Improvement in Quality of Life and Decrease in Large-Volume Paracentesis Requirements With the Automated Low-Flow Ascites Pump.

The automated low-flow ascites pump (alfapump) is an implantable device that drains ascites directly into the urinary bladder. We studied its safety (absence of serious complications) and efficacy (decreased large-volume paracentesis [LVP] requirement and improved quality of life [QoL]) in the management of ascites in a cohort of North American patients with cirrhosis and recurrent ascites ineligible for transjugular intrahepatic portosystemic shunt (TIPS). QoL was measured by the Chronic Liver Disease Questionnaire (CLDQ) and Ascites Questionnaire (Ascites Q). Following alfapump implantation, patients were monitored for ascites control, laboratory abnormalities, QoL, adverse events, and survival at 12 months. A total of 30 patients (60.0 ± 9.9 years; 57% male; Model for End-Stage Liver Disease score, 11.4 ± 2.7) received an alfapump, mostly by an interventional radiology approach (97%), followed by longterm prophylactic antibiotics. The alfapump removed a mean ascites volume of 230.6 ± 148.9 L/patient at 12 months, dramatically reducing the mean LVP frequency from 2.4 ± 1.4/patient/month before pump implantation to 0.2 ± 0.4/patient/month after pump implantation. All surviving patients had improved QoL (baseline versus 3 months; CLDQ, 3.9 ± 1.21 versus 5.0 ± 1.0; Ascites Q, 51.7 ± 21.9 versus 26.7 ± 18.6; P < 0.001 for both) and a better biochemical index of nutritional status (prealbumin 87.8 ± 37.5 versus 102.9 ± 45.3 mg/L at 3 months; P = 0.04). Bacterial infections (15 events in 13 patients), electrolyte abnormalities (11 events in 6 patients), and renal complications (11 events in 9 patients) were the most common severe adverse events. By 12 months, 4 patients died from complications of cirrhosis. Alfapump insertion may be a definitive treatment for refractory ascites in cirrhosis, especially in patients who are not TIPS candidates.

Rifaximin treatment in hepatic encephalopathy.

BACKGROUND: Hepatic encephalopathy is a chronically debilitating complication of hepatic cirrhosis. The efficacy of rifaximin, a minimally absorbed antibiotic, is well documented in the treatment of acute hepatic encephalopathy, but its efficacy for prevention of the disease has not been established. METHODS: In this randomized, double-blind, placebo-controlled trial, we randomly assigned 299 patients who were in remission from recurrent hepatic encephalopathy resulting from chronic liver disease to receive either rifaximin, at a dose of 550 mg twice daily (140 patients), or placebo (159 patients) for 6 months. The primary efficacy end point was the time to the first breakthrough episode of hepatic encephalopathy. The key secondary end point was the time to the first hospitalization involving hepatic encephalopathy. RESULTS: Rifaximin significantly reduced the risk of an episode of hepatic encephalopathy, as compared with placebo, over a 6-month period (hazard ratio with rifaximin, 0.42; 95% confidence interval [CI], 0.28 to 0.64; P<0.001). A breakthrough episode of hepatic encephalopathy occurred in 22.1% of patients in the rifaximin group, as compared with 45.9% of patients in the placebo group. A total of 13.6% of the patients in the rifaximin group had a hospitalization involving hepatic encephalopathy, as compared with 22.6% of patients in the placebo group, for a hazard ratio of 0.50 (95% CI, 0.29 to 0.87; P=0.01). More than 90% of patients received concomitant lactulose therapy. The incidence of adverse events reported during the study was similar in the two groups, as was the incidence of serious adverse events. CONCLUSIONS: Over a 6-month period, treatment with rifaximin maintained remission from hepatic encephalopathy more effectively than did placebo. Rifaximin treatment also significantly reduced the risk of hospitalization involving hepatic encephalopathy. (ClinicalTrials.gov number, NCT00298038.)

The impact of race/ethnicity on the clinical epidemiology of autoimmune hepatitis.

