Coinfection with hepatitis B and C or B, C and δ viruses results in severe chronic liver disease and responds poorly to terferon-a treatment

SUMMARY. Chronic coinfection with the hepatitis B (HBV) and hepatitis δ (HDV) viruses is known to cause severe liver disease, but the importance of coinfection with hepatitis C virus (HCV) and HBV has not been well documented. In the present study, the clinical and pathological severity of liver disease among patients with hepatitis resulting from multiple viruses was examined and an open trial of the efficacy of interferon-α2b (IFN-α) treatment was conducted. Nineteen patients with chronic HBV and HCV infection and 17 with HBV, HCV and HDV infection were studied: 12 in each group underwent liver biopsy. For each coinfected patient, two patients infected with HCV alone were selected as controls, and these were matched for age and risk factor and were estimated to have been infected for a similar duration. Coinfection with HBV and HCV or HBV, HCV and HDV was associated with more severe liver disease than HCV alone (P < 0.01); total Scheer score, portal and lobular inflammation and fibrosis were all worse in coinfected subjects. Eight patients with chronic HBV and HCV were treated with recombinant IFN-α2b [3 million units (MU), thrice weekly for 6 months]. Liver function tests normalized in two patients and one lost hepatitis B surface antigen (HBsAg). Seven patients with hepatitis B, C and δ coinfection were treated with the same regimen and only one normalized serum alanine aminotransferase (ALT) during (and after) treatment. It is concluded that coinfection with multiple hepatitis viruses is associated with histologically more severe liver disease than HCV alone. Short-and long-term responses to doses of IFN-α that are used to treat HCV are infrequent, but further studies are required to determine whether higher-dose IFN-α may benefit patients with combined hepatitis virus infections.     

Management of Hepatitis B Virus Coinfection: HIV, Hepatitis C Virus, Hepatitis D Virus

Coinfection of hepatitis B virus (HBV) with HIV, hepatitis C virus (HCV) and hepatitis D virus (HDV) is common because of shared modes of transmission. Increasing prevalence of high risk sexual behavior and intra venous drug use (IVDU) contributes to a majority of the cases with coinfection. Occult HBV or prior HBV infection is frequently encountered in patients coinfected with HIV or HCV. Although HBV is a preventable disease, failure to screen and inadequate vaccination in the high risk individuals account for vast under-recognition of the cases with HBV infection. Chronic liver disease from viral hepatitis B and C has emerged as the major cause of morbidity and mortality worldwide as well as in the United States. This is especially true in cases coinfected with HIV. The potential long term risks of untreated hepatitis include cirrhosis and hepatocellular carcinoma. There have been several advancements in the understanding of natural history and management options of chronic viral hepatitis. This article discusses and reviews the natural history, epidemiology, and management of HBV patients coinfected with HIV, HCV, or HDV. It includes an updated summary of the outcomes with liver transplantation and post transplant recurrence in the coinfected population with HBV. It also discusses the role of occult HBV in HIV and HCV coinfection respectively.     

Hepatitis B transplantation: special conditions

Patients with hepatitis B virus (HBV) infection may be coinfected with other viral diseases, such as hepatitis C virus (HCV) and/or D virus (HDV), or have serious diseases secondary to the hepatitis, such as hepatocellular carcinoma. These coexisting conditions have an impact on the success of treatment and of liver transplantation. Patients with HBV and HDV are at lower risk for HBV recurrence than are patients with HBV alone; likewise, patients with HBV/HCV coinfection appear to have a higher 5-year survival rate posttransplantation. Treatment of coinfection is similar to that used for HBV alone. Hepatitis B immune globulin and interferon have been found to be effective in varying degrees. Recurrence or reinfection of disease after liver transplantation presents many clinical problems that will require new therapeutic approaches. Future studies will help to begin solving these challenges.     

