Risk Factors for Hepatotoxicity in HIV-1--Infected Patients Receiving Ritonavir and Saquinavir with or without Stavudine

Gisolf, Elizabeth H.; Dreezen, C; Danner, Sven A.; Weel, Jan; Weverling, Gerrit Jan

doi:10.1086/317449

Cited by 87 publications

(64 citation statements)

References 18 publications

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“…Similar results were obtained in other studies, emphasizing the role of chronic hepatitis B and C, nevirapine-and ritonavir-containing regimens, alcoholism and higher transaminase baseline values as the most important predictors of liver toxicity in HIV-positive persons receiving HAART [75][76][77][78].…”

Section: Haart-associated Hepatotoxicitysupporting

confidence: 89%

“…With regard to the individual contribution of nucleoside analogue reverse transcriptase inhibitors (NRTIs) to the occurrence of liver toxicity, stavudine and didanosine have been incriminated more frequently as potential risk factors [75,79,80], but zidovudine-containing regimens were also involved [77], and the real impact of different available NRTIs on liver damage appearance is still largely unknown.…”

Section: Haart-associated Hepatotoxicitymentioning

confidence: 99%

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Human Immunodeficiency Virus and Hepatitis C Virus Coinfection: Epidemiology, Natural History, Therapeutic Options and Clinical Management

et al. 2004

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Due to shared risk factors for transmission, coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a very common event. The prevalence of HCV infection among HIV-positive patients averages about 35% in the United States and Europe, but in clinical populations where there is a great prevalence of intravenous drug use as a risk factor for acquiring HIV, this value may be as high as 80-90%. Several studies have confirmed that HIV coinfection accelerates the natural course of chronic hepatitis C and an increased risk of liver cirrhosis, hepatocellular carcinoma, and decompensated liver disease has been found in coinfected subjects. Other studies have shown an increased risk of progression to acquired immunodeficiency syndrome (AIDS) and AIDS-related death among HIV-HCV-positive persons, suggesting that HCV coinfection may accelerate the course of HIV disease. In addition, hepatitis C may affect the management of HIV infection, increasing the incidence of liver toxicity associated with the antiretroviral regimens. The optimal therapeutic approach to HCV infection in HIV coinfected patients is still uncertain, because of the complex pathogenesis of both infections, potential drugdrug interactions, and the poor literature and information available about safety and efficacy of an interferon (IFN) and ribavirin combination in this clinical population. Available data show that the sustained virological response rates in coinfected persons treated with standard IFN plus ribavirin range from 18-40%, and several studies with pegylated IFN plus ribavirin are ongoing.

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Section: Haart-associated Hepatotoxicitysupporting

confidence: 89%

Section: Haart-associated Hepatotoxicitymentioning

confidence: 99%

Human Immunodeficiency Virus and Hepatitis C Virus Coinfection: Epidemiology, Natural History, Therapeutic Options and Clinical Management

et al. 2004

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“…[16][17][18][19] Given this association, it is speculated that hepatic injury after ARV therapy in the presence of chronic viral hepatitis may represent immune reconstitution against cells expressing viral antigens rather than direct effects of medication. 2,17 Other known risk factors for HAART-related liver injury include ARV-naïve patients undergoing their first HAART regimen, recent start of nevirapine, high-dose ritonavir, higher baseline levels of alanine aminotransferase, and female gender.…”

mentioning

confidence: 99%

Liver Enzymes Elevation and Immune Reconstitution Among Treatment-Naïve HIV-Infected Patients Instituting Antiretroviral Therapy

