didanosine and Liver-Diseases

Although women account for a substantial proportion of the global population infected with HIV, most clinical trials evaluating the safety and efficacy of specific antiretroviral therapy regimens have been preformed in predominantly male cohorts. Our knowledge of the sex differences associated with responses to these treatments is therefore limited. Potentially sex-specific influences, such as endogenous or exogenous hormones, could impact antiretroviral tolerance. Women also have different pharmacokinetic profiles for selected antiretrovirals compared with men. These factors could influence how women respond and react to antiretrovirals. Several observational studies have described a higher frequency of antiretroviral-related adverse effects among women compared with men. Women appear to be at an especially high risk for lactic acidosis, nevirapine-associated rashes and hepatotoxicity, and fat redistribution after highly active antiretroviral therapy exposure. Although a statistical association between antiretroviral toxicity and pregnancy has not been described, pregnancy may provide an additional influence on the toxicity of several antiretrovirals or antiretroviral combinations. Potential tolerability should be an important component in discussions of antiretroviral options among women.

Topics: Acidosis, Lactic; Anti-Retroviral Agents; Didanosine; Exanthema; Female; HIV Infections; Humans; Liver Diseases; Male; Nevirapine; Pregnancy; Pregnancy Complications, Infectious; Randomized Controlled Trials as Topic; Sex Factors; Stavudine

Topics: Anti-HIV Agents; Didanosine; HIV Infections; Humans; Liver Diseases; Mass Screening

Liver disease of unknown cause in HIV-infected persons is rare but increasingly being reported. Noncirrhotic portal hypertension is the main feature in a subset of these patients, in whom gastrointestinal bleeding is the most frequent and potentially life-threatening clinical presentation.. We describe the epidemiological, clinical and histological features of 12 HIV-positive individuals presenting with noncirrhotic portal hypertension.. An interpretable liver biopsy was available in 11, and cirrhosis was absent in all patients. Three patients had nodular regenerative hyperplasia of the liver, whereas eight showed morphological features previously described as 'hepatoportal sclerosis'. In four of the later group, a distinctive lesion was noted characterized by massive absence of portal veins along with focal fibrous obliteration of small portal veins. All patients had been treated with didanosine for long periods and inflammatory and thrombotic processes hypothetically triggered by this purine analogue in the hepatic microvasculature might result in this form of obliterative portal venopathy.. Noncirrhotic portal hypertension is a rare but unique entity presenting in HIV-positive individuals generally with prior prolonged exposure to didanosine, which shows an obliteration of portal veins as the most distinctive histological finding in the liver.

Topics: Adult; Anti-Retroviral Agents; Didanosine; Female; Gastrointestinal Hemorrhage; HIV Infections; Humans; Hypertension, Portal; Liver Diseases; Male; Middle Aged

Unexpected cases of severe liver disease in HIV-infected patients have been reported and an association with didanosine (ddI) has been suggested. Transient elastography (TE) might detect patients harbouring such a condition. Our objective was to search for the presence of abnormal liver stiffness (LS) in a cohort of HIV-infected patients without HBV or HCV coinfection and to assess the related factors.. A cross-sectional prospective study was conducted. LS was assessed by TE in 258 HIV-infected patients without HBV or HCV coinfection and with no evidence of acute hepatotoxicity or other origins of liver disease. LS values > or =7.2 kPa were considered abnormal. Multivariate analyses were performed to identify factors associated with abnormal LS.. Abnormal LS was observed in 29 (11.2%) patients. A total of 18 (16.4%) patients previously treated with ddI and 11 (7.4%) of those who never received ddI had LS values > or =7.2 kPa (P=0.02). The prevalence of abnormal LS was higher in patients previously treated with abacavir than in those who had never received abacavir (15 [21.7%] versus 14 [7.4%]; P=0.001). After multivariate analyses, age (adjusted odds ratio [AOR] 1.05, 95% confidence interval [CI] 1.002-1.1; P=0.004) alcohol intake >50 g/day (AOR 7.2, 95% CI 2.6-19.7; P<0.0001), CD4(+) T-cell count <200 cells/ml (AOR 3.4, 95% CI 1.06-11.007; P=0.03), time on ddI treatment (AOR 1.31, 95% CI 1.12-1.52; P=0.001) and previous abacavir exposure (AOR 3.01, 95% CI 1.18-7.67; P=0.02) were independently associated with abnormal LS.. The prevalence of abnormal LS in HIV-infected patients without HBV or HCV coinfection is substantial. Long-term exposure to ddI is a major cause of liver damage in these patients.

Topics: Adult; Anti-HIV Agents; Cross-Sectional Studies; Didanosine; Elasticity; Elasticity Imaging Techniques; Female; HIV Infections; Humans; Liver; Liver Diseases; Male; Middle Aged; Prevalence; Reverse Transcriptase Inhibitors; Risk Factors; Time Factors

Topics: Adult; Anti-Retroviral Agents; Didanosine; Esophageal and Gastric Varices; HIV Infections; HIV-1; Humans; Hyperplasia; Hypertension, Portal; Liver; Liver Diseases; Liver Regeneration; Middle Aged

Topics: Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Chemical and Drug Induced Liver Injury; Didanosine; Female; HIV Infections; HIV-1; Humans; Hyperplasia; Liver; Liver Diseases; Liver Regeneration; Middle Aged; Nevirapine; Zidovudine

Liver damage is frequently seen in HIV-positive subjects, often resulting from coinfection with hepatitis B and/or C viruses (HCV), alcohol abuse, etc. However, the etiology of liver disease still remains unknown for a small subset of individuals.. Cryptogenic liver disease (CLD) was defined as persistently elevated aminotransferases levels in the absence of hepatitis C and/or B viruses replication and of other common causes of liver disease (alcohol, medications, etc). We identified cases initially meeting this definition by examining all HIV-positive subjects attended during the year 2004 in 2 large HIV clinics in Spain. Their clinical charts were retrospectively reviewed, and their assessment completed when needed to rule out other less frequent causes of liver disease. The stage of liver fibrosis was assessed by liver biopsy and/or elastography. To assess which factors could be associated with CLD, HIV-positive controls were chosen and matched by age, gender, and CD4 status.. CLD was diagnosed in 17 (0.5%) out of 3200 HIV-positive patients. Their mean age was 43 years, 82.4% were male, and 76% had acquired HIV through homosexual relationships. The mean time from HIV diagnosis was >15 years, and all patients had been exposed to antiretroviral therapy. Nevirapine, stavudine, and didanosine were the drugs more frequently used by this subset of patients. None of them had liver function test abnormalities before initiating antiretroviral therapy. Advanced liver fibrosis (F3-F4 Metavir scores) was recognized in 10 (58.8%) individuals, and 9 (52.9%) had developed symptomatic liver complications, including ascites (8), portal thrombosis (6), variceal bleeding (5), and encephalopathy (2). In the case-control analysis, prolonged didanosine exposure was the only independent predictor of developing CLD in this population.. CLD is an uncommon condition in HIV-positive individuals and might be associated with prolonged didanosine exposure. It may evolve causing severe liver complications, with variceal bleeding and portal thrombosis being particularly frequent.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Ascites; Budd-Chiari Syndrome; Case-Control Studies; Didanosine; Female; Hemorrhage; HIV Infections; Humans; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Nevirapine; Spain; Stavudine; Time Factors; Transaminases

Topics: Acquired Immunodeficiency Syndrome; Adult; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Didanosine; Fatty Liver; Gilbert Disease; Humans; Liver Diseases; Male; Pancreatitis; Transaminases