Multicentre, randomised, placebocontrolled trial of extract of Japanese herbal medicine Daikenchuto to prevent bowel dysfunction after adult liver transplantation (DKB 14 Study)

Introduction: This multicentre randomised controlled clinical trial will aim to determine the ability of an extract (TJ-100) of Daikenchuto (traditional Japanese herbal medicine; Kampo) to prevent bowel dysfunction in at least 110 patients after liver transplantation (LT). Methods and analysis: The following co-primary end points will be evaluated on postoperative day 7: total oral and enteral caloric intake, abdominal distension and abdominal pain. The secondary end points will comprise sequential changes of total oral and enteral caloric intake after LT, sequential changes in numeric rating scales for abdominal distension and pain, elapsed time to the first postoperative passage of stool, quality of life assessment using the Gastrointestinal Symptom Rating Scale score (Japanese version), postoperative liver function, liver regeneration rate, incidence of bacteraemia and bacterial strain, trough level of immunosuppressants, occurrence of acute cellular rejection, discharge or not within 2 months after LT, sequential changes of portal venous flow to the graft and ascites discharge. The two arms of the study will comprise 55 patients per arm. Ethics and dissemination: The study has been conducted according to the CONSORT statement. All participants signed a written consent form, and the study has been approved by the institutional review board of each participating institute and conducted in accordance with the Declaration of Helsinki of 1996. The findings will be disseminated through scientific and professional conferences, and in peer-reviewed journals

Pretransplant serum hepatitis C virus RNA levels predict response to antiviral treatment after living donor liver transplantation.

[Background]Given the limited efficacy and high adverse event rate associated with treatment of recurrent hepatitis C after liver transplantation, an individualized treatment strategy should be considered. The aim of this study was to identify predictors of response to antiviral therapy for hepatitis C after living donor liver transplantation (LDLT) and to study the associated adverse events. [Methods]A retrospective chart review was performed on 125 hepatitis C virus (HCV)-positive LDLT recipients who received interferon plus ribavirin and/or peginterferon plus ribavirin therapy at Kyoto University between January 2001 and June 2011. [Results]Serum HCV RNA reached undetectable levels within 48 weeks in 77 (62%) of 125 patients, and these patients were defined as showing virological response (VR). Of 117 patients, 50 (43%) achieved sustained VR (SVR). Predictive factors associated with both VR and SVR by univariate analysis included low pretransplant serum HCV RNA levels, a non-1 HCV genotype, and low pretreatment serum HCV RNA levels. In addition, LDLT from ABO-mismatched donors was significantly associated with VR, and white cell and neutrophil counts before interferon therapy were associated with SVR. Multivariate analysis showed that 2 variables–pretransplant serum HCV RNA level less than 500 kIU/mL and a non-1 HCV genotype–remained in models of both VR and SVR and that an ABO mismatch was associated with VR. No variables with a significant effect on treatment withdrawal were found. [Conclusions]Virological response to antiviral therapy in patients with hepatitis C recurring after LDLT can be predicted prior to transplant, based on pretransplant serum HCV-RNA levels and HCV genotype. LDLT from ABO-mismatched donors may contribute to more efficacious interferon therapy

Impact of Hepatic Steatosis on Disease-Free Survival in Patients with Non-B Non-C Hepatocellular Carcinoma Undergoing Hepatic Resection.

[Background]Although the prevalence of non-B non-C hepatocellular carcinoma (NBNC HCC) has increased, its clinicopathologic characteristics remain unclear. [Methods]We retrospectively analyzed 518 HCC patients who underwent hepatic resection. Hepatitis B surface antigen- and hepatitis C antibody-negative patients were categorized into the NBNC HCC group (n = 145); others were categorized into the hepatitis B or C HCC (BC HCC) group (n = 373). We subdivided the etiologies of NBNC HCC according to alcohol intake and presence of steatosis. [Results]NBNC HCC was associated with nonalcoholic fatty liver disease (NAFLD) (13.1 %), fatty liver disease with moderate alcohol intake (9.0 %), alcoholic liver disease (ALD) (29.7 %), cryptogenic disease (44.1 %), and other known etiologies (4.1 %). The prevalence of obesity, diabetes mellitus, and hypertension was higher and hepatic function was better in the NBNC HCC group, which had significantly larger tumors than the BC HCC group. The entire NBNC HCC group displayed similar overall and disease-free survival as the BC HCC group. Among the subdivisions, NAFLD-associated HCC patients had significantly better disease-free survival than ALD-associated HCC and BC HCC patients. Microvascular invasion (hazard ratio [HR] 2.30; 95 % confidence interval [CI] 1.33–3.96) and steatosis area <5 % of noncancerous region (HR 2.13; 95 % CI 1.21–3.93) were associated with disease-free survival in NBNC HCC patients. [Conclusions]The prognosis of NBNC HCC was similar to that of BC HCC. Among NBNC HCC patients, NAFLD-associated HCC patients had a relatively low recurrence risk. Absence of steatosis in hepatic parenchyma had a significant impact on disease-free survival in NBNC HCC patients

