Taiji Tohyama

Biological markers of hepatocellular carcinoma for use as selection criteria in liver transplantation

The Milan criteria (MC) have been widely accepted as an effective way of selecting patients with early‐stage hepatocellular carcinoma (HCC) for curative liver transplantation (LT). However, since a substantial subset of HCC patients exists that is beyond the MC but with the potential for good outcomes after LT, several institutions have recently proposed new extended criteria. To explore optimal criteria that can reasonably predict the risk of recurrence, it is considered that new markers of biological behavior are needed in addition to morphological tumor size and number. Several promising candidates for such biological markers have been reported, including serum tumor markers such as alpha‐fetoprotein and des‐gamma‐carboxy prothrombin, inflammatory markers such as C‐reactive protein and neutrophil‐to‐lymphocyte ratio, response to pre‐transplant treatments for bridging therapy or down‐staging, and fluorine‐18‐fluorodeoxyglucose positron emission tomography. However, the role of these biological markers in patient selection criteria for LT has yet to be clarified. This review article aims to summarize the results of recent reported studies and to display perspectives for the establishment of optimal criteria that incorporate such biological markers.

A Nationwide Survey of Hepatitis E Virus Infection and Chronic Hepatitis E in Liver Transplant Recipients in Japan

Background Recently, chronic hepatitis E has been increasingly reported in organ transplant recipients in European countries. In Japan, the prevalence of hepatitis E virus (HEV) infection after transplantation remains unclear, so we conducted a nationwide cross-sectional study to clarify the prevalence of chronic HEV infection in Japanese liver transplant recipients. Methods A total of 1893 liver transplant recipients in 17 university hospitals in Japan were examined for the presence of immunoglobulin G (IgG), IgM and IgA classes of anti-HEV antibodies, and HEV RNA in serum. Findings The prevalence of anti-HEV IgG, IgM and IgA class antibodies was 2.9% (54/1893), 0.05% (1/1893) and 0% (0/1893), respectively. Of 1651 patients tested for HEV RNA, two patients (0.12%) were found to be positive and developed chronic infection after liver transplantation. In both cases, HEV RNA was also detected in one of the blood products transfused at the perioperative period. Analysis of the HEV genomes revealed that the HEV isolates obtained from the recipients and the transfused blood products were identical in both cases, indicating transfusion-transmitted HEV infection. Interpretation The prevalence of HEV antibodies in liver transplant recipients was 2.9%, which is low compared with the healthy population in Japan and with organ transplant recipients in European countries; however, the present study found, for the first time, two Japanese patients with chronic HEV infection that was acquired via blood transfusion during or after liver transplantation.

Impact of psoas muscle index on short-term outcome after living donor liver transplantation.

BACKGROUND/AIMS Living donor liver transplantation is an operation with high morbidity and mortality rates. The purpose of this study was to examine factors affecting the short-term outcome after living donor liver transplantation. MATERIALS AND METHODS Forty-seven adult patients who underwent living donor liver transplantation from September 2001 to December 2014 were included. Short-term post-transplant outcomes were evaluated in terms of the onset of postoperative complications of grade 3a and above (Clavien-Dindo classification) and postoperative 120-day mortality. Univariate and multivariate analyses were used to determine possible predictive factors among perioperative variables such as preoperative psoas muscle index (PMI), blood laboratory test results, perioperative nutritional therapy, and operative factors. RESULTS Lower PMI (lower than the first quartile of PMI of donors), higher blood urea nitrogen level (≥14 mg/dL), and blood type incompatibility were independent risk factors for the development of postoperative complications. The 120-day survival rates were significantly lower for the lower PMI group (n=30, 66.7%) than for the higher PMI group (n=17, 94.1%, p=0.034). CONCLUSION A significant correlation was observed between preoperative PMI and short-term postoperative outcomes. Sarcopenia estimated by PMI may serve as a measure of patient frailty and a target for risk stratification.

Protective Effect of Adeno-Mediated Human Bcl-xL Gene Transfer to the Mouse Liver in a Partial Ischemia/Reperfusion Model

