Safety and Efficacy of Bariatric Surgery in Cirrhosis Patients With Extreme Obesity.

OBJECTIVE: To assess the safety and efficacy of bariatric surgery in patients with cirrhosis. SUMMARY BACKGROUND DATA: Bariatric surgery may be a viable option for patients with cirrhosis and extreme obesity. However, the risk of liver decompensation after surgery is not thoroughly investigated. METHODS: We conducted a case-controlled study with 106 obese patients with cirrhosis (cases) and 317 age, sex, body mass index-, and type of surgery-matched obese patients without cirrhosis (controls) who underwent bariatric surgery. RESULTS: Patients with cirrhosis were predominantly Child-Pugh class A (97%) with the diagnosis established prior to surgery in only 46%. In the cirrhosis group, there was no death in the first 30 days compared with 1 patient in the control group. At 90 days there was 1 death in the cirrhosis group but no additional deaths in the control group. In total, 12 months after the surgery, there were 3 deaths in the cirrhosis group and 1 in the control group (2.8% vs 0.6%, P = 0.056). The surgery-related length of stay was significantly longer in patients with cirrhosis (3.7 ±â€Š4.0 vs 2.6 ±â€Š2.4 d, P = 0.001), but the 30-day readmission rate was lower (7.5% vs 11.9%, P = 0.001). The percent of total weight loss at 30 and 90-days was not significantly different between the groups and remained that way even at 1 year (29.1 ±â€Š10.9 vs 31.2 ±â€Š9.4%, P = 0.096). CONCLUSIONS: Bariatric surgery in obese cirrhotic patients is not associated with excessive mortality compared with noncirrhotic obese patients.

Pharmacokinetic and pharmacodynamic alterations in the Roux-en-Y gastric bypass recipients.

OBJECTIVE: We conducted a pharmacokinetic (PK) study and a pharmacodynamic (PD) study to assess whether Roux-en-Y gastric bypass (RYGB) surgery is associated with significant changes to PK and PD of oral medications. BACKGROUND: The effect of RYGB on oral drug disposition is not well understood. METHODS: An oral cocktail of probe drugs for major drug-metabolizing enzymes (caffeine, tolbutamide, omeprazole, dextromethorphan, and oral and intravenous midazolam) was administered to 18 RYGB recipients and 18 controls. Timed blood and urine samples were obtained for PK analyses. Forty mg of oral furosemide was administered to 13 RYGB recipients and 14 controls, and urine and blood samples were collected for assessing furosemidePK, and urine volume and urine sodium excretion for PD analyses. RESULTS: Compared with controls, the RYGB group had significantly lower time to maximum plasma concentration (tmax) for caffeine (0.58 ± 0.5 vs 2.1 ± 2.2 hours, P < 0.0001), tolbutamide (1.4 ± 1.8 vs 2.1 ± 2.2 hours, P = 0.0001), omeprazole (1.1 ± 1.1 vs 4.4 ± 1.3 hours, P < 0.0001), and oral midazolam (0.5 ± 0.2 vs 0.7 ± 0.4 hours, P < 0.01). However, maximum plasma concentration, half-life, area under the curve, and oral bioavailability were not different. Compared with controls, the RYGB group had brisk natriuresis, with significantly lower tmax for urine sodium (1.3 ± 0.5 vs 3.1 ± 2.3 hours, P < 0.02) and correspondingly lower tmax for furosemide (1.8 ± 0.3 vs 4.2 ± 1.2 hours, P = 0.006). However, 6-hour urine sodium and 6-hour urine volume were not different between the two groups. CONCLUSIONS: RYGB recipients have significantly shorter tmax for the studied orally administered medications, but otherwise no other significant changes in PK were reported.

Presence and significance of microvesicular steatosis in nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Liver biopsies from patients with nonalcoholic fatty liver disease (NAFLD) sometimes exhibit non-zonal aggregates of hepatocytes with microvesicular steatosis, but its prevalence and significance are unclear. In this study, we have evaluated the frequency of microvesicular steatosis and assessed its association with histological markers of disease severity in a large sample of NAFLD liver biopsies. METHODS: Liver biopsies from a large cohort of adults who participated in two studies conducted by the NASH Clinical Research Network (NASH CRN) were included in this cross-sectional study. Liver histology was assessed centrally and various histological features scored in a systematic fashion. The relationship between microvesicular steatosis and various histological features that characterize NAFLD was tested by multiple logistic regression, after controlling for age, gender, race, body mass index, and diabetes. RESULTS: Among 1022 liver biopsies included, 102 (10%) had microvesicular steatosis. No demographic differences were noted between patients with or without microvesicular steatosis. The presence of microvesicular steatosis was associated with higher grades of steatosis (p<0.001), ballooning cell injury (p<0.001), presence of Mallory-Denk bodies (p<0.007), presence of megamitochondria (p<0.0001), higher NAS scores (p<0.0001), more advanced fibrosis (p<0.0001), and diagnosis of borderline or definite NASH (p<0.0001). CONCLUSIONS: Microvesicular steatosis correlates with more advanced histology of NAFLD. Longitudinal studies are needed to address the role of microvesicular steatosis in mediating cellular injury and disease progression in NAFLD.

