Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prevalence of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection ranges from nearly 30% to over 50%, depending on the population. Shared modes of transmission and the success of current antiretroviral regimens have contributed to the emergence of HCV as a significant pathogen in the HIV-positive population. HIV coinfection appears to worsen HCV infection, with studies showing more severe fibrosis, a higher frequency of cirrhosis, and increased deaths from liver disease. HIV coinfection may also increase the rate of maternal-fetal transmission of HCV. Similarly, studies suggest a more rapid progression to AIDS or death for HCV genotypes 1a and 1b than for other genotypes in HIV-infected patients with hemophilia. Highly active antiretroviral therapy (HAART), such as HIV protease inhibitors, has no effect on HCV infection and may transiently increase ALT, AST, and hepatitis C viral load. Hepatotoxicity associated with HAART may or may not be related to the presence of HCV and may depend on the specific agents used. Data suggest that treating chronic hepatitis C in HIV-co-infected patients can decrease fibrosis, increase T-cell responsiveness to HCV antigens, and decrease the rate of fatal hepatomas. Interferon alpha may provide sustained biochemical or virologic responses in HIV/HCV-coinfected patients. The combination of interferon-alpha and ribavirin may also be a treatment option but is more complex, and additional research is needed. Treating HCV infection in HIV/HCV-coinfected individuals may help lower the hepatitis C viral load and permit treatment with protease inhibitors.
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PMID:Hepatitis C virus and human immunodeficiency virus: clinical issues in coinfection. 1065 64

New treatment options for chronic hepatitis C (HCV) infection are examined. Studies show the efficacy of interferon alfa-2b in normalization of serum alanine aminotransferase and histological improvement in necroinflammatory liver disease. However, 70 to 80 percent experiencing normalization usually relapse within 1 year after treatment. Ten to 20 percent will have a sustained response lasting at least 3 years. Ideas for improving treatment response include longer initial treatment regimens, increasing dosages of interferon alpha, or adding another agent to interferon alpha. Based on encouraging study results, the interferon/ribavirin combination has been approved by the Food and Drug Administration (FDA) in HCV patients relapsing following interferon alpha monotherapy. So far the FDA has approved interferon alfa-2b, interferon alfa-2a, alfacon-1, and interferon alfa-2b/ribavirin as treatments for HCV; ribavirin alone is not effective against HCV infection. Other drugs are being tested with interferon alpha but have not generated enough substantive data. Thymosin, an immune modulator that enhances the body's production of interferon and interleukin rather than attacking HCV directly, is also being investigated. Oral dosing of interferon is in clinical trials for hepatitis B, and the results may be applicable to HCV. Alternative therapies are gaining wider interest such as using milk thistle for liver regeneration or using licorice root for quelling liver inflammation. As for transmission risk, there is little evidence supporting sexual activity as a major risk factor, however, some risk is reported with anal intercourse, sex during the menstrual cycles, and years of cohabitation with an infected partner.
J Int Assoc Physicians AIDS Care 1998 Jul
PMID:Can science meet the challenges of the HCV pandemic: new treatment options for chronic hepatitis C. 1136 38

HIV/AIDS is a multifactorial and multi-step disease. No single treatment against AIDS can save a patient. Our last report showed that vitamin A, vitamin E and beta-carotene were decreased while malondialdehyde (MDA) was increased. This report aims to evaluate biochemical and hematological parameters in HIV/AIDS patients in Chiang Mai, Thailand by holistic approaches. Sera from HIV/AIDS patients were examined for sugar, cholesterol, uric acid, total protein, albumin, urea, creatinine, AST, ALT, ALP, total/direct bilirubin, vitamin E, MDA, total antioxidant capacity (TAC), beta-carotene, complete blood cell counts, platelet count, CD4 count, prothrombin time, partial prothrombin time and soluble Fas (sFas). The results found that sFas levels in sera prior to holistic approach was not different from reference values and not significantly correlate with CD4 and absolute lymphocyte count. sFas could not serve as putative marker for CD4 destruction. After 3 months CD4 count, MDA, vitamin E and TAC did not change statistically. This approach had no effect on liver and kidney functions, red blood cell, white blood cell, platelet counts, and blood clotting factors. This presentation may be some alternative approaches to combat HIV infections and AIDS, leading to stabilize or extend survival time which should further be elucidated.
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PMID:Biochemical and hematological manifestations of HIV/AIDS in Chiang Mai, Thailand. 1194 6

