HIV and hepatitis virus infection

As the life expectancy of patients with HIV infection increases, greater attention will need to be focused on concurrent illnesses, such as viral hepatitis, that may increase mid- to long-range morbidity and mortality. The incidence of viral hepatitis is increased in patients with HIV disease, reflecting the epidemiologic risks that these two conditions share. Coinfection with HIV seems to adversely affect the natural history of hepatitis C but may actually reduce the hepatic damage associated with hepatitis B. Immunosuppression due to HIV does not seem to significantly affect hepatitis A, E, or G. Clinicians have been reluctant to treat viral hepatitis in the HIV-infected population, but this therapeutic nihilism is unwarranted. Most studies have concluded that the treatment of hepatitis C in HIV-infected patients results in an initial efficacy and a long-term response similar to those seen in the HIVseronegative population. Although the efficacy of interferon is reduced against hepatitis B, some nucleoside analogues are effective.     

HIV and hepatitis virus infection

As the life expectancy of patients with HIV infection increases, greater attention will need to be focused on concurrent illnesses, such as viral hepatitis, that may increase mid- to long-range morbidity and mortality. The incidence of viral hepatitis is increased in patients with HIV disease, reflecting the epidemiologic risks that these two conditions share. Coinfection with HIV seems to adversely affect the natural history of hepatitis C but may actually reduce the hepatic damage associated with hepatitis B. Immunosuppression due to HIV does not seem to significantly affect hepatitis A, E, or G. Clinicians have been reluctant to treat viral hepatitis in the HIV-infected population, but this therapeutic nihilism is unwarranted. Most studies have concluded that the treatment of hepatitis C in HIVinfected patients results in an initial efficacy and a long-term response similar to those seen in the HIV-seronegative population. Although the efficacy of interferon is reduced against hepatitis B, some nucleoside analogues are effective.     

Hepatitis C virus/human immunodeficiency virus coinfection: clinical management issues.

The use of highly active antiretroviral therapy (HAART) has extended the healthy lifespan of patients infected with human immunodeficiency virus (HIV); deaths among people with AIDS declined for the first time in 1996, after the institution of this therapeutic approach. As the life expectancy of HIV-infected patients increases, greater attention will need to be focused on the recognition and management of potentially severe concurrent illnesses that may increase their mid- to long-range morbidity and mortality. The incidence of infection by hepatitis C virus (HCV) is increased among patients with HIV disease, reflecting shared epidemiological risks. HCV not only may have an impact on the health status of HIV-infected patients but also may decrease their quality of life and increase their health care costs. Although clinicians have been reluctant to treat viral hepatitis C in the HIV-infected population, this therapeutic nihilism is unwarranted. The majority of studies have concluded that treatment of hepatitis C in HIV-infected patients results in an initial efficacy and long-term response similar to those in the HIV-seronegative population. Furthermore, treatment of HCV infection in HCV/HIV-coinfected patients may improve tolerance for antiretroviral medications. Physicians caring for patients with HIV infection require up-to-date information to make rational decisions regarding HCV coinfection to ensure that morbidity and mortality are minimized and that quality of life and medical care costs are optimized.     

Hepatitis C in the HIV-Infected Person

Because of shared routes of transmission, hepatitis C virus (HCV) infection is common in HIV-infected persons, who have been experiencing increasing HCV-related morbidity and mortality since the advent of effective antiretroviral therapy. Infection with HIV appears to adversely affect the outcome of hepatitis C, leading to increased viral persistence after acute infection, higher levels of viremia, and accelerated progression of HCV-related liver disease. In addition, hepatitis C may affect the course and management of HIV infection. The medical management of hepatitis C in HIV-infected persons is complicated by immune suppression, potential drug interactions and toxicities, and other forms of liver disease. In addition, there is little published experience with the safety and efficacy of the best available anti-HCV medications in HIV-infected persons. Thus, current efforts must be directed at preventing HCV and HIV infections and applying the principles learned in treating persons with either infection to manage those with both. Future efforts should include studies of the pathogenesis of HCV infection in HIV-infected persons and large, prospective studies that demonstrate the optimal management of persons co-infected with HIV and HCV. Such efforts will help to eliminate HCV-related liver disease as an emerging threat to HIV-infected persons.     

