Telaprevir or boceprevir triple therapy in patients with chronic hepatitis C and varying severity of cirrhosis.

BACKGROUND: Risks and benefits of protease inhibitor (PI) (telaprevir or boceprevir) triple therapy in hepatitis C virus (HCV)-infected patients with mildly decompensated cirrhosis, including those wait-listed for liver transplantation (LT), are incompletely known. AIM: To assess virological responses and safety of PI triple therapy in patients with mildly decompensated Child-Pugh (CP) CP ≥6 vs. compensated (CP = 5) cirrhosis. METHODS: Multicentre cohort of 160 adults with cirrhosis treated with peginterferon/ribavirin (peg-IFN/RBV) plus telaprevir (69%) or boceprevir (31%), comparing outcomes between those with CP = 5 and CP ≥6. RESULTS: Patients, 47% with CP ≥6 cirrhosis (CP range 6-10), received PI triple therapy for a targeted duration of 48 weeks. The cohort was median age 59 years, 32% female, 59% genotype 1a, 35% previous null/partial responders. Sustained virological response at 12 weeks (SVR12) was achieved by 35% of patients with CP ≥6 vs. 54% of those with CP = 5 (P = 0.02). CP = 5, achievement of rapid virological response and genotype 1b/other, independently predicted SVR12. Compared to those with CP = 5, patients with CP ≥6 had more peg-IFN dose reductions, eltrombopag use, transfusions and hospitalisations to manage adverse events (all P < 0.05). Overall, 67 (42%) discontinued treatment early. Nine wait-listed patients were treated for a median of 97 days (IQR 60-160) prior to liver transplantation and five achieved post-LT SVR. CONCLUSIONS: In the presence of mild decompensation (Child-Pugh ≥6), SVR12 rates with protease inhibitor triple therapy are significantly reduced and adverse events increased. Thus, treatment with protease inhibitor triple therapy, if judged as necessary, should be undertaken with close monitoring and awareness of the significant risks.

Pseudomembranous colitis without diarrhea presenting clinically as acute intestinal pseudo-obstruction.

Pseudomembranous colitis usually presents with diarrhea in a clinical setting of recent antibiotic use. It is uncommon to see it as a cause of obstipation and colonic pseudo-obstruction. We report an unusual case of an elderly woman with hypertension, congestive heart failure, chronic obstructive pulmonary disease, chronic renal insufficiency, and diabetes mellitus, who was admitted with fever, abdominal pain, and distension without diarrhea. She presented with decreased stool frequency and obstipation. She did not respond to conservative management. Colonoscopy revealed a picture of pseudomembranous colitis, and Clostridium difficile toxin was positive. She responded well to metronidazole therapy.

Spontaneous intrahepatic hemorrhage and hepatic rupture in the HELLP syndrome: four cases and a review.

Subcapsular hemorrhage and hepatic rupture are unusual catastrophic complications of the HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. A high index of suspicion and prompt recognition are keys to proper diagnosis and management of affected patients. The optimal management of these patients is evolving. An aggressive multidisciplinary approach has considerably improved the morbidity and mortality associated with these complications. We present our experience with four cases of hepatic hemorrhage occurring in association with the HELLP syndrome and review the literature on this subject. All of our patients were multiparous, and three had a history of eclampsia/preeclampsia in a previous pregnancy. All four patients developed intrahepatic hemorrhage; two developed hepatic rupture requiring surgical intervention. Three patients developed disseminated intravascular coagulation and acute renal failure. Two patients developed pericardial effusion, pleural effusions, and ascites. One patient died of septic complications after multiple surgical interventions.

Antibiotic therapy of Helicobacter pylori infection reduces healthcare expenditures related to duodenal ulcer.

OBJECTIVE: To test whether eradication of Helicobacter pylori saves costs in the treatment of duodenal ulcer disease, compared with conventional antisecretory therapy. STUDY DESIGN: A prospective, double-blind clinical trial was conducted at 132 sites in the United States. PATIENTS AND METHODS: Adult patients with active duodenal ulcer and confirmed H pylori infection were randomized to receive treatment with clarithromycin plus omeprazole, omeprazole alone, or ranitidine alone. Utilization of ulcer-related healthcare resources was documented during 1 year following therapy. Costs were calculated by multiplying the number of health resources utilized by the cost of each resource. Resource costs were obtained from a database containing actual average costs spent by managed care organizations on outpatient and inpatient treatment. RESULTS: Of the 819 patients enrolled, 727 completed the study: 243 received clarithromycin plus omeprazole, 248 omeprazole alone, and 236 ranitidine alone. Ulcer-related health resource utilization and total ulcer-related healthcare costs were decreased after treatment with clarithromycin plus omeprazole, compared to treatment with omeprazole or ranitidine alone. In multivariate linear regression analyses, type of treatment was found to be a significant predictor of total costs. Specific costs associated with endoscopic examinations, clinic visits, and medications were also significantly reduced by treatment with clarithromycin plus omeprazole as compared to other treatment forms. CONCLUSIONS: In a managed care environment, therapy with clarithromycin and omeprazole to eradicate H pylori in patients with duodenal ulcer disease would result in significant cost savings secondary to a reduction in the utilization of healthcare resources.

Hepatic fibrosis and cirrhosis in tropical countries (including portal hypertension).

The spectrum of diseases seen in patients from certain 'tropical areas' requires that a physician be aware of some of the syndromes discussed here. A high index of suspicion for less usual causes of cirrhosis is imperative when evaluating such patients presenting with hepatocellular disease. The differential must be expanded and the work-up complete. Liver biopsy should be performed as early in the course of disease as is feasible and will often provide valuable diagnostic information. It will not only facilitate treatment but allow for needed clinical trials and may help to increase our understanding of the various disease processes.