Terlipressin plus albumin was associated with greater improvement in renal function vs albumin alone in patients with cirrhosis and HRS-1. Patients had similar rates of HRS reversal with terlipressin as they did with albumin. ClinicalTrials.gov no: NCT01143246.

Background and Aim Pre-transplant sarcopenia (reduced skeletal muscle mass) predicts poor outcome in cirrhosis. In contrast, whether muscle mass increases post orthotopic liver transplantation (OLT) is not known and was studied prospectively. Methods Consecutive patients who underwent a comprehensive nutritional evaluation in a liver transplant nutrition clinic were included. Core abdominal muscle area was measured on abdominal CT obtained pre- and post-OLT. Age and gender based controls were used to define sarcopenia. Measures of body composition pre-transplant were correlated with CT measurements. Predictors and clinical impact of post-OLT change in muscle area were examined. In 3 subjects post-OLT and 3 controls, expression of genes regulating skeletal muscle mass were quantified. Results During the study period, 53 patients (M:F 41:12; age 56.9±7.5 years) were followed up after OLT for 19.3±9 months. Five patients died and another 5 had acute graft rejection. Pre-OLT sarcopenia was present in 33 (66.2%). Pre-transplant clinical characteristics including Child’s score, MELD score and nutritional status or post transplantation immunosuppression regimen did not predict post transplant change in muscle mass. New onset post-OLT sarcopenia developed in 14 patients. Loss of muscle mass post-OLT increased risk of diabetes mellitus and a trend towards higher mortality. Skeletal muscle expression of myostatin was higher and that of ubiquitin proteasome proteolytic components lower post-OLT than in controls. Conclusions Post transplantation sarcopenia is common and could not be attributed to pre-transplant characteristics or the type or duration of post-OLT immunosuppression. Post-transplant sarcopenia contributes to adverse consequences and strategies targeting myostatin may be beneficial.

Background Skeletal muscle loss (sarcopenia) is a major clinical complication in alcoholic cirrhosis with no effective therapy. Skeletal muscle autophagic proteolysis and myostatin expression (inhibitor of protein synthesis) are increased in cirrhosis and believed to contribute to anabolic resistance. A prospective study was performed to determine the mechanisms of sarcopenia in alcoholic cirrhosis and potential reversal by leucine. Methods In 6 well-compensated, stable alcoholic cirrhotic patients and 8 controls, serial vastus lateralis muscle biopsies were obtained before and 7h after a single oral BCAA mixture enriched with leucine (BCAA/LEU). Primed-constant infusion of L-[ring-2H5]-phenylalanine was used to quantify whole body protein breakdown (WbPB) and muscle protein fractional synthesis rate (FSR) using liquid chromatography/mass spectrometry. Muscle expression of myostatin, mTOR targets, autophagy markers, protein ubiquitination and intracellular amino acid deficiency sensor, general control of nutrition 2 (GCN2) were quantified by immunoblots and leucine transporter (SLC7A5) and glutamine exchanger (SLC38A2) by real time PCR. Results Following oral administration, plasma BCAA concentrations showed a similar increase in cirrhosis and controls. Skeletal muscle FSR was 9.63±0.36%/h in controls and 9.05±0.68%/h in cirrhotics (p=0.54). Elevated WbPB in cirrhosis was reduced with BCAA/LEU (p=0.01). Fasting skeletal muscle molecular markers showed increased myostatin expression, impaired mTOR signaling and increased autophagy in cirrhosis compared to controls (p<0.01). BCAA/LEU did not alter myostatin expression but mTOR signaling, autophagy measures and GCN2 activation were consistently reversed in cirrhotic muscle (p<0.01). SLC7A5 expression was higher in basal state in cirrhosis than controls (p<0.05) but increased with BCAA/LEU only in controls (p<0.001). Conclusions We demonstrate that impaired mTOR1 signaling and increased autophagy in skeletal muscle of alcoholic cirrhosis patients is acutely reversed by BCAA/LEU.

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Hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide, affecting 175 million people globally. Over 80% of acutely infected patients go on to develop chronicity, but only 20% to 25% will develop end-stage liver disease and its complications. The sequelae of HCV-induced chronic liver disease accounts for 8,000 to 10,000 deaths annually in the United States and is currently the leading indication for liver transplantation. To date, there are no accurate noninvasive markers of disease activity and fibrosis. Liver biopsy is indicated to exclude other forms of liver pathologies and to establish the stage of liver disease. In this study, the role of liver biopsy in chronic hepatitis C was evaluated. Additionally, we calculated a discriminant score to predict cirrhosis in chronic hepatitis C infection. Our results showed that additional diagnoses or unsuspected diagnoses are less frequent than clinicians' suspected. We confirmed that the discriminant score for predicting cirrhosis is inferior to liver biopsy. In conclusion, the majority of patients with chronic hepatitis C will require a liver biopsy, which has an important implication on staging of the liver disease, prognosis, and possibly further management options. (HEPATOLOGY 2001;33:196-200.)