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Post-liver transplantation sarcopenia in cirrhosis: a prospective evaluation.

ABSTRACT: 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.Consecutive patients who underwent a comprehensive nutritional evaluation in a liver transplant nutrition clinic were included. Core abdominal muscle area was measured on abdominal computed tomography obtained pre- and post-OLT. Age- and gender-based controls were used to define sarcopenia. Measures of body composition pre-transplant were correlated with computed tomography measurements. Predictors and clinical impact of post-OLT change in muscle area were examined. In three subjects post-OLT and three controls, expression of genes regulating skeletal muscle mass were quantified.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 five 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 toward higher mortality. Skeletal muscle expression of myostatin was higher and that of ubiquitin proteasome proteolytic components lower post-OLT than in controls.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.

SUBMITTER: Tsien C

PROVIDER: S-EPMC4024321 | biostudies-other | 2014 Jun

REPOSITORIES: biostudies-other

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Post-liver transplantation sarcopenia in cirrhosis: a prospective evaluation.

Tsien Cynthia C Garber Ari A Narayanan Arvind A Shah Shetal N SN Barnes David D Eghtesad Bijan B Fung John J McCullough Arthur J AJ Dasarathy Srinivasan S

Journal of gastroenterology and hepatology 20140601 6

<h4>Background and aim</h4>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.<h4>Methods</h4>Consecutive patients who underwent a comprehensive nutritional evaluation in a liver transplant nutrition clinic were included. Core abdominal muscle area was measured on abdominal computed tomography obtained pre- and post-OLT. Age- ...[more]

PMID: 24443785

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Project description:BackgroundAdequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data.MethodsConsecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF.ResultsFor 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram.ConclusionsThe combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram.Trial registrationClinicaltrials.gov Identifier: NCT04076631.

Project description:Chronic hepatitis C virus (HCV) infection with advanced cirrhosis or post-liver transplantation recurrence represents a high unmet medical need with no approved therapies effective across all HCV genotypes. The open-label ALLY-1 study assessed the safety and efficacy of a 60-mg once-daily dosage of daclatasvir (pan-genotypic NS5A inhibitor) in combination with sofosbuvir at 400 mg once daily (NS5B inhibitor) and ribavirin at 600 mg/day for 12 weeks with a 24-week follow-up in two cohorts of patients with chronic HCV infection of any genotype and either compensated/decompensated cirrhosis or posttransplantation recurrence. Patients with on-treatment transplantation were eligible to receive 12 additional weeks of treatment immediately after transplantation. The primary efficacy measure was sustained virologic response at posttreatment week 12 (SVR12) in patients with a genotype 1 infection in each cohort. Sixty patients with advanced cirrhosis and 53 with posttransplantation recurrence were enrolled; HCV genotypes 1 (76%), 2, 3, 4, and 6 were represented. Child-Pugh classifications in the advanced cirrhosis cohort were 20% A, 53% B, and 27% C. In patients with cirrhosis, 82% (95% confidence interval [CI], 67.9%-92.0%) with genotype 1 infection achieved SVR12, whereas the corresponding rates in those with genotypes 2, 3, and 4 were 80%, 83%, and 100%, respectively; SVR12 rates were higher in patients with Child-Pugh class A or B, 93%, versus class C, 56%. In transplant recipients, SVR12 was achieved by 95% (95% CI, 83.5%-99.4%) and 91% of patients with genotype 1 and 3 infection, respectively. Three patients received peritransplantation treatment with minimal dose interruption and achieved SVR12. There were no treatment-related serious adverse events.The pan-genotypic combination of daclatasvir, sofosbuvir, and ribavirin was safe and well tolerated. High SVR rates across multiple HCV genotypes were achieved by patients with post-liver transplantation recurrence or advanced cirrhosis.

