Incidence Of Severe Hepatotoxicity Research Articles

Hepatotoxicity from first line antiretroviral therapy: an experience from a resource limited setting.

Highly active antiretroviral therapy (HAART) has been associated with liver toxicity. The role of monitoring for liver toxicity has not been well studied in resource-limited settings (RLS). To determine the background prevalence and incidence of liver injury and describe the associated signs and symptoms of acute hepatitis after initiating HAART; and to determine the role of liver enzyme tests in monitoring hepatotoxicity. In this prospective study, in Mulago Hospital AIDS Clinics, we consecutively enrolled adult patients initiated on one of three first line HAART regimens [Stavudine (d4T)-Lamivudine (3TC) and nevirapine (NVP); Zidovudine (AZT)-3TC and Efavirenz (EFV) or d4T-3TC-EFV]. We monitored ALT (alanine aminotransferase) and clinical evidence of acute hepatitis at baseline, 2(nd), 6(th), 10(th) and 14(th) week of therapy. Two hundred and forty HIV-positive HAART- naïve patients were enrolled in the study. The baseline prevalence of transaminitis was 1.7% with an incidence of 4.2% at 14 weeks. Grade 3-4 hepatotoxicity was documented in 1.3%. Jaundice was seen in grade 2-4 ALT elevations. Being on concurrent HAART and antituberculous drugs was associated with grade 2-4 toxicity compared to those who were only on HAART [OR; 16.0 (95% CI; 2.4-104.2)]. Incidence of severe hepatotoxicity within three months of first-line antiretroviral therapy was low, suggesting that routine measurement of transaminases may not be necessary in all patients initiating HAART in RLS. Routine measurement may be important in following patients on HAART and concurrent TB treatment as well as those with jaundice to avoid missing hepatotoxicity.

Incidence of Severe Hepatotoxicity Related to Antiretroviral Therapy in HIV/HCV Coinfected Patients

Introduction. Hepatotoxicity is a concern in HIV/hepatitis C virus (HCV) coinfected patients due to their underlying liver disease. This study assessed the incidence of hepatotoxicity in HIV/HCV co-infected patients in two outpatient infectious diseases clinics. Methods. HIV/HCV co-infected adults were included in this retrospective study if they were PI or NNRTI naïve at their first clinic visit and were initiated on an NNRTI- and/or PI-based antiretroviral regimen. Patients were excluded if they had active or chronic hepatitis B virus (HBV). The primary objective was to determine the overall incidence of severe hepatotoxicity. Results. Fifty-six of the 544 patients identified met inclusion criteria. The incidence of severe hepatotoxicity was 10.7% (6/56 patients). Severe hepatotoxicity occurred with efavirenz (N = 2), nevirapine (N = 1), indinavir (N = 1), nelfinavir (N = 1), and saquinavir/ritonavir (N = 1). Conclusion. The incidence of severe hepatotoxicity appears to be low in this retrospective analysis of HIV/HCV co-infected patients receiving a PI-and/or NNRTI-based regimen.

Can we prevent fatalities due to antituberculous drugs?

Objective: To assess the incidence and risk factors for liver toxicity in patients on anti-tuberculosis treatment. Method: All patients with a diagnosis of tuberculosis, who were to receive ATT during the study period, were included in the present study for prospective periodic laboratory monitoring for the development of hepatotoxicity. Results: Of the 352 patients studied, 61 patients (17%) had elevated hepatic transaminases value after starting antituberculous therapy (ATT), 36 grade 1 (10%), 7 grade 2 (2%), 12 grade 3 (3.4%), and 6 patients grade 4 (1.7%). The incidence of severe hepatotoxicity (grades 3, 4) among treated patients was 5.1% (18 patients). The mean duration of treatment before onset of hepatotoxicity was 36 days. Although the majority of patients developed hepatic dysfunction within the first 2 months of treatment, significant hepatotoxicity (grades 3, 4) did occur at a later date in some patients (28%). Univariate analysis did not show any significant relationship between age, sex, and ethnic origin with hepatotoxicity in this study. The only significant risk factor was coexisting hepatitis B or C. None of our patients died from complications of liver-related illness attributed to anti-TB drugs.

