Biomedical subjects

Supriya Joshi

Publications and source records attributed to Supriya Joshi.

3 recordsLinked to original sources

PubMed2003

Ramipril-associated hepatotoxicity.

CONTEXT: Angiotensin-converting enzyme inhibitors are prescribed for many cardiovascular and renal diseases. Adverse hepatic events, especially cholestasis, have rarely been reported with captopril, enalapril, lisinopril, and fosinopril. To date, hepatic injury associated with ramipril has not been reported. OBJECTIVE: To describe 3 patients who developed hepatitis, with or without jaundice, after receiving ramipril. DESIGN: Medical records and liver biopsies of the 3 patients were reviewed. Clinical, laboratory, and histologic findings were compared with findings in other cases of angiotensin-converting enzyme inhibitor-induced liver injury reported in the literature. RESULTS: The 3 patients were middle-aged men. In 2 patients, jaundice appeared 4 and 8 weeks after starting ramipril. Bilirubin levels peaked at 15.5 and 5 mg/dL, and alkaline phosphatase values peaked at 957 and 507 U/L. Aminotransferase levels were mildly elevated. Endoscopic retrograde cholangiopancreatography and ultrasonography showed no bile duct obstruction. Liver biopsies from the jaundiced patients were similar, with cholestasis, duct necrosis, and extravasation of bile, ductular proliferation, and portal inflammation. Cholestasis improved in 1 patient 6 weeks after stopping ramipril and was prolonged for 14 months in the other, in whom biliary cirrhosis was present on biopsy. The third patient developed hepatitis without jaundice 3 weeks after starting ramipril; symptoms resolved after stopping the drug. Ramipril-associated liver injury is similar to that seen with other angiotensin-converting enzyme inhibitors, but liver biopsy findings of duct necrosis and extravasation of bile have not been reported previously. CONCLUSION: Prolonged cholestatic hepatitis and biliary cirrhosis may result from the use of ramipril. Monitoring of liver enzymes is advisable for patients starting on ramipril.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2002

Primary biliary cirrhosis with additional features of autoimmune hepatitis: response to therapy with ursodeoxycholic acid.

Patients with primary biliary cirrhosis (PBC) may have additional features of autoimmune hepatitis (AIH). Corticosteroids usually contraindicated in PBC have been advocated for these patients. Patients with antimitochondrial antibody (AMA)-positive PBC from two previous randomized, controlled trials were assessed for features of AIH. Their biochemical, immunologic, and histologic responses to ursodeoxycholic acid (UDCA) versus placebo were compared with those without AIH features. The survival of patients testing positive or negative for antinuclear antibodies (ANA) was also examined. Features of AIH were defined by the presence of 2 or more of the following: 1) alanine transaminase (ALT) > 5 x the upper limit of normal (ULN); 2) immunoglobulin G (IgG) > 2 x ULN or positive anti-smooth muscle antibody (ASMA); and 3) moderate to severe lobular inflammation on pretreatment liver biopsy. Testing for AMA, ASMA, and ANA was done by immunofluorescence. The change in serum bilirubin, alkaline phosphatase (ALP), transaminases, IgM, and IgG from baseline to 2 years was compared. Of the 331 patients randomized, 16 (4.8%) had features of AIH (12 UDCA, 4 placebo). The median percent change in serum biochemistry and immunoglobulin values were similar in patients with PBC +/- features of AIH after 2 years of therapy with UDCA. Over 2 years, little change in histologic features of AIH was observed. Survival was similar for patients with PBC with and without ANA. In conclusion, features of AIH in PBC may be transient and response to UDCA therapy similar to patients with PBC without features of AIH.

Adult↗

PubMed2002

Antimitochondrial antibody profiles: are they valid prognostic indicators in primary biliary cirrhosis?

OBJECTIVE: Retrospective studies have reported that subtypes of antimitochondrial antibodies (AMAs) discriminate between a benign and a progressive course in patients with primary biliary cirrhosis (PBC). Four AMA profiles (A-D) were defined: profiles A and B associated with a benign course and C and D with a progressive course. We aimed to confirm whether AMA profiles predict prognosis in a large sample of North American patients with PBC. METHODS: Stored pretreatment sera from patients with PBC from two centers were tested for AMA profiles using standard techniques. Proportions of patients in each profile group reaching the endpoints of liver transplantation or death from liver disease were compared. Kaplan-Meier curves were constructed comparing AMA profiles. RESULTS: All 472 patients studied had AMA positive, biopsy-confirmed PBC. Mean age at diagnosis was 53 yr, 90% were female, mean follow-up was 7.6 yr (range = 0.5-23), and 51% received ursodeoxycholic acid for >6 months. Profile A was not detected; 16.7% had profile B; 51.1%, profile C; and 32.2%, profile D. Duration of follow-up was comparable among the different profile groups. The proportions of patients reaching endpoints of death from liver disease or transplantation did not differ among the AMA profiles. No difference in the Kaplan-Meier curves between the different profile groups was observed (p > 0.05). CONCLUSION: AMA profiles do not predict prognosis in patients with PBC.

Autoantibodies↗