Summary Portal vein thrombosis is not uncommon in candidates for transplantation. Partial thrombosis is more common than complete thrombosis. Despite careful screening at evaluation, a number of ...patients are still found with previously unrecognized thrombosis per-operatively. The objective is to recanalize the portal vein or, if recanalization is not achievable, to prevent the extension of the thrombus so that a splanchnic vein can be used as the inflow vessel to restore physiological blood flow to the allograft. Anticoagulation during waiting time and transjugular intrahepatic portosystemic shunt (TIPS) are two options to achieve these goals. TIPS may achieve recanalization in patients with complete portal vein thrombosis. However, a marked impairment in liver function, which is a characteristic feature of most candidates for transplantation, may be a contraindication for TIPS. Importantly, the MELD score is artificially increased by the administration of vitamin K antagonists due to prolonged INR. When patency of the portal vein and/or superior mesenteric vein is not achieved, only non-anatomical techniques (renoportal anastomosis or cavoportal hemitransposition) can be performed. These techniques, which do not fully reverse portal hypertension, are associated with higher morbidity and mortality risks. Multivisceral transplantation including the liver and small bowel needs to be evaluated. In the absence of prothrombotic states that may persist after transplantation, there is no evidence that pre-transplant portal vein thrombosis justifies long term anticoagulation post-transplantation, provided portal flow has been restored through conventional end-to-end portal anastomosis.
Background & Aims Waiting-list mortality in patients with cirrhosis and a relatively low MELD score is a matter of concern. The aim of this study was to determine whether a marker of muscle waste ...could improve prognostication. Methods A pre-MELD cohort (waiting time-based allocation; n = 186) and a MELD-era cohort (n = 376) were examined. At evaluation, transversal psoas muscle thickness (TPMT) was measured on a computed tomography (CT) image at the level of the umbilicus. In the pre-MELD cohort, TPMT/height (mm/m) and the MELD score were entered in univariate and multivariate models to predict mortality after registration. Applicability of pre-MELD findings was tested in the MELD-era. Results In the pre-MELD cohort, the MELD score and TPMT/height were significantly associated with mortality. The discrimination of a score combining MELD and TPMT/height (MELD-psoas) was 0.84 (95% CI, 0.62–0.95). In the MELD-era, TPTM/height was significantly associated with mortality, independent of the MELD and MELD-Na scores. There was a 15% increase in mortality risk per unit decrease in TPMT/height. The discrimination of MELD-psoas score (0.82; 95% CI, 0.64–0.93) was superior to that of the MELD score and similar to that of the MELD-Na score. In patients with refractory ascites, mortality was significantly higher when TPMT/height was <16.8 mm/m (42% vs. 9%, p = 0.02). Conclusions TPMP/height on CT at the level of the umbilicus, an objective marker of muscle waste, may be predictive of mortality in cirrhotic patients, independent of the MELD and MELD-Na scores. It may help to better assess the prognosis of patients with refractory ascites.
In hepatitis C virus (HCV)‐infected patients, transplantation can be justified by decompensated cirrhosis, hepatocellular carcinoma (HCC) or both. During the last decade, HCV infection accounted for ...about 30% of the indications for transplantation in Europe and North America. Direct antiviral agents (DAAs) are highly effective at curing HCV, even in patients with end‐stage cirrhosis. In the future, the incidence of HCV‐related decompensated cirrhosis will continue to decrease. The incidence of HCC will also decrease, but a large cohort of patients with cirrhosis will still be at risk of developing HCC even after HCV has been cured. They will continue to represent potential candidates for transplantation. Overall, HCV will account for a significantly lower proportion of indications for transplantation in the future. However, generalization of DAAs is unlikely to affect the total transplantation volume as the gap between donors and potential recipients markedly exceeds 30%. In addition, non‐alcoholic steatohepatitis (NASH) is a rapidly growing indication for transplantation. The high barrier to resistance nucleos(t)ide analogues (NUCs) have been used for several years to treat hepatitis B virus (HBV) infection. Decompensated HBV cirrhosis now represents a very uncommon indication for transplantation. HCC remains the leading indication in HBV‐infected patients awaiting transplantation. NUCs plus anti‐HBs immune globulins or NUCs alone are highly effective at preventing post‐transplant HBV recurrence. However, continuous prophylaxis is still needed as extrahepatic HBV particles persist with a potential for recurrence. Post‐transplant immunosuppression facilitates recurrence. In the future, an important challenge will be to cure HBV by eliminating residual HBV particles
Long-term outcomes in portopulmonary hypertension (PoPH) are poorly studied in the current era of pulmonary hypertension management. We analysed the effect of pulmonary arterial hypertension ...(PAH)-targeted therapies, survival and predictors of death in a large contemporary cohort of patients with PoPH.
