Aims/hypothesis Exendin-4 is a 39 amino acid agonist of the glucagon-like peptide receptor and has been approved for treatment of type 2 diabetes. Many reports describe an increased incidence of acute pancreatitis in humans treated with exendin-4 (exenatide). Previous studies have evaluated the effect of exendin-4 on beta cells and beta cell function. We evaluated the histological and biochemical effects of exendin-4 on the pancreas in rats. Methods We studied 20 Sprague-Dawley male rats, ten of which were treated with exendin-4 and ten of which were used as controls. The study period was 75 days. Serum and pancreatic tissue were removed for biochemical and histological study. Blood glucose, amylase, lipase, insulin and adipocytokines were compared between the two groups. Results Animals treated with exendin-4 had more pancreatic acinar inflammation, more pyknotic nuclei and weighed significantly less than control rats. They also had higher serum lipase than control animals. Exendin-4 treatment was associated with lower insulin and leptin levels as well as lower HOMA values than in the untreated control group. Conclusions/interpretation Although the use of exendin-4 in rats is associated with decreased weight gain, lower insulin resistance and lower leptin levels than in control animals, extended use of exendin-4 in rats leads to pancreatic acinar inflammation and pyknosis. This raises important concerns about the likelihood of inducing acute pancreatitis in humans receiving incretin mimetic therapy.

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Summary Non‐alcoholic fatty liver disease is a clinicopathological condition that comprises a wide spectrum of liver damage, ranging from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. Non‐alcoholic steatohepatitis represents only a stage within the spectrum of non‐alcoholic fatty liver disease and is defined pathologically by the presence of steatosis together with necro‐inflammatory activity. The true prevalence of non‐alcoholic fatty liver disease is unknown, but it is estimated that it affects 10–24% of the general population in different countries. The diagnosis of non‐alcoholic fatty liver disease is based upon convincing evidence of absent or minimal alcohol consumption, compatible histological changes in liver biopsy and the exclusion of other liver diseases. The natural history of non‐alcoholic fatty liver disease remains to be defined. Patients with pure steatosis on liver biopsy follow a relatively benign course, whereas patients with histological necro‐inflammatory changes and/or fibrosis may progress to end‐stage liver disease. An initial step in the treatment of non‐alcoholic fatty liver disease is the management of associated conditions, such as obesity, diabetes mellitus and hyperlipidaemia. Non‐alcoholic fatty liver disease patients with steatohepatitis and/or fibrosis on liver biopsy may benefit from investigational pharmacological therapy. Patients with decompensated cirrhosis from non‐alcoholic fatty liver disease may be candidates for liver transplantation.

Hematological abnormalities including neutropenia, anemia, and thrombocytopenia are commonly seen in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. The aim of this study was to identify factors which would help to predict the development of hematological abnormalities in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. During a 4-year period, all patients with chronic hepatitis C started on treatment with pegylated interferon and ribavirin were identified. Patients were defined as having hematological abnormalities if they had the presence of either anemia, neutropenia, thrombocytopenia, or a combination of the above during treatment with pegylated interferon and ribavirin. A total of 136 patients with chronic hepatitis C were included in this study. Fifty-two (38.2%) of the patients developed significant hematological abnormalities during treatment with pegylated interferon and ribavirin with 28 (20.6%), 30 (22.1%), and 11 (8.1%) developed neutropenia, anemia, and thrombocytopenia, respectively. Genotype 1, history of hypertension, low baseline platelet count, low baseline hemoglobin, as well as a raised creatinine were significant factors associated with the development of hematological abnormalities. Significant hematological abnormalities are commonly present in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. This study identifies pretreatment parameters that may help identify high-risk patients who are more likely to develop hematological abnormalities during treatment for chronic hepatitis C.

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