Elevated ALT in Antiretroviral-Naive African Patients
Elevated ALT in Antiretroviral-Naive African Patients
Background Alanine aminotransferase (ALT) is commonly used to measure liver injury in resource-limited settings. Elevations in ALT are predictive of increased mortality from liver disease and may influence the choice of first-line antiretroviral therapy (ART).
Methods A cross-sectional analysis of the prevalence and predictors of elevated ALT (defined as > 40 IU/L) was conducted. ART-naïve, HIV-infected adults with a baseline ALT measurement who were enrolled in any of the 18 HIV Care and Treatment Clinics in Dar es Salaam, Tanzania between November 2004 and December 2009 were included in the study. Median values were calculated and log-binomial regression models were used to examine predictors of elevated ALT.
Results During the study period, 41 891 adults had a baseline ALT measurement performed. The prevalence of ALT > 40, > 120 and > 200 IU/L was 13, 1 and 0.3%, respectively. In multivariate analyses, male sex, CD4 T lymphocyte count < 200 cells/μL and higher World Health Organization (WHO) clinical stages were associated with a significantly higher risk of ALT > 40 IU/L (all P < 0.01). Hypertryglyceridaemia, hyperglycaemia and hepatitis B virus (HBV) coinfection (positive for HBV surface antigen) were significantly associated with a higher risk of elevated ALT. Pregnancy, anaemia, low-density lipoprotein cholesterol > 130 mg/dL and current tuberculosis treatment were associated with a significantly reduced risk for elevated ALT.
Conclusions In this HIV-infected, ART-naïve Tanzanian population, extreme elevations in ALT were infrequent but minor elevations were not uncommon. Antiretrovirals with potentially hepatotoxic side effects should be initiated with caution in male patients, and in patients with HBV coinfection, advanced immunosuppression and components of the metabolic syndrome.
In 2008, an estimated 22.4 million people were living with HIV in sub-Saharan Africa (SSA). As a result of considerable efforts by national governments and international organizations in scaling up HIV Care and Treatment services in SSA, approximately 3 million HIV-infected patients were receiving antiretroviral therapy (ART) by the end of 2008. Since the large scale rollout of ART, significant declines in HIV-related morbidity and mortality have been observed. Following improved life expectancy with ART, non-AIDS-defining diseases are now emerging as leading causes of death in HIV-infected populations, with liver disease as the most frequent cause of death in developed countries. Similar changes in patterns of mortality can be expected to occur in SSA as access to ART improves.
Alanine aminotransferase (ALT) is a liver enzyme commonly used to measure liver disease in resource-limited settings. Elevated ALT is a highly specific indicator for liver injury and has been shown to be associated with deaths from liver disease in non-HIV-infected populations. As it is often the only marker used to monitor liver disease in HIV-infected individuals in resource-limited settings, understanding the prevalence and risks associated with elevations in ALT in these settings is important. Liver enzyme elevation is common in HIV-infected patients in SSA and various risk factors have been described, mainly in Europe and North America, including: male sex, HIV itself, viral hepatitis, most antiretrovirals, anti-tuberculosis and lipid-lowering drugs, alcohol, and metabolic syndrome.
In SSA, few studies have examined the prevalence of elevated ALT and risk factors associated with elevations in ALT in HIV-infected individuals, particularly mild elevations of ALT or ALT elevations in the absence of ART exposure. Such studies are necessary as HIV-infected individuals may be at much higher risk of liver injury in SSA because of additional competing risks of liver disease specific to these settings, including the presence of more advanced immunosuppression, coinfections and exposure to aflatoxins. In addition, elevations prior to ART initiation may impact responses to treatment with ART.
In this study, we report the prevalence of elevated ALT levels and associated risk factors in a cohort of ART-naïve HIV-infected patients enrolled in a large urban HIV Care and Treatment program in Dar es Salaam, Tanzania.
Abstract and Introduction
Abstract
Background Alanine aminotransferase (ALT) is commonly used to measure liver injury in resource-limited settings. Elevations in ALT are predictive of increased mortality from liver disease and may influence the choice of first-line antiretroviral therapy (ART).
Methods A cross-sectional analysis of the prevalence and predictors of elevated ALT (defined as > 40 IU/L) was conducted. ART-naïve, HIV-infected adults with a baseline ALT measurement who were enrolled in any of the 18 HIV Care and Treatment Clinics in Dar es Salaam, Tanzania between November 2004 and December 2009 were included in the study. Median values were calculated and log-binomial regression models were used to examine predictors of elevated ALT.
Results During the study period, 41 891 adults had a baseline ALT measurement performed. The prevalence of ALT > 40, > 120 and > 200 IU/L was 13, 1 and 0.3%, respectively. In multivariate analyses, male sex, CD4 T lymphocyte count < 200 cells/μL and higher World Health Organization (WHO) clinical stages were associated with a significantly higher risk of ALT > 40 IU/L (all P < 0.01). Hypertryglyceridaemia, hyperglycaemia and hepatitis B virus (HBV) coinfection (positive for HBV surface antigen) were significantly associated with a higher risk of elevated ALT. Pregnancy, anaemia, low-density lipoprotein cholesterol > 130 mg/dL and current tuberculosis treatment were associated with a significantly reduced risk for elevated ALT.
Conclusions In this HIV-infected, ART-naïve Tanzanian population, extreme elevations in ALT were infrequent but minor elevations were not uncommon. Antiretrovirals with potentially hepatotoxic side effects should be initiated with caution in male patients, and in patients with HBV coinfection, advanced immunosuppression and components of the metabolic syndrome.
Introduction
In 2008, an estimated 22.4 million people were living with HIV in sub-Saharan Africa (SSA). As a result of considerable efforts by national governments and international organizations in scaling up HIV Care and Treatment services in SSA, approximately 3 million HIV-infected patients were receiving antiretroviral therapy (ART) by the end of 2008. Since the large scale rollout of ART, significant declines in HIV-related morbidity and mortality have been observed. Following improved life expectancy with ART, non-AIDS-defining diseases are now emerging as leading causes of death in HIV-infected populations, with liver disease as the most frequent cause of death in developed countries. Similar changes in patterns of mortality can be expected to occur in SSA as access to ART improves.
Alanine aminotransferase (ALT) is a liver enzyme commonly used to measure liver disease in resource-limited settings. Elevated ALT is a highly specific indicator for liver injury and has been shown to be associated with deaths from liver disease in non-HIV-infected populations. As it is often the only marker used to monitor liver disease in HIV-infected individuals in resource-limited settings, understanding the prevalence and risks associated with elevations in ALT in these settings is important. Liver enzyme elevation is common in HIV-infected patients in SSA and various risk factors have been described, mainly in Europe and North America, including: male sex, HIV itself, viral hepatitis, most antiretrovirals, anti-tuberculosis and lipid-lowering drugs, alcohol, and metabolic syndrome.
In SSA, few studies have examined the prevalence of elevated ALT and risk factors associated with elevations in ALT in HIV-infected individuals, particularly mild elevations of ALT or ALT elevations in the absence of ART exposure. Such studies are necessary as HIV-infected individuals may be at much higher risk of liver injury in SSA because of additional competing risks of liver disease specific to these settings, including the presence of more advanced immunosuppression, coinfections and exposure to aflatoxins. In addition, elevations prior to ART initiation may impact responses to treatment with ART.
In this study, we report the prevalence of elevated ALT levels and associated risk factors in a cohort of ART-naïve HIV-infected patients enrolled in a large urban HIV Care and Treatment program in Dar es Salaam, Tanzania.
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