Hepatitis C virus infection in HIV-infected patients

Due to shared routes of acquisition, hepatitis C virus (HCV) infection is common in HIV-infected persons. Because the lives of HIV-infected persons have been extended by the use of effective antiretroviral therapies, HCV-related morbidity and mortality have emerged as major health problems. Coinfection with HIV appears to adversely affect all stages of hepatitis C infection, leading to increased viral persistence following acute infection, higher levels of viremia, and accelerated progression of HCVrelated liver disease. In addition, hepatitis C may impact the course and management of HIV infection, increasing the incidence of hepatotoxicity caused by antiretroviral medications. The medical management of hepatitis C in HIV-infected persons remains complex, due largely to the paucity of published clinical trials, potential drug-drug interactions, and the presence of significant comorbid conditions. Nonetheless, in light of an accelerated HCV disease course, the National Institutes of Health Consensus Development Conference Statement (2002) recommends that HIV-infected patients be considered for HCV treatment. Further research is urgently needed on the management of hepatitis C in HIV-infected patients.     

Liver involvement in human immunodeficiency virus infection

The advances in management of patients with acquired immunodeficiency syndrome (AIDS) with highly effective anti-retroviral therapy (HAART) have resulted in increased longevity of patients with human immunodeficiency virus (HIV) infection. AIDS-related illnesses now account for less than 50 % of the deaths, and liver diseases have emerged as the leading cause of death in patients with HIV infection. Chronic viral hepatitis, drug-related hepatotoxicity, non-alcoholic fatty liver disease, and opportunistic infections are the common liver diseases that are seen in HIV-infected individuals. Because of the shared routes of transmission, co-infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are very common in HIV-infected persons. Hepatitis C is the most common viral hepatitis seen in HIV-infected patients. With the availability of directly acting agents, treatment outcome of HCV is comparable to that seen in non HIV-infected patients. Careful monitoring is required for drug interactions and drug-induced hepatotoxicity and modification of drugs should be done where necessary. The results of liver transplantation in select HIV-infected patients can be comparable with those of HIV-negative patients.     

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.     

Hepatitis B and C virus infections in the immune compromised

PURPOSE OF REVIEW: This review compares and contrasts the natural history and treatment of hepatitis B and C virus infections in three principal populations of immune compromised individuals: (1) patients co-infected with HIV; (2) patients with liver failure secondary to hepatitis B or C virus infection who undergo liver transplantation, and (3) patients with hepatitis B or C virus infection who undergo anticancer chemotherapy. RECENT FINDINGS: Chronic liver disease resulting from hepatitis B or C virus infection progresses more rapidly in patients co-infected with HIV than in HIV negative patients. Treatment protocols for antiviral therapy are, however, similar to those used in immunocompetent individuals and although few long-term results are available, the efficacy of interferon and ribavirin therapy in hepatitis C virus/HIV infection and lamivudine in HIV/hepatitis B virus infection has been proven in the short-term. Perhaps the most important consideration is the timing of administering treatments to co-infected patients. For patients with well preserved CD4 counts and hepatitis C virus/HIV co-infection, the hepatitis infection should be treated as early as possible to avoid drug interactions of hepatitis C virus antivirals with antiretroviral therapy. Also, response to hepatitis C virus treatment appears better when treatment is administered in the context of preserved immune function. Conversely, in hepatitis B virus/HIV co-infection, hepatitis B virus antivirals are best administered with anti-retroviral therapy, thus preventing the selection of HIV viral species which may be resistant to the drugs used for hepatitis B virus. Improved graft and patient survival after liver transplant and with anticancer chemotherapy in hepatitis B virus infected patients has been proven using lamivudine prophylaxis. However, although therapy for hepatitis C virus recurrence after liver transplantation would seem rational, limited success with current treatment protocols has been achieved. SUMMARY: Although the prognosis of hepatitis B and C virus infections in the immune compromised may be inferior to that of immunocompetent individuals, such patients should have full evaluation of their viral hepatitis, and antiviral therapy should be considered.     

Vaccination against hepatitis a and b in patients with hiv

Patients coinfected with HIV and viral hepatitis A or B are at increased risk for liver-related morbidity and mortality. Although vaccination is safe and effective in the general population, hepatitis A virus and hepatitis B virus transmission may continue in high-risk populations because vaccine response rates lag behind those seen in healthy populations. Poor immune response to vaccine, atypical markers of prior exposure, and difficulty reaching those at risk underlie the challenges facing clinicians and their HIV-infected patients.     

