Human immunodeficiency virus and hepatotropic viruses comorbidities as the inducers of liver injury progression

Hepatotropic viruses induced hepatitis progresses much faster and causes more liver-related health problems in people co-infected with human immunodeficiency virus(HIV). Although treatment with antiretroviral therapy has extended the life expectancy of people with HIV, liver disease induced by hepatitis B virus(HBV) and hepatitis C virus(HCV) causes significant numbers of non-acquired immune deficiency syndrome(AIDS)-related deaths in coinfected patients. In recent years, new insights into the mechanisms of accelerated fibrosis and liver disease progression in HIV/HCV and HIV/HBV co-infections have been reported. In this paper, we review recent studies examining the natural history and pathogenesis of liver disease in HIV-HCV/HBV co-infection in the era of direct acting antivirals(DAA) and antiretroviral therapy(ART). We also review the novel therapeutics for management of HIV/HCV and HIV/HBV coinfected individuals.     

Management of patients co-infected with hepatitis B virus and HIV

The management of chronic hepatitis B virus (HBV) infection poses specific problems in the presence of HIV co-infection, since therapeutic approaches have to consider both HBV and HIV infections. There are currently four drugs approved for the treatment of chronic HBV infection (interferon alpha, lamivudine, adefovir, and entecavir); the dual antiviral activity of tenofovir and emtricitabine broadens the armamentarium against HBV in HBV/HIV co-infected patients. Nucleotide analogues--eg, adefovir and tenofovir--have the advantage of a higher genetic barrier to the development of resistance compared with nucleoside analogues--eg, lamivudine and emtricitabine. Fortunately, the two families do not share resistance mutations, allowing salvage therapy and the possibility of combination therapy for drug-naive individuals. Although response to interferon alpha is poorer in HBV/HIV co-infected patients compared with HIV-negative individuals, especially in hepatitis B e antigen-negative HBV infection, the more potent pegylated forms of interferon alpha have brought new hope.     

Hepatitis C in human immunodeficiency virus co-infected individuals: Is this still a “special population”?

A substantial proportion of individuals with chronic hepatitis C virus(HCV) are co-infected with human immunodeficiency virus(HIV). Co-infected individuals are traditionally considered as one of the "special populations" amongst those with chronic HCV, mainly because of faster progression to end-stage liver disease and suboptimal responses to treatment with pegylated interferon alpha and ribavirin, the benefits of which are often outweighed by toxicity. The advent of the newer direct acting antivirals(DAAs) has given hope that the majority of co-infected individuals can clear HCV. However the "special population" designation may prove an obstacle for those with co-infection to gain access to the new agents, in terms of requirement for separate pre-licensing clinical trials and extensive drug-drug interaction studies. We review the global epidemiology, natural history and pathogenesis of chronic hepatitis C in HIV co-infection. The accelerated course of chronic hepatitis C in HIV co-infection is not adequately offset by successful combination antiretroviral therapy. We also review the treatment trials of chronic hepatitis C in HIV co-infected individuals with DAAs and compare them to trials in the HCV mono-infected. There is convincing evidence that HIV co-infection no longer diminishes the response to treatment against HCV in the new era of DAA-based therapy. The management of HCV co-infection should therefore become a priority in the care of HIV infected individuals, along with public health efforts to prevent new HCV infections, focusing particularly on specific patient groups at risk, such as men who have sex with men and injecting drug users.     

Prevalence of hepatitis B virus infection in Japanese patients with HIV.

Patients with HIV infection are frequently infected with hepatitis viruses, which are presently the major cause of mortality in HIV-infected patients after the widespread use of highly active antiretrovirus therapy. We previously reported that approximately 20% of HIV-positive Japanese patients were also infected with hepatitis C virus (HCV). Hepatitis B virus (HBV) infection may also be an impediment to a good course of treatment for HIV-infected patients, because of recurrent liver injuries and a common effectiveness of some anti-HIV drugs on HBV replication. However, the status of co-infection with HIV and HBV in Japan is unclear. We conducted a nationwide survey to determine the prevalence of HIV-HBV co-infection by distributing a questionnaire to the hospitals belonging to the HIV/AIDS Network of Japan. Among the 5998patients reported to be HIV positive, 377 (6.4%) were positive for the hepatitis B surface antigen. Homosexual men accounted for two-thirds (70.8%) of the HIV-HBV co-infected patients, distinct from HIV-HCV co-infection in Japan in which most of the HIV-HCV co-infected patients were recipients of blood products. One-third of HIV-HBV co-infected patients had elevated serum alanine aminotransferase levels at least once during the 1-year observation period. In conclusion, some HIV-infected Japanese patients also have HBV infection and liver disease. A detailed analysis of the progression and activity of liver disease in co-infected patients is needed.     

