regardless of disease severity, vaccination should be routinely administered to patients upon diagnosis of HCV infection. Early vaccination is important because response to vaccination is reduced as liver disease progresses. Prevaccination and postvaccination serology testing is recommended in specific populations. A new combination hepatitis A and hepatitis B vaccine has been shown to be as safe and effective as monovalent hepatitis A and B vaccines and is currently under review by the United States Food and Drug Administration. A combination vaccine would offer ease of administration and convenience and could increase compliance in patients with hepatitis C or other chronic liver disease: two groups that should be more aggressively targeted by healthcare professionals.     

Treatment of patients with dual hepatitis C virus and hepatitis B virus infection: Resolved and unresolved issues

Dual hepatitis C virus (HCV)/hepatitis B virus (HBV) infection is not uncommon in HCV or HBV endemic areas and among subjects at risk of parenteral transmission. In patients dually infected with hepatitis C and B, the disease manifestations are usually more severe than those with either virus infection. In the past decade, the following issues have been resolved. In dually infected patients with active hepatitis C, combined pegylated interferon alfa plus ribavirin was effective, the treatment outcomes being similar to patients with HCV monoinfection. During long‐term follow‐up, the HCV response was sustained in around 97% of patients; and the long‐term outcomes including the development of hepatocellular carcinoma and liver‐related mortality were improved. However, several clinical issues remain to be resolved. First, host and viral factors influencing the long‐term outcomes and treatment options in patients with dual HCV/HBV infection await further studies. Second, about 60% of dually infected patients with baseline undetectable serum HBV DNA levels develop HBV reactivation after the start of treatment. How to prevent and treat HBV reactivation should be clarified. Third, about 30% of dually infected patients lose hepatitis B surface antigen at 5 years after the end of combination therapy; the mechanisms need further investigations. Fourth, the optimal treatment strategies for dually infected patients with active hepatitis B or established cirrhosis should be explored in future clinical trials. Finally, the role of new direct‐acting antiviral‐based therapy for the treatment of patients with dual HCV/HBV infection also remains to be evaluated.     

Can we foresee the end of the alphabet in viral hepatitis?

There is a number of viruses which may cause acute or chronic liver damage. Only some of them belong into the group of hepatotropic viruses and only the latter are the cause of acute or chronic viral hepatitis. So far we know seven hepatotropic viruses. The virus of hepatitis A (HAV), virus of hepatitis B (HBV), virus of hepatitis C (HCV), virus of hepatitis D (HDV), virus of hepatitis E (HEV), virus of hepatitis G (HGV) and Transfusion-Transmitted-Virus (TTV). For HAV and HEV orofaecal transmission is typical, the others are transmitted by the parenteral route. All cause acute hepatitis. Only HAV and HEV infections develop into the chronic stage. The decisive finding for the dynamic development of the problem of viral hepatitis was the discovery of the Australian antigen (Au antigen) by B. Blumberg in 1965. The discovery made it possible to recognize viral hepatitis B and by the application of new biotechnologies the genes of other viruses were detected. Some of them were not visualized so far. A great advance was alpha interferon and lamivudine treatment in patients with chronic hepatitis B and alpha interferon treatment along with ribavirine in chronic hepatitis C.     

Reactivation of hepatitis B virus during interferon‐free therapy with daclatasvir and asunaprevir in patient with hepatitis B virus/hepatitis C virus co‐infection

Direct‐acting antiviral agents (DAA) for hepatitis C virus (HCV) are not effective for hepatitis B virus (HBV), which may be suggestive of reactivation of anti‐HBe hepatitis during interferon (IFN)‐free DAA therapy in HBV/HCV co‐infected patients with inactive HBV. A 69‐year‐old male patient was diagnosed with chronic hepatitis due to HBV/HCV co‐infection with serum levels of alanine aminotransferase (ALT) of 94 U/L, HCV RNA of 4.2 log IU/mL and HBV DNA of 2.5 log copies/mL. HCV was thought to be responsible for the hepatitis activity because of low level of HBV core‐related antigen (3.1 log U/mL). He was treated with combination therapy of daclatasvir and asunaprevir. Serum ALT gradually increased, and reached 237 U/L on day 43 in spite of undetectable HCV RNA. Serum HBV DNA was increasing to 7.0 log copies/mL at that time. The treatment was stopped due to suspicion of drug‐induced liver injury and/or HBV reactivation. Administration of entecavir reduced HBV DNA levels, followed by improvement in ALT levels. This report proposes that close monitoring of HBV DNA during the anti‐HCV DAA therapy and the commencement of anti‐HBV therapy with nucleoside analogs after the increase of HBV DNA should be considered in patients with HBV/HCV co‐infection.     

Hepatitis C virus in the setting of HIV or hepatitis B virus coinfection

Because of shared routes of transmission, coinfection with hepatitis C virus (HCV) or hepatitis B virus (HBV), or both, is common among HIV-infected persons, affecting approximately 15 to 30% and 10 to 15% of patients, respectively. Advances in antiretroviral therapy have improved the life expectancy of patients infected with HIV, and, as a consequence, HCV-related liver disease has emerged as a significant comorbid disease among such patients. Concurrent HIV infection may be associated with higher serum HCV RNA levels, accelerated progression of hepatic fibrosis, increased risk of end-stage liver disease, hepatocellular carcinoma and death among persons coinfected with hepatitis C. Similarly, coinfection with HCV and HBV may lead to more severe liver disease and greater risk of hepatocellular carcinoma (HCC) than does HCV infection alone. Although definitive randomized controlled trials are not yet completed, current guidelines recommend the use of pegylated interferon alfa plus ribavirin for the treatment of chronic HCV in eligible HIV-infected persons. Conversely, the optimal treatment of chronic HCV in persons with chronic HBV infection has not been defined but may include pegylated interferon alfa plus ribavirin, with or without additional antiviral agents, such as lamivudine or adefovir, or both.     

Spectrum of viral hepatitis in thalassemic children receiving multiple blood transfusions.

AIM: To investigate the prevalence of infection with hepatitis viruses in children with thalassemia receiving multiple blood transfusions. METHODS: Sera from 50 children with thalassemia aged 5-15 years (30 boys), who had each received over 80 units of blood, were evaluated for the presence of markers for hepatitis A virus (HAV; IgG and IgM anti-HAV), hepatitis B virus (HBV; HBsAg, and IgG and IgM anti-HBc), hepatitis C virus (HCV; IgG and IgM anti-HCV, and HCV RNA) and hepatitis E virus (HEV; IgG and IgM anti-HEV). IgM anti-hepatitis D virus (HDV) was looked for only in HBsAg or IgM anti-HBc positive sera. RESULTS: No child had evidence of recent HAV or HDV infection. IgG anti-HAV was positive in 12 children. One patient had acute HBV infection. Nine patients were HBsAg-positive. HCV infection was present in 15 cases; six of them were HCV RNA positive, and three had superinfection with hepatitis B. Recent HEV infection was present in 5 cases. CONCLUSION: Thalassemic patients receiving multiple blood transfusions often acquire hepatitis B (20%) and C (30%) infections. Recent hepatitis E infection was documented in 10% in this one-point study.     

Virushepatitis A–E

Five hepatotropic hepatitis viruses have been identified: hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis E virus (HEV). HAV and HEV are transmitted orally, HBV, HCV and HDV via blood and other body fluids. This review summarizes the biological characteristics of the different viruses and the established means of preventing infection.     

Incidence of HAV and HBV infections and vaccination rates in patients with autoimmune liver diseases

OBJECTIVES: Hepatitis A virus (HAV) or hepatitis B virus (HBV) superinfection is associated with an increased mortality in patients with chronic liver diseases (CLD). Despite official recommendations, it was reported that the vaccination rate against HAV is low in patients with chronic hepatitis C infection. To evaluate the situation in patients with autoimmune liver diseases, we conducted a retrospective cohort study. METHODS: Susceptibility to HAV and HBV infections, course of HAV and HBV infections, vaccination rates against HAV and HBV, and efficacy of hepatitis A/B vaccines were evaluated by antibody testing in 225 patients with autoimmune liver diseases during 1,677 person-years. RESULTS: Susceptibility to HAV/HBV infection was 51/86%. Incidence of HAV/HBV infection was 1.3/1.4 per 1,000 person-years. One HAV infection occurred, but the patient recovered spontaneously. Two patients were HBV-infected after receiving an anti-HBc-positive (antibody to hepatitis B core antigen) donor graft during orthotopic liver transplantation, and one of them developed chronic HBV infection. Vaccination rates were 11% (HBV) and 13% (HAV), respectively. Seventy-six percent of the vaccinated patients (HBV vaccine) developed anti-HBs (antibody to hepatitis surface antigen) >or=10 UI/L. Ten out of 13 vaccinated patients, showing a low or nonresponse to hepatitis B vaccine, had concomitant immunosuppressive therapy. Anti-HAV was detectable in all patients after administration of HAV vaccine. CONCLUSIONS: Patients with autoimmune liver diseases have a high susceptibility to HAV and HBV infections. Vaccination rates are low in this patient cohort and efficacy of hepatitis B vaccine is reduced due to immunosuppressive therapy. Improving adherence to vaccine recommendations is essential to prevent HAV and HBV infections in patients with autoimmune liver diseases.     

Prevalence and clinical relevance of occult hepatitis B in the fibrosis progression and antiviral response to INF therapy in HIV-HCV-coinfected patients

Occult hepatitis B virus (HBV) infection is diagnosed when HBc antibodies (HBcAb) and HBV DNA are detectable in serum while hepatitis B surface antigen (HBsAg) is not. This situation has been frequently described in patients with chronic hepatitis C virus (HCV) infection. The objective of this study was to evaluate the prevalence of occult hepatitis B in HIV-HCV-coinfected patients and its clinical relevance in liver histology and viral response after interferon therapy for HCV. A total of 238 HIV-HCV-infected patients,negative for HBsAg, were included. Serum samples were analyzed for the presence of HBV DNA and HBcAb.HBV DNA quantification was determined with the Cobas TaqMan HBV Test (detection limit 6 IU/ml). Data from liver biopsy and laboratory tests were also analyzed. HBcAb resulted in 142 (60%) patients, being the independent associated factors: male gender, previous history of intravenous drug use, age, CD4 count,and HAV antibody presence. Among 90 HBcAb patients that we could analyze, HBV DNA was positive in 15 (16.7% of occult hepatitis B infection in this group, and 6.3% in the whole HIV-HCV cohort studied). No baseline factors, liver histology, or HCV therapy response were related to the presence of HBV DNA. We found that occult hepatitis B is a frequent condition present in at least 6.3% of our HCV-HIV patients and in more than 16% of those with HBcAb. Despite the high prevalence, this phenomenon does not seem to affect the clinical evolution of chronic hepatitis C or modify the viral response to interferon-based HCV therapies     

Treatment predictors of a sustained virologic response in hepatitis B and C

Treatment predictors are important tools for the management of therapy in patients with chronic hepatitis B and C virus (HBV, HCV) infection. In chronic hepatitis B, several pretreatment parameters have been identified for prediction of virologic response to interferon alfa-based antiviral therapies or treatment with polymerase inhibitors. In interferon alfa and pegylated interferon alfa-treated patients, low baseline HBV DNA concentrations, HBV genotype A (B), and high baseline ALT levels are significantly associated with treatment response. In patients treated with nucleos(t)ide analogues, low baseline HBV DNA but not viral genotype is positively associated with virologic response. During treatment the best predictor of response is HBV DNA kinetics. Early viral suppression is associated with favourable virologic response and reduced risk for subsequent resistance mutations. For the current standard treatment with pegylated interferon alfa and ribavirin in patients with chronic hepatitis C, infection with HCV genotypes 2 and 3, baseline viral load below 400,000-800,000IU/ml, Asian and Caucasian ethnicity, younger age, low GGT levels, absence of advanced fibrosis/cirrhosis, and absence of steatosis in the liver have been identified as independent pretreatment predictors of a sustained virologic response. After initiation of treatment, initial viral decline with undetectable HCV-RNA at week 4 of therapy (RVR) is the best predictor of sustained virologic response independent of HCV genotype.     

Management of HBV, HCV, and HDV coinfection

Worldwide, chronic hepatitis B virus (HBV) infection is the most common cause of chronic liver disease. Concurrent hepatitis C (HCV) or hepatitis D (HDV) infection is common because of their shared routes of transmission. Studies show that concurrent HBV/HCV or HBV/HDV infections may be associated with a fulminant course of acute hepatitis, more severe forms of chronic liver disease, and higher risk for development of hepatocellular carcinoma. Virologic markers in HBV patients coinfected with HCV or HDV are dynamic and have different patterns. The replication of one virus may dominate the other and antiviral therapeutic strategies should target the dominant virus. Standard interferon-α or pegylated interferon is usually the treatment of choice for HBV/HCV and HBV/HDV coinfection. Adding ribavirin or lamivudine may benefit HBV patients coinfected with HCV but is ineffective against HDV. Treatment guidelines have not been established for chronic HBV coinfection with either HCV or HDV; therefore, management decisions usually depend on the clinical experience of the treating physician and the sparse data available regarding treatment options.     

Current therapy for hepatitis C or D or immunodeficiency virus concurrent infection with chronic hepatitis B

Concurrent hepatitis C virus (HCV), hepatitis delta virus (HDV), or human immunodeficiency virus (HIV) infection with chronic hepatitis B virus (HBV) appears to increase the risk of progressive liver disease including liver cirrhosis and hepatocellular carcinoma. There is a 10% prevalence of HCV infection in chronic HBV or HDV infection. Serological evidence of previous exposure to HBV is found in more than 80% of HIV-positive patients in the high risk group. Notably, the most recently acquired virus tends to suppress the pre-existing virus. In chronic HBV infection acquired perinatally or in early childhood, usually HCV is dominant and may suppress or even displace HBV and HDV. Less frequently, HBV or HDV suppresses HCV. It is generally agreed that the dominant virus should be identified in order to make appropriate treatment decisions. Studies with standard interferon (IFN) to treat patients with HCV dominantly dual HBV/HCV infection have showed only limited virological response. But high dose of IFN has been demonstrated with better response rate. Combined ribavirin with standard or pegylated IFN therapy could achieve a sustained HCV clearance rate comparable with those infected with HCV alone. On the contrary, patients with HBV dominantly dual viral infection might indicate more appropriate addition of lamivudine to IFN than ribavirin. Additionally, patients with concurrent infection of HBV and HDV, IFN seems to be the only effective agent. However, the efficacy of IFN is related to the dose. High dose of IFN [9 MU tiw (thrice per week)] and longer treatment duration (at least 2 years) have been shown to achieve adequate virological response. In patients with concurrently infected HBV and HIV, anti-HBV therapy should be considered for all patients with evidence of liver disease, irrespective of the CD4 cell count. In patients not requiring antiretroviral therapy, HBV therapy should be preferentially based on IFN, adefovir, or telbivudine. In contrast, in patients with CD4 cell counts <350 cells/μl or those already on antiretroviral therapy, agents with double anti-HBV and anti-HIV activity are preferred. At present, the evidence of therapeutic efficacy is not sufficient to make a recommendation in treating patients with dual HBV/HCV or HBV/HDV or HBV/HIV infection. Further studies of the well-designed, larger scale are needed to elucidate the role of different regimens or combination in the treatment of dual viral infection.     

De novo hepatitis B virus infection in hepatocellular carcinoma following eradication of hepatitis C virus by interferon therapy

Epidemiological studies have revealed that hepatocellular carcinoma (HCC) is still observed in hepatitis C virus (HCV)‐positive patients with a sustained response to interferon (IFN) treatment, although a substantial decrease in the incidence of hepatocellular carcinoma (HCC) has been achieved in those patients. Why HCC develops in patients who have a complete clearance of HCV remains unclear. Here, we provided evidence of latent hepatitis B virus (HBV) infection in an initially HCV‐positive chronic hepatitis patient who developed HCC after the complete eradication of HCV by IFN therapy. Although he was initially negative for anti‐hepatitis B surface antigen (HBsAg) or circulating HBV DNA but positive for anti‐hepatitis B core antigen (anti‐HBc) in his sera, he developed HBsAg and HBV DNA during the course of the management of a series of cancers. HBV DNA was detectable in the liver tissues before HBV reactivation and the viral sequences derived from his anti‐HBc‐positive liver showed 100% homology to that from the serum after HBsAg appearance. These findings indicates that HCV‐positive individuals who are positive for anti‐HBc in the absence of HBsAg could have latent HBV infection in their liver tissues and intrahepatic HBV infection may play a pivotal role in the development of HCC after the IFN‐mediated eradication of HCV.     

Therapeutic effects of pegylated interferon plus ribavirin in chronic hepatitis C patients with occult hepatitis B virus dual infection

Background and Aim: Occult hepatitis B virus (HBV) infection is defined by the detectable serum HBV–DNA in HBV surface antigen‐negative patients. This retrospective study aims to evaluate the therapeutic effects of combined pegylated interferon (PEG–IFN) plus ribavirin (RBV) in patients with concurrent occult HBV/hepatitis C virus (HCV) dual infection. Methods: In total, 126 consecutive chronic hepatitis C (CHC) patients who received combined PEG–IFN and RBV therapy were included. Patients were divided into the occult HBV/HCV dual infection group or the HCV‐monoinfected group according to whether or not they had the detectable serum HBV–DNA. The biochemical and virological responses to combined therapy were compared between these two groups. Serum HCV‐RNA and HBV–DNA were checked before treatment, at the end of treatment as well as at 6‐ and 12‐months' follow up in the occult HBV/HCV group. Result: Six patients were seropositive for HBV–DNA and were included in the occult HBV/HCV dual infection group. There were no statistical differences in the biochemical and virological responses to combined therapy between these two groups. Undetectable serum HBV–DNA was noted at the end of the treatment and the 6‐ and 12‐months' follow up in patients with occult HBV/HCV dual infection. Conclusion: Occult HBV infection in CHC patients is rare. The biochemical and virological responses to combined PEG–IFN and RBV therapy might be similar in CHC patients with or without occult HBV infection. The serum HBV–DNA level was low in patients with occult HBV/HCV dual infection who responded to combined therapy.     

Clinical and histological impact of previous hepatitis B virus infection in patients with chronic hepatitis C

Background: Recent reports suggest that hepatitis C virus (HCV) carriers with serological markers of prior hepatitis B virus (HBV) infection have more advanced liver fibrosis, irrespective of HBV‐DNA detection. Aims: We sought to assess the prevalence and impact of previous HBV infection in patients with HCV chronic infection. Methods: This cross‐sectional study included hepatitis B surface antigen‐ and human immunodeficiency virus‐negative subjects with positive HCV‐RNA. All patients had prior parenteral exposure as the probable source of HCV infection. Serum samples were tested for HBV‐DNA using a commercial assay. The METAVIR system was used for histological analysis. Results: One‐hundred and eleven patients were evaluated. Thirty‐one out of 111 patients (28%) tested positive for antihepatitis B core antigen (anti‐HBc). HBV‐DNA was not detected in any sample. Anti‐HBc‐positive patients showed higher histological grading, staging and a higher fibrosis progression rate. By multivariate analysis, anti‐HBc‐positivity was predictive of moderate to severe activity [odds ratio (OR)=3.532; P=0.032] and significant hepatic fibrosis (OR=3.364; P=0.017). After approximately 20 years of infection, advanced liver fibrosis (F3/F4) can be expected in 13% of anti‐HBc‐negative subjects who acquired HCV before the age of 30 and in 57% of those anti‐HBc‐positive patients who were infected by HCV after 30 years of age (P<0.001). Conclusion: Previous HBV infection is common among HCV carriers and may exert a negative impact on the natural history of HCV infection, independently of the presence of significant HBV replication.     

Hepatitis vaccines

The development of highly effective and safe inactivated HAV vaccines and highly effective and safe recombinant HBsAg subunit HBV vaccines represents major advances in the control of viral hepatitis, but many challenges remain. Because current HAV immunization recommendations target high-risk groups only, infection rates are unlikely to fall dramatically until universal childhood immunization programs are implemented. Routine HBV vaccination of infants, children, adolescents, and individuals at high risk will reduce the incidence of infection, but vaccine nonresponsiveness and escape mutants are important potential challenges. Whether either HAV or HBV vaccine provide lifelong protection remains to be determined. Vaccines for HDV, HEV, and HCV are not yet available.