Liver transplantation in delta virus infection

Liver transplantation is the only therapy for patients with end-stage liver disease, hepatocellular carcinoma, or fulminant hepatitis due to hepatitis D virus (HDV) and hepatitis B virus (HBV) coinfection or superinfection. Patients chronically coinfected with HDV are less at risk of HBV recurrence and have a better survival rate than patients infected with HBV alone. Patients coinfected with HDV generally do not require pretransplant antiviral therapy. Rates of recurrent HBV-HDV infection are lower than 5% using low-dose intramuscular (IM) HBIg and antiviral prophylaxis in combination. Few studies have evaluated the possibility of using shorter-term HBIg (12-24 months) then switching to antiviral therapy. Although HBV replication can be controlled by potent HBV-polymerase inhibitors, reappearance of HBsAg and/or the persistence of HBV DNA in serum, liver, or peripheral blood mononuclear cells might have deleterious consequences in the setting of HBV-HDV coinfection as they may provide the biologic substrate to the reactivation of HDV. No effective antiviral drug is available for the treatment of graft infection with HDV.     

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.     

Hepatitis B virus/hepatitis C virus coinfection: epidemiology, clinical features, viral interactions and treatment

Because of the shared modes of transmission, hepatitis B virus (HBV)/hepatitis C virus (HCV) coinfection is not uncommon in highly endemic areas and among subjects with a high risk of parenteral infections. The worldwide prevalence of HBV/HCV coinfection is unknown and might be underestimated with the phenomenon of silent (occult) HBV infection. HCV superinfection in patients with chronic HBV infection was the most common clinical features of coinfection in Asia-Pacific countries. Further, most, but not all, clinical observations suggested that interference between the two viruses was more frequently characterized by an inhibition of HBV replication exerted by HCV. However, longitudinal follow-up studies have demonstrated that the virological patterns in coinfection cases are widely divergent and have dynamic profiles over time. As compared with monoinfected patients, HBV/HCV coinfected persons tend to have more severe liver injury, a higher probability of liver cirrhosis and hepatic decompensation, and a higher incidence of hepatocellular carcinoma. Detailed serological and virological evaluations are required for coinfected patients before initiation of antiviral therapy. Previous studies demonstrated that HBV/HCV coinfected patients responded poorly to interferon (IFN) monotherapy. Currently, for patients with dominant HCV infection and low level HBV viremia (<10(4) IU/mL), IFN or pegylated IFN plus ribavirin can achieve comparable sustained virus response as expected with HCV monoinfection. However, phenomenon of reciprocal viral interference can happen, and resultant "flare" of hepatitis activity may cause liver function deterioration. For coinfected patients with dually-active HBV/HCV, the optimal regimen for therapy remains unclear although adding oral nucleos(t)ide analogs to pegylated IFN and ribavirin seems a reasonable empiric option.     

Understanding the pathogenesis and management of hepatitis B/HIV and hepatitis B/hepatitis C virus coinfection

The approach to the hepatitis B virus (HBV)-infected patient who is also infected with HIV or hepatitis C virus (HCV) is very different from the approach to the patient with only one virus infection. HBV/HIV coinfection is common. Agents that have dual activity against HBV and HIV should be considered as treatment of choice in combination regimens in HBV/HIV-coinfected patients beginning antiretroviral therapy. In HBV/HCV coinfection HCV usually tends to predominate over HBV. More investigation is needed into the mechanisms by which viral pathogenesis is altered and the optimal treatment modalities for coinfected patients.     

