Among patients with chronic HCV infection and advanced hepatic fibrosis, sustained virological response to interferon-based treatment was associated with lower all-cause mortality.

Background & Aims There is no histologic classification system to determine prognoses of patients with alcoholic hepatitis (AH). We identified histologic features associated with disease severity and created a histologic scoring system to predict short-term (90 day) mortality. Methods We analyzed data from 121 patients admitted to the Liver Unit (Hospital Clinic, Barcelona, Spain) from January 2000 through January 2008 with features of AH, and developed a histologic scoring system to determine risk of death using logistic regression. The system was tested and updated in a test set of 96 patients from 5 academic centers in the US and Europe, and a semi-quantitative scoring system was developed, called the alcoholic hepatitis histologic score (AHHS). The system was validated in an independent set of 109 patients. Inter-observer agreement was evaluated by weighted statistic analysis. Results Degree of fibrosis, neutrophil infiltration, type of bilirubinostasis, and presence mega-mitochondria were independently associated with 90 day mortality. We used these 4 parameters to develop the AHHS to identify patients with low (0–3 points), moderate (4–5 points), and high (6–9 points) risks of death within 90 days (3%, 19%, and 51%, respectively; P<.0001). The AHHS estimated 90 day mortality in the training and test sets with an area under the receiver operating characteristic value of 0.77 (95% confidence interval, 0.71–0.83). Inter-rate agreement values were 0.65 for fibrosis, 0.86 for bilirubinostasis, 0.60 for neutrophil infiltration, and 0.46 for megamitochondria. Interestingly, the type of bilirubinostasis predicted the development of bacterial infections. Conclusions We identified histologic features associated with severity of AH and developed a patient classification system that might be used in clinical decision making.

Failure of liver stiffness measurement (LSM) by transient elastography (TE, FibroScan) and unreliable results occur in %5% and 15% of patients, respectively, mainly due to obesity. In this multicenter study, we evaluated the feasibility and performance of the novel FibroScan XL probe in 276 patients with chronic liver disease (42% viral hepatitis, 46% nonalcoholic fatty liver disease [NAFLD]) and a body mass index (BMI) !28 kg/m 2 . Patients underwent liver biopsy and TE with the standard M and XL probes. TE failure was defined as no valid LSMs and unreliable examinations as <10 valid LSMs or an interquartile range (IQR)/LSM >30% or success rate <60%. Probe performance for diagnosing !F2 fibrosis and cirrhosis (F4) versus biopsy were examined using areas under receiver operating characteristic curves (AUROC). FibroScan failure was less frequent with the XL probe than the M probe (1.1% versus 16%) and the XL probe was more often reliable (73% versus 50%; both P < 0.00005). Reliable results with the XL probe were obtained in 61% of patients in whom the M probe was unreliable. Among 178 patients with !10 valid LSMs using both probes, liver stiffness was highly correlated between probes (q 5 0.86; P < 0.0005); however, median liver stiffness was lower using the XL probe (6.8 versus 7.8 kPa; P < 0.00005). The AUROC of the XL and M probes were similar for !F2 fibrosis (0.83 versus 0.86; P 5 0.19) and cirrhosis (0.94 versus 0.91; P 5 0.28). Conclusion: Compared with the M probe, the FibroScan XL probe reduces TE failure and facilitates reliable LSM in obese patients. Although the probes have comparable accuracy, lower liver stiffness cutoffs will be necessary when the XL probe is used to noninvasively assess liver fibrosis.

