RECAM-J 2023-Validation and development of the Japanese version of RECAM for the diagnosis of drug-induced liver injury.

AIM: The diagnosis of drug-induced liver injury (DILI) is challenging. We modified the revised electronic version of the Roussel Uclaf Causality Assessment Method (RUCAM) for the diagnosis of DILI (RECAM), the scoring system developed in US and Spanish cohorts in 2022, and developed RECAM-J 2023 to align with the clinical practice in Japan. In the current study, we introduce RECAM-J 2023 and verify its performance in the context of Japanese patients with DILI. METHODS: After translation of RECAM into Japanese, modifications were made to develop RECAM-J 2023 without any alteration to the scores. To examine the validity and performance of RECAM-J 2023, clinical information on DILI and non-DILI cases in Japan were retrospectively collected. The diagnosis of DILI was made by expert's decision. Then we scored each case using RECAM-J 2023, and calculated area under curve (AUC) values for identification for DILI. RESULTS: We collected data from 538 DILI and 128 non-DILI cases. The sum of highly probable (HP) and probable (PR) cases categorized by RECAM-J 2023 were only 206 (38%) in DILI cases. As the primary cause of low scores was the deduction with missing hepatitis virus markers, which is unlikely to be an issue in prospective applications, we rescored without these deductions. At this time, the sum of HP and PR was raised to 421 (78%). The AUCs of RECAM-J 2023 without deductions were 0.70 and 0.88 for identifying at least HP, and at least PR, respectively. CONCLUSION: RECAM-J 2023, when prospectively used without any missing hepatitis virus markers, provides acceptable performance for identifying at least PR DILI cases in Japanese daily clinical practice.

Narrowing the Patient-Physician Gap Based on Self-Reporting and Monthly Hepatologist Feedback for Patients With Alcohol-Related Liver Disease: Interventional Pilot Study Using a Journaling Smartphone App.

BACKGROUND: Screening and intervention for alcohol use disorders (AUDs) are recommended to improve the prognosis of patients with alcohol-related liver disease (ALD). Most patients' smartphone app diaries record drinking behavior for self-monitoring. A smartphone app can be expected to also be helpful for physicians because it can provide rich patient information to hepatologists, leading to suitable feedback. We conducted this prospective pilot study to assess the use of a smartphone app as a journaling tool and as a self-report-based feedback source for patients with ALD. OBJECTIVE: The aims of this study were assessment of whether journaling (self-report) and self-report-based feedback can help patients maintain abstinence and improve liver function data. METHODS: This pilot study used a newly developed smartphone journaling app for patients, with input data that physicians can review. After patients with ALD were screened for harmful alcohol use, some were invited to use the smartphone journaling app for 8 weeks. Their self-reported alcohol intake, symptoms, and laboratory data were recorded at entry, week 4, and week 8. Biomarkers for alcohol use included gamma glutamyl transferase (GGT), percentage of carbohydrate-deficient transferrin to transferrin (%CDT), and GGT-CDT (GGT-CDT= 0.8 × ln[GGT] + 1.3 × ln[%CDT]). At each visit, their recorded data were reviewed by a hepatologist to evaluate changes in alcohol consumption and laboratory data. The relation between those outcomes and app usage was also investigated. RESULTS: Of 14 patients agreeing to participate, 10 completed an 8-week follow-up, with diary input rates between 44% and 100% of the expected days. Of the 14 patients, 2 withdrew from clinical follow-up, and 2 additional patients never used the smartphone journaling app. Using the physician's view, a treating hepatologist gave feedback via comments to patients at each visit. Mean self-reported alcohol consumption dropped from baseline (100, SD 70 g) to week 4 (13, SD 25 g; P=.002) and remained lower at week 8 (13, SD 23 g; P=.007). During the study, 5 patients reported complete abstinence. No significant changes were found in mean GGT and mean %CDT alone, but the mean GGT-CDT combination dropped significantly from entry (5.2, SD 1.2) to the week 4 visit (4.8, SD 1.1; P=.02) and at week 8 (4.8, SD 1.0; P=.01). During the study period, decreases in mean total bilirubin (3.0, SD 2.4 mg/dL to 2.4, SD 1.9 mg/dL; P=.01) and increases in mean serum albumin (3.0, SD 0.9 g/dL to 3.3, SD 0.8 g/dL; P=.009) were recorded. CONCLUSIONS: These pilot study findings revealed that a short-term intervention with a smartphone journaling app used by both patients and treatment-administering hepatologists was associated with reduced drinking and improved liver function. TRIAL REGISTRATION: UMIN CTR UMIN000045285; http://tinyurl.com/yvvk38tj.

