Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Simvastatin, a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is a commonly used cholesterol-lowering agent. The long-term safety profile of simvastatin, established over 10 years of clinical use, is excellent. HMG-CoA reductase inhibitors block 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in cholesterol synthesis. However, other important nonsterol compounds, such as coenzyme Q10 (CoQ10), are also derived from the same synthetic pathway. CoQ10 is an essential carrier in the mitochondrial respiratory chain that participates in oxidative phosphorylation. Simvastatin and other HMG-CoA reductase inhibitors have been documented to lower serum concentrations of CoQ10. It has been suggested that the adverse effect of myopathy caused by HMG-CoA reductase inhibitors is due to CoQ10 deficiency in the tissue mitochondria. Documentation of this cause-and-effect phenomenon, however, has been lacking. We offer evidence that lactic acidosis may develop as a complication of simvastatin therapy. Our patient also manifested the well-known HMG-CoA reductase inhibitor drug toxicities of rhabdomyolysis and hepatitis. The occurrence of these known adverse events with lactic acidosis in our patient suggests that interference of the mitochondrial respiratory chain may play a role in the toxicity of this class of drugs.
 ...
PMID:Simvastatin-induced lactic acidosis: a rare adverse reaction? 1238 48

Cases of acute hepatitis induced by statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have been reported. A 65-year-old woman was admitted to our hospital because of fatigue, jaundice and altered liver function tests while on treatment with atorvastatin. On the basis of clinical, serological and histological findings, a score leading to a diagnosis of autoimmune hepatitis was reached. We suggest that atorvastatin may have revealed an underlying autoimmune hepatitis.
 ...
PMID:Autoimmune hepatitis revealed by atorvastatin. 1582 53

Consumption of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) inhibitors, known as statins, has been associated with elevated transaminase levels but rarely with acute hepatitis. Recently, several cases of acute hepatitis secondary to atorvastatin therapy have been published. We report the case of a 72-year-old man who developed acute cholestatic hepatitis after reinitiating treatment with atorvastatin at a higher dose than that previously prescribed. After treatment discontinuation, the patient made a full recovery, with normalization of clinical and laboratory findings.
 ...
PMID:[Acute cholestatic hepatitis after atorvastatin reintroduction]. 1639 26

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins are the most successful cardiovascular drugs of all time. By interrupting cholesterol synthesis in the liver, they activate hepatocyte low-density lipoprotein (LDL) receptors and produce consistent and predictable reductions in circulating LDL cholesterol with resulting reproducible improvements in cardiovascular risk by retarding or even regressing the march of atherosclerosis in all major arterial trees (coronary, cerebral and peripheral). Clinical trials have demonstrated their capacity not only to extend life, but also to improve its quality by retarding the progression of diabetes mellitus and chronic renal disease and by enhancing central and peripheral blood flow. They are amongst the most extensively investigated pharmaceutical agents in current clinical use. In cardiovascular end-point trials they have proven ability to help prevent that first and all important myocardial infarction and to reduce the likelihood of a recurrence in those who do succumb. They are equally effective in men and women of all ages and at all levels of cardiovascular risk, whether caused by hypercholesterolaemia, hypertension, cigarette smoking, diabetes mellitus or the metabolic syndrome. In addition, they improve the outlook of patients with familial hypercholesterolaemia whose LDL receptor function is deficient or defective; and all of this comes at minimal risk to the recipient. Their most important potential side effect is myopathy, which on very rare occasions may lead to rhabdomyolysis. Clinical experience shows that myopathic symptoms with creatine kinase levels raised to more than 10 times the upper limit of normal is seen in <0.01% of recipients and progression to fatal rhabdomyolysis because of renal failure has been recorded in only 0.15 cases per million prescriptions. Liver function abnormalities are also, rarely, seen. Again, the frequency of raised aspartate or alanine aminotransferase to more than three times the normal limit is encountered in no more than 1-2% of all treated patients and is completely reversible upon withdrawal of treatment. Progression to hepatitis or liver failure does not occur. This constellation of benefits with little side effect penalty has resulted in the comparison of statins with antibiotics in the global battle against cardiovascular disease.
 ...
PMID:Who should receive a statin these days? Lessons from recent clinical trials. 1696 68

We studied the effect of high-cholesterol diet and factors inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase on the development of liver fibrosis in C57Bl/6 mice with CCl4- or zymosan-induced hepatitis. Feeding a high-cholesterol diet led to a sharp increase in collagen content in the liver tissue of animals with CCl4-induced or zymosan-induced hepatitis. Atorvastatin and calcitriol produced less pronounced fibrogenic effects. Mevalonate partially prevented the development of cholesterol-induced fibrogenesis. High-cholesterol diet led to accumulation of oxysterols, cholesterol esters, and triglycerides and increased the expression of transforming growth factor-beta1 mRNA in liver tissue. Cholesterol-induced potentiation of the fibrogenic response is probably associated with transforming growth factor-beta1 induction due to accumulation of lipids and oxysterols in the liver.
 ...
PMID:Cholesterol-induced stimulation of postinflammatory liver fibrosis. 1911 May 52