Severe hepatitis in three AIDS patients treated with indinavir

Bräu, Norbert; Leaf, Howard L.; Wieczorek, Rosemary; Margolis, David M.

doi:10.1016/s0140-6736(05)62700-6

Cited by 104 publications

(47 citation statements)

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“…Another limitation was that our HIV-positive population was not reflective of the present HIV-positive population, which often receives HAART; however, this fact allows a better demonstration of a more severe liver disease induced by HIV coinfection, because HAART has been reported to worsen HCV infection despite improvement of HIV parameters 22,23 or to induce hepatotoxicity. [24][25][26][27] The long-term follow-up, up to 15 years, in this study, permitted us to confirm that HCVrelated liver disease was able to cause death, even in HIVinfected patients whose survival was not improved by new antiretroviral therapies. This observation in injection drug users is consistent with that reported in hemophiliacs.…”

Section: Discussionmentioning

confidence: 58%

The influence of human immunodeficiency virus coinfection on chronic hepatitis C in injection drug users: A long-term retrospective cohort study

et al. 2001

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In this study we analyzed the influence of human immunodeficiency virus (HIV) infection on the course of chronic hepatitis C through multivariate analysis including age, alcohol consumption, immune status, and hepatitis C virus (HCV)-related virologic factors. Eighty HIV-positive and 80 HIV-negative injection drug users included between 1980 and 1995 were matched according to age, gender, and duration of HCV infection and followed-up during 52 months. The progression to cirrhosis was the primary outcome measure. The impact of HIV on HCV-RNA load, histologic activity index, response to interferon therapy, and liver-related death was also considered. In HIV-positive patients, chronic hepatitis C was characterized by higher serum HCV-RNA levels (P ‫؍‬ .012), higher total Knodell score (P ‫؍‬ .011), and poorer sustained response to interferon therapy (P ‫؍‬ .009). High serum HCV-RNA level was associated with low CD4-lymphocyte count (P ‫؍‬ .001). Necroinflamatory score was higher in HIV-positive patients (P ‫؍‬ .023) independently of the CD4-lymphocyte count, whereas increased fibrosis was related to decreased CD4-lymphocyte count (P ‫؍‬ .011). The progression to cirrhosis was accelerated in HIV-positive patients with low CD4 cell count (RR ‫؍‬ 4.06, P ‫؍‬ .024) and in interferon-untreated patients (RR ‫؍‬ 4.76, P ‫؍‬ .001), independently of age at HCV infection (P ‫؍‬ .001). Cirrhosis caused death in 5 HIV-positive patients. The risk of death related to cirrhosis was increased in heavy drinkers (RR ‫؍‬ 10.8, P ‫؍‬ .001) and in HIV-positive patients with CD4 cell count less than 200/mm 3 (RR ‫؍‬ 11.9, P ‫؍‬ .007). In this retrospective cohort study, HIV coinfection worsened the outcome of chronic hepatitis C, increasing both serum HCV-

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Section: Discussionmentioning

confidence: 58%

The influence of human immunodeficiency virus coinfection on chronic hepatitis C in injection drug users: A long-term retrospective cohort study

et al. 2001

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“…As well as being effective in individuals with lamivudineresistant HBV, tenofovir is also effective in individuals who fail alpha interferon (IFN-␣) therapy (61). Initiation of antiretroviral therapy (ART) for HIV-1 can lead to severe acute hepatitis with or without clearance of HBV (16,18). Better understanding of how the immune system responds to HBV following ART and how infection with HIV-1 alters this response is needed.…”

mentioning

confidence: 99%

Reduced Hepatitis B Virus (HBV)-Specific CD4⁺T-Cell Responses in Human Immunodeficiency Virus Type 1-HBV-Coinfected Individuals Receiving HBV-Active Antiretroviral Therapy

