All-oral direct-acting antiviral therapy in HCV-advanced liver disease is effective in real-world practice: observations through HCV-TARGET database.

BACKGROUND: Chronic hepatitis C virus therapy in patients with advanced liver disease remains a clinical challenge. HCV-TARGET collects data in patients treated at tertiary academic and community centres. AIM: To assess efficacy of all-oral HCV therapy in advanced liver disease. METHODS: Between December 2013 and October 2014, 240 patients with a MELD score of ≥10 initiated HCV treatment with an all-oral regimen. Data from the 220 patients who completed 12-week follow-up were analysed. RESULTS: Genotype 1 (GT1) patients had higher sustained virological response (SVR) when treated with sofosbuvir plus simeprevir ± ribavirin than with sofosbuvir plus ribavirin (66-74% vs. 54%); GT1b vs GT1a (84% vs. 64%). SVR for GT2 was 72% with sofosbuvir plus ribavirin, while GT3 patients had a substantially lower response (35%). A decrease in MELD score was not clearly related to SVR over the short course of follow-up although some had improvements in MELD score, serum bilirubin and albumin. A predictor of virological response was albumin level while negative predictors were elevated bilirubin level and GT1a. Most patients with GT1 were treated with approximately 12-week duration of sofosbuvir and simeprevir ± ribavirin therapy while GT2 and GT3 patients were treated with approximately 12 and 24 weeks of sofosbuvir plus ribavirin respectively. CONCLUSIONS: All-oral therapies are effective among patients with advanced liver disease with high levels of success in GT2 and GT1b, and may serve to reduce the severity of liver disease after SVR. Treatment for GT3 patients remains an unmet need. Clinical trial number: NCT01474811.

Response to intraluminal gas in irritable bowel syndrome. Motility versus perception.

Our aim was to evaluate the response to intraluminal gas in irritable bowel syndrome and to determine whether this response was consequent upon disordered motility or altered perception. We evaluated 10 patients who satisfied the clinical criteria for the diagnosis of irritable bowel syndrome and 10 healthy controls. An eight-lumen perfused catheter assembly was positioned to monitor motor activity in the duodenum and proximal jejunum; a separate side port in the distal duodenum permitted gas infusion. Subjects recorded symptoms of abdominal pain, bloating, and nausea throughout the study, using a visual analog scale. Following an overnight fast and a 60-min basal recording period in the fasted state, subjects ate a standard meal; 60 min later, "sham" gas was administered for 20 min, followed by the actual infusion of nitrogen gas at 40 ml/min. Subjects were randomized to receive atropine (7 micrograms/kg) or placebo intravenously during the period of actual gas infusion. Patients with irritable bowel syndrome described more pain (score, mean +/- SE, control versus irritable bowel: 0.22 +/- 0.16 vs 1.65 +/- 0.5, P < 0.01) and nausea (0.25 +/- 0.21 vs 1.45 +/- 0.64, P < 0.04) during sham gas; motility indices were similar in both groups. During active gas, irritable bowel syndrome patients reported more pain (0.40 +/- 0.39 vs 2.94 +/- 1.16, P < 0.03); motility indices at all sites were similar in both groups. Symptom severity in irritable bowel syndrome subjects randomized to receive atropine was similar to control subjects during active gas infusion; motility indices were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastric emptying and orocecal transit in portal hypertension and end-stage chronic liver disease.

Our aim was to evaluate gastric emptying and orocecal transit in patients with end-stage liver disease and portal hypertension undergoing evaluation for liver transplantation. Although gastric emptying half-times for both liquid and solid emptying were similar in patients with chronic liver disease and control subjects, orocecal transit, as measured by a scintigraphic technique, was significantly prolonged in the patients with liver disease (transit time, minutes, mean +/- SEM, patients versus controls: 127 +/- 10.5 versus 80 +/- 9.5, P < .003). Serum levels of progesterone and estradiol were similar in patients and controls. We conclude that small intestinal transit is delayed in patients with advanced liver disease and portal hypertension and may contribute to gastrointestinal symptoms and promote sepsis of enteric origin in this patient population.

Delayed gastric emptying of both the liquid and solid components of a meal in chronic liver disease.

OBJECTIVES: To evaluate gastric emptying in patients with chronic liver disease and portal hypertension. METHODS: We measured gastric emptying of both the liquid and solid components of a meal in 10 consecutive patients with chronic liver disease and portal hypertension, but free of ascites, and 14 age- and sex-matched healthy controls. In the patients with liver disease, relationships between emptying and liver function were examined. To measure gastric emptying, subjects consumed a test meal that consisted of scrambled eggs labeled with 99mTc-sulfur colloid and 4 oz of water labeled with 111In-diethylene triamine pentacetic acid (DTPA). RESULTS: Patients with liver disease and portal hypertension demonstrated delayed emptying of both the liquid (t1/2, min, mean +/- SE, patients vs. CONTROLS: 69.4 +/- 19.4 vs. 31.4 +/- 1.8, p < 0.01) and solid (post-lag phase solid emptying: 141 +/- 32.9 vs. 69.8 +/- 4.6, p < 0.006) components of the meal. We could not identify any correlation between gastric emptying and tests of liver function. CONCLUSIONS: Gastric emptying is delayed in patients with liver disease and portal hypertension; this abnormal gastric motor function may contribute to the pathophysiology of foregut complaints in this patient population.

The nature of complications following liver biopsy in transplant patients with Roux-en-Y choledochojejunostomy.

Liver biopsy is an important diagnostic tool in the management of patients following orthotopic liver transplant. We evaluated complications following percutaneous liver biopsy in a group of liver transplant patients who had Roux-en-Y choledochojejunostomies fashioned as part of their biliary reconstruction during liver transplantation. Complications were divided into two major groups: septic complications (including fever, symptomatic bacteremia, cholangitis, infected hematoma and hypotension related to sepsis) and bleeding (defined as hypotension requiring volume expansion greater than 500 cm3 or blood transfusion, hemothorax, intrahepatic or peritoneal hemorrhage and hemobilia occurring within 1 wk of liver biopsy). One hundred ninety-two biopsies were performed in 46 patients with choledochojejunostomies, and 118 biopsies were carried out in an age- and sex-matched control group of patients with choledochocholedochostomy biliary anastomosis. There were no septic complications in the choledochojejunostomy patients and one (0.32%) septic complication in the choledochocholedochostomy patients (NS). Eight bleeding complications occurred (2.6%) in eight patients (8.3%). Five (2.6%) occurred in five (10.8%) of the choledochojejunostomy patients, vs. three (2.5%) in three (6.5%) choledochocholedochostomy patients (NS). None of the bleeding complications required surgical intervention or was fatal. We conclude that liver biopsy in posttransplant patients with Roux-en-Y choledochojejunostomies is a safe procedure and that the incidences of complications were similar in our two groups. The negligible incidence of septic complications in the choledochojejunostomy patients does not appear to warrant the administration of prophylactic antibiotics, as has been previously suggested.