GOALS: To evaluate race/ethnicity-specific variations in autoimmune hepatitis (AIH) with a focus on Asians and Hispanics, the fastest growing populations in the United States. BACKGROUND: AIH is a chronic inflammatory disease in which race/ethnicity-specific variations in clinical epidemiology have been reported. However, earlier studies were small or did not include a comprehensive analysis of Asians and Hispanics, the 2 fastest growing population cohorts in the United States. STUDY: A retrospective study analyzing patient data from 1999 to 2010 in a large tertiary-care community hospital to assess AIH epidemiology among a racially diverse population. RESULTS: One hundred eighty-three patients with AIH were included in the study with 81 patients having "definite" AIH by International Autoimmune Hepatitis Group criteria and 63 were diagnosed with overlap syndromes. Women and whites were the largest cohorts. The average age of diagnosis was similar among all groups. Biopsy-confirmed cirrhosis was present in 34% of AIH patients with Hispanics demonstrating the highest prevalence of cirrhosis (55%). When compared with whites, Asians had higher international normalized ratio (INR) (1.4 U vs. 1.1 U, P<0.01), and Hispanics had lower serum albumin (3.3 g/dL vs. 3.7 g/dL, P<0.001) and platelets (123.8 thousand/mcL vs. 187.5 thousand/mcL, P<0.001) and higher international normalized ratio (1.5 U vs. 1.1 U, P=0.05). Kaplan-Meier survival analysis demonstrated a trend toward worse outcomes among Asians. CONCLUSIONS: Among AIH patients, Hispanics had the highest prevalence of cirrhosis, and Asians had poorer survival outcomes. Race/ethnicity-specific disparities in AIH epidemiology may reflect underlying genetic differences, contributing to variations in disease severity, response to therapy, and overall mortality.

Development of hepatocellular carcinoma in autoimmune hepatitis patients: a case series.

BACKGROUND: The risk of hepatocellular carcinoma (HCC) among patients with autoimmune hepatitis (AIH) is believed to be low compared with other chronic liver diseases, and uncertainty exists over the need to perform HCC surveillance. If surveillance is initiated, the optimal timing is also not yet defined. AIMS: The aim of the study was to investigate the prevalence of HCC among AIH patients. METHODS: This was a retrospective study analyzing patient data from 1999 to 2009 in a large tertiary-care community hospital to assess the prevalence of HCC among AIH patients. RESULTS: Among 322 AIH cases, cancer screening identified six patients that developed HCC (prevalence: 459 per 100,000 patient-years). All six patients were extracted from the subset of AIH patients with cirrhosis (n = 50), resulting in a prevalence of 1,920 per 100,000 patient-years. In the AIH with HCC cohort, mean age of AIH diagnosis was 51.8 years (range, 24-70) and mean age of HCC diagnosis was 60.0 years (range, 37-71). The mean interval between diagnosis of AIH and HCC was 10.0 years. Three patients had AJCC stage ≥2 cancer at diagnosis, and two had BCLC stage B or C. CONCLUSIONS: The risk of HCC among AIH patients with cirrhosis is 1.9% per year. This is comparable to HCC risk among patients with cirrhosis secondary to HBV, HCV, hemochromatosis, or alcohol-related liver disease. Although this data needs to be confirmed in prospective studies, routine cancer screening and surveillance among this cohort for early detection and treatment should be conducted.

Mitochondrial dysfunction in liver disease and organ transplantation.

The mitochondria play a crucial role in maintaining hepatocyte integrity and functions. Mitochondrial defects are either inherited or acquired. Mitochondria dysfunction occurs when the hepatocyte experience excessive physiologic stress. Its clinical presentation depends on the severity of the stress. It varies from mild abnormalities in liver biochemical tests to manifestations of acute or chronic liver failure. Mitochondria dysfunction is implicated in most liver disease and in early graft dysfunction after liver transplantation. This review will address the role of mitochondria in liver disease.