A giant Brunner gland hamartoma successfully treated by endoscopic excision followed by transanal retrieval: A case report.

RATIONALE: Brunner gland hamartoma (BGH) is a rare tumor of the duodenum. Although BGH is a benign tumor, larger lesion with gastrointestinal symptoms requires tumor removal. We report a giant BGH, successfully treated by endoscopic excision followed by transanal retrieval. PATIENT CONCERNS: A 38-year-old woman complained of severe anemia, tarry stool, and vomiting. DIAGNOSES: Esophagogastroduodenoscopy (EGD) showed a pedunculated giant submucosal mass at the duodenal bulb. INTERVENTIONS: We attempted to remove it because the lesion seemed to be responsible for patient's anemia and vomiting. The lesion had clear but bulky stalk. We carefully cut the stalk using needle-knife and IT knife2. We tried to retrieve specimen, but the mass could not pass through the pyloric ring because of its size. Then we tried to obtain the specimen from anus. Polyethylene glycol solution was administered to accelerate rapid excretion. OUTCOMES: The mass was successfully removed and was histologically confirmed as a giant BGH, measuring 55 mm in size. LESSONS: Reports about endoscopic resection of giant BGH are rare. Moreover, our case is the first report of transanal retrieval of resected specimen using polyethylene glycol solution. Endoscopic resection of BGH is less-invasive but can be more challenging if the mass is large. Our case provides useful option for endoscopic treatment of giant BGH.

Efficacy of microwave ablation versus radiofrequency ablation for hepatocellular carcinoma: a propensity score analysis.

PURPOSE: To evaluate the efficacy and safety of radiofrequency ablation (RFA) and new-generation microwave ablation (MWA) for the treatment of hepatocellular carcinoma (HCC). METHODS: The propensity score matching method was applied to patients with HCC treated with MWA (93 patients) or RFA (156 patients) at a single institution from January 2014 to April 2020. The local tumor progression (LTP), intrahepatic distant recurrence (IDR), and recurrence-free survival (RFS) of the two matched therapies were analyzed using the Kaplan-Meier method. Cox proportional hazard models were used to identify risk factors for LTP and RFS. The therapeutic effects and complications of the two treatments were also compared. RESULTS: The LTP, IDR, and RFS of MWA and RFA were equivalent (LTP: hazard ratio [HR] = 0.87; 95% confidence interval [95% CI] 0.36- 2.07; P = 0.746, IDR: HR = 1.03; 95% CI 0.61-1.73; P = 0.890, RFS: HR = 1.15; 95% CI 0.69-1.91; P = 0.566). Para-vessel lesions was the only risk factor for LTP, whereas age, previous treatment, Albumin-Bilirubin score, and tumor diameter were risk factors for RFS. On the other hand, the ablation time per nodule (6.79 ± 2.73 and 9.21 ± 4.90 min; P = 0.008) and number of sessions per nodule required to achieve technical success (1.16 ± 0.39 and 1.34 ± 0.57; P = 0.009) were significantly lower in MWA than in RFA. The major complication rate of MWA and RFA was also equivalent. CONCLUSION: MWA and RFA have similar therapeutic effects and safety, although MWA has advantages over RFA regarding efficacy, including shorter ablation time and fewer sessions required.

Use of Nakanuma staging and cytokeratin 7 staining for diagnosing recurrent primary biliary cholangitis after living-donor liver transplantation.

AIM: Diagnosis of primary biliary cholangitis (PBC), which recurs in approximately 30% of liver transplant recipients, is histology-based, but no staging system has been established for recurrent PBC (rPBC). We used the Nakanuma staging system and cytokeratin 7 (CK7) staining to examine post-transplant liver biopsy specimens retrospectively and to evaluate histological features of rPBC. METHODS: From 107 patients who underwent living donor liver transplantation for PBC, 60 recipients with 214 liver biopsies after 1-year post transplant were enrolled. Fibrosis, bile duct loss (BL), cholangitis activity, hepatitis activity, and CK7-positive hepatocytes were scored. Nakanuma staging was based on fibrosis and BL scores. We examined the correlation of scores and clinicolaboratory data among rPBC patients. We also evaluated whether chronological change of stage was correlated with liver-related failure. RESULTS: Of 214 biopsies, 52 were protocol biopsy; 162 were episodic. Higher BL, cholangitis activity, and hepatitis activity scores were associated with rPBC diagnosis. At median follow up of 10.0 years (range 1.4-18.7 years), 29 (48%) patients were diagnosed with rPBC at 4.6 years (range 1.3-14.5 years). Liver-related failure occurred in five rPBC cases; three from rPBC, and two from chronic rejection. At rPBC diagnosis, higher BL and CK7 scores were more frequent in patients who developed liver-related failure than in other patients (P = 0.04, P < 0.01, respectively). In failure patients, the Nakanuma stage increased over time, and reached up to stage 4, whereas the Scheuer stage did not reach above stage 3. CONCLUSIONS: Nakanuma staging is associated with rPBC and disease progression. Scores for BL and CK7 might be early markers for progressive rPBC.

