Interferon alfacon-1 and ribavirin versus interferon alpha-2b and ribavirin in the treatment of chronic hepatitis C.

Despite advances in the therapy of chronic hepatitis C, a large number of patients do not respond to current therapies. The study objective was to assess whether a combination of interferon (IFN) alfacon-1 and ribavirin improves the response rate compared with a combination of INF alpha-2b and ribavirin in chronic hepatitis C subjects. The study was designed as an open-label, prospective, randomized, controlled study; 128 subjects with chronic hepatitis C were randomized to INF alfacon-1, 15 microg three times per week, plus ribavirin, 1 g/day, or IFN-alpha2b, 3 million units three times per week, plus ribavirin, 1 g/day for 48 weeks. The end point of the study was a sustained viral response, defined as undetectable HCV RNA at 24 weeks post 48 weeks of treatment. Overall, 57% of subjects in the INF alfacon-1/ribavirin group achieved a sustained antiviral response, compared with 40% of subjects in the IFN-alpha2b/ribavirin group (P = 0.052). In the subset of subjects with a high viral load, HCV RNA was successfully eradicated in more individuals who received INF alfacon-1/ribavirin than subjects who received IFN-alpha2b/ribavirin (57 versus 31%; P = 0.025). Among individuals with genotype 1 and a high viral load, the sustained antiviral response was significantly higher with INF alfacon-1/ribavirin than with IFN-alpha2b/ribavirin (46 versus 14%; P = 0.019). Adverse events were similar in both treatment groups. In conclusion, this study demonstrated that the combination of INF alfacon-1 and ribavirin provides a significantly better treatment response compared with the combination of IFN-alpha2b and ribavirin in chronic HCV subjects infected with genotype 1 and a high viral RNA load.

Wireless capsule endoscopy in a community gastroenterology practice.

GOALS: This study was performed to evaluate the use of wireless capsule endoscopy in a community gastroenterology practice. BACKGROUND: Experience with wireless capsule endoscopy at referral centers has been reported, but little has been reported about community gastroenterologists' experience. STUDY: A retrospective review of charts and wireless capsule endoscopies performed at a community hospital was performed. RESULTS: A total of 99 wireless capsule endoscopies were reviewed and complete data were available in 72 cases. Indications included suspected obscure GI bleeding in 97% of cases; 55% of patients were taking anti-platelet or anti-coagulant medications; 71% of examinations were complete. Pathologic findings included angioectasias (36%), gastritis/erosions (21%), bleeding (18%), small bowel ulcers (16%), duodenitis (7%), and small bowel erosions (6%). Strictures, Crohn's disease, and tumors were each seen in 3%. There were no abnormal findings in 37%. One complication, nonnatural excretion of the capsule, caused a transient bowel obstruction but passed without endoscopic intervention or surgery. CONCLUSIONS: In a community-based gastroenterology setting, wireless capsule endoscopy is a safe tool that shows abnormalities in a significant proportion of exams.

Impact of diabetes and hepatitis after kidney transplantation on patients who are affected by hepatitis C virus.

Complications associated with use of donor hepatitis C-positive kidneys (DHCV+) have been attributed primarily to posttransplantation liver disease (as a result of hepatitis C disease). The role of posttransplantation diabetes has not been explored in this setting. With the use of the United States Renal Data System database, 28,942 Medicare KT recipients were studied from January 1, 1996, through July 31, 2000. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (AHR) for the association of sero-pairs for HCV (D+/R-, D+/R+, D-/R+ and D-/R-) with Medicare claims for de novo posttransplantation HCV and posttransplantation diabetes. The peak risk for posttransplantation HCV was in the first 6 mo after transplantation. The incidence of posttransplantation HCV after transplantation was 9.1% in D+/R-, 6.3% in D+/R+, 2.4% in D-/R+, and 0.2% in D-/R-. The incidence of posttransplantation diabetes after transplantation also peaked early and was 43.8% in D+/R-, 46.6% in D+/R+, 32.3% in D-/R+, and 25.4% in D-/R-. Associations for both complications were significant in adjusted analysis (Cox regression). Both posttransplantation HCV (AHR, 3.36; 95% confidence interval, 2.44 to 4.61) and posttransplantation diabetes (AHR, 1.81; 95% confidence interval, 1.54 to 2.11) were independently associated with an increased risk of death, but posttransplantation diabetes accounted for more years of life lost, particularly among recipients of DHCV+ kidneys. Posttransplantation diabetes may contribute substantially to the increased risk of death associated with use of DHCV+ kidneys and accounts for more years of life lost than posttransplantation HCV. Because HCV infection acquired after transplantation is so difficult to treat, methods that have been shown to reduce viral transmission warrant renewed attention.

Hepatitis C and renal transplantation in the era of modern immunosuppression.