Data from patients with PoPH consecutively enrolled in the French Pulmonary Hypertension Registry between 2007 and 2017 were collected. The effect of initial treatment strategies on functional class, exercise capacity and cardiopulmonary haemodynamics were analysed. Survival and its association with PAH- and hepatic-related characteristics were also examined.
Six hundred and thirty-seven patients (mean age 55 ± 10 years; 58% male) were included. Fifty-seven percent had mild cirrhosis, i.e. Child-Pugh stage A. The median model for end-stage liver disease (MELD) score was 11 (IQR 9–15). Most patients (n = 474; 74%) were initiated on monotherapy, either with a phosphodiesterase-5 inhibitor (n = 336) or with an endothelin-receptor antagonist (n = 128); 95 (15%) were initiated on double oral combination therapy and 5 (1%) on triple therapy. After a median treatment time of 4.5 months, there were significant improvements in functional class (p <0.001), 6-minute walk distance (6MWD) (p <0.0001) and pulmonary vascular resistance (p <0.0001). Overall survival rates were 84%, 69% and 51% at 1, 3 and 5 years, respectively. Baseline 6MWD, sex, age and MELD score or Child-Pugh stage were identified as independent prognostic factors. Survival from PoPH diagnosis was significantly better in the subgroup of patients who underwent liver transplantation (92%, 83% and 81% at 1, 3 and 5 years, respectively).
Survival of patients with PoPH is strongly associated with the severity of liver disease. Patients who underwent liver transplantation had the best long-term outcomes.
Portopulmonary hypertension is defined by the presence of pulmonary arterial hypertension in the context of chronic liver disease and is characterized by progressive shortness of breath and exercise limitation. The presence of severe pulmonary arterial hypertension in liver transplant candidates represents a contraindication for such a surgery; however, treatments targeting pulmonary arterial hypertension are efficacious, allowing for safe transplantation and conferring good survival outcomes in those who undergo liver transplantation.
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•Portopulmonary hypertension is a severe complication of portal hypertension.•Therapies targeting pulmonary arterial hypertension improve cardiopulmonary haemodynamics.•Combining these therapies and liver transplantation is associated with excellent long-term outcomes.
Osteoporosis in candidates for liver transplantation (LT) is often underdiagnosed despite the important consequences of morbidity.
We included 376 patients with cirrhosis evaluated for LT with ...available computed tomography (CT) scans. Prevalent vertebral fractures (VFs) were identified on CT reconstructions, and bone density was assessed by measuring CT attenuation of the L1 vertebra (L1-CT).
We identified 139 VFs in 55 patients (14.6%). Logistic regression models showed that low L1-CT was the only independent determinant of VF.
In patients with cirrhosis evaluated for LT, CT scans identified persons with severe osteoporosis without additional costs.
Cirrhosis is a major risk factor for the development of hepatocellular carcinoma but remains underdiagnosed in the compensated stage. Fibrosis progression and cirrhosis are associated with changes in ...blood serum glycomic profiles. Previously, the serum glycomics-based GlycoCirrhoTest was shown to identify 50% to 70% of compensated cirrhosis cases in chronic liver disease cohorts, at >90% specificity. This study assessed GlycoCirrhoTest for the risk of hepatocellular carcinoma development in compensated cirrhosis.
Serum glycomics were analyzed in sera of 133 patients, with compensated cirrhosis collected between 1995 and 2005 in a surveillance protocol for hepatocellular carcinoma using an optimized glycomic technology on a DNA sequencer.
