Pdf hepatotoxicity associated with statins researchgate. Among the statininduced hepatitis cases, atorvastatin and simvastatin showed more incidences of hepatic damage bjornsson, 2017. Statin therapy is associated with reduced incidence of hypoxic hepatitis in critically ill patients. Although significant statininduced idiosyncratic liver injury is rare, as refected by the fdas relabeling of recommended liver function test monitoring with statins, 7 physicians should be aware of its occurrence. The risk of statininduced rhabdomyolysis increases with older age, use of interacting medications such as fibrates, and hypothyroidism. Conclusions druginduced hepatotoxicity will remain a problem that carries both. The myth of statininduced hepatotoxicity ted bader, md, facg1. It can be differentiated from autoimmune hepatitis by the normalization of aspartate aminotransferase and alanine aminotransferase levels after the withdrawal of statins therapy. Drug safety statininduced liver injury in an area endemic for hepatitis b virus infection.
Hepatotoxicity from hepatic toxicity implies chemicaldriven liver damage. A subset of liver injury caused by statins called autoimmunelike drug induced liver injury can mimic autoimmune hepatitis. Statins also called hmgcoa reductase inhibitors block an enzyme called hmgcoa reductase 3hydroxy3methylglutaryl coenzyme a reductase that is involved in the synthesis of mevalonate, a naturally occurring substance that is then used by the body to make sterols, including cholesterol. Accahanhlbi clinical advisory on the use and safety of statins. Druginduced liver injury is a cause of acute and chronic liver disease the liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Atorvastatin related hepatotoxicity has been associated. The risk of statin induced rhabdomyolysis increases with older age, use of interacting medications such as fibrates, and hypothyroidism. High cholesterol and lipid treatment options beyond the basics. Drug induced acute hepatic injury occurs in 5 to 10 % of patients hospitalised for jaundice. Hmgcoareductaseinhibitors pregnancycategoryx indications.
Dosing, side effects, drug interactions of lipidlowering drugs effects of lipid lowering drugs on serum lipids properties of statins drug ratings in pregnancy us food and drug administration cytochrome p450 3a inhibitors and inducers. Bonkovsky7 the hmgcoa reductase inhibitors statins are widely prescribed for patients with. We calculate the risk of jaundice caused by statin drugs, from sale in the whole country of iceland, to be one in 17,434 users a year. Lipid lowering agents that cause druginduced hepatotoxicity. Dosing, side effects, drug interactions of lipidlowering drugs effects of lipid lowering drugs on serum lipids properties of statins drug ratings in pregnancy us food and drug administration cytochrome p450 3a inhibitors and inducers related topics. Changes up until 2008 were minor, adding only new indications, drug interactions, or adverse reactions. A striking feature of some cases of statininduced liver injury was the prolonged latency. Coq10 supplements are sometimes used to treat statin associated myopathy, though evidence of their efficacy is lacking as of 2017. Moreover, elderly patients are prone to pharmacologic interactions due to multiple medications. Route onset peak duration atorvastatin atorevastatin. Amiodarone, hydralazine, methyldopa, quinidine, statins atorvastatin and simvastatin. These diseases include lupus erythematosus, dermatomyositis, lichen planus, and others. Among their recommendations was that regulatory agencies reconsider the statinlabeling recommendation at that time, which required poststatin liver enzyme testing. Nov 11, 2011 we describe four patients with jaundice caused by drug induced liver injury, where the most likely agent was a statin drug, over a period of approximately three year in iceland.
The risk of hepatic injury caused by statins is estimated to. I read with interest the nicely designed study of chalasani et al. We suspected drug induced autoimmune hepatitis and then referred him to the department of gastroenterology for further examination and treatment. Furthermore, simvastatininduced hepatitis is rare 5 of 1188 cases of druginduced liver injury. This prolonged time to onset is unusual, in that most cases of drug induced liver injury present within 6 months. Despite the increasing use of statin therapy and potential consequences of statin induced ali, it remains unclear if patients prescribed a statin are at increased risk of ali compared to statin nonusers in the setting of hivhcv coinfection, hcv monoinfection, and hiv monoinfection. Risk of developing hepatotoxicity from statins in hepatitis c. Most cases were caused by secondgeneration statins, such as simvastatin and atorvastatin. Statins have also been implicated in drug induced dermatomyositis and other types of autoimmune skin diseases, such as lichen planus pemphigoides 6, 7. The burden of acute nonfulminant druginduced hepatitis in a united states tertiary referral center corrected. Nevertheless, clinical trials are not enough to assess their scarce adverse effects such as idiosyncratic drug induced liver injury dili.