Ofotokun

Smithson

et al. 2007

The American Journal of the Medical Sciences

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Objectives-Because liver enzymes elevation (LEE) complicates antiretroviral (ARV) therapy, and because the strongest risk factor for ARV-related LEE is HBV/HCV coinfection, it is speculated that ARV-related LEE may be a form of immune reconstitution disease. This study summarizes the relation between immune reconstitution, ARV-induced LEE, and HBV/HCV coinfection.Methods-Medical records of ARV-naïve HIV-infected patients initiating ARV were reviewed for hepatitis coinfection, LEE (grade ≥2 AST/ALT) and changes in CD4 T-cell counts over time in an urban HIV clinic. Risk factors for LEE were statistically evaluated, and changes in CD4 Tcell counts were estimated by a mixed-effects linear model. (OR = 6.44) and stavudine use (OR = 2.33). Nelfinavir use was protective (OR = 0.45). The mean rate of change in CD4 T-cell counts was higher in HBV/HCV coinfected subjects who developed LEE (99 cells/μL per month) compared with non-coinfected subjects who did not develop LEE (59 cells/μL per month, P = 0.03), non-coinfected subjects who developed LEE (36 cells/μL per month, P = 0.01), and coinfected subjects who did not develop LEE, 38% higher (62 cells/μL per month; P = 0.11) Conclusions-A more robust immune restoration was observed among HBV/HCV coinfected subjects who developed liver enzyme elevation after antiretroviral initiation compared with other groups. This finding suggests that ARV-related liver enzyme elevation may be related in part to immune reconstitution, as measured by changes in CD4 T-cell counts. Liver enzymes elevations (LEE) of varying degree have been reported with all classes of antiretroviral (ARV) drugs approved by the Food and Drug Administration for the treatment of HIV infection. [1][2][3][4][5][6][7][8][9][10][11][12] Severe cases of hepatotoxicity with fatal outcomes have been reported with ARV therapy and LEE is a common reason for highly active antiretroviral therapy (HAART) discontinuation in clinical practice. Results-Predictors of LEE included HBV/HCV coinfection KEY INDEXING TERMS NIH Public AccessThe mechanisms of ARV induced hepatic injury are still poorly understood. Mitochondrial toxicity resulting from nucleoside reverse transcriptase inhibitors (NRTIs) use and hypersensitivity reactions to non nucleoside reverse transcriptase inhibitors (NNRTIs) are speculated to be partly responsible. It is however unclear whether the protease inhibitors (PIs) directly induce liver injury. Although higher plasma concentrations for PIs have been reported among HIV infected subjects with hepatic impairment (often due to HBV/HCV coinfection), [13][14][15] there are no published data linking elevated serum PI levels to the development of LEE.In studies addressing ARV-associated liver injury, 30-50% of subjects were coinfected with either HBV and/or HCV, and the strongest independent risk factor for ARV-associated hepatotoxicity was coinfection with HBV and/or HCV. [16][17][18][19] Given this association, it is speculated that hepatic injury after ARV therapy in the presence of chronic viral h...

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“…Liver fibrosis and inflammation activity scores are lower and fibrosis rates slower in HIV-HCV coinfected subjects receiving combination antiretroviral therapy compared with those receiving no treatment [125]. Nevertheless, the incidence of liver toxicity and other adverse effects with this kind of treatment is generally higher in co-infected individuals (Table 4) [125][126][127][128][129][130][131][132][133][134][135][136][137].…”

Section: Hiv-hcv Co-infectionmentioning

confidence: 99%

Inflammation and Repair in Viral Hepatitis C

et al. 2007

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Hepatitis C viral infection (HCV) results in liver damage leading to inflammation and fibrosis of the liver and increasing rates of hepatic decompensation and hepatocellular carcinoma (HCC). However, the host's immune response and viral determinants of liver disease progression are poorly understood. This review will address the determinants of liver injury in chronic HCV infection and the risk factors leading to rapid disease progression. We aim to better understand the factors that distinguish a relatively benign course of HCV from one with progression to cirrhosis. We will accomplish this task by discussion of three topics: (1) the role of cytokines in the adaptive immune response against the HCV infection; (2) the progression of fibrosis; and (3) the risk factors of co-morbidity with alcohol and human immunodeficiency virus (HIV) in HCV-infected individuals. Despite recent improvements in treating HCV infection using pegylated interferon alpha (PEGIFN-alpha) and ribavirin, about half of individuals infected with some genotypes, for example genotypes 1 and 4, will not respond to treatment or cannot be treated because of contraindications. This review will also aim to describe the importance of IFN-alpha-based therapies in HCV infection, ways of monitoring them, and associated complications.

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Risk Factors for Hepatotoxicity in HIV-1--Infected Patients Receiving Ritonavir and Saquinavir with or without Stavudine

Cited by 87 publications

References 18 publications

Human Immunodeficiency Virus and Hepatitis C Virus Coinfection: Epidemiology, Natural History, Therapeutic Options and Clinical Management

Human Immunodeficiency Virus and Hepatitis C Virus Coinfection: Epidemiology, Natural History, Therapeutic Options and Clinical Management

Liver Enzymes Elevation and Immune Reconstitution Among Treatment-Naïve HIV-Infected Patients Instituting Antiretroviral Therapy

Inflammation and Repair in Viral Hepatitis C

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