BACKGROUND The protective effect of heat preconditioning has been ascribed to the induction of heat shock proteins (HSP) in the liver. We detected an increase in Bcl-xL expression prior to HSP 70 expression in the rat liver after heat preconditioning. The net effect of overexpression of human Bcl-xL with a recombinant adenovector was estimated in a partial ischemia/reperfusion model of the mouse liver. MATERIALS AND METHODS The time courses of the expression of HSP, Bcl-xL, Bcl-2, Bax, and Bag-1 in the SD rat liver after heat preconditioning were studied by Western blotting. The localizations of Bcl-xL, Bcl-2, and Bax at 6 h after preconditioning were examined by immunostaining. The expression of Bcl-xL in the C57/BL mouse liver after intravenous injection of the recombinant adenovector was assessed by Western blotting and immunostaining. The protective effect of overexpression of Bcl-xL was estimated in a 60-min partial ischemia/reperfusion model of the mouse liver. RESULTS The expression of Bcl-xL peaked 12 h after heat preconditioning. The overexpression of Bcl-xL decreased enzyme release, histological cell injury, and the number of TUNEL-positive cells. CONCLUSION Transfer of the human Bcl-xL gene to the liver had a protective effect against ischemia/reperfusion injury in a mouse model.

Recovery After Critical Illness Polyneuropathy in a Patient With Orthotopic Liver Transplantation: A Case Report

After liver transplantation, some patients show neuromuscular abnormalities. A 43-year-old man with liver cirrhosis due to hepatitis C virus underwent living-donor liver transplantation. He developed severe neuromuscular dysfunction after sepsis, and acute respiratory distress syndrome. After the inflammatory reaction gradually improved, we observed bilateral weakness of the extremities and foot drop. Electrophysiological studies indicated primary axonal degeneration of peripheral motor and sensory fibers without inflammation. Critical illness polyneuropathy was diagnosed. During follow-up, complaints gradually recovered with rehabilitation by approximately 1 year later. Based on this case, we suggest that paralysis should be evaluated for critical illness polyneuropathy in patients with unexplained muscle weakness.

Localized 18F-fluorodeoxyglucose uptake at the pancreatic head during remission phase of autoimmune pancreatitis: A case report

Autoimmune pancreatitis (AIP) is a unique form of pancreatitis, histopathologically characterized by dense lymphoplasmacytic infiltration and fibrosis of the pancreas with obliterative phlebitis. AIP is associated with a good response to steroid therapy. Differentiation between AIP and pancreatic cancer to determine a preoperative diagnosis is often challenging, despite the use of various diagnostic modalities, including computed tomography (CT), magnetic resonance imaging and endoscopic retrograde cholangiopancreatography. It has been reported that 18F-fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET)/CT may be a useful tool for distinguishing between the two diseases. In the present case report, a 71-year-old male patient presented with a well-circumscribed, solitary, nodular and homogenous 18F-FDG uptake at the pancreatic head, while receiving maintenance steroid therapy in the remission phase of AIP; preoperatively, the patient had been strongly suspected of having pancreatic cancer. Pathological examination revealed post-treatment relapse of AIP. The present case highlights the diagnostic and management difficulties with AIP in the remission phase. In certain cases, it remains challenging to differentiate the two diseases, even using the latest modalities.

Quality of life after single-incision laparoscopic cholecystectomy: A randomized, clinical trial

Background: Controversy continues as to whether single‐incision laparoscopic cholecystectomy, with the somewhat larger incision at the umbilicus, may lead to a worse postoperative quality of life and more pain compared with the more classic 4‐port laparoscopic cholecystectomy. The aim of this study was to compare single‐incision and 4‐port laparoscopic cholecystectomy from the perspective of quality of life. Methods: This study was a multicenter, parallel‐group, open‐label, randomized clinical trial. A total of 120 patients who were scheduled to undergo elective cholecystectomy were randomly assigned 1:1 into the single‐incision laparoscopic cholecystectomy or the 4‐port laparoscopic cholecystectomy group and then assessed continuously for 2 weeks during the postoperative period. The primary outcome was quality of life, defined as the time to resume normal daily activities. Postoperative pain was also assessed. To explore the heterogeneity of treatment effects, we assessed the interactions of sex, age, and working status on recovery time. Results: A total of 58 patients in the single‐incision group and 53 in the 4‐port group (n = 111, 47 male, mean age 57 years) were analyzed. The mean time to resume daily activities was 10.2 days and 8.8 days, respectively, for single‐incision and 4‐port laparoscopic cholecystectomy (95% confidence interval –0.4 to 3.2, P = .12). Similarly, the time to relief from postoperative pain did not differ significantly between the groups. Statistically insignificant but qualitative interactions were noted; in the subgroups of women, full‐time workers, and patients younger than 60 years, recovery tended to be slower after single‐incision laparoscopic cholecystectomy. Conclusion: Postoperative quality of life did not differ substantially between single‐incision laparoscopic cholecystectomy and 4‐port laparoscopic cholecystectomy. Patients younger than 60 years, women, and full‐time workers tended to have a somewhat slower recovery after single‐incision laparoscopic cholecystectomy.