In this setting, failure to discontinue drug therapy can lead to. The burden of acute nonfulminant drug induced hepatitis in a united states tertiary referral center corrected. The american journal of gastroenterology volume 105 may 2010. Pdf statininduced rhabdomyolysis, acute kidney injury, and. Liver failure is a possible but uncommon complication of drug induced hepatitis. Capitals indicate lifethreatening, underlines indicate most frequent. Druginduced liver injury from statins clinics in liver disease. Interactions between certain hiv or hepatitis c drugs and cholesterollowering statin drugs can increase the risk of muscle injury. Risk of acute liver injury after statin initiation by human. Druginduced liver injury dili accounts for hepatotoxicity. Statin induced liver injury, however, could only be confirmed with rechallenge in 3 of the 73 cases in the study by bjornsson and colleagues. Incidence of statin hepatotoxicity in patients with hepatitis c.
Since that time, new drug applications for statin medications have. Apr 30, 2019 statin use is not indicated and should be discontinued in acute hepatitis and decompensated cirrhosis. Its major influence is on the important cause of liver injury. Supportive care for acute liver failure and even liver transplantation may be required. In the 2006 report of the national lipid associations statin safety task force, a panel of experts in hepatology published their findings on specific questions related to the liver blood testing during statin therapy. Statins and lupus erythematosus rheumatology oxford academic. In summary, we report a rare case of symptomatic statininduced cholestatic hepatitis confirmed on rechallenge. Google scholar see all references the repository first used the portable document format and then transitioned to the new technology called the structured product label for use in the national library of medicine. Dec 07, 2010 this suggests that once the autoimmune muscle disease process is initiated by statin use, high levels of hmgcr in regenerating muscle cells continue to fuel the aggressive and painful autoimmune response, even after statins are withdrawn. Quick reference drug list statins buckeye health plan.
Statin therapy is associated with reduced incidence of. Incidence of statin hepatotoxicity in patients with hepatitis. Genetic polymorphisms among enzymes involved in drug metabolism and hla types may account for some of the differences in individual susceptibility to drug hepatotoxicity. Despite the increasing use of statin therapy and potential consequences of statininduced ali, it remains unclear if patients prescribed a statin are at increased risk of ali compared to statin nonusers in the setting of hivhcv coinfection, hcv monoinfection, and hiv monoinfection. Statins play an important role in the care of patients with cardiovascular disease and have a good safety record in clinical practice. Experience with statin use in patients with chronic hepatitis c infection. Indeed, 5 of the 22 patients had been taking the agent for a year or more before onset of acute injury.
A subset of liver injury caused by statins called autoimmunelike druginduced liver injury can mimic autoimmune hepatitis. Jul 23, 2015 unfortunately, other than the use of nacetylcysteine for paracetamol hepatotoxicity, there are no specific antidotes for drug induced liver disease. Experience of the druginduced liver injury network download the pdf here mark w. It is rare that patients treated with a statin exhibit severe myositis characterized by muscle aches, soreness or weakness and associated with elevated creatine kinase levels, generally greater than 10 times the uln. The viral hepatitis serologies, ama, lkm1 antibody and ana were negative, but his igg level was slightly elevated 1,857mgdl. Abstract statins are generally well tolerated and adverse effects are relatively rare. A clinicians guide to statin drugdrug interactions.
This is especially true when 10% of the adult population is taking statins, since, when a case of idiopathic alf arises, 1 in 10 will be taking a statin by chance alone. Patients with chronic liver diseasecirrhosis should not take. Cholestaticmixed liver injury appeared to be more predominant in patients taking atorvastatin. Longterm safety is an important consideration in the selection and use of drugs, such as lipidlowering agents, that are prescribed to reduce the risk of clinical events during long periods. Although significant statininduced idiosyncratic liver injury is rare, as refected by the fdas relabeling of recommended liver function test monitoring with statins, 7. Statin use is not indicated and should be discontinued in acute hepatitis and decompensated cirrhosis.