Hepatic and extrahepatic cancer in cirrhosis: a longitudinal cohort study.

OBJECTIVES: We conducted a retrospective cohort study in cirrhotic patients to understand (i) the risk of developing hepatocellular carcinoma (HCC) after an initial negative screening computed tomography (CT) scan and its relationship with underlying etiology and (ii) the risk of extrahepatic cancers (EHCs). METHODS: Our cohort consisted of 952 cirrhotics who had at least one contrast-enhanced CT scan over a 5-year period from 1997 to 2002. We assessed their risk of HCC and EHC until the study closure (31 December 2007). Using data from the Indiana State Cancer Registry (ISCR), standardized incidence ratios (SIRs) were calculated for HCC and EHC. RESULTS: The cohort's follow-up was 4.7±3.0 years. The frequency of HCC at baseline and during follow-up was 6.9 and 7.2%, respectively. The 1-, 3-, and 5-year HCC incidence after an initial negative CT scan was 1.2, 4.4, and 7.8%, respectively. The 1-, 3-, and 5-year EHC incidence was 2.2, 4.5, and 6.8%, respectively. The most common EHCs were breast, lung, and lymphoma. Incidence of both HCC (P=0.016) and EHC (P=0.004) varied significantly by the etiology of underlying cirrhosis. The SIRs for HCC and EHC were 186 (95% confidence interval (CI) 140-238) and 1.83 (95% CI 1.36-2.36), respectively. Compared with adjusted ISCR data, cirrhosis due to alcohol (SIR 2.73, 95% CI 1.14-4.33) but not other etiologies had significantly higher incidence of EHC. CONCLUSIONS: This study furthers our understanding of HCC and EHC risk in cirrhosis. If confirmed by other studies, these data will assist in developing optimal strategies for monitoring of cancer in individuals with cirrhosis.

Incidence and predictors of 30-day readmission among patients hospitalized for advanced liver disease.

BACKGROUND & AIMS: The rate of readmission to the hospital 30 days after discharge (30-day readmission rate) is used as a quality measure for hospitalized patients, but it has not been studied adequately for patients with advanced liver disease. We investigated the incidence and factors that predict this rate and its relationship with mortality at 90 days. METHODS: We analyzed data from patients with advanced liver disease who were hospitalized to an inpatient hepatology service at 2 large academic medical centers in 2008. Patients with elective admission and recipients of liver transplants were not included. During the study period, there were 447 patients and a total of 554 eligible admissions. Multivariate analyses were performed to identify variables associated with 30-day readmission and to examine its relationship with mortality at 90 days. RESULTS: The 30-day readmission rate was 20%. After adjusting for multiple covariates, readmission within 30 days was associated independently with model for end-stage liver disease scores at discharge (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02-1.09; P = .002), the presence of diabetes (OR, 1.78; 95% CI, 1.07-2.95; P = .027), and male sex (OR, 1.73; 95% CI, 1.03-2.89; P = .038). After adjusting for age, sex, and model for end-stage liver disease score at discharge, the 90-day mortality rate was significantly higher among patients who were readmitted to the hospital within 30 days than those who were not (26.8% vs 9.8%; OR, 2.6; 95% CI, 1.36-5.02; P = .004). CONCLUSIONS: Patients with advanced liver disease frequently are readmitted to the hospital within 30 days after discharge; these patients have a higher 90-day mortality rate than those who are not readmitted in 30 days. These data might be used to develop strategies to reduce early readmission of hospitalized patients with cirrhosis.

Use of statins in patients with liver disease.

Cardiovascular disease is as common in individuals with chronic liver disease as in the general population. Moreover, recent data suggest that patients with nonalcoholic fatty liver disease (NAFLD) may have a cardiovascular risk greater than that conferred by the conventional risk factors. There is unequivocal evidence that cardiovascular disease is an important cause of morbidity and mortality in this patient population and thus requires consideration of aggressive therapy with lipid-lowering agents such as statins. Because all statins are hepatically cleared and can cause elevations in liver biochemistries, there is a concern that patients with underlying liver disease may be at increased risk for hepatotoxicity. However, recent data, along with an assessment of statin safety by the Liver Expert Panel, suggest that statins are generally well tolerated in patients with chronic liver disease such as NAFLD, primary biliary cirrhosis, and hepatitis C virus. These drugs also appear to be safe in patients with stable/compensated cirrhosis. However, decompensated cirrhosis and acute liver failure should be considered contraindications for lipid-lowering therapy as these patients are unlikely to benefit because of their generally grave prognosis. Although routine hepatic biochemical test monitoring is recommended, the cost-effectiveness of this approach has been questioned. The benefit of statins in patients with underlying liver disease who are otherwise important candidates for statin therapy far outweighs the risk of a very rare event of serious liver injury.