Although sarcopenia is a common complication of cirrhosis, its diagnosis remains nonconsensual: computed tomography (CT) scan determinations vary and no cutoff values have been established in cirrhotic populations undergoing liver transplantation (LT). Our aim was to compare the accuracy of the most widely used measurement techniques and to establish useful cutoffs in the setting of LT. From the 440 patients transplanted between January 2008 and May 2011 in our tertiary center, we selected 256 patients with cirrhosis for whom a recent CT scan was available during the 4 months prior to LT. We measured different muscle indexes: psoas muscle area (PMA), PMA normalized by height or body surface area (BSA), and the third lumbar vertebra skeletal muscle index (L3SMI). Receiver operating characteristic curves were evaluated and prognostic factors for post-LT 1-year survival were then analyzed. PMA offered better accuracy (area under the curve [AUC] = 0.753) than L3SMI (AUC = 0.707) and PMA/BSA (AUC = 0.732), and the same accuracy as PMA/squared height. So, for its accuracy and simplicity of use, the PMA index was used for the remainder of the analysis and to define sarcopenia. In men, the better cutoff value for PMA was 1561 mm (Se = 94%, Sp = 57%), whereas in women, it was 1464 mm (Se = 52%, Sp = 91%). A PMA lower than these values defined sarcopenia in patients with cirrhosis awaiting LT. One- and 5-year overall survival rates were significantly poorer in the sarcopenic group (n = 57) than in the nonsarcopenic group (n = 199), at 59% versus 94% and 54% versus 80%, respectively (P < 0.001). In conclusion, pre-LT PMA is a simple tool to assess sarcopenia. We established sex-specific cutoff values (1561 mm in men, 1464 mm in women) in a cirrhotic population and showed that 1-year survival was significantly poorer in sarcopenic patients. Liver Transplantation 23 143-154 2017 AASLD.

Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is widely considered as a terminal condition. Therefore, the role of surgery is uncertain in this case. The purpose of this study was to identify the prognostic factors of survival after post-LT HCC recurrence and to evaluate the impact of surgery in this setting. All patients transplanted for HCC between 1991 and 2013 in a single institution and who further developed a post-LT recurrence were included in this study. Univariate and multivariate analyses were performed to identify factors affecting postrecurrence survival. Of the 493 patients transplanted for HCC, a total of 70 (14.2%) consecutive patients developed a recurrence after a median disease-free interval of 17 months. Median survival (MS) from the time of recurrence was 19 months, with a 3-year postrecurrence survival of 26%. Most recurrences were extrahepatic (lung, lymph node, and bone; n = 51; 72.9%), whereas only intrahepatic recurrences were observed in 2 (2.8%) patients. Both intrahepatic and extrahepatic locations were found in 17 (24.3%) patients. A total of 22 (31.4%) patients underwent macroscopically complete resection of the recurrence (intrahepatic [n = 2] and extrahepatic [n = 20]). The MS for resected patients after transplantation was 35 months compared with 15 months for nonresected patients (P < 0.001). In multivariate analysis, the independent unfavorable factors of postrecurrence survival were alpha-fetoprotein level > 100 ng/mL at relapse (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.1-4.1; P = 0.03), intrahepatic location (HR, 1.8; 95% CI, 1.0-3.2; P = 0.05), and multifocal recurrence (HR, 1.8; 95% CI, 1.1-3.1; P = 0.04). The management including surgery (HR, 0.4; 95% CI, 0.2-0.7; P = 0.004) was identified as an independent favorable factor. In conclusion, recurrence of HCC after LT is associated with a poor prognosis. However, resection is associated with improved survival and should therefore be considered when feasible. Liver Transplantation 23 440-447 2017 AASLD.

As a reflection of both hypoperfusion and tissue damage, the assay of arterial LCEOT ≥5 mmol/L appears to be a strong predictor of early graft outcomes and may be used as an endpoint in studies assessing the impact of perioperative management. Its accessibility and low cost could impose it as a reliable parameter to anticipate postoperative management and help clinicians for decision-making in the first PODs.

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This multicenter study compares the outcomes of patients with cirrhosis undergoing liver transplantation (LT) or liver resection (LR) between January 2002 and July 2015 who had intrahepatic cholangiocarcinoma (iCCA) or combined hepatocellularcholangiocarcinoma (cHCC-CCA) found incidentally in the native liver. A total of 49 (65%) LT and 26 (35%) LR patients with cirrhosis and histologically confirmed iCCA/cHCC-CCA ≤5 cm were retrospectively analyzed. LT patients had significantly lower tumor recurrence (18% versus 46%; P = 0.01), for which the median diameter of the largest nodule (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.02-1.12]; P = 0.006) and tumor differentiation (HR, 3.74; 95% CI 1.71-8.17; P = 0.001) were independently predictive. The LT group had significantly higher 5-year recurrence-free survival (RFS; 75% versus 36%; P = 0.004). In patients with tumors >2 cm but ≤5 cm, LT patients had a lower recurrence rate (21% versus 48%; P = 0.06) and a higher 5-year RFS (74% versus 40%; P = 0.06). Independent risk factors for recurrence were LT (protective; HR, 0.23; 95% CI, 0.07-0.82; P = 0.02), the median diameter of the largest nodule (HR, 1.10; 95% CI, 1.02-1.73; P = 0.007), and tumor differentiation (HR, 4.16; 95% CI, 1.37-12.66; P = 0.01). In the LT group, 5-year survival reached 69% and 65% (P = 0.40) in patients with tumors ≤2 cm and >2-5 cm, respectively, and survival was also comparable between iCCA and cHCC-CCA patients (P = 0.29). LT may offer a benefit for highly selected patients with cirrhosis and unresectable iCCA/cHCC-CCA having tumors ≤5 cm. Efforts should be made to evaluate tumor differentiation, and these results need to be confirmed prospectively in a larger population. Liver Transplantation 26 785-798 2020 AASLD. SEE EDITORIAL ON PAGE 748Intrahepatic cholangiocarcinoma (iCCA) accounts for 20%-25% of all cholangiocarcinoma (CCA) cases, and its incidence is rising at an average of 14% per year in Western countries. (1,2) Moreover, the mixed form of iCCA and hepatocellular carcinoma (HCC), referred to as combined hepatocellularcholangiocarcinoma (cHCC-CCA), is well recognized and increasingly reported. (3) Liver cirrhosis is a major risk factor for iCCA, with an odds ratio of 22.92 (95% confidence interval [CI], 18.24-28.79), De Martin et al. De Martin et al. liver transplantatiOn, June 2020

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Future prevention and management may include pharmacological slowing of proliferation, drug or physical modulation of portal flow to reduce shear-stress, stem cells or immortalized hepatocytes injection, and liver bioreactors. Everything must be done to avoid the need for transplantation, which remains today the most efficient treatment of liver failure.