Clinical, Biochemical, and Histological Remission of Severe Chronic Active Liver Disease: A Controlled Study of Treatments and Early Prognosis

Soloway, Roger D.; Summerskill, W.H.J.; Baggenstoss, Archie H.; Geall, Michael G.; Gitnick, Gary; Elveback, Lila R.; Schoenfield, Leslie J.

doi:10.1016/s0016-5085(19)33223-8

Cited by 674 publications

(417 citation statements)

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“…Patients with immune cholangitis and AIH-PBC and AIH-PSC overlap syndromes frequently require long-term therapy as well [7,8]. Azathioprine has been used successfully in autoimmune hepatitis patients for 40 years [9,10]. Azathioprine is primarily employed as a steroid-sparing drug.…”

Section: Discussionmentioning

confidence: 99%

Mycophenolate Mofetil for Autoimmune Hepatitis: A Single Practice Experience

et al. 2008

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Autoimmune hepatitis (AIH) is refractory to standard therapy with prednisone and azathioprine in 20% of patients. Investigators are exploring alternative immunosuppressant treatments, including mycophenolate mofetil (MMF). We assessed the outcome of MMF therapy in patients with AIH and related disorders. A retrospective analysis was performed in 16 patients with AIH, immune cholangitis, and overlap syndromes between AIH, primary biliary cirrhosis, and primary sclerosing cholangitis. MMF was used in lieu of azathioprine on account of patients' intolerance to azathioprine, disease that was refractory to prednisone plus azathioprine, or the perceived potency of MMF. With initiation of MMF, median ALT decreased from 81.5 U/l to 42.5 U/l (P = 0.03). Median prednisone dose decreased from 10 mg to 2.5 mg (P = 0.01). Prednisone was completely withdrawn in three patients. Five of 16 patients (31%) achieved biochemical remission, defined as a reduction in ALT from greater than to less than twice normal. Seven additional patients (44%) were maintained in biochemical remission. Two patients had an incomplete response to MMF and two patients experienced treatment failure. MMF was tolerated well in all but one patient, who discontinued the drug on account of paresthesias. MMF may be a safe and effective alternative to azathioprine in patients with AIH and related disorders.

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Section: Discussionmentioning

confidence: 99%

Mycophenolate Mofetil for Autoimmune Hepatitis: A Single Practice Experience

et al. 2008

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“…Patients with classical autoimmune hepatitis typically improve rapidly during corticosteroid therapy, and patients with drug-induced autoimmune-like hepatitis would be expected to improve as quickly. Most patients with classical autoimmune hepatitis experience laboratory resolution within 3-6 months of treatment [211][212][213][214], and histological resolution occurs 3-8 months later [215,216].…”

Section: Treatmentmentioning

confidence: 99%

“…Improvement in liver tissue lags behind clinical and laboratory resolution in classical autoimmune hepatitis [215][216][217], and corticosteroid withdrawal based on normal laboratory tests may be associated with laboratory exacerbations that reflect inadequate treatment of residual histological disease rather than relapse. This behavior may obscure the distinction between the two diagnostic considerations.…”

Section: Treatmentmentioning

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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“…1,2 A prospective study has indicated that as many as 40% of patients with untreated severe disease die within 6 months of diagnosis. 3 Cirrhosis develops in at least 40% of survivors. 4 An acute onset of illness is common, [5][6][7][8] and fulminant presentation is possible.…”

Section: Introductionmentioning

confidence: 99%