Chang

Wightman

Bartholomeusz

et al. 2005

J Virol

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Functional hepatitis B virus (HBV)-specific T cells are significantly diminished in individuals chronicallyinfected with HBV compared to individuals with self-limiting HBV infection or those on anti-HBV therapy. In individuals infected with human immunodeficiency virus type 1 (HIV-1), coinfection with HBV is associated with an increased risk of worsening liver function following antiviral therapy and of more rapid HBV disease progression. Total HBV-specific T-cell responses in subjects with diverse genetic backgrounds were characterized by using a library of 15-mer peptides overlapping by 11 amino acids and spanning all HBV proteins. The magnitude and breadth of CD4 ؉ and CD8 ؉ T-cell responses to HBV in peripheral blood were examined by flow cytometry to detect gamma interferon production following stimulation with HBV peptide pools. Chronic HBV carriers (n ‫؍‬ 34) were studied, including individuals never treated for HBV infection (n ‫؍‬ 7), HBV-infected individuals receiving anti-HBV therapy (n ‫؍‬ 13), and HIV-1-HBV-coinfected individuals receiving anti-HBV therapy (n ‫؍‬ 14). CD4؉ and CD8 ؉ HBV-specific T-cell responses were more frequently detected and the CD8 ؉ T-cell responses were of greater magnitude and breadth in subjects on anti-HBV treatment than in untreated chronic HBV carriers. There was a significant inverse correlation between detection of a HBVspecific T-cell response and HBV viral load. HBV-specific CD4؉ and CD8 ؉ T-cell responses were significantly (fivefold) reduced compared with HIV-specific responses. Although, the frequency and breadth of HBV-specific CD8 ؉ T-cell responses were comparable in the monoinfected and HIV-1-HBV-coinfected groups, HBV-specific CD4 ؉ T-cell responses were significantly reduced in HIV-1-HBV-coinfected individuals. Therefore, HIV-1 infection has a significant and specific effect on HBV-specific T-cell immunity.There are 350 million individuals chronically infected with hepatitis B virus (HBV) worldwide (36,42,59). Each year 1 million to 1.5 million carriers die from HBV-related liver disease and liver cancer such as hepatocellular carcinoma (36,48). In the United States, Europe, and Australia, approximately 6 to 7% of individuals infected with human immunodeficiency virus type 1 (HIV-1) are also coinfected with HBV (23, 41). Liver disease is now a major comorbidity in HIV-1-infected individuals (11,66). Although hepatitis C virus (HCV)-HIV-1 coinfection is more common than HBV infection, liver failure occurs more frequently with persistent HBV infection (60, 63). Coinfection of HBV with HIV-1 leads to elevated HBV DNA levels, a lower rate of seroconversion to HBeAg, and lower alanine aminotransferase (ALT) levels than those in HBV monoinfection (21, 31). Spontaneous flares and HBeAg seroconversion occur in 5% of HBV-monoinfected individuals; however, in the setting of HIV-1-HBV coinfection, spontaneous flares or seroconversion to HBeAg is rare (18). In individuals infected with HIV-1 who subsequently acquire HBV infection, there is an increased risk of persisten...

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“…Drug should be used within two hours after meals. Several Protease Inhibitors are used with other drugs for HIV treatment [12]. Metabolization of PIs is by the CYP450 system.…”

Section: Saquinavirmentioning

confidence: 99%

“…Individuals who are using protease inhibitors have the highest risk of developing hepatotoxic related problems [11][12][13]. Hepatotoxicity is defined by severe changes in the aminotransferase levels.…”

Section: Introductionmentioning

confidence: 99%

Anti-Retroviral Drug Hepatotoxicity and Risk Factors in HIV Patients with or Without Hepatitis B and C: A Review

JR¹,

PE²

2015

J Infect Dis Ther

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Physicians are treating patients infected with human immunodeficiency virus and/or hepatitis B or hepatitis C in their practice more often. Long-term complications of this diseases are multifactorial and can be related to the virus itself or to adverse effects of antiretroviral therapy. The liver is the main organ for regulating the internal environment of a body. There is no way to compensate for the loss of a liver function. It has major influences on the flow of nutrients as well as controlling carbohydrate, protein and fat metabolism. Drugs are significant in causing liver injury. More than nine hundred drugs, herbs and toxins have been documented as being hepatotoxic in line with different risk factors. The incidences of severe hepatic injury vary among different study cohorts as well as the differences in risk factors. Patients with a co-infection of HIV and Hepatitis B or C are at a risk of getting liver injury from antiretroviral drugs because the co-infections accelerate liver injury that may lead to cirrhosis or hepatocellular carcinoma. The risk of liver damage for those with a monoinfection of HIV alone is lower than in co-infections. This review explores risk factors for hepatotoxicity, its hepatotoxic antiretroviral drugs and the mechanisms of toxicity. It is meant to highlight the hepatotoxic potential of different antiretroviral drugs currently in use by HIV infected individuals.

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Severe hepatitis in three AIDS patients treated with indinavir

Cited by 104 publications

References 0 publications

The influence of human immunodeficiency virus coinfection on chronic hepatitis C in injection drug users: A long-term retrospective cohort study

The influence of human immunodeficiency virus coinfection on chronic hepatitis C in injection drug users: A long-term retrospective cohort study

Reduced Hepatitis B Virus (HBV)-Specific CD4⁺T-Cell Responses in Human Immunodeficiency Virus Type 1-HBV-Coinfected Individuals Receiving HBV-Active Antiretroviral Therapy

Anti-Retroviral Drug Hepatotoxicity and Risk Factors in HIV Patients with or Without Hepatitis B and C: A Review

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Severe hepatitis in three AIDS patients treated with indinavir

Cited by 104 publications

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The influence of human immunodeficiency virus coinfection on chronic hepatitis C in injection drug users: A long-term retrospective cohort study

The influence of human immunodeficiency virus coinfection on chronic hepatitis C in injection drug users: A long-term retrospective cohort study

Reduced Hepatitis B Virus (HBV)-Specific CD4+T-Cell Responses in Human Immunodeficiency Virus Type 1-HBV-Coinfected Individuals Receiving HBV-Active Antiretroviral Therapy

Anti-Retroviral Drug Hepatotoxicity and Risk Factors in HIV Patients with or Without Hepatitis B and C: A Review

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Reduced Hepatitis B Virus (HBV)-Specific CD4⁺T-Cell Responses in Human Immunodeficiency Virus Type 1-HBV-Coinfected Individuals Receiving HBV-Active Antiretroviral Therapy