Shared epidemiological risks have resulted in HIV-infected populations having a high prevalence of hepatitis B virus (HBV) co-infection. Several prospective studies have investigated the impact of HBV co-infection on HIV disease progression; most of them were negative. On the contrary, there is evidence that HIV may modify the natural history of HBV infection. HIV positive subjects have higher rates of HBV chronification, higher HBV replication, lower ALT levels and lower rates of seroconversion to anti-HBe and anti-HBs. The impact of HIV co-infection on the outcome of HBV infection is still controversial, even if some studies have shown an accelerated progression towards decompensated cirrhosis in HIV co-infected subjects. HBV co-infection is a risk factor for severe hepatotoxicity during HAART. Vaccination for HBV is mandatory in nonimmune HIV subjects, however its efficacy in immunosuppressed patients is still controversial. HIV co-infection decreases the effectiveness of Interferon in the treatment of HBV infection. Because of its activity against both HBV and HIV, lamivudine is used in HIV-HBV co-infected patients at doses of 300 mg/daily and as part of an antiretroviral regimen, but the rate of sustained response is poor and HBV strains with mutations associated with lamivudine resistance occur at a rate of 20% per year. Trials of new drugs with activity against HBV, some of them with activity also against HIV, and some of them without cross-resistance with lamivudine, are now underway. Highly Active Anti-Hepatitis B Therapy will probably soon come of age.
AIDS Rev
PMID:Hepatitis B virus co-infection in human immunodeficiency virus-infected subjects. 1199 81

The use of all potent drugs is associated with toxicities and antiretroviral (ARV) drugs are no exception. Antiretroviral therapy-associated hepatic toxicity is of increasing concern in the management of patients with HIV/AIDS. Liver toxicity has been reported in some HIV-infected patients being treated with drugs from all of these classes of ARV drugs: protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Although the majority of cases involve asymptomatic elevations of liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), severe, and, in a minority of cases, life threatening, liver disease has been reported in patients treated with ARV drugs. The exact causes of elevated plasma levels of AST and ALT are complex and, in many cases, obscure. The combination of viral hepatic disease, drugs that act adversely directly on the liver and drugs that act on other systems of the body which in turn, adversely affect the liver, can result in hepatic toxicity. Such toxicity may be inappropriately attributed solely to the direct effect of a drug. Knowledge of the possible causes of liver toxicity, and ways to avoid it, should reduce the risk of developing hepatotoxicity. The physician's task is to prevent the development of liver toxicity, e.g., by choosing appropriate therapeutic regimens and by careful management of the patient. This involves frequent monitoring of the patient, both clinically and by utilizing liver function tests on a regular basis. If signs and symptoms of liver disease do develop, prompt and expert management is essential. This review discusses the influence of a number of factors on hepatic toxicity including viral hepatitis, insulin resistance and the specific ARV drugs used in the treatment of patients with HIV/AIDS.
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PMID:Managing antiretroviral-associated liver disease. 1456 56

We examined the risk and determinants of developing severe liver toxicity in 108 HIV-infected patients showing adherence to nevirapine- and efavirenz-containing regimens. Between January 1997 and December 2000, 70 patients were treated with nevirapine- and 38 patients with efavirenz-containing regimens, for a median period of 127 days (interquartile range 65-240). Severe liver toxicity was defined as grade 3-4 elevations (>5 x upper limit of normal) of aminotransferases AST or ALT. A total of 22 (20%) patients showed severe liver toxicity, 17 of them were treated with nevirapine- and five with efavirenz-containing regimens (relative risk [RR]: 1.85, 95% confidence intervals [CIs] 0.74-4.61; P=not significant). Multivariate analysis showed the association of severe liver toxicity with hepatitis C antibody positive (RR 7.64; 95% CI: 1.48-39.52; P=0.01), nevirapine- or efavirenz-containing regimens combined with a protease inhibitor (RR: 3.07, 95% CI: 1.01-9.32, P=0.04) and alcohol intake greater than 40 g per day (RR: 3.09, 95% CI: 1.27-7.54, P=0.01). These findings have potential implications for selecting and monitoring antiretroviral therapy in HIV-infected patients with hepatitis C virus coinfection and for avoiding alcohol intake during antiretroviral therapy.
Int J STD AIDS 2003 Nov
PMID:Risk and determinants of developing severe liver toxicity during therapy with nevirapine-and efavirenz-containing regimens in HIV-infected patients. 1462 43

