Evidence Of Autoimmune Hepatitis Research Articles

Statin-Induced Liver Injury Mimicking Autoimmune Hepatitis

Introduction: HMG CoA reductase inhibitors (statins) are known to be a cause of hepatic dysfunction, with an incidence of transaminimitis from 0.5 to 3 percent, usually within the first 3 to 4 months of initiating therapy. Here we present a case of acute statin induced liver injury mimicking autoimmune hepatitis. Case Patient is a 70 year old male who initially presented with fatigue, scleral icterus, and a 50 pound weight loss over 3 months. Four months before, he had been started on atorvastatin 40 mg daily which was held on admission. Initial workup showed AST 113 IU/L, ALT 197 IU/L, alkaline phosphatase 944 IU/L (with elevated GGT), and total bilirubin 7.6 g/dL. His INR was 1.15 and creatinine and blood urea nitrogen were 9.53 mg/dL and 121 mg/dL, respectively (no preceding renal dysfunction). Viral hepatitis serologies were negative, and the patient denied any alcohol or acetaminophen use. An MRCP was negative for any biliary obstruction. Urinalysis showed granular casts consistent with acute tubular necrosis. He also had positive smooth muscle antibody, elevated IgG at 2458 mg/dL, positive ANA with 1:1280 titer in a speckled pattern, and positive C-ANCA with a 1:320 titer. P-ANCA, anti-glomerular basement membrane antibody, liver-kidney microsomal antibody, and anti-mitochondrial antibody were negative. Liver biopsy revealed mild mixed portal inflammation and reactive changes with portal fibrosis consistent with a drug reaction, without evidence of autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, or hypotensive changes. Kidney biopsy showed mild acute tubulointerstitial nephritis. His AST and ALT also normalized within 3 weeks, to 24 and 38 IU/L, respectively. His alkaline phosphatase improved more slowly, down to 476 IU/L within 3 weeks and total bilirubin improved to 1.3 g/dL. His renal function recovered with supportive care, with creatinine of 0.85 mg/dL within 3 weeks. At outpatient follow up 1 month later, the patient had already gained back 10 pounds, with no residual scleral icterus and improved fatigue. Discussion Statin-associated drug induced liver injury triggering autoimmune hepatitis is rare, with only ten such cases encountered in literature review. These reports often note a liver biopsy consistent with autoimmune hepatitis, which we did not observe. Most cases have required treatment with immunosuppressant medications, while our patient has so far recovered just by holding the statin medication.

If at first you don't succeed: Try, try again

If at first you don't succeed: Try, try again

Pre-S Deletion and Complex Mutations of Hepatitis B Virus Related to Advanced Liver Disease in HBeAg-Negative Patients

This longitudinal study investigated the interactions and roles of hepatitis B virus (HBV) genotypes, pre-S deletions, and core promoter and precore mutations on the progression of liver disease in hepatitis B e antigen (HBeAg)-negative patients. A total of 141 HBeAg-negative patients without liver cirrhosis or hepatocellular carcinoma at study entry were recruited for this study, including 45 inactive HBV carriers and 96 patients with HBeAg-negative chronic hepatitis B. The HBV genotypes and the sequences of pre-S, core promoter, and precore regions were determined. Compared with patients without developing liver cirrhosis, patients with the development of liver cirrhosis had higher rates of genotype C; pre-S deletions; C or G1753, T1762/A1764, T1766, and/or A1768 mutants; and G1799 variant. Cox regression analysis showed that older age, higher total bilirubin and HBV DNA levels, pre-S deletions, and T1766 and/or A1768 mutants were significantly associated with the development of liver cirrhosis. HBV with a complex mutation pattern (pre-S deletion, T1762/A1764, and T1766 and/or A1768 mutants) rather than a single mutation was associated with the development of liver cirrhosis, and the patterns of mutation combinations differed between HBV genotype B and C. Moreover, pre-S deletion was a significant risk factor for hepatocellular carcinoma. This study indicated that pre-S deletion and combined mutations of HBV are useful molecular markers for predicting the clinical outcomes of HBeAg-negative patients.

Do antinuclear antibodies in primary biliary cirrhosis patients identify increased risk for liver failure?

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease with a variable clinical course. Identification of serologic markers associated with increased risk of liver failure would assist in management of PBC patients. The objective of this study was to identify antinuclear antibody (ANA) markers that may be used to predict PBC outcome. Indirect immunofluorescence was used to identify ANAs in 492 PBC patients. chi2 and Kaplan-Meier analyses were used to examine the association between ANAs and liver failure. A greater percentage of ANA-positive, compared to ANA-negative, PBC patients developed liver failure (41% vs 25%, P = .005). The presence of anti-centromere antibodies was associated with liver failure (anti-centromere antibody positive vs negative, 58% vs 33%, P = .001). The time to liver failure was shorter in ANA-positive, compared with ANA-negative, patients (log rank score 5.8, P = .02). After 8.9 years (the median follow-up for patients without liver failure), 68% of ANA-positive and 81% of ANA-negative patients were free of liver failure. Anti-centromere antibodies were also associated with a shorter time to liver failure (log rank score 8.4, P = .004). After 8.9 years, 52% of anti-centromere antibody positive and 74% of anti-centromere antibody negative patients were without liver failure. ANAs in general, and anti-centromere antibodies in particular, are associated with liver failure in PBC. PBC patients with ANAs may be candidates for treatment with experimental therapies to prolong the interval between diagnosis and liver failure. ANA-negative patients, who appear to have a relatively benign clinical course, should perhaps be treated with ursodeoxycholic acid alone.