Alcohol relapse and its predictors after liver transplantation for alcoholic liver disease: a systematic review and meta-analysis.

BACKGROUND: Alcoholic liver disease (ALD) is the leading cause of liver transplantation (LT). The magnitude and risk factors of post-LT alcohol relapse are not well described. We conducted a meta-analysis to evaluate alcohol relapse rate and its predictors after LT. METHODS: Searches of MEDLINE and SCOPUS identified eligible published studies of alcohol relapse after LT published up to 31 March 2018. Alcohol relapse was defined as any alcohol consumption post-LT, and heavy alcohol relapse was defined as a relapse of alcohol consumption that was associated with a significant harm. Data for the proportion of alcohol relapse was pooled using a meta-analysis for pooling proportion. An odds ratio (OR) of the predictor of alcohol relapse was extracted and pooled using meta-analysis for the pooling risk factor. Data were analyzed using a random effect model if heterogeneity was presented; otherwise, a fixed effect model was applied. The study was registered at PROSPERO (CRD42017052659). RESULTS: Ninety-two studies with over 8000 cases were recruited for pooling proportion of alcohol relapse. The alcohol relapse rate and heavy alcohol relapse rate after LT during the mean follow-up time of 48.4 ± 24.7 months were 22% (95% confidence interval (CI): 19-25%) and 14% (95%CI: 12-16%). Psychiatric comorbidities (odds ratio (OR) 3.46, 95%CI: 1.87-6.39), pre-transplant abstinence of less than 6 months (OR 2.76, 95%CI: 2.10-3.61), unmarried status (OR 1.84, 95%CI: 1.39-2.43), and smoking (OR 1.72, 95%CI: 1.21-2.46) were associated with alcohol relapse after LT. However, we noticed publication bias of unpublished negative studies and high heterogeneity of results. CONCLUSIONS: Post-transplant alcohol relapse occurred in about one-fifth of patients who underwent alcohol-related LT. Psychiatric comorbidities represented the strongest predictor of alcohol relapse. Psychiatric comorbidities monitoring and pre-LT alcohol abstinence for at least 6 months may decrease alcohol relapse after LT.

Clinical Outcomes after Liver Transplantation for Hepatorenal Syndrome: A Systematic Review and Meta-Analysis.

AIMS: Hepatorenal syndrome (HRS) decreases survival of cirrhotic patients. The outcomes of HRS after liver transplantation (LT) were inconsistently reported. We conducted a systematic review and meta-analysis study to estimate the post-LT rates of death and HRS reversal. METHODS: A thorough search of literatures was performed on PubMed, Scopus, and conference abstracts for reports on post-LT survival and HRS reversal. Data for the posttransplant rates of HRS reversal, death, and acute rejection were extracted. The rates were pooled using inverse variance method if there was no heterogeneity between studies. Otherwise, the random effect model was applied. RESULTS: Twenty studies were included. Pooling HRS reversal rates indicated high heterogeneity with a pooled rate of 0.834 (95% CI: 0.709-0.933). The pooled overall death rates for HRS and non-HRS after LT were 0.25 (95% confidence interval (CI): 0.18-0.33) and 0.19 (95% CI: 0.14-0.26). The risk ratio of death between HRS and non-HRS patients was 1.29 (95% CI: 1.14-1.47, P < 0.001). The probability of death at 1, 3, and 5 years tended to be higher among HRS. CONCLUSIONS: HRS is reversible in about 83% of patients after LT. However, the posttransplant mortality rate of HRS patients is still increased.

The use of hepatitis B immunoglobulin with or without hepatitis B vaccine to prevent de novo hepatitis B in pediatric recipients of anti-HBc-positive livers.

