Craig J. Peine

A Randomized, Double-Blinded, Placebo-Controlled Multicenter Trial of Etanercept in the Treatment of Alcoholic Hepatitis

BACKGROUND & AIMS Alcoholic hepatitis is a cause of major morbidity and mortality that lacks effective therapies. Both experimental and clinical evidence indicate that the multifunctional cytokine tumor necrosis factor-alpha (TNF-alpha) contributes to pathogenesis and clinical sequelae of alcoholic hepatitis. A pilot study demonstrated that the TNF-alpha-neutralizing molecule etanercept could be an effective treatment for patients with alcoholic hepatitis. METHODS Forty-eight patients with moderate to severe alcoholic hepatitis (Model for End-Stage Liver Disease score > or = 15) were enrolled and randomized to groups that were given up to 6 subcutaneous injections of either etanercept or placebo for 3 weeks. Primary study end points included mortality at 1- and 6-month time points. RESULTS There were no significant baseline differences between the placebo and etanercept groups in demographics or disease severity parameters including age, gender, and Model for End-Stage Liver Disease score. The 1-month mortality rates of patients receiving placebo and etanercept were similar on an intention-to-treat basis (22.7% vs 36.4%, respectively; OR, 1.8; 95% CI, 0.5-6.5). The 6-month mortality rate was significantly higher in the etanercept group compared with the placebo group (57.7% vs 22.7%, respectively; OR, 4.6; 95% CI, 1.3-16.4; P = .017). Rates of infectious serious adverse events were significantly higher in the etanercept group compared with the placebo group (34.6% vs 9.1%, respectively, P = .04). CONCLUSIONS In patients with moderate to severe alcoholic hepatitis, etanercept was associated with a significantly higher mortality rate after 6 months, indicating that etanercept is not effective for the treatment of patients with alcoholic hepatitis.

The non-bleeding visible vessel versus the sentinel clot: natural history and risk of rebleeding

Non-bleeding visible vessel and sentinel clot are terms used interchangeably to describe protuberances in the base of ulcers that have recently bled, but a consensus as to their definition or natural history does not exist. In patients with severe ulcer hemorrhage, non-bleeding protuberances were classified as vessels, with or without a small attached clot, or as sentinel clots, according to a schema based on the appearance of the protuberance at endoscopy but not subjected to pathologic correlation. Endoscopic therapy was not performed at the index endoscopic evaluation, and natural evolution was prospectively documented with daily videoendoscopy. Eleven (46%) of 24 patients with non-bleeding protuberances had rebleeding. Independent classification by three authors concurred in 18 (75%) of 24 lesions. Ten (91%) of 11 vessels with or without attached clot rebled versus 0 (0%) of 7 sentinel clots and 1 (17%) of 6 lesions without unanimous classification (p < 0.01, vessels versus other groups). Rebleeding occurred in 5 (71%) of 7 nonpigmented (pale or white), 6 (38%) of 16 red or purple, and 0 (0%) of 1 black protuberances. In general, vessels persisted until rebleeding, whereas sentinel clots disappeared within 1 to 3 days. We conclude that nonbleeding protuberances in ulcer bases can be separated into vessels, which have a high risk of rebleeding, and sentinel clots, which have a low risk of rebleeding.

Nonsystemic vasculitic mononeuropathy multiplex, cryoglobulinemia, and hepatitis C.

A 39‐year‐old man developed sequential acute mononeuropathies involving both median, both ulnar, and the right radial and left peroneal nerves. Electrophysiology demonstrated an asymmetric sensorimotor axonal polyneuropathy; nerve biopsy confirmed a vasculitis. Laboratory evaluation revealed a mixed cryoglobulinemia and active hepatitis C infection. The patient stabilized with prednisone/cyclophosphamide/interferon‐α. Hepatitis C should be considered in the differential diagnosis of mononeuropathy multiplex. Accurate diagnosis is important, as interferon‐α may prevent transition to chronic hepatitis/cirrhosis.

High-dose vitamin E supplementation does not diminish ribavirin-associated haemolysis in hepatitis C treatment with combination standard alpha-interferon and ribavirin

Background : Ribavirin is associated with haemolytic anaemia. Antioxidants have been reported to decrease severity of this anaemia.

Efficacy of Daily Induction Dosing vs Standard Thrice Weekly Dosing of Interferon-α2B for Initial Treatment of Chronic Hepatitis C

The aim of this study was to compare the effect on HCV RNA levels of using induction dosing with 5 MU interferon-α2b (IFN) given daily for four weeks followed by 5 MU IFN given three times a week (TIW) for 44 weeks vs standard noninduction TIW dosing of 5 MU IFN for 48 weeks. We randomly assigned 135 patients with chronic hepatitis C to induction therapy or noninduction therapy. After four weeks of therapy 17/65 (26.1%) patients had undetectable HCV viral levels in the induction group compared with 16/64 (25.0%) patients in the noninduction group. The mean HCV viral levels were similar at four weeks in patients who received induction and noninduction therapy. Mean HCV viral titers in the induction group increased from 4 to 16 weeks, whereas the mean viral titers in the noninduction group decreased during this time (P < 0.0001). HCV RNA was undetectable at the end of therapy in 17/66 (25.8%) in the induction group and 21/68 (30.9%) in the noninduction group. The sustained virologic response rate 24 weeks after the end of therapy was 14/67 (20.9%) in the induction group compared with 13/68 (19.1%) in the noninduction group. These results indicate that an initial four week period of daily interferon confers no benefit in the treatment of patients with chronic hepatitis C.

A comparison of standard and induction interferon therapy with and without initial ribavirin in treatment na

A COMPARISON OF STANDARD AND INDUCTION INTERFERON THERAPY WITH AND WITHOUT INITIAL RIBAVIRIN IN TREATMENT NA. Craig J. Peine, Jeffrey H. Albrecht, Joseph P. Roel, Betty A. Gundersen, John P. Kirchner, Bradley Zins, Daniel McKee, Samuel B. Ho, Theresa Smith, Hennepin County Med O r, Minneapolis, MN; Marshfield Clin, Marshfield, WI; Billings Clin, Billings, MT; St Lukes Hosp, Duluth, MN; Veterans Affairs Med Ctr, Minneapolis, MN; Duluth Clin, Duluth, MN.