Baseline GlycoCirrhoTest values were significantly increased in patients who developed hepatocellular carcinoma after a median follow-up of 6.4 years as compared with patients who did not. For patients with a baseline GlycoCirrhoTest exceeding 0.2, the HR for hepatocellular carcinoma development over the entire study (Cox regression) was 5.1 95% confidence interval (CI), 2.2-11.7;
< 0.001, and the HR for hepatocellular carcinoma development within 7 years was 12.1 (95% CI, 2.8-51.6;
= 0.01) based on the cut-off value optimized in the same cohort. An absolute increase in GlycoCirrhoTest of 0.2 was associated with an HR of 10.29 (95% CI, 3.37-31.43;
< 0.001) for developing hepatocellular carcinoma. In comparison, the HR for the development of hepatocellular carcinoma within 7 years for AFP levels above the optimal cutoff in this study (5.75 ng/mL) was 4.65 (95% CI, 1.59-13.61).
This prognostic study suggests that GlycoCirrhoTest is a serum biomarker that identifies compensated cirrhotic patients at risk for developing hepatocellular carcinoma. Screening strategies could be guided by a positive test on GlycoCirrhoTest.
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Patients with cirrhosis and acute-on-chronic liver failure (ACLF) have immunosuppression, indicated by an increase in circulating immune-deficient monocytes. The aim of this study was to investigate ...simultaneously the major blood-immune cell subsets in these patients.
Blood taken from 67 patients with decompensated cirrhosis (including 35 critically ill with ACLF in the intensive care unit), and 12 healthy subjects, was assigned to either measurements of clinical blood counts and microarray (genomewide) analysis of RNA expression in whole-blood; microarray (genomewide) analysis of RNA expression in blood neutrophils; or assessment of neutrophil antimicrobial functions.
Several features were found in patients with ACLF and not in those without ACLF. Indeed, clinical blood count measurements showed that patients with ACLF were characterized by leukocytosis, neutrophilia, and lymphopenia. Using the CIBERSORT method to deconvolute the whole-blood RNA-expression data, revealed that the hallmark of ACLF was the association of neutrophilia with increased proportions of macrophages M0-like monocytes and decreased proportions of memory lymphocytes (of B-cell, CD4 T-cell lineages), CD8 T cells and natural killer cells. Microarray analysis of neutrophil RNA expression revealed that neutrophils from patients with ACLF had a unique phenotype including induction of glycolysis and granule genes, and downregulation of cell-migration and cell-cycle genes. Moreover, neutrophils from these patients had defective production of the antimicrobial superoxide anion.
Genomic analysis revealed that, among patients with decompensated cirrhosis, those with ACLF were characterized by dysregulation of blood immune cells, including increases in neutrophils (that had a unique phenotype) and macrophages M0-like monocytes, and depletion of several lymphocyte subsets (including memory lymphocytes). All these lymphocyte alterations, along with defective neutrophil superoxide anion production, may contribute to immunosuppression in ACLF, suggesting targets for future therapies.
In patients with polycystic liver disease (PLD), development of cysts induces hepatic venous outflow obstruction (HVOO) and parenchymal modifications, challenging the paradigm of a normal noncystic ...liver parenchyma. The aims were to reappraise the pathology of the noncystic parenchyma, by focusing on HVOO lesions; and to investigate the association with outflow obstruction at imaging and perioperative course after liver resection. This is a retrospective study conducted in one tertiary center between 1993 and 2014. PLD patients (n = 125) who underwent resection (n = 90) or transplantation (n = 35) were included. HVOO parenchymal lesions were assessed for all patients and a liver congestion score was built. Imaging was analysed for 45 patients with computed tomography scan, and perioperative course was assessed in resected patients. At pathology, 92% of patients had HVOO lesions, with sinusoidal dilatation being the most common feature. HVOO was more severe in patients who underwent transplantation compared to liver resection, as assessed by the congestion score. At imaging, all patients had HVOO with at least two hepatic veins involved. Mosaic enhancement pattern of the parenchyma was associated with the severity of hepatic vein obstruction (P = 0.045) and the compression of the inferior vena cava (P = 0.014). In case of liver resection, intraoperative course was characterized by hemorrhage, related to HVOO at imaging. Ascites (44%) and liver failure (9%) in the postoperative period were associated with blood losses and transfusions. Conclusion: Hepatic venous outflow obstruction, including development of venous collaterality and parenchymal changes, is frequent in PLD and has major consequences on intraoperative bleeding and postoperative ascites and liver failure. Hepatic venous outflow obstruction should be taken into account to choose the most appropriate surgical treatment. (Hepatology 2017).
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