Prophylactic measures are used to reduce DNHB after HBsAg-negative patients receive anti-HBc-positive liver grafts. This study investigated the incidence of DNHB and clinical outcomes in pediatric LT recipients under HBIG prophylaxis, with or without hepatitis B vaccination. Between 1995 and 2013, 51 HBsAg-negative pediatric recipients underwent living-donor LT from anti-HBc-positive donors. The median (range) age was 4 (0.1-17) years, 23 (45%) were male, and 71% were negative for both anti-HBc and anti-HBc. During a median follow-up of 12.1 (0.06-19.9) years, 13 (25.4%) developed DNHB; 7 of the 13 achieved HBsAg seroconversion after administration of LAM or ETV. Among studied patients, 20 (39%) received hepatitis B vaccination, and 2 of them (10%) developed DNHB. At last follow-up, 41% (21/51) discontinued HBIG either after successful HBV vaccination (n = 17) or retransplantation with anti-HBc-negative grafts (n = 4). In conclusion, pediatric LT recipients of anti-HBc-positive grafts, most of them were naïve to HBV infection, were at high risk of DNHB, and consistent monitoring for the early detection of DNHB was necessary. A combination use of post-LT vaccination is promising prophylactic strategy against DNHB.

NELFCD and CTSZ loci are associated with jaundice-stage progression in primary biliary cholangitis in the Japanese population.

Approximately 10-20% of patients with primary biliary cholangitis (PBC) progress to jaundice stage regardless of treatment with ursodeoxycholic acid and bezafibrate. In this study, we performed a GWAS and a replication study to identify genetic variants associated with jaundice-stage progression in PBC using a total of 1,375 patients (1,202 early-stage and 173 jaundice-stage) in a Japanese population. SNP rs13720, which is located in the 3'UTR of cathepsin Z (CTSZ), showed the strongest association (odds ratio [OR] = 2.15, P = 7.62 × 10-7) with progression to jaundice stage in GWAS. High-density association mapping at the CTSZ and negative elongation factor complex member C/D (NELFCD) loci, which are located within a strong linkage disequilibrium (LD) block, revealed that an intronic SNP of CTSZ, rs163800, was significantly associated with jaundice-stage progression (OR = 2.16, P = 8.57 × 10-8). In addition, eQTL analysis and in silico functional analysis indicated that genotypes of rs163800 or variants in strong LD with rs163800 influence expression levels of both NELFCD and CTSZ mRNA. The present novel findings will contribute to dissect the mechanism of PBC progression and also to facilitate the development of therapies for PBC patients who are resistant to current therapies.

Medium-chain triglycerides supplement therapy with a low-carbohydrate formula can supply energy and enhance ammonia detoxification in the hepatocytes of patients with adult-onset type II citrullinemia.

Citrin, encoded by SLC25A13, constitutes the malate-aspartate shuttle, the main NADH-shuttle in the liver. Citrin deficiency causes neonatal intrahepatic cholestasis (NICCD) and adult-onset type II citrullinemia (CTLN2). Citrin deficiency is predicted to impair hepatic glycolysis and de novo lipogenesis, resulting in hepatic energy deficit. Secondary decrease in hepatic argininosuccinate synthetase (ASS1) expression has been considered a cause of hyperammonemia in CTLN2. We previously reported that medium-chain triglyceride (MCT) supplement therapy with a low-carbohydrate formula was effective in CTLN2 to prevent a relapse of hyperammonemic encephalopathy. We present the therapy for six CTLN2 patients. All the patients' general condition steadily improved and five patients with hyperammonemic encephalopathy recovered from unconsciousness in a few days. Before the treatment, plasma glutamine levels did not increase over the normal range and rather decreased to lower than the normal range in some patients. The treatment promptly decreased the blood ammonia level, which was accompanied by a decrease in plasma citrulline levels and an increase in plasma glutamine levels. These findings indicated that hyperammonemia was not only caused by the impairment of ureagenesis at ASS1 step, but was also associated with an impairment of glutamine synthetase (GS) ammonia-detoxification system in the hepatocytes. There was no decrease in the GS expressing hepatocytes. MCT supplement with a low-carbohydrate formula can supply the energy and/or substrates for ASS1 and GS, and enhance ammonia detoxification in hepatocytes. Histological improvement in the hepatic steatosis and ASS1-expression was also observed in a patient after long-term treatment.

Impact of Donor Age on Recipient Survival in Adult-to-Adult Living-donor Liver Transplantation.

OBJECTIVE: To investigate the influence of donor age on recipient outcome after living-donor partial liver transplantation (LDLT). BACKGROUND: Donor age is a well-known prognostic factor in deceased donor liver transplantation; however, its role in LDLT remains unclear. METHODS: We retrospectively analyzed 315 consecutive cases of primary adult-to-adult LDLT in our center between April 2006 and March 2014. Recipients were divided into 5 groups according to the donor age: D-20s (n = 60); D-30s (n = 72); D-40s (n = 57); D-50s (n = 94); and D-60s (n = 32). The recipient survival and the association with various clinical factors were investigated. RