Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two young human immunodeficiency virus (HIV)-infected patients, a 25-year-old woman and a 26-year-old man, consumed large amounts of germanium lactate citrate 18% as an "immunostimulant" for 9 months. The woman, who had stage II HIV infection, developed severe renal dysfunction (creatinine clearance, 7 mL/min/1.73 m2) and slight proteinuria (0.28 g/d) after ingesting 260 g germanium lactate citrate 18%. Hepatomegaly with liver dysfunction (SGOT, 102 U/L; gamma-glutamyl transferase (GT), 159 U/L) and lactic acidosis (plasma lactate, 7.3 mmol/L) developed simultaneously. Renal biopsy revealed tubulointerstitial nephropathy with vacuolar cell degeneration and periodic acid-Schiff-positive intracellular deposits mainly in distal tubules. Liver biopsy disclosed severe hepatic steatosis; liver function tests returned to normal within 5 weeks. Since renal failure persisted for 2 years after ingestion of germanium (creatinine clearance, 14 mL/min/1.73 m2; proteinuria, 0.84 g/d), a second renal biopsy was performed, which showed marked but focal distal tubular atrophy and slight interstitial fibrosis. The male patient, who had stage III HIV infection, had ingested the same compound; he presented with a creatinine clearance of 43 mL/min/m2 and proteinuria of 0.36 g/d. Renal biopsy disclosed tubulointerstitial changes similar to those found in the female patient. After 9 months off germanium, creatinine clearance remained unchanged. Neutron activation analysis of all biopsy specimens in both cases documented germanium concentrations 10 to 70 times normal in renal tissue and 140 times normal in liver tissue.
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PMID:Tubulointerstitial nephropathy persisting 20 months after discontinuation of chronic intake of germanium lactate citrate. 848 24

During a 6-and-a-half month period, we identified 10 human immunodeficiency virus (HIV)-infected men who were receiving antiretroviral regimens, including nucleoside analogues, and who developed unexplained reproducible hyperlactatemia in association with either abdominal symptoms or an unaccounted-for elevated alanine aminotransferase level, or both. After careful consideration of the possible etiologies, antiretrovirals were discontinued; lactate levels normalized in all patients. The estimated incidence of this phenomenon in our clinic was 20.9 cases per 1000 person-years of nucleoside analogue treatment. These observations extend the spectrum of the nucleoside analogue-induced lactic acidosis/hepatic steatosis syndrome by the identification of a subtle and perhaps earlier form, which has characteristic symptoms and laboratory abnormalities, and a favorable prognosis on discontinuation of antiretroviral therapy.
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PMID:Hyperlactatemia and hepatic abnormalities in 10 human immunodeficiency virus-infected patients receiving nucleoside analogue combination regimens. 1091 16

The lipodystrophies are rare disorders characterized by selective but variable loss of adipose tissue. Metabolic complications, such as insulin resistance, diabetes mellitus, hypertriglyceridemia, and fatty liver, increase in severity with the extent of fat loss. The lipodystrophies can be classified into two major types: familial and acquired. The main subtypes of familial lipodystrophies are congenital generalized lipodystrophy, an autosomal recessive disorder characterized by near complete lack of metabolically active adipose tissue from birth, and familial partial lipodystrophy, Dunnigan type, an autosomal dominant disorder characterized by loss of subcutaneous fat from the extremities at puberty and excess fat accumulation in the face and neck. Recently, a gene for congenital generalized lipodystrophy was localized to chromosome 9q34, and a gene for familial partial lipodystrophy, Dunnigan type, to chromosome 1q21-22; the genes, however, remain to be identified. Patients with acquired generalized lipodystrophy have generalized loss of subcutaneous fat, but those with acquired partial lipodystrophy have fat loss limited to the face, trunk, and upper extremities. Both varieties occur approximately three times more often in women, begin during childhood, and have underlying autoimmunity. Patients infected with the human immunodeficiency virus (HIV) who are receiving therapy that includes HIV-1 protease inhibitors have been reported to develop a lipodystrophy characterized by loss of subcutaneous fat from the extremities and face but excess fat deposition in the neck and trunk. Localized lipodystrophies can be caused by drugs, pressure, panniculitis, or unknown mechanisms. Current management of patients includes cosmetic surgery, diet, and drug therapy for control of diabetes and dyslipidemia.
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PMID:Lipodystrophies. 1112 8

The mechanism by which human immunodeficiency virus (HIV) protease inhibitor therapy adversely induces lipodystrophy and hyperlipidemia has not been defined. This study explored the mechanism associated with the adverse effects of the prototype protease inhibitor ritonavir in mice. Ritonavir treatment increased plasma triglyceride and cholesterol levels through increased fatty acid and cholesterol biosynthesis in adipose and liver. Ritonavir treatment also resulted in hepatic steatosis and hepatomegaly. These abnormalities, which were especially pronounced after feeding a Western type high fat diet, were due to ritonavir-induced accumulation of the activated forms of sterol regulatory binding protein (SREBP)-1 and -2 in the nucleus of liver and adipose, resulting in elevated expression of lipid metabolism genes. Interestingly, protease inhibitor treatment did not alter SREBP mRNA levels in these tissues. Thus, the adverse lipid abnormalities associated with protease inhibitor therapy are caused by the constitutive induction of lipid biosynthesis in liver and adipose tissues due to the accumulation of activated SREBP in the nucleus.
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PMID:HIV protease inhibitor induces fatty acid and sterol biosynthesis in liver and adipose tissues due to the accumulation of activated sterol regulatory element-binding proteins in the nucleus. 1154 71

Type B lactic acidosis is a rare and often fatal complication seen in patients receiving the nucleotide analogues zidovudine, stavudine, didanosine, and lamivudine. We describe a case of a 51-year-old human immunodeficiency virus (HIV)-positive woman receiving three nucleotide analogues. She presented with nausea, vomiting, abdominal pain, and hepatic steatosis. Signs of mitochondrial toxicity were demonstrated by diffuse myopathy and pancreatitis. Serum riboflavin levels documented a deficiency that was treated with 50 mg of riboflavin daily. Immediately after treatment, serum blood urea nitrogen level, lactic acid levels, and arterial blood pH all returned to normal values. Her signs of mitochondrial toxicity also improved after treatment with riboflavin. Successful reversal of the patient's type B lactic acidosis after riboflavin therapy suggested that riboflavin deficiency plays a direct role in the development of nucleotide analogue-induced lactic acidosis. It is impossible to predict which patients are predisposed to the development of this syndrome. For this reason, it may be important to screen and treat riboflavin deficiency in patients on nucleoside analogues.
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PMID:Emerging role of riboflavin in the treatment of nucleoside analogue-induced type B lactic acidosis. 1178 75

Steatosis or fatty liver in individuals with human immunodeficiency virus (HIV) may result from HIV itself, the use of nucleoside analogues, concurrent infection with hepatitis B or C, alcohol use, diabetes mellitus, obesity, or combinations of these factors. Nucleoside analogues have been the focus of increasing concern, because several fatal cases of severe macrosteatosis, lactic acidosis, and hepatomegaly have been linked to the use of nucleoside analogues. Other classes of antiretroviral drugs, as well as opportunistic infections, can also cause hepatic injury without steatosis. The additive effect of these different risk factors, especially in the presence of underlying hepatic steatosis, likely contributes to the increased prevalence of hepatic abnormalities among HIV-infected individuals. The conditions under which some patients rapidly progress to hepatic failure and/or cirrhosis need to be defined. This is a US government work. There are no restrictions on its use.
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PMID:The fatty liver in AIDS. 1194 34

Abnormalities of glucose regulation, including impaired glucose tolerance and insulin resistance, are often seen among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy. Insulin resistance in this population may result from antiviral medication directly impairing glucose uptake in the muscle, effects of HIV per se, or indirect effects, such as fat redistribution. Insulin resistance may increase the risk of coronary heart disease among this population of patients, in part by inhibiting normal thrombolysis. The optimal treatment for insulin resistance and impaired glucose intolerance in HIV-infected patients is not known, but preliminary studies have suggested that metformin, an insulin sensitizing agent, improves insulin sensitivity, blood pressure, and waist circumference. Initial studies of thiazolidinediones also suggest the potential utility of such agents to improve insulin sensitivity, decrease hepatic steatosis, and increase subcutaneous fat. Further studies are needed to determine the optimal treatment strategy for insulin resistance in this population.
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PMID:Mechanisms and strategies for insulin resistance in acquired immune deficiency syndrome. 1294 79

Nucleoside reverse transcriptase inhibitors (NRTIs), which are used for the treatment of human immunodeficiency virus (HIV) infection have been associated with a wide spectrum of clinical manifestations, including hepatic steatosis, lipodystrophy, myopathy, and lactic acidosis. Such adverse effects are postulated to result from the inhibition of mitochondrial DNA gamma polymerase, which causes the depletion of mitochondrial DNA and eventual the disruption of oxidative phosphorylation. Although cases of severe decompensated lactic acidosis are rare, this syndrome is associated with a high mortality rate. We report upon the first Korean case, of severe lactic acidosis in an acquired immunodeficiency syndrome (AIDS) patient receiving stavudine, an anti-HIV drug.
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PMID:A case of lactic acidosis caused by stavudine in an AIDS patient. 1505 48

The development of novel compounds that can effectively inhibit both wild type and the most consensus resistant strains of human immunodeficiency virus type 1 (HIV-1) is the primary focus in HIV disease management. Combination therapy, comprising at least three classes of drugs, has become the standard of care for acquired immunodeficiency syndrome (AIDS) or HIV-infected individuals. The drug cocktail can comprise all three classes of HIV inhibitors, including nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI). Due to their competitive mode of inhibition and requirement for metabolic activation, almost all NRTI drugs lack the virological potency of NNRTI or PI drugs. However, data from clinical trials indicate that sustained viral suppression could not be achieved with NRTI, NNRTI or PIs alone. Therefore, the NRTIs will remain essential components of highly active antiretroviral therapy (HAART) for the foreseeable future, because they enhance the virological potency of the regimen, they do not bind excessively to protein and most regimens are small pills/tablets given once a day. It has become apparent in recent years that the prolonged use of certain NRTIs exhibits adverse events as a class, limiting the length of time for which they can be safely used. Of major clinical concern is their association with the potentially fatal lactic acidaemia and hepatic steatosis. These class events, as well as individual drug effects, such as peripheral neuropathy, are linked to delayed mitochondrial destruction. In addition to toxicity, the development of resistance-conferring mutations against exposure to nucleoside analogs currently in use influences long-term therapeutic benefits. Of critical importance for the evaluation of new NRTIs are recent studies showing that the efficiency of discrimination or excision by pyrophosphorolysis in the presence of nucleotides of a given NRTI is a key determinant in the emergence of one or the other resistance pathway.
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PMID:Nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase. 1513 48

As the prevalence of the metabolic syndrome increases, 2 comorbid conditions--hepatic steatosis and human immunodeficiency virus (HIV) lipodystrophy--have become difficult clinical challenges. Dyslipidemia in patients with nonalcoholic fatty liver disease or nonalcoholic steatohepatitis may improve with use of statins, fibrates, niacin, and thiazolidinediones, but the data are presently very limited. HIV lipodystrophy is associated with a marked risk of coronary artery disease (CAD), and more aggressive management of the dyslipidemia is likely necessary to improve the prognosis.
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PMID:Management of dyslipidemia in patients with complicated metabolic syndrome. 1609 39


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