Further prospective and rcts are needed to confirm the benefit of statins in patients with chronic liver disease. Four months after initial presentation, the patient consulted with a hepatologist at a partnering regional medical center. Statins, mainly atorvastatin can induce autoimmune hepatitis. Populationrepresentative incidence of druginduced acute liver failure based on an analysis of an integrated health care system. This prolonged time to onset is unusual, in that most cases of druginduced liver injury present within 6 months. Drug induced hepatotoxicity is a wellrecognized adverse reaction, and the proportion of cases of hepatic disease known to be drug related continues to increase. Statins have also been implicated in druginduced dermatomyositis and other types of autoimmune skin diseases, such as lichen planus pemphigoides 6, 7. Statin use linked to rare autoimmune muscle disease, study. Cureus autoimmunelike druginduced liver injury caused by. Johnson, md, provides clinical commentary on an article published in the july 2006 issue of clin gastroenterol hepatol that explored the risk for. Populationrepresentative incidence of drug induced acute liver failure based on an analysis of an integrated health care system. Accahanhlbi clinical advisory on the use and safety of. Changes up until 2008 were minor, adding only new indications, drug interactions, or. All patients were evaluated in a standard fashion and followed for at least 6 months.
Statininduced liver injury in an area endemic for hepatitis. Atorvastatinrelated hepatotoxicity has been associated. The existing guidelines state that liver enzymes should be. Among their recommendations was that regulatory agencies reconsider the statin labeling recommendation at that time, which required post statin liver enzyme testing. Drug safety statin induced liver injury in an area endemic for hepatitis b virus infection. Lata and chudy, 2006, and three of the five recently reported patients russo et al. Pravastatininduced eczematous eruption mimicking psoriasis. Druginduced hepatotoxicity is a wellrecognized adverse reaction, and the proportion of cases of hepatic disease known to be drug related continues to increase. An assessment by the statin liver safety task force. This prolonged time to onset is unusual, in that most cases of drug. Coenzyme q10 ubiquinone levels are decreased in statin use. There is currently no way to reimburse for the absence of liver function. We calculate the risk of jaundice caused by statin drugs, from sale in the. Among 1188 cases of druginduced liver injury enrolled between 2004 and 2012 in a prospective registry.
Experience of the druginduced liver injury network mark w. Johnson, md, provides clinical commentary on an article published in the july 2006 issue of clin gastroenterol hepatol that explored the risk for statin hepatotoxicity in patients with hcv. Statininduced liver injury, however, could only be confirmed with rechallenge in 3 of the 73 cases in the study by bjornsson and colleagues. Coq10 supplements are sometimes used to treat statinassociated myopathy, though evidence of their efficacy is lacking as of 2017. Due to some conditions, such as concomitant usage drugdrug interaction using an identical metabolising enzyme and genetic polymorphisms, there is an increasing concern about their safety. Druginduced liver injury dili is a major complication with many drugs. Romeogabriel mih ail a lucian blaga university of sibiu, faculty of medi cine, romania abstract there are interactions between lipid metabolism and hepatitis c virus hcv which are still in study. A striking feature of some cases of statin induced liver injury was the prolonged latency. In this article, we will summarize the current data on statinassociated hepatotoxicity and idiosyncratic druginduced liver injury dili. The patients cmps were followed and her lfts continued to decline with one elevation of unknown cause table 1 and figures. Drug induced liver injury is a cause of acute and chronic liver disease the liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. We describe four patients with jaundice caused by druginduced liver injury, where the most likely agent was a statin drug, over a period of approximately three year in iceland. Drug induced liver injury from statins is rare and characterized by variable patterns of injury, a range of. Mar 15, 2011 statins play an important role in the care of patients with cardiovascular disease and have a good safety record in clinical practice.
623 43 1093 412 1435 5 1214 925 701 1469 652 813 1343 393 563 1453 530 622 850 894 873 1279 215 151 1231 973 873 969 903 973 411 771 1518 1415 337 344 18 1246 1441 384 1089 31 751 1447 798