Co-infection VIH-VHB au sud du Sahara : données épidémiologiques, cliniques et thérapeutiques

In sub-Saharan Africa, co-infection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) has several characteristics, one of which is its high prevalence. The rate of HBV infection, however, appears to be similar in HIV-positive and HIV-negative individuals. In cases of co-infection, the prognosis is poorer because of the often-late detection of HVB infection (screening for co-infection is not systematic) at an advanced stage of HIV infection, when antiretroviral therapy (HAART) has already been started. The difficulties in treating this co-infection are exacerbated by limits on antiretroviral drug (ARV) subsidies. In co-infected patients requiring HAART, lamivudine is the only covered drug active against HBV. Improving the prognosis and quality of care in these patients depends on finding solutions to these problems and applying the recommendations for the management of HIV/HBV co-infection.     

Hepatitis B and human immunodeficiency virus co-infection

Hepatitis B and human immunodeficiency virus (HBV and HIV) infection share transmission patterns and risk factors, which explains high prevalence of chronic HBV infection in HIV infected patients. The natural course of HBV disease is altered by the HIV infection with less chance to clear acute HBV infection, faster progression to cirrhosis and higher risk of liver-related death in HIV-HBV co-infected patients than in HBV mono-infected ones. HIV infected patients with chronic hepatitis B should be counseled for liver damage and surveillance of chronic hepatitis B should be performed to screen early hepatocellular carcinoma. Noninvasive tools are now available to evaluate liver fibrosis. Isolated hepatitis B core antibodies (anti-HBc) are a good predictive marker of occult HBV infection. Still the prevalence and significance of occult HBV infection is controversial, but its screening may be important in the management of antiretroviral therapy. Vaccination against HBV infection is recommended in non-immune HIV patients. The optimal treatment for almost all HIV-HBV co-infected patients should contain tenofovir plus lamivudine or emtricitabine and treatment should not be stopped to avoid HBV reactivation. Long term tenofovir therapy may lead to significant decline in hepatitis B surface Antigen. The emergence of resistant HBV strains may compromise the HBV therapy and vaccine therapy.     

The British HIV Association national audit on the management of subjects co-infected with HIV and hepatitis B/C

The aim of this work was to survey current service provision and adherence to the British HIV Association (BHIVA) guidelines for the management of HIV and hepatitis B/C co-infected patients in the UK. Sites were invited to complete a survey of local care arrangements for co-infected patients. A case-note audit of all co-infected attendees during a six-month period in 2009 was performed. Data including demographics, clinical parameters, hepatitis disease status, antiretroviral and hepatitis B/C therapy were collected. Using BHIVA guidelines as audit standards, the proportion of sites and subjects meeting each standard was calculated. One-hundred and forty sites (75%) responded and data from 973 eligible co-infected patients were submitted. Approximately a third of sites reported not re-checking hepatitis serology or vaccination titres annually. Of all co-infected patients, 122 (13%) were neither vaccinated nor immune to hepatitis A and 26 (5%) of patients with hepatitis C were neither vaccinated nor naturally immune to hepatitis B. Of HBsAg-positive subjects, 25 (6%) were receiving lamivudine as the sole drug with antihepatitis B activity. In the UK, the management of HIV and hepatitis B/C co-infection remains highly variable. Optimizing the care of this high-risk patient group is a priority.     

Survival in patients with HIV infection and viral hepatitis B or C: a cohort study

AIM: To assess survival in patients with HIV and viral hepatitis co-infection. METHODS: A prospective university clinic cohort of 472 patients with HIV infection who were followed for 8343 patient-months. The outcome measures were the survival from HIV or liver disease assessed by the Kaplan-Meier method. Multivariable analysis using a Cox regression model identified variables associated with mortality. RESULTS: Patients were divided into four subgroups: HIV/hepatitis B virus (HBV) (n = 72), HIV/hepatitis C virus (HCV) (n = 256), multiple hepatitides (n = 18) and HIV alone (n = 126). One hundred and thirty-four patients (28.4%) died during follow-up. Liver mortality was noted in 55 patients, representing 12% of the cohort and 41% of the total mortality. Survival curves were similar in patients with HIV alone and those with any viral hepatitis co-infection. Liver deaths were more common in patients with multiple hepatitides (28%) HIV/HBV (15%), HIV/HCV co-infection (13%) versus HIV alone (6%). Liver mortality was comparable in HIV/HBV as in HIV/HCV co-infected patients and was not associated with gender, ethnicity, age, or mode of infection. HIV deaths were similar in patients co-infected with viral hepatitis compared with those with HIV alone. In patients with viral hepatitis co-infection, initial CD4 cell count > 200 x 10(6) cells/l and use of highly active antiretroviral therapy (HAART) were associated with significantly reduced liver mortality. CONCLUSIONS: Patients with HIV and viral hepatitis had greater liver mortality than patients with HIV alone, but had comparable HIV mortality. Co-infection with hepatitis B is associated with hepatic outcomes similar to hepatitis C. Control of immunosuppression with HAART and CD4 counts > 200 x 10(6) cells/l are associated with better hepatic outcomes and should be the first priority in patients with HIV and viral hepatitis.     