Role of hepatitis B, C, and D viruses in dual and triple infection: influence of viral genotypes and hepatitis B precore and basal core promoter mutations on viral replicative interference

The interactions among hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) were studied by measuring HBV-DNA and HCV-RNA levels and by determining the influence of viral genotypes and mutations in HBV basal core promoter (BCP) and precore regions. We included 65 consecutive patients, 25 HBV/HCV, 18 HBV/HDV, and 22 HBV/HCV/HDV. Controls consisted of 55 patients with chronic HBV and 55 with chronic HCV infection. HBV-DNA and HCV-RNA levels were lower in coinfections than in single infections (P <.05). HBV/HCV coinfection was associated with lower HBV viremia (8.2 x 10(4) copies/mL) and lower HCV-RNA levels (7 x 10(5) IU/mL), than the corresponding control group (P <.05), with more marked decrease in HBV replication (P <.05). Moreover, in HBV/HCV coinfection and in triple coinfection we observed an inverse relationship between HBV-DNA and HCV-RNA levels (P <.05). HBV/HDV coinfection was associated with lower HBV viremia (2.5 x 10(4) copies/mL) than that found in HBV infection (P <.05). Patients with triple coinfection showed lower HBV-DNA and HCV-RNA levels than control groups (P <.05). Prevalence of precore mutations was lower in HCV coinfections (P <.05). No significant association was observed between HCV-RNA levels and HBV precore mutations, BCP mutations or HBV genotypes, or between HBV-DNA levels and HCV genotypes (P <.05). In conclusion, HCV exhibited stronger inhibitory action in the reciprocal inhibition seen in HBV/HCV coinfection. HDV was the dominant virus in HBV/HDV coinfection and in triple coinfection, and had a greater unfavorable influence on HCV than on HBV replication. The reciprocal inhibition of viral replication seemed to be little influenced by the inherent genomic factors studied.     

Epidemiology, natural history, and treatment of hepatitis B virus and hepatitis C virus coinfection

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are important global public health problems. Coinfection with HBV and HCV is not uncommon due to the shared route of parenteral transmission. The interaction between HBV and HCV in coinfected individuals is complex, and viral interference has been well described. Patients who are coinfected with HBV and HCV have faster rates of fibrosis progression, more severe liver disease, and are at markedly increased risk of developing hepatocellular carcinoma as compared to those with HBV or HCV monoinfection. Therefore, treatment of HBV-HCV coinfection is important, but it is a challenging and evolving field. Hepatitis A virus (HAV) superinfection is associated with a high risk of liver failure and death in patients with underlying chronic liver disease, and all individuals with HBV-HCV coinfection should receive the HAV vaccine.     

Longitudinal evaluation reveals a complex spectrum of virological profiles in hepatitis B virus/hepatitis C virus-coinfected patients

Hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection is often associated with severe forms of liver disease. However, comprehensive studies are lacking, and scant information is available regarding the virological behavior over time in coinfected patients. This study enrolled 133 untreated HBV/HCV-positive patients (male/female = 102/31; median age 51 years [range: 22-83 years]) who were longitudinally followed up for 1 year with bimonthly evaluation of HBV/HCV viremia levels and liver biochemistry. Thirty of these patients had triple infection with hepatitis Delta virus (HDV), while 103 patients were HDV-negative. In the HDV-negative group, active infection with both HBV and HCV was revealed in 24 cases, inactive infection by both viruses was seen in 15 cases, active HBV/inactive HCV was seen in 15 cases, and inactive HBV/active HCV was seen in 49 cases. However, 32 subjects (31%) presented dynamic virological profiles characterized by fluctuation of HBV and/or HCV viremia levels that at different time points were over or under the cutoff limits. Consequently, a correct diagnosis could be performed in these subjects only by serially repeating the virological tests 1 year apart. Similarly, 15 of the 30 HDV-positive subjects showed active HBV and/or HCV infection, with fluctuating virological patterns in 8 cases. In conclusion, this study showed that the virological patterns in HBV/HCV coinfection are widely divergent and have dynamic profiles. A careful longitudinal evaluation of the viremia levels of both viruses is essential for making a correct diagnosis and tailoring the appropriate therapeutic schedule in coinfected patients.     

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.     

HIV and hepatitis C coinfection

Coinfection with HIV and the hepatitis C virus (HCV) or hepatitis B virus (HBV) is a growing public health concern. Because the diseases are spread in similar ways--notably through shared use of needles to inject drugs and sexual activity--many people are coinfected with HIV and HCV, HIV and HBV, or even all three viruses. Hepatitis C and hepatitis B are viral infections of the liver; over time they can lead to serious consequences including liver cirrhosis and liver cancer. Most studies show that HIV infection leads to more aggressive hepatitis C or hepatitis B and a higher risk of liver damage. Studies of how HCV and HBV affect HIV disease are less clear. Most research shows that HCV does not accelerate HIV disease progression, but HIV/HCV coinfection may impair immune system recovery after starting antiretroviral therapy. Coinfection can complicate treatment. People with liver damage due to chronic hepatitis are more likely to experience hepatotoxicity (liver toxicity) related to anti-HIV drugs. In addition, drugs used to treat HIV and hepatitis can interact and side effects may be exacerbated. Most experts recommend that HIV should be controlled first before a person begins HCV treatment. With careful management, most people with HIV/HCV or HIV/HBV coinfection can be successfully treated for both diseases. In fact, several recent studies suggest that HIV/HCV-coinfected people with well-controlled HIV disease and relatively high CD4 cell counts may do as well as those with HCV alone.     

Management of hepatic complications in HIV-infected persons

In the era of effective antiretroviral therapy (ART), liver disease is the second most common cause of death among persons with human immunodeficiency virus (HIV) infection. Liver disease-related deaths mostly result from chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV). In addition, recent reports suggest that HCV infection may be transmitted sexually between HIV-infected men who have sex with men. Management of these conditions in HIV-infected persons requires careful consideration, balancing the potential benefits of therapy with the potential for significant treatment-related adverse effects (HCV infection) and viral resistance and/or hepatitis flares (HBV infection). Furthermore, several antiretroviral agents are active against HBV infection, including lamivudine, emtricitabine, tenofovir, and, more recently, entecavir. Despite the complexity and potential for antiretroviral-associated hepatotoxicity, ART usually is safe for patients with viral hepatitis coinfection, and, in some cases, treatment for HIV infection may be beneficial for the liver.     

Coinfections with hepatitis g and/or c virus in hepatitis B-related chronic liver disease

Concurrent infections with HGV and/or HCV (HGV/HCV) were investigated in 196 patients with HBV-related chronic liver disease (115 chronic hepatitis, 31 liver cirrhosis, 50 hepatocellular carcinoma), and in 100 HBsAg carriers. Coinfections were detected in 18 (9.2%) patients with HGV (10) or HCV (5) or both agents (3), but in none of the HBsAg carriers. Patients with coinfection were more frequently exposed to blood transfusions (55.6% vs 5.6%) and also were more commonly anti-HBe positive. Serum levels of HBV-DNA were lower in patients with HCV coinfection than in those coinfected with HGV. Interferon was administered to 39 patients with chronic active hepatitis including 7 patients with HGV/HCV coinfection. Sustained clearance of HBV-DNA was observed in 10 (25.6%) patients who were solely infected with HBV. These patients were significantly younger and had much lower histological scores than non-responders. Patients with HCV coinfection had significantly higher pre-treatment histological scores than those without HCV. After interferon treatment, a significant reduction in histological scores was observed in all patients except those coinfected with HGV/HCV. None of the 7 patients with coinfection had sustained clearance of HBV-DNA or HCV-RNA, and only one had cleared HGV-RNA. These results suggest that parenteral exposure is a risk factor for HGV/HCV coinfection in chronic HBV infection. HGV infection shows no significant impact on chronic HBV infection. HCV coinfection appears to inhibit HBV replication, but causes more severe chronic hepatitis and increases resistance to interferon therapy.     

Hepatitis B virus and hepatitis C virus dual infection

Hepatitis B virus (HBV) and hepatitis C virus (HCV) share common mode of transmission and both are able to induce a chronic infection. Dual HBV/HCV chronic coinfection is a fairly frequent occurrence, especially in high endemic areas and among individuals at high risk of parenterally transmitted infections. The intracellular interplay between HBV and HCV has not yet been sufficiently clarified, also due to the lack of a proper in vitro cellular model. Longitudinal evaluation of serum HBV DNA and HCV RNA amounts has revealed that complex virological profiles may be present in coinfected patients. Dual HBV/HCV infection has been associated to a severe course of the liver disease and to a high risk of developing hepatocellular carcinoma. Despite the clinical importance, solid evidence and clear guidelines for treatment of this special population are still lacking. This review summarizes the available data on the virological and clinical features as well as the therapeutic options of the dual HBV/HCV infection, and highlights the aspects that need to be better clarified.     

Optimizing Management Strategies in Special Patient Populations

Chronic hepatitis B infection presents a number of challenges to clinicians. There are additional considerations when defining management strategies for individuals with advanced liver disease, or coinfection, or those at high risk of developing hepatocellular carcinoma (HCC). Treatment of decompensated cirrhosis is particularly important. Evidence suggests that suppression of viral replication through nucleos(t)ide analog therapy leads to longer time to transplantation, improved liver function, and improved survival times. The use of interferon in patients with decompensated hepatitis B is associated with serious complications and is currently contraindicated for these patients by the AASLD Practice Guidelines. Hepatitis B coinfection is often associated with more extensive disease. In patients with HBV/HCV coinfection, one disease is usually dominant and consequently should be the focus of therapy. HIV/HBV coinfection increases the risk of progressive liver disease. Therapeutic agents active against both viruses should be utilized at the correct dose to limit the development of resistance. Agents specific for HBV, e.g. , entecavir, enable hepatitis to be treated while avoiding the risk of HIV resistance developing. Dual infection with HBV and HDV is particularly challenging. Nucleos(t)ide analogs are ineffective in treating HDV infection, and there is limited data concerning the efficacy of interferon in this setting. The association between chronic hepatitis B infection and hepatocellular carcinoma (HCC) is well established. In patients at high risk of HCC, screening regimes may be effective. Furthermore, there is an increasing body of evidence indicating that effective suppression of viral replication may be associated with a reduced risk of HCC.     

Viral hepatitis and HIV coinfection

Persons at high risk for human immunodeficiency virus (HIV) infection are also likely to be at risk for other infectious pathogens, including hepatitis B virus (HBV) or hepatitis C virus (HCV). These are bloodborne pathogens transmitted through similar routes; for example, via injection drug use (IDU), sexual contact, or from mother to child during pregnancy or birth. In some settings, the prevalence of coinfection with HBV and/or HCV is high. In the context of effective antiretroviral therapy (ART), liver disease has emerged as a major cause of morbidity and mortality in HIV-infected persons. Further, coinfection with viral hepatitis may complicate the delivery of ART by increasing the risk of drug-related hepatoxicity and impacting the selection of specific agents (e.g., those dually active against HIV and HBV). Expert guidelines developed in the United States and Europe recommend screening of all HIV-infected persons for infection with HCV and HBV and appropriate management of those found to be chronically infected. Treatment strategies for HBV infection include the use of nucleos(t)ide analogues with or without anti-HIV activity and/or peginterferon alfa (PegIFN) whereas HCV treatment is limited to the combination of PegIFN and ribavirin (RBV). Current approaches to management of HIV-infected persons coinfected with HBV or HCV are discussed in this review.     

Influence of GB virus-C/hepatitis G virus infection on the long-term course of chronic hepatitis B