Effect of sarcopenia on survival of patients with cirrhosis: A meta-analysis

The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, by sex, underlying liver disease etiology, and severity of hepatic dysfunction.PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with additional manual search of bibliographies of relevant articles. Cohort studies of ?100 patients with cirrhosis and ?12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included.22 studies with 6965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), higher in male patients, patients with alcohol associated liver disease (ALD), patients with CTP grade C, and when sarcopenia was defined in patients by lumbar 3- skeletal muscle index (L3-SMI). Sarcopenia was associated with the increased risk of mortality in patients with cirrhosis (adjusted-hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in sensitivity analysis of cirrhosis patients without HCC (aHR 2.35, 95% CI 1.95-2.83) and in subgroup analysis by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the poor prognosis for patients with sarcopenia (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in all analyses.Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis.The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% in patients with ALD or Child's class C cirrhosis. Sarcopenia was independently associated with about 2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer period of having sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized

Characteristics of Nutritional Status and the Effect of Pre-transplant Branched-chain Amino Acid Administration in Patients Undergoing Living Donor Liver Transplantation

Background: Protein-energy malnutrition is common in patients with end-stage liver disease undergoing liver transplantation. We examined the characteristics of nutritional status and impact of pre-admission branched-chainamino- acids treatment on skeletal muscle mass, nutritional/metabolic parameters and on post-transplant outcomes. Methodology: Preoperative skeletal muscle mass and nutritional/metabolic parameter levels were compared in 129 patients undergoing adult-to-adult living donor liver transplantation whether received branched-chain-aminoacids treatment before admission or not. We examined relationships among these parameters, and risk factors for post-transplant bacteremia and early mortality after LT focusing on nutritional parameters. Results: Pre-albumin and branched-chain-amino-acids-to-tyrosine ratio were significantly higher while tyrosine was lower in branched-chain-amino-acids-pre-supplemented than non-pre-supplemented group, while skeletal muscle mass, total lymphocyte count, zinc, branched-chain-amino-acids and ammonia levels were not significantly different. Skeletal muscle mass positively correlated with tyrosine (r=0.437, P<0.001) and branched-chain-aminoacids (r=0.282, P=0.001) and negatively with branched-chain-amino-acids-to-tyrosine-ratio (r=-0.259, P=0.003). Multivariate predictors of post-transplant bacteremia were: Child-Pugh class C (P=0.012), low preoperative total lymphocyte count (P=0.027), operative blood loss ≥ 10 L (P=0.039) and absence of pre-admission branched-chainamino- acids treatment (P=0.040). Nutritional/metabolic parameters and pre-admission branched-chain-amino-acids treatment were not crucial for post-transplant early mortality. Conclusion: Pre-admission branched-chain-amino-acid therapy could ameliorate preoperative amino acid imbalance and the incidence of post-transplant bacteremia

Current Status of Liver Transplantation Using Marginal Grafts

The use of marginal liver grafts has become an inevitable option because of the continuous increase in the number of patients awaiting liver transplantation and the severe shortage of suitable donors. Recently, several approaches have been adapted to expand the donor pool and improve the outcome of marginal grafts in both deceased and living donor liver transplantation. Accordingly, this review discusses the various types of marginal grafts in both deceased and living donor liver transplantation, their outcome and the up-to-date innovations or strategies to extend the donor pool and improve the patient and graft survival post-transplant

Long-term outcomes of hepatic resection versus living donor liver transplantation for hepatocellular carcinoma: a propensity score-matching study.

Hepatic resection (HR) and liver transplantation (LT) are surgical treatment options for hepatocellular carcinoma (HCC). However, it is clinically impossible to perform a randomized, controlled study to determine the usefulness of these treatments. The present study compared survival rates and recurrence rates of HR versus living donor LT (LDLT) for HCC by using the propensity score method. Between January 1999 and August 2012, 936 patients (732 HR, 204 LDLT) underwent surgical therapy for HCC in our center. Using the propensity score matching, 80 well-balanced patients were defined. The 1- and 5-year overall survival rates were 90% and 53% in the HR group and 82% and 63% in the LT group, respectively. They were not significantly different between the two groups. The odds ratio estimated using the propensity score matching analysis was 0.842 (P = 0.613). The 1- and 5-year recurrence rates were significantly lower in the LT group (9% and 21%) than in the HR group (43% and 74%) (P < 0.001), and the odds ratio was 0.214 (P = 0.001). In conclusion, HR should be considered a valid alternative to LDLT taking into consideration the risk for the living donor based on the results of this propensity score-matching study

Legislative Documents

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