Hepatitis B virus and human immunodeficiency virus co-infection in sub-Saharan Africa: a call for further investigation.

A growing body of evidence indicates that human immunodeficiency virus (HIV)-positive individuals are more likely to be infected with hepatitis B virus (HBV) than HIV-negative individuals, possibly as a result of shared risk factors. There is also evidence that HIV-positive individuals who are subsequently infected with HBV are more likely to become HBV chronic carriers, have a high HBV replication rate, and remain hepatitis Be antigen positive for a much longer period. In addition, it is evident that immunosuppression brought about by HIV infection may cause reactivation or reinfection in those previously exposed to HBV. Furthermore, HIV infection exacerbates liver disease in HBV co-infected individuals, and there is an even greater risk of liver disease when HIV and HBV co-infected patients are treated with highly active anti-retroviral therapy (HAART). Complicating matters further, there have been several reports linking HIV infection to 'sero-silent' HBV infections, which presents serious problems for diagnosis, prevention, and control. In sub-Saharan Africa, where both HIV and HBV are endemic, little is known about the burden of co-infection and the interaction between these two viruses. This paper reviews studies that have investigated HIV and HBV co-infection in sub-Saharan Africa, against a backdrop of what is currently known about the interactions between these two viruses.     

Current treatment options for hepatitis C patients co-infected with HIV

With the availability of all-oral, direct acting antivirals (DAAs), hepatitis C virus (HCV) therapy has been revolutionized for HIV/HCV co-infected patients. Indeed HCV cure rates are now no longer different between HCV mono and HIV/HCV co-infected persons and are both greater than 95%. Therefore, current treatment guidelines no longer separate these two groups. Indications for HCV treatment and choice of DAA combination are now the same for all HCV patients. In HIV/HCV co-infection however, drug interactions between HIV and HCV agents need be checked prior to starting HCV therapy. Finally, the higher risk of hepatic decompensation in HIV/HCV co-infected patients, including those receiving successful antiretroviral therapy, continues to make these patients a high priority group for receiving access to modern DAA combination therapy.     

Management of hepatitis C virus infection in HIV/HCV co-infected patients： Clinical review

Nearly one fourth of individuals with human immunodeficiency virus （HIV） infection have hepatitis C virus （HCV） infection in the US and Western Europe. With the availability of highly active antiretroviral therapy and the consequent reduction in opportunistic infections, resulting in the prolongation of the life span of HIV-infected patients, HCV co-infection has emerged as a significant factor influencing the survival of HIV patients. Patients with HIV/HCV co-infection have a faster rate of fibrosis progression resulting in more frequent occurrences of cirrhosis, end-stage liver disease, and hepatocellular carcinoma. However, the mechanism of interaction between the two viruses is not completely understood. The treatment for HCV in co-infected patients is similar to that of HCV monoinfection; i.e., a combination of pegylated interferon and ribavirin. The presence of any barriers to anti- HCV therapy should be identified and eliminated in order to recruit all eligible patients. The response to treatment in co-infected patients is inferior compared to the response in patients with HCV mono-infection. The sustained virologic response rate is only 38% for genotype-1 and 75% for genotype-2 and -3 infections. Liver transplantation is no longer considered a contraindication for end-stage liver disease in coinfected patients. However, the 5 year survival rate is lower in co-infected patients compared to patients with HCV mono-infection （33% vs 72%, P = 0.07）. A betterunderstanding of liver disease in co-infected patients is needed to derive new strategies for improving outcome, and survival.     