Genetic variation in IL28B and treatment-induced clearance of hepatitis C virus in HIV-positive patients with acute and chronic hepatitis C

Recently, a IL28B (rs 12979860) gene polymorphism was identified as a predictor for response to hepatitis C virus-specific treatment in human immunodeficiency virus (HIV)-uninfected and -infected patients with chronic hepatitis C. In an analysis of HIV-infected patients with acute hepatitis C, we found that the IL28B genotype was associated with serum levels of hepatitis C virus RNA, g-GT, and CD4 cell count. In contrast to HIV-infected patients with chronic hepatitis C, the IL28B genotype was not significantly associated with treatment response rates in patients with acute hepatitis C. Thus, effects of the IL28B single-nucleotide polymorphism may differ in HIV-infected patients with chronic and acute hepatitis C.     

Silymarin treatment of viral hepatitis: a systematic review

Silymarin from the milk thistle herb (Silybum marianum) is used by many patients with chronic viral hepatitis, but its efficacy remains unknown. We performed a systematic review of silymarin for the treatment of chronic viral hepatitis B and C. An exhaustive search strategy identified 148 papers that studied silymarin compounds in liver disease. Of these, four trials included patients with hepatitis C, one included hepatitis B patients, and two, unspecified chronic viral hepatitis. However, only one trial exclusively studied patients with hepatitis C, and none involved patients with only hepatitis B. Silymarin treatment resulted in a decrease in serum transaminases compared with baseline in four studies, and compared with placebo in only one study. There is no evidence that silymarin affects viral load or improves liver histology in hepatitis B or C. No studies were found that investigated the use of silymarin concomitantly with interferon, nucleoside analogues, or other conventional treatments for hepatitis B or C. In conclusion, silymarin compounds likely decrease serum transaminases in patients with chronic viral hepatitis, but do not appear to affect viral load or liver histology. Nevertheless it may be worthwhile to determine its effects in conjunction with standard antiviral treatment.     

HIV Infection and Clinical Spectrum of Associated Vasculitides

Various infections have been causative in the pathogenesis of systemic vasculitides, and HIV infection is not spared. In an immunocompromised host, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, herpes simplex virus, hepatitis B and hepatitis C virus, and mycobacteria, along with HIV infection can cause vasculitis. Herein we emphasize the spectrum of vasculitides, their pathogenesis, presentation, course, and therapy in the HIV-infected population. Every spectrum and size of the blood vessel involvement have been seen in HIV-associated vasculitides. We review each spectrum in detail and describe our experience with polyarteritis nodosa, the most common presentation occurring in HIV-infected patients. We also discuss the differences in HIV, hepatitis B, and hepatitis C- related polyarteritis nodosa in detail.     

Update on chronic hepatitis C in HIV/HCV-coinfected patients: viral interactions and therapy

With highly active antiretroviral therapy (HAART), HIV-infected patients can now live longer and healthier lives, and other comorbid diseases, such as chronic hepatitis C, have emerged as a significant health concern. Coinfection with the hepatitis C virus (HCV) may limit life expectancy because it can lead to serious liver disease including decompensated liver cirrhosis and hepatocellular carcinoma. HCV-induced fibrosis progresses faster in HIV/HCV-coinfected persons, although HAART may be able to decrease this disease acceleration. Combination therapy for HCV with interferon and ribavirin can achieve a sustained viral response, although at a lower rate than in HCV-monoinfected patients. Combination treatment with pegylated interferon and ribavirin will probably emerge as the next HCV therapy of choice for HIV/HCV-coinfected patients. HCV combination therapy is generally safe, but serious adverse reactions, like lactic acidosis, may occur. Cytopenia may present a problem leading to dose reductions, but the role of growth factors is under study. All HIV/HCV-coinfected patients should be evaluated for therapy against the hepatitis C virus. A sustained viral load will probably lead to regression of liver disease, and even interferon-based treatment without viral clearance may slow down progression of liver disease. HIV/HCV-coinfected patients who have progressed to end-stage liver disease have few therapeutic options other than palliative care, since liver transplants are generally unavailable. The mortality post-transplant may be higher than in HCV-monoinfected patients. We are entering an era where safe and effective HCV therapy is being defined for HIV/HCV-coinfected patients, and all eligible patients should be offered treatment.     