Kidneys from donors who are positive for hepatitis C virus (DHCV+) have recently been identified as an independent risk factor for mortality after renal transplantation. However, it has not been determined whether risk persists after adjustment for baseline cardiac comorbidity or applies in the era of modern immunosuppression. Therefore, a historical cohort study was conducted of US adult cadaveric renal transplant recipients from January 1, 1996, to May 31, 2001; followed until October 31, 2001. A total of 36,956 patients had valid donor and recipient HCV serology. Cox regression analysis was used to model adjusted hazard ratios for mortality and graft loss, respectively, adjusted for other factors, including comorbid conditions from Center for Medicare and Medicaid Studies Form 2728 and previous dialysis access-related complications. It was found that DHCV+ was independently associated with an increased risk of mortality (adjusted hazard ratio, 2.12, 95% confidence interval, 1.72 to 2.87; P < 0.001), primarily as a result of infection. Mycophenolate mofetil was associated with improved survival in DHCV+ patients, primarily related to fewer infectious deaths. Adjusted analyses limited to recipients who were HCV+, HCV negative, or age 65 and over, or by use of mycophenolate mofetil confirmed that DHCV+ was independently associated with mortality in each subgroup. It is concluded that DHCV+ is independently associated with an increased risk of mortality after renal transplantation adjusted for baseline comorbid conditions in all subgroups. Recipients of DHCV+ organs should be considered at high risk for excessive immunosuppression.

Hospitalized gastrointestinal bleeding and procedures after renal transplantation in the United States.

The risk of hospitalized gastrointestinal bleeding (GIB) in renal transplant recipients has not been studied in a national renal transplant population. Therefore, 42,906 renal transplant recipients in the United States Renal Data System (USRDS) from 1 July 1994 - 30 June 1998 were analyzed in an historical cohort study of hospitalizations with a primary discharge diagnosis of GIB (ICD9 Code 578.9x) using Cox regression analysis. The 1997 National Hospital Discharge Survey was used to obtain rates of GIB for the general population. Renal transplant recipients had a cumulative incidence of hospitalizations for GIB of 334 events/100,000 person-years. In 1997, compared to the general population, renal transplant recipients had an age-adjusted rate ratio for GIB of 10.69 at one year of follow-up. The strongest risk factors for GIB in Cox regression analysis were graft loss (adjusted hazard ratio, 4.28 (2.84-6.47) and African American recipients who experienced allograft rejection (AHR, 3.04, 95% CI, 1.45-6.37). GIB was associated with increased all-cause mortality (hazard ratio 1.78, 95% CI, 1.39-2.28). GIB is significantly more common in renal transplant recipients than in the general population, and the strongest risk factors are graft loss and African Americans who experience rejection.

Donor hepatitis C seropositivity: clinical correlates and effect on early graft and patient survival in adult cadaveric kidney transplantation.

The impact of hepatitis C virus-positive donor kidneys on patient survival has not been analyzed in a national study. This study analyzed 20,111 adult (age, > or =16 yr) recipients having solitary cadaveric kidney transplants from adult donors with valid donor hepatitis C serologies from July 1, 1994, to June 30, 1998, in an historical cohort study (the 2000 United States Kidney Data System) of patient survival. Analysis was by the Cox proportional hazards models, which corrected for characteristics thought to affect outcomes. Of 484 kidneys positive for hepatitis C virus serology, 165 (34%) were given to recipients with confirmed negative hepatitis C serologies. Unadjusted 3-yr patient survival was 93% in all recipients of donor hepatitis C-negative kidneys versus 85% in all recipients of donor hepatitis C-positive kidneys (P = 0.01). Among hepatitis C-positive recipients, those who received hepatitis C-positive kidneys had worse survival than recipients of hepatitis C-negative kidneys. Among elderly hepatitis C-negative recipients, those who received hepatitis C-positive kidneys also had worse survival; in fact, all recipients of donor hepatitis C-positive kidneys had increased risk of mortality (P = 0.028). There were no significant interactions between donor hepatitis C positivity and either recipient hepatitis C positivity or older recipient age. The use of hepatitis C-positive kidneys in recipients who were hepatitis C-negative was fairly common and contrary to some current recommendations. Recipients of donor hepatitis C-positive kidneys were at independently increased risk of mortality, with no evidence that any subgroups were less affected.

"Ecstasy"-induced hepatitis in an active duty soldier.

3,4-Methylenedioxymethamphetamine, or "Ecstasy," is a drug commonly used at "rave" parties to heighten energy and intimacy. Although its complications have been well described in Europe, including less common side effects such as hepatic failure and rhabdomyolysis, physicians in the United States have less experience with this drug because of the shorter duration of its use in this country. We present a case of an active duty soldier who was admitted for acute hepatitis secondary to Ecstasy ingestion and describe its proposed pathophysiology. We believe that with the increased use of Ecstasy in the United States, especially among younger patients, including soldiers, military physicians will need to be more familiar with this potentially deadly drug.