Management of hepatitis C virus infection in HIV/HCV co-infected patients: Clinical review

Nearly one fourth of individuals with human immunodeficiency virus (HIV) infection have hepatitis C virus (HCV) infection in the US and Western Europe. With the availability of highly active antiretroviral therapy and the consequent reduction in opportunistic infections, resulting in the prolongation of the life span of HIV-infected patients, HCV co-infection has emerged as a significant factor influencing the survival of HIV patients. Patients with HIV/HCV co-infection have a faster rate of fibrosis progression resulting in more frequent occurrences of cirrhosis, end-stage liver disease, and hepatocellular carcinoma. However, the mechanism of interaction between the two viruses is not completely understood. The treatment for HCV in co-infected patients is similar to that of HCV monoinfection; i.e., a combination of pegylated interferon and ribavirin. The presence of any barriers to anti- HCV therapy should be identified and eliminated in order to recruit all eligible patients. The response to treatment in co-infected patients is inferior compared to the response in patients with HCV mono-infection. The sustained virologic response rate is only 38% for genotype-1 and 75% for genotype-2 and -3 infections. Liver transplantation is no longer considered a contraindication for end-stage liver disease in coinfected patients. However, the 5 year survival rate is lower in co-infected patients compared to patients with HCV mono-infection (33% vs 72%, P = 0.07). A better understanding of liver disease in co-infected patients is needed to derive new strategies for improving outcome and survival.     

Alcohol use disorder and its impact on chronic hepatitis C virus and human immunodeficiency virus infections

Alcohol use disorder(AUD) and hepatitis C virus(HCV) infection frequently co-occur. AUD is associated with greater exposure to HCV infection, increased HCV infection persistence, and more extensive liver damage due to interactions between AUD and HCV on immune responses, cytotoxicity, and oxidative stress. Although AUD and HCV infection are associated with increased morbidity and mortality, HCV antiviral therapy is less commonly prescribed in individuals with both conditions. AUD is also common in human immunodeficiency virus(HIV) infection, which negatively impacts proper HIV care and adherence to antiretroviral therapy, and liver disease. In addition, AUD and HCV infection are also frequent within a proportion of patients with HIV infection, which negatively impacts liver disease. This review summarizes the current knowledge regarding pathological interactions of AUD with hepatitis C infection, HIV infection, and HCV/HIV co-infection, as well as relating to AUD treatment interventions in these individuals.     

Hepatitis C virus infection: co-infection with HIV and HBV.

Hepatitis C shares common routes of infection with hepatitis B (HBV) and the human immunodeficiency virus (HIV). It is, therefore, not surprising to find that some patients with HCV are co-infected with either HIV and/or HBV. Until recently, the effects of HIV on HCV infection have not been investigated--sadly patients with HIV died long before their liver disease became problematic. However, the development of successful therapies for HIV have led to dramatic improvements in life expectancy for patients infected with this virus and in these patients, with well controlled HIV, it is becoming clear that hepatitis C may lead to the early onset of advanced liver disease. The optimal treatment for these patients is unknown but it seems likely that combination antiviral therapy will be required. The effects of HBV on HCV are also beginning to be investigated and, again, it is clear that co-infection leads to more aggressive liver disease with the two viruses interacting in poorly defined ways to increase the rate of hepatic fibrosis. Management of combined HCV/HBV infection is still under investigation and will probably involve combination therapy.     

Could anti-HCV treatment prevent recurrence of hepatocellular carcinoma in HIV-infected patients? Two case reports

Highly active antiretroviral therapy (HAART) has proven long-term efficacy in human immunodeficiency virus (HIV) infection. Combination therapy with pegylated interferon and ribavirin has become the standard of care in patients with both hepatitis C virus (HCV) chronic hepatitis and HIV/HCV co-infection. Data on the safety and efficacy of combination therapy in chronic hepatitis C patients with hepatocellular carcinoma (HCC) is scarce and even more so in HIV/HCV co-infected subjects. We report the successful administration of both HAART and anti-HCV therapies in two HIV/HCV co-infected patients after HCC eradication. These encouraging results might argue for the feasibility of an aggressive approach in the management of co-infected patients with HCC.     