OBJECTIVES:Limitations of the Model for End-Stage Liver Disease (MELD) score include its failure to assess the nutritional and functional status of cirrhotic patients. Our objectives were to evaluate the impact of sarcopenia in cirrhosis and whether the inclusion of muscularity assessment within MELD could improve the prediction of mortality in patients with cirrhosis.METHODS:We included 669 cirrhotic patients who were consecutively evaluated for liver transplantation. Skeletal muscle index at the third lumbar vertebra (L3 SMI) was measured by computed tomography, and sarcopenia was defined using previously published gender and body mass index–specific cutoffs. Using Cox proportional hazards regression, a novel MELD-sarcopenia score was derived.RESULTS:Sarcopenia was present in 298 patients (45%); sarcopenic patients had shorter median survival than non-sarcopenic patients (20±3 vs. 95±24 months, P<0.001). By Cox regression analysis adjusted for age, gender, and hepatocellular carcinoma, both MELD (hazard ratio (HR) 1.08, 95% confidence interval (CI) 1.06–1.10, P<0.001), and the L3 SMI (HR 0.97, 95% CI 0.96–0.99, P<0.001) were associated with mortality. Overall, the c-statistics for 3-month mortality were 0.82 (95% CI 0.78–0.87) for MELD and 0.85 (95% CI 0.81–0.88) for MELD-sarcopenia (P=0.1). Corresponding figures for 1-year mortality were 0.73 (95% CI 0.69–0.77) and 0.77 (95% CI 0.73–0.80), respectively (P=0.03). The c-statistics for 3-month mortality in patients with MELD<15 (0.85 vs. 0.69, P=0.02) and refractory ascites (0.74 vs. 0.71, P=0.01) were significantly higher for MELD-sarcopenia compared with MELD.CONCLUSIONS:Modification of MELD to include sarcopenia is associated with improved prediction of mortality in patients with cirrhosis, primarily in patients with low MELD scores. External validation of this prognostic index in larger cohorts of cirrhotic patients is warranted.

The CAP is a promising tool for the noninvasive detection of hepatic steatosis. Advantages of CAP include its ease of measurement, operator-independence and simultaneous availability with LSM for fibrosis assessment.

Abbreviation: ADLs, activities of daily living.

Loss of muscle mass and function, or sarcopenia, is a common feature of cirrhosis and contributes significantly to morbidity and mortality in this population. Sarcopenia is a main indicator of adverse outcomes in this population, including poor quality of life, hepatic decompensation, mortality in patients with cirrhosis evaluated for liver transplantation (LT), longer hospital and intensive care unit stay, higher incidence of infection following LT, and higher overall health care cost. Although it is clear that muscle mass is an important predictor of LT outcomes, many questions remain, including the best modality for assessing muscle mass, the optimal cut-off values for sarcopenia, the ideal timing and frequency of muscle mass assessment, and how to best incorporate the concept of sarcopenia into clinical decision making. For these reasons, we assembled a group of experts to form the North American Working Group on Sarcopenia in Liver Transplantation to use evidence from the medical literature to address these outstanding questions regarding sarcopenia in LT. We believe sarcopenia assessment should be considered in all patients with cirrhosis evaluated for liver transplantation. Skeletal muscle index (SMI) assessed by computed tomography constitutes the best-studied technique for assessing sarcopenia in patients with cirrhosis. Cut-off values for sarcopenia, defined as SMI < 50 cm 2 /m 2 in male and < 39 cm 2 /m 2 in female patients, constitute the validated definition for sarcopenia in patients with cirrhosis. Conclusion: The management of sarcopenia requires a multipronged approach including nutrition, exercise, and additional pharmacological therapy as deemed necessary. Future studies should evaluate whether recovery of sarcopenia with nutritional management in combination with an exercise program is sustainable as well as how improvement in muscle mass might be associated with improvement in clinical outcomes.

chronic kidney disease; CST, Canadian Society of Transplantation; CT, computed tomography; DASI, Duke activity status index; DEXA, dual energy X-ray absorptiometry; ESRD, end-stage renal disease; FFP, fried frailty phenotype; HR, hazard ratio; HRQO, health-related quality of life; MCSD, mechanical circulatory support device; MELDNa, model for end-stage liver disease and sodium; MRI, magnetic resonance imaging; SPPB, short physical performance battery.