HIV caregivers face many challenges following initiation of ART. The development of jaundice is uncommon but worrisome. In this case, two distinct and contrasting episodes of jaundice were observed. In the first instance, isolated elevation of the indirect bilirubin without elevation of the alkaline phosphatase was noted. The normal PT and serum aminotransferase levels indicate the absence of intrinsic liver dysfunction. Elevations in the indirect bilirubin may result from either impaired uptake/conjugation or excess production. The latter, usually from acquired hemolysis, may be a complication of an occult NHL. A work-up for this AIDS-related malignancy was not initiated since the caregivers recognized jaundice as a complication of IDV, which inhibits UDP-glucuronyl transferase and produces a Gilbert's-like syndrome. Physicians can expect to encounter this syndrome even more frequently with ATV. Experienced patients given RTV-boosted ATV have experienced elevations of unconjugated hyper-bilirubinemia in up to 45 percent of cases in clinical trials. However, such elevations do not reflect liver dysfunction and symptomatic jaundice requiring dosage reduction that occurred infrequently (7 to 8 percent of study patients). Counseling patients about this syndrome may promote adherence and prevent self-directed interruptions of ATV that compromise efficacy. The second case of jaundice provides a more formidable diagnostic challenge. The triad of LFT abnormalities (mild elevation of aminotransferases, normal PT, and marked cholestatic jaundice) implies an acute process that is mildly toxic to hepatocytes without affecting their synthetic function. The subacute nature of the patient's cholestatic jaundice suggests either intrahepatic infiltrative disease of the liver or extrahepatic obstruction of the biliary tree, most likely due to the patient's relatively modest level of pain and lack of fever. Despite LFT abnormalities occurring 17 months after a switch in his ART, cumulative drug-related toxicities must still be considered. Ritonavir can produce significant elevations in the AST/ALT, especially with pre-existing chronic liver disease as with hepatitis C virus coinfection. The NRTIs can produce hepatic steatosis, a result of mitochondrial toxicity and impaired fatty acid oxidation. However, jaundice and cholestasis are not typical of the latter syndrome. With a negative contrast CT that excludes parenchymal liver disease, investigation of the biliary tree to assess the presence of AIDS-related cholangitis was the next step. Performing a sphincterotomy or stent placement, and obtaining brushings or biopsy specimens to determine the extent of extrahepatic obstruction may help define a pathogen and be life-saving. The negative results of the ERCP justify the final diagnostic step, a liver biopsy to evaluate microscopic infiltrative disease that might not have been detected on contrast abdominal CT. Examples might include granulomatous disease (MAC), fungal etiologies (histoplasmosis), carcinomatosis (lymphoma, hepatoma, cholangiocarcinoma), and microvascular disease (bacillary angiomatosis). The failure to observe granulomatous inflammation in the liver does not exclude MAC infection, as MAC may involve other peri-aortic or mesenteric lymph nodes. This form of IRIS is unlikely given the abdominal CT findings, lack of systemic complaints, and extended persistence of liver aminotransferases. The nonspecific results of the liver biopsy are a common outcome in advanced AIDS patients with elevated alkaline phosphatase levels. Despite not having identified a pathogen, the biopsy establishes chronic liver disease and prompts re-evaluation and change of treatment to NFV. The subsequent normalization of the patient's aminotransferase levels suggests a prior adverse effect of LPV/r in the setting of unexplained, chronic liver disease. Most importantly, this case highlights the importance of HIV caregivers to review ART for safety when noting chronic liver dysfunction. Patients need to be counseled to minimize acetaminophen use, to consume alcohol in moderation, and to avoid behavior with risk for hepatitis C. Finally, all HIV patients should receive appropriate vaccination against hepatitis A and B if serology shows lack of protective immunity.
J Int Assoc Physicians AIDS Care (Chic)
PMID:Clinical vignette in antiretroviral therapy: jaundice. 1498 14

The declining incidence of AIDS-related opportunistic diseases among people with HIV infection has shifted the focus of clinical management to prevention and treatment of comorbidities such as chronic liver disease. The increased risk of hepatitis C virus (HCV)-related advanced liver disease in people with HIV infection makes early HCV diagnosis a priority. To assess HCV prevalence and predictors of HIV/HCV coinfection, we have conducted a retrospective analysis of people enrolled in the CAESAR (Canada, Australia, Europe, South Africa) study, a multinational randomized placebo-controlled study of the addition of lamivudine to background antiretroviral therapy. The impact of HCV on HIV disease progression was also examined. Anti-HCV antibody testing on 1649 CAESAR study participants demonstrated a HIV/HCV coinfection prevalence of 16.1%, which varied from 1.9% in South Africa to 48.6% in Italy. The strongest predictor of HIV/HCV coinfection was HIV exposure category (P<0.0001), with odds ratios (ORs) compared to homosexual as follows: injecting drug use (IDU), 365 [95% confidence interval (CI): 179-742]; transfusion or blood products, 32.2 (95% CI: 15.2-67.6); homosexual and IDU, 22.9 (95% CI: 8.5-62.1). The prevalence of HIV/HCV was low (3.7%) among homosexual men without reported IDU. Other predictors of HIV/HCV coinfection were alanine aminotransferase (ALT), country of residence, ethnicity and stage of HIV disease. A history of IDU or ALT > or =40 U/L at baseline had a positive predictive value (PPV) of 35%, negative predictive value (NPV) of 96%, sensitivity of 82% and specificity of 71% for HIV/HCV coinfection. HIV disease progression was similar in HIV monoinfected and HIV/HCV coinfected patients. People with HIV and a history of IDU or elevated liver function tests should be targeted for HCV testing. The low prevalence of HIV/HCV coinfection among homosexual men without a history of IDU suggests low efficiency of sexual HCV transmission.
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PMID:HIV and hepatitis C coinfection within the CAESAR study. 1513 84

Abnormal liver function tests are frequently observed in HIV-infected individuals receiving nevirapine (NVP). Here we investigate the relationship between total and unbound plasma concentrations of NVP and the liver enzymes alanine aminotransferase (ALT) and gamma-glutamyl transferase (gammaGT). HIV-infected individuals [n = 85, 22 female, 34 hepatitis C or B virus (HCV or HBV(+))] receiving NVP (200 mg bd; median duration 66 weeks, range 3-189) and two nucleoside reverse transcriptase inhibitors (NRTIs) were enrolled into this study. Blood samples were taken at C(trough) (12 hr postdose) for measurement of NVP and liver function tests (ALT and gammaGT). Plasma protein bound and unbound drug was separated using ultrafiltration and NVP concentrations quantified using HPLC-MS/MS. A linear relationship was observed between total and unbound NVP C(trough) (r(2) = 0.77, p < 0.0001). Patients with elevated ALT (>37 IU/liter; n = 31) had higher NVP unbound C(trough) than those with ALT within the normal range (median 2268 vs. 1694 ng/ml, p = 0.04) but there was no difference in total C(trough). Logistic regression revealed no association between higher NVP C(trough) and ALT elevations. Significantly higher NVP total and unbound C(trough) were observed in patients with increased gammaGT (>40 IU/liter; n = 63; total 6747 vs. 4530 ng/ml, p = 0.001; unbound 2113 vs. 1557 ng/ml, p = 0.03). Significantly higher unbound NVP C(trough) was observed in HCV/HBV(+) (median 2275 vs. 1726 ng/ml, p = 0.02) and on bivariate analysis, higher NVP C(trough) was associated with HCV/HBV coinfection (chi(2) = 4.228; p = 0.04). Overall we found no strong association between NVP concentrations and hepatotoxicity. Although in this study NVP was well tolerated in HCV/HBV coinfected patients, higher plasma concentrations were observed.
AIDS Res Hum Retroviruses 2004 Jul
PMID:The relationship between nevirapine plasma concentrations and abnormal liver function tests. 1530 17

In order to evaluate the occurrence of hepatotoxicity in patients treated with antiretroviral therapy (ART) who switch protease inhibitor (PI), and the role of viral hepatitis in its development, we performed a retrospective study on 182 HIV patients treated with ART for 24 months. The presence of hepatitis viruses and alanine transaminase levels were evaluated. Hepatotoxicity developed in a low number of subjects without co-infection, but was significantly higher in co-infected patients (14/51 versus 62/131, P = 0.01). Ritonavir was associated with higher rates of severe hepatotoxicity in the co-infected group. Patients presenting any problems related to ART, including the development of hepatotoxicity, continued therapy by switching PI. The occurrence of hepatotoxicity with second/third choice PIs, including ritonavir, remained stable. Our results suggest that switching PI does not increase the occurrence of drug-related liver toxicity.
Int J STD AIDS 2005 Feb
PMID:Development of hepatotoxicity in HIV patients switching at least one protease inhibitor. 1582 50


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