The implications of antiviral drugs with activity against hepatitis B virus and HIV

PURPOSE OF REVIEW: Around 10% of individuals infected with HIV suffer from chronic hepatitis B virus infection. This represents at least 4 million people worldwide. HIV infection modifies the course of hepatitis B virus associated liver disease with faster progression to cirrhosis. The number of anti-hepatitis B virus drugs has increased within the last few years, and some of them also exert activity against HIV-1. The aim of this article is to update the current knowledge on antiviral therapy for chronic hepatitis B in HIV-infected patients. RECENT FINDINGS: In the absence of successful anti-hepatitis B virus therapy, morbidity and mortality associated with liver disease are increased in hepatitis B virus/HIV coinfected individuals. Data derived from studies using new more potent anti-hepatitis B virus drugs are very promising, and strategies to use these antivirals sequentially and/or in combination are being developed. Hopefully, this success will help bring a halt to liver-related complications and death in the hepatitis B virus/HIV coinfected population. SUMMARY: Appropriate diagnosis and monitoring of chronic hepatitis B, including the use of noninvasive tools for assessing liver fibrosis, measurement of serum hepatitis B virus-DNA, and drug resistance testing, along with wise use of antivirals may convert hepatitis B virus/HIV coinfection into a manageable disease.     

HIV and hepatitis C virus co-infection

Since the decline in HIV-related morbidity and mortality after introduction of highly active antiretroviral therapy (HAART) in 1996, liver disease caused by chronic infection with hepatitis C virus (HCV) has become an increasingly important cause of morbidity and mortality among HIV-infected patients infected parenterally with HCV in more developed countries. A third of HIV-infected individuals in Europe and the USA have HCV co-infection. HIV accelerates HCV liver disease especially when HIV-associated immunodeficiency progresses. With the introduction of pegylated interferon in combination with ribavirin, greatly improved treatment options for patients with HIV and HCV co-infection have become available and have led to sustained virological response rates of up to 40%. Furthermore, recent cohort analyses have shown that immune reconstitution induced by HAART can improve the course of hepatitis C leading to a decline in liver-related mortality. However, patients with HCV co-infection are at increased risk of hepatotoxicity from HAART. Owing to the high rates of HIV and HCV co-infection worldwide, new improved treatment strategies and guidelines for the management of co-infection remain a major future goal.     

Outcomes and management of viral hepatitis and human immunodeficiency virus co-infection in liver transplantation

Liver transplantation for human immunodeficiency virus(HIV)positive patients with viral hepatitis co-infection is increasingly offered in many North American and European liver transplant centers.Prior studies have demonstrated acceptable post-transplant outcomes and no increased risk of HIV complications in patients coinfected with hepatitis B virus(HBV).However,liver transplantation in HIV positive patients with hepatitis C virus(HCV)has poorer outcomes overall,requiring careful selection of candidates.This review aims to summarize the published literature on outcomes after transplant in HIV patients with HBV or HCV related end-stage liver disease and recommendations for management.In particular the pre-transplant factors impacting outcomes in HCV/HIV co-infected candidates and importance of multidisciplinary management will be discussed.     

Hepatitis C virus infection in patients with HIV-1: epidemiology,natural history and management

Hepatitis C virus (HCV)-related liver diseases have contributed to increased morbidity and mortality in HIV-1-infected individuals in the era of effective antiretroviral therapy. HCV transmission patterns have changed among the HIV co-infected population during the last decade, with acute HCV infection emerging worldwide. HIV infection accelerates the progression of HCV-related liver diseases and consequently cirrhosis, liver failure, and hepatocellular carcinoma. However, the current standard treatment of HCV infection with pegylated interferon plus ribavirin results in only a limited viral response. Furthermore, cumbersome pill regimens, antiretroviral related hepatotoxicity, and drug interactions of HCV and HIV regimens complicate therapy strategies. Fortunately, in the near future, new direct-acting anti-HCV agents will widen therapeutic options for HCV/HIV co-infection. Liver transplantation is also gradually accepted as a therapeutic option for end stage liver disease of HCV/HIV co-infected patients.     

Challenges and opportunities for hepatitis C drug development in HIV-hepatitis C virus-co-infected patients

The approval of the first direct-acting antivirals (DAAs) against the hepatitis C virus (HCV) has been eagerly expected for treating chronic hepatitis C in HIV individuals given that progression to cirrhosis and end-stage liver disease occurs faster in the co-infected population. The appropriate and judicious use of DAAs may provide cure to a large number of HIV-HCV patients. On the contrary, the widespread use of DAAs will occasionally be off-label or under unsatisfactory medical conditions, which may result in undesirable toxicities, drug interactions or selection of drug resistance in HCV. As a result of using first-generation DAAs in HIV-HCV-co-infected patients, a growing proportion of the remaining hepatitis C individuals will be those harboring non-HCV 1 genotypes or drug-resistant HCV variants. Over time, the largest reservoir of HCV genotype 1 patients will accumulate in resource-poor nations where access to hepatitis C therapy has been elusive and HIV treatment remains the primary health issue for the co-infected population.