HCV and HIV Coinfection

Chronic hepatitis C (CHC) is estimated to affect about 20% of the 34 million individuals currently living with HIV worldwide, with greater rates (~ 75%) in intravenous drug users or persons exposed to blood products. Individuals who are coinfected with HIV and hepatitis C virus (HCV) show an accelerated course of liver disease, with faster progression to cirrhosis and its clinical complications. The combination of pegylated interferon plus ribavirin given for 6–18 months leads to sustained HCV clearance in no more than half of HIV-HCV coinfected patients. Thus, new direct anti-HCV drugs are eagerly awaited for this population. Appropriate diagnosis and monitoring of CHC, including the use of noninvasive tools for assessing liver fibrosis (eg, elastometry) as well as provision of therapy guided by early viral kinetics and IL28B genotyping, are improving the management of CHC in HIV-infected persons.     

Prevalence of hepatitis B and hepatitis C coinfections in an adult HIV centre population in Gaborone, Botswana

The objective of this study was to assess the prevalence of hepatitis B and hepatitis C coinfections in human immunodeficiency virus (HIV) -infected adults at an HIV center in Gaborone, Botswana. A retrospective review was performed of charts of currently active HIV-infected adult patients in the Family Model Clinic (FMC) of the Botswana-Baylor Children's Clinical Center of Excellence (BCOE) in Gaborone, Botswana, for the results of serum hepatitis B surface antigen (HBsAg) and antihepatitis C IgG tests performed between January 1, 2005 and December 15, 2009. Of 308 active FMC patients, 266 underwent HBsAg serology testing within the period of study. The HBsAg coinfection prevalence was 5.3% (14/266); 2 of 252 patients had at least one positive antihepatitis C IgG serology, a 0.8% prevalence. Hepatitis B coinfection is relatively common in HIV-infected adults at our center in Botswana, whereas hepatitis C coinfection is rare. In this setting, where the diagnosis of hepatitis B coinfection with HIV has implications for choice of first-line antiretroviral therapy and prevention of perinatal hepatitis B transmission, broader sampling to establish the true population prevalence of hepatitis B coinfection and the desirability of adding screening to HIV management should be considered. These findings provide little justification for adding hepatitis C coinfection screening to the management of HIV infection in Botswana.     

Hepatitis B virus infection in HIV-infected persons

Coinfection with HIV and hepatitis B virus (HBV) is common due to shared modes of transmission. The extended life expectancy of HIV-infected persons from effective antiretroviral therapy has led to the emergence of chronic hepatitis B (CHB) as an important problem. HIV adversely affects CHB, leading to accelerated progression of liver disease, as evidenced by an increased incidence of cirrhosis and liver-related mortality in coinfected persons. Furthermore, CHB increases the risk of hepatotoxicity from antiretroviral therapy, potentially jeopardizing the efficacy of HIV treatment. For these reasons, HIV-infected persons must be evaluated for coinfection with HBV and, if present, must be considered for CHB treatment. Management of CHB in HIV-infected persons is particularly complex due to lack of controlled trials, inability for current therapeutics to eradicate HBV, overlap in therapeutic agents for both viruses, and potential for development of drug-resistant HBV and HIV. Thus, treatment of HIV-HBV-coinfected patients requires simultaneous consideration of both viral infections. Further research is needed to determine the optimum management of CHB in HIV-infected persons.     

European AIDS Clinical Society (EACS) guidelines for the clinical management and treatment of chronic hepatitis B and C coinfection in HIV-infected adults

