Autoimmune hepatitis revealed by atorvastatin

Pelli, N.; Setti, Maurizio; Ceppa, Paola; Toncini, Carlo; Indiveri, Francesco

doi:10.1097/00042737-200308000-00014

Cited by 83 publications

(44 citation statements)

References 7 publications

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“…3 Instances of autoimmune-like injury attributed to statins also have been reported. [45][46][47] Although no apparent correlation exists between the risk of myopathy and hepatotoxicity from statins, 48 muscle injury can, at times, cause elevated LAEs that might be confused with drug injury. 49 The labeled contraindication to the use of statins in active liver disease seems to be based largely on the assumption that acute hepatotoxicity developing in a patient with impaired liver function would likely be more serious, although evidence-based data to support this theory are lacking.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease: Results of a prospective, randomized, double-blind, placebo-controlled, multicenter trial

et al. 2007

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The hepatotoxic potential of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in patients with underlying chronic liver disease remains controversial. We performed a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial that compared pravastatin (80 mg) to a placebo administered once daily to hypercholesterolemic subjects greater than 18 years of age with at least a 6-month history of compensated chronic liver disease and with a low-density lipoprotein cholesterol (LDL-C) level greater than or equal to 100 mg/dL and a triglyceride (TG) level lower than 400 mg/dL. The efficacy was determined by the percentage change in LDL-C [along with the total cholesterol (TC), high-density lipoprotein cholesterol, and TG] from the baseline to week 12. The safety was analyzed by the proportion of subjects who developed at least 1 alanine aminotransferase (ALT) value greater than or equal to 2 times the upper limit of normal for those with normal ALT at the baseline or a doubling of the baseline ALT for those with elevated ALT at the baseline during 36 weeks of treatment. A total of 630 subjects were screened, and 326 subjects were randomized; nonalcoholic fatty liver disease was present in 64%, and chronic hepatitis C was present in 23%. In the intent-to-treat population, pravastatin (80 mg/day) significantly lowered the mean LDL-C, TC, and TG values at week 12 and at other times (weeks 4, 8, 24, and 36) in comparison with the placebo. The incidence of subjects who met the primary prespecified ALT event definition was lower in the pravastatin group at all times over the 36 weeks of therapy in comparison with the placebo group, although the difference was not statistically significant. No differences were seen on the basis of the baseline ALT values or among the different liver disease groups. Conclusion: High-dose pravastatin (80 mg/day) administered to hypercholesterolemic subjects with chronic liver disease significantly lowered LDL-C, TC, and TGs in comparison with the placebo and was safe and well tolerated. The concern over an increased potential for statin-induced hepatotoxicity in patients with chronic liver disease appears to be lessened on the basis of these results.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease: Results of a prospective, randomized, double-blind, placebo-controlled, multicenter trial

et al. 2007

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“…Drugs that have been implicated in multiple case reports but which are withdrawn or used less frequently are tienilic acid, dihydralazine, oxiphenisatin, halothane, clometacine, isoniazid, and methydopa [35]. Drugs that have been implicated in less than five reports are benzarone [66], diclofenac [67], fenofibrate [68], meloxicam [69], methylphenidate [70], papaverine [71], pemoline [72], propylthiouracil [73,74], prometrium [27], cephalexin [27], atorvastatin [75][76][77][78], rosuvastatin [79], phenprocoumon [80], terbinafine [81], indometacin [82], imatinib [83], infliximab [84][85][86], and adalimumab [87,88]. Nutritional supplements (hydroxycut) [89], herbal medicines (dai-saiko-to, black cohosh, ma huang, germander) [90][91][92][93][94][95], and an environmental pollutant (trichloroethylene) [96] complement the list of agents that have a weak, uncertain, or rare association with an autoimmunelike hepatitis (Table 1).…”

Section: Etiological Candidates For Drug-induced Autoimmunelike Hepatmentioning

confidence: 99%

Drug-Induced Autoimmune-Like Hepatitis

2011

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The clinical phenotype of classical autoimmune hepatitis can be mimicked by idiosyncratic drug-induced liver injury, and differentiation can be difficult. The goals of this review are to enumerate the major agents of drug-induced autoimmune-like hepatitis, describe the clinical findings and risk factors associated with it, detail the clinical tools by which to assess causality, discuss putative pathogenic mechanisms, and describe treatment and outcome. The frequency of drug-induced autoimmune-like hepatitis among patients with classical features of autoimmune hepatitis is 9%. Minocycline and nitrofurantoin are implicated in 90% of cases. Female predominance, acute onset, and absence of cirrhosis at presentation are important clinical manifestations. Genetic factors affecting phase I and phase II transformations of the drug, polymorphisms that protect against cellular oxidative stress, and human leukocyte antigens that modulate the immune response may be important pathogenic components. Clinical judgment is the mainstay of diagnosis as structured diagnostic methods for drug-induced liver injury are imperfect. The covalent binding of a reactive drug metabolite to a hepatocyte surface protein (commonly a phase I or phase II enzyme), formation of a neoantigen, activation of CD8 T lymphocytes with nonselective antigen receptors, and deficient immune regulatory mechanisms are the main bases for a transient loss of self-tolerance. Discontinuation of the offending drug is the essential treatment. Spontaneous improvement usually ensues within 1 month. Corticosteroid therapy is warranted for symptomatic severe disease, and it is almost invariably effective. Relapse after corticosteroid withdrawal probably does not occur, and its absence distinguishes drug-induced disease from classical autoimmune hepatitis.

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“…53 These three patients double the reported instances of this association. [54][55][56] Classical features of AILD include strong female preponderance (true for most auto-immune diseases), chronicity for Ͼ6 months (albeit arbitrary), the presence of hyperglobulinemia, circulating autoantibodies, extrahepatic clinical autoimmune syndromes, overrepresentation of HLA DR3 or DR4, and a low rate of spontaneous remission. 57 …”

Section: Herbert L Bonkovsky; Autoimmune Dili: Clinicalmentioning

confidence: 99%