Project description:BackgroundDiagnostic criteria for sarcopenia have not been established in Chinese. This study established criteria based on the L3-skeletal muscle index (L3-SMI) and assessed its value for outcomes predicting in cirrhotic Chinese patients.MethodsTotally 911 subjects who underwent a CT scan at two centres were enrolled in Cohort 1 (394 male and 417 female subjects, aged 20-80 years). The data of those subjects younger than 60 years (365 male and 296 female subjects) were used to determine the reference intervals of the L3-SMI and its influencing factors. Cohort 2 consisted of 480 patients (286 male and 184 female patients) from three centres, and their data were used to investigate the prevalence of sarcopenia and evaluate the value of L3-SMI for predicting the prognosis and complications of cirrhosis.ResultsAge and sex had the greatest effects on the L3-SMI (P < 0.001). The L3-SMI scores were clearly higher in male patients than in female patients (52.94 ± 8.41 vs. 38.91 ± 5.65 cm2 /m2 , P < 0.001) and sharply declined in subjects aged ≥ 60 years. Based on the mean -1.28 × SD among adults aged < 60 years, the L3-SMI cut-off value for sarcopenia was 44.77 cm2 /m2 in male patients and 32.50 cm2 /m2 in female patients. Using these values, 22.5% of the cirrhotic patients (28.7% of male patients and 11.9% of female patients) were diagnosed with sarcopenia. Compared with non-sarcopenia individuals, sarcopenia patients had lower body mass index (21.28 ± 3.01 vs. 24.09 ± 3.39 kg/m2 , P < 0.001) and serum albumin levels (31.54 ± 5.93 vs. 32.93 ± 5.95 g/L, P = 0.032), longer prothrombin times (16.39 ± 3.05 vs. 15.71 ± 3.20 s, P = 0.049), higher total bilirubin concentrations (41.33 ± 57.38 vs. 32.52 ± 31.48 μmol/L, P = 0.039), worse liver function (Child-Pugh score, 8.05 ± 2.11 vs. 7.32 ± 2.05, P = 0.001), higher prevalence of cirrhosis-related complications (81.82% vs. 62.24%, P < 0.001) and mortality (30.68% vs. 11.22%, P < 0.001). Overall survival was significantly lower in the sarcopenia group [risk ratio (RR) = 2.643, 95% confidence interval (CI) 1.646-4.244, P < 0.001], accompanied with an increased cumulative incidence of ascites (RR = 1.827, 95% CI 1.259-2.651, P = 0.002), spontaneous bacterial peritonitis (RR = 3.331, 95% CI 1.404-7.903, P = 0.006), hepatic encephalopathy (RR = 1.962, 95% CI 1.070-3.600, P = 0.029), and upper gastrointestinal varices (RR = 2.138, 95% CI 1.319-3.466, P = 0.002). Subgroup analysis showed sarcopenia shortened the survival of the patients with Model For End-Stage Liver Disease score > 14 (RR = 4.310, 95% CI 2.091-8.882, P < 0.001) or Child-Pugh C (RR = 3.081, 95% CI 1.516-6.260, P = 0.002).ConclusionsSarcopenia is a common comorbidity of cirrhosis and can be used to predict cirrhosis-related complications and the prognosis.

Project description:Background & aimsLiver transplantation (LT) is the only available treatment for end-stage non-alcoholic fatty liver disease (NAFLD) (related decompensated cirrhosis and/or hepatocellular carcinoma). The aim of our study was to evaluate the risk of disease recurrence after LT and the factors influencing it.MethodThis retrospective multicenter study included adults transplanted for NAFLD cirrhosis between 2000 and 2019 in 20 participating French-speaking centers. Disease recurrence (steatosis, steatohepatitis and fibrosis) was diagnosed from liver graft biopsies.ResultsWe analyzed 150 patients with at least one graft liver biopsy available ≥6 months after transplantation, among 361 patients transplanted for NAFLD. The median (IQR) age at LT was 61.3 (54.4-64.6) years. The median follow-up after LT was 4.7 (2.8-8.1) years. The cumulative recurrence rates of steatosis and steatohepatitis at 5 years were 80.0% and 60.3%, respectively. Significant risk factors for steatohepatitis recurrence in multivariate analysis were recipient age at LT <65 years (odds ratio [OR] 4.214; p = 0.044), high-density lipoprotein-cholesterol <1.15 mmol/L after LT (OR 3.463; p = 0.013) and grade ≥2 steatosis on the graft at 1 year after LT (OR 10.196; p = 0.001). The cumulative incidence of advanced fibrosis (F3-F4) was 20.0% at 5 years after LT and significant risk factors from multivariate analysis were metabolic syndrome before LT (OR 8.550; p = 0.038), long-term use of cyclosporine (OR 11.388; p = 0.031) and grade ≥2 steatosis at 1 year after LT (OR 10.720; p = 0.049). No re-LT was performed for NAFLD cirrhosis recurrence.ConclusionOur results strongly suggest that recurrence of initial disease after LT for NAFLD is inevitable and progressive in a large proportion of patients; the means to prevent it remain to be further evaluated.Impact and implicationsNon-alcoholic fatty liver disease (NAFLD) is a growing indication for liver transplantation, but the analysis of disease recurrence, based on graft liver biopsies, has been poorly studied. Cumulative incidences of steatosis, steatohepatitis and NAFLD-related significant fibrosis recurrence at 5 years were 85.0%, 60.3% and 48.0%, respectively. Grade ≥2 steatosis on graft biopsy at 1 year (present in 25% of patients) is highly predictive of recurrence of steatohepatitis and advanced fibrosis: bariatric surgery should be discussed in these patients specifically.

Dataset Information

Post-liver transplantation sarcopenia in cirrhosis: a prospective evaluation.

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Post-liver transplantation sarcopenia in cirrhosis: a prospective evaluation.

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