OBJECTIVES: With the decline in HIV-associated morbidity and mortality following the introduction of highly active antiretroviral therapy (HAART), liver disease has emerged as a major cause of death in HIV/hepatitis B virus (HBV) and HIV/hepatitis C virus (HCV) coinfected persons. Therefore, screening for underlying viral hepatitis coinfection and the provision of management and treatment recommendations for patients with chronic viral hepatitis are of great importance in preventing, as far as possible, the development of liver disease. With the introduction of new agents for the treatment of hepatitis B and increased knowledge of how best to manage hepatitis C, an update of current guidelines for management of HBV and HCV coinfection with HIV is warranted. SUMMARY: Clearly, all HIV-infected patients should be screened for hepatitis A, B and C, taking into account shared pathways of transmission. Patients who are seronegative for hepatitis A and B should be considered for vaccination. In HIV-infected patients with chronic hepatitis B, the first important differentiation is whether HAART is required or not. In the setting of stable HIV infection, with no need for HAART, several treatment options are available, namely treatment with interferon, early initiation of HAART, or selective non-HIV active anti-HBV nucleoside therapy, with the aim of achieving undetectable HBV DNA levels. In most cases, undetectable HBV DNA can only be achieved with combination therapy. With regard to hepatitis C, individualized tailoring of the duration of HCV therapy is advisable, taking into account rapid or delayed virological response. In patients who do not achieve at least a 2 log drop in HCV RNA at week 12, treatment can be terminated because of the low probability of achieving sustained virological response. Overall, with the currently available treatment algorithms, HCV can be eradicated in over 50% of patients. Therefore, HCV therapy should be considered and discussed with the patient if an indication for HCV therapy (elevated liver enzymes, positive HCV RNA and >F1 fibrosis) is present. CONCLUSIONS: Management of underlying hepatitis B and/or C in patients with HIV infection is of great importance in preventing liver disease-associated morbidity and mortality.     

Hepatitis C in the HIV (human immunodeficiency virus) Atlanta V.A. (Veterans Affairs Medical Center) Cohort Study (HAVACS): the effect of coinfection on survival.

To examine the prevalence of and survival rates for coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), data were analyzed from all HIV-infected patients tested for HCV antibody from January 1992 until May 1997. The prevalence of HCV infection among 350 HIV-infected patients was 33%. By univariate analysis, HCV-positive (HCV+) patients were more likely to be older (P = .003), be positive for hepatitis B core antibody (P = .006), be black (P = .001), be intravenous drug users (P = .001), and have an abnormal level of aspartate aminotransferase (AST) (P = .001). In a logistic regression model, only intravenous drug abuse and abnormal AST level remained independently associated with HCV positivity. Length of survival, as determined by the Cox proportional hazards model, was similar for HCV+ vs. HCV- patients when analyzed for three different endpoints: time from diagnosis of HIV to diagnosis of AIDS, time from diagnosis of HIV to death, and time from diagnosis of AIDS to death. The prevalence of HCV infection in this population is high but does not appear to affect HIV progression or survival.     

Hepatitis C and human immunodeficiency virus coinfections

Hepatitis C virus (HCV) has become a major contributor to morbidity and mortality in patients with human immunodeficiency virus (HIV). It is estimated that 30% to 50% of patients with HIV are coinfected with HCV. Advances in antiretroviral therapy and improved life expectancy of HIV patients have resulted in an emergence of HCV-induced liver disease as a leading cause of significant morbidity and death in this population. Clinically, hepatitis C is a more severe disease in HIV-infected individuals, characterized by rapid progression toward end-stage liver disease. Highly active antiretroviral therapy is the mainstay of current acquired immunodeficiency syndrome management. One of the limiting side effects of combination therapy for HIV is hepatotoxicity, which is more common and often more serious in patients with underlying liver disease. Management of coinfected patients has no strict guidelines, but it is generally accepted that HIV infection needs to be treated before HCV. Hepatitis C in coinfected individuals is probably best treated using combination therapy (interferon alpha and ribavirin). It appears that combination therapy can safely be administered to this population and that previous concerns about ribavirin/zidovudine antagonism are unsubstantiated in clinical practice. Although initial results using only interferon alpha showed poor results in HIV coinfected patients, combination therapy seems to be as effective as in the general population. All HIV-HCV coinfected patients should be vaccinated against hepatitis B and hepatitis A; vaccines are safe and effective.     

Autoimmune hepatitis in an HIV-infected patient: an intriguing association

Abnormal levels of liver enzymes are common in HIV-infected patients and may be caused by multiple factors, including co-infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) infection and in the majority of cases by antiretroviral drug-related liver injury. This report, however, describes a patient with HIV infection and abnormal liver function tests where further diagnostics revealed concomitant autoimmune hepatitis (AIH). The association of immune dysfunction in patients with HIV infection/AIDS and the development of autoimmune diseases is intriguing. The precise mechanism causing the emergence or unmasking of autoimmune conditions in HIV infection remains unclear, but it is important to demonstrate that autoimmune diseases do occur in HIV-infected patients. Therefore, clinicians should include AIH in the differential diagnosis of increased liver enzymes when there is no improvement despite changing antiretroviral therapy.