Abstract: Aims/Background: The clinical significance of GB virus-C/hepatitis G virus (GBV-C/HGV) infection in chronic hepatitis B is not well known and its role in the outcome of liver disease was investigated. Methods: HGV-RNA and antibody to HGV (anti-E2) were studied in 125 patients with chronic hepatitis B (41 with multiple hepatitis virus exposure), 82 asymptomatic HBsAg carriers and 103 healthy adults. Results: In chronic hepatitis B, HGV-RNA was more frequent in patients with HDV infection and/or anti-HCV positivity than in those without (29% vs 6%, p<0.0001), mainly in drug addicts (38%). At diagnosis the overall prevalence of any marker (HGV-RNA plus anti-E2) was similar in chronic hepatitis due to HBV alone (17%), in HBsAg carriers (16%) and in healthy adults (17%) and increased to 58% in those exposed to HDV and/or HCV. During 1–11 years of follow-up, HGV infection persisted in 70% of patients with chronic hepatitis B. About 40% of HGV persistently coinfected patients underwent sustained biochemical remission, whereas continuing disease activity was observed in 80% of patients who cleared HGV-RNA. Conclusions: In chronic HBV infection the rate of exposure to HGV is similar to that in healthy adults, except for high risk patients. Long lasting HGV coinfection or anti-E2 seroconversion did not modify the course of chronic hepatitis B.     

Interferon Alpha-2b Therapy in Chronic Hepatitis Delta

Background:

Approximately 5% of hepatitis B virus (HBV) carriers are coinfected with hepatitis D virus (HDV). HBV/HDV coinfection is a major cause of cirrhosis and end stage liver disease in chronic HBsAg carriers. The only approved therapy for chronic hepatitis delta is interferon alpha (IFN α) in either pegylated or conventional forms. Although higher doses and longer durations of IFN α therapy in HBV/HDV coinfected patients are currently applied, yet treatment response is low.

Objectives:

We aimed to determine the efficacy of IFN α-2b therapy in patients with HBV/HDV coinfection.

Patients and Methods:

In this cross sectional study, 20 HBsAg carriers with positive Anti-HDVAb and RT-PCR for HDV RNA were recruited and treated for three year duration with 5 million units (MU) of IFN α-2b, three times weekly or one year with 5 MU of IFN α-2b daily. Sustained virological response (SVR) was defined as a negative qualitative HDV RT-PCR, 6 months after treatment cessation.

Results:

Overall, 3 (15%) subjects achieved SVR, 10 cases (50%) relapsed after treatment cessation and 7 (35%) patients did not clear HDV during the treatment.

Conclusions:

HDV coinfection with HBV had very low response rate to high doses and long durations of IFN α-2b therapy.     

Suppression of hepatitis C virus (HCV) replication by hepatitis D virus (HDV) in HIV-infected hemophiliacs with chronic hepatitis B and C

Most hemophiliacs who are coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) have high serum levels of HCV RNA. To study the impact of multiple hepatitis virus infections, we evalated all eight chronic carriers of hepatitis B surface antigen (HBsAg) from a previously studied cohort of 99 hemophiliacs with chronic HIV and HCV infections. Stored serum or plasma samples were tested for antibody to hepatitis D virus (anti-HDV) by ELISA; qualitatively for HCV RNA, HBV DNA, and HDV RNA by the polymerase chain reaction (PCR); and quantitively for HIV RNA, HCV RNA, and hepatitis B virus (HBV) DNA by a quantitative branched DNA signal amplification assay. HCV RNA was detected in only one of five patients with HDV infections on a cross-sectional study, and this individual had low levels (<3.5×10⁵ genome eq/ml) of HCV RNA. In contrast, all three without HDV infections had high levels (>1.5×10⁷ genome eq/ml) of HCV RNA. HIV RNA was present in all eight patients. There was no correlation between the level of HIV RNA and the presence of hepatitis viruses. Three of the eight patients (38%) died of liver failure and another has hypersplenism with hypoprothrombinemia. We conclude that HDV infection appears to suppress HCV replication and that liver failure is common in adult HIV-infected hemophiliacs with chronic HCV and HBV infections. These findings have implications for the therapy of HCV-infected hemophiliacs who are HBsAg positive.This study was supported by the Brandywine Valley Hemophilia Foundation, and the Alice Livingston Trout Family Fund.Dr. Battegay was supported by the Swiss National Science Foundation, the Conrad Gessner Stipendium, and the Schweizerische Stiftung fur medizinisch biologische stipendien.