Atazanavir en la coinfección por VIH y virus de la hepatitis B y/o C

Atazanavir is a protease inhibitor indicated, in combination with other antiretrovirals, as an initial treatment of HIV infection or in previously treated patients. Antiretroviral treatment based on atazanavir has been associated with a low incidence of hepatotoxicity, both in Clinical Trials as well as in cohort studies. However, the finding of hyperbilirubinaemia has been common in these studies, although it usually does not involve withdrawing the treatment. In patients co-infected with hepatitis B or C, the level of virological response to does not appear to be affected and the incidence of adverse effects, except the higher incidence of hepatotoxicity, is no higher than in non-coinfected subjects. The incidence of severe hepatotoxicity (grade 3-4) in patients coinfected by HIV and HVC who receive drug combinations that contain atazanavir is 6%. Atazanavir has a favourable tolerance and safety profile in patients coinfected with hepatitis virus even in the presence of significant fibrosis. The lower association of atazanavir with the development of insulin resistance, a fact that has been associated with increasing the progression to hepatic fibrosis and lower treatment response rates, could be an added benefit of the use atazanavir in coinfected patients and could serve as an additional argument for its use in these patients.

Risk of severe hepatotoxicity associated with antiretroviral therapy in the HIV-NAT Cohort, Thailand, 1996-2001.

To examine rates and predictors of severe hepatotoxicity with combination antiretroviral therapy in a developing country setting: the eight HIV-NAT randomized controlled trials in Thailand. All patients (n = 692) received at least two nucleoside reverse transcriptase inhibitors; 215 also received a non-nucleoside reverse transcriptase inhibitor (NNRTI) and 135 also received a protease inhibitor. Severe hepatotoxicity was defined as an increase in alanine aminotransferase (ALT) level to five times the upper limit of normal and an increase of at least 100 U/l from baseline. Liver function tests were available at baseline and weeks 4, 8, 12, 24, 36 and 48. Hepatitis B virus (HBV) and hepatitis C virus (HCV) testing was performed on stored serum. Mean age was 32.3 years; 52% were male, 11% had Centers for Disease Control and Prevention category C HIV disease at baseline, and 22% had received prior antiretroviral therapy. Prevalence of HBV, HCV and HBV/HCV coinfection was 8.7%, 7.2%, and 0.4%, respectively. Incidence of severe hepatotoxicity was 6.1/100 person-years [95% confidence interval (CI), 4.3-8.3/100]. In multivariate analysis, predictors of severe hepatotoxicity were HBV or HCV coinfection, and NNRTI-containing therapy. Incidence of severe hepatotoxicity was particularly high among patients receiving nevaripine (18.5/100 person-years; 95% CI, 11.6-27.8) and nevirapine/efavirenz (44.4/100 person-years; 95% CI, 12.1-113.7). Incidence and risk factors for severe hepatotoxicity appear similar among these Thai patients to those in other racial groups. Development of standardized antiretroviral therapy regimens for developing country settings should consider potential toxicity and capabilities for monitoring of toxicity.

Methotrexate hepatotoxicity in psoriatics: report of 104 patients from Nova Scotia, with analysis of risks from obesity, diabetes and alcohol consumption during long term follow-up.

Methotrexate (MTX) hepatotoxicity in psoriatic patients is well recognized, but there are discrepancies in the reported incidence and associated risk factors. This retrospective study describes 104 Nova Scotian patients with psoriasis seen between 1979 and 1990. Patients received MTX over one to 11 years (mean 3.38), with baseline and annual follow-up liver biopsies. Clinical data were obtained by chart review. Statistical analysis evaluated the risks associated with obesity, diabetes, alcohol consumption and duration of therapy, with the histological grade of liver biopsies. Of the 104 patients, 35 were obese, 10 were diabetic and 37 occasionally consumed alcohol. At the end of the study, 21 patients had developed severe hepatic fibrosis (grade IIIB), and three developed liver cirrhosis (grade IV). Significant risk of severe hepatotoxicity is related to diabetes (P = 0.02) but not to obesity (P = 0.12) or alcohol consumption (P = 0.12). All patients with cirrhosis took MTX for two years in standard doses of 20 to 25 mg/week. In this first Canadian study evaluating MTX hepatotoxicity in psoriatics, the incidence of severe hepatotoxicity is high: 23.1% (24 of 104 patients). This study shows that diabetic patients are particularly at increased risk of MTX hepatotoxicity. Occasional alcohol consumption is not associated with increased risk. Three patients who developed cirrhosis over two years of standard MTX therapy may represent a subset of psoriatics with increased hepatic susceptibility to MTX. Another three patients whose severe hepatic fibrosis had regressed upon discontinuation of MTX, but who developed accelerated recurrence of the severe hepatic fibrosis upon resumption of MTX therapy, also suggest the possibility of unusual sensitivity to the drug. These cases emphasize the need for continuing surveillance, with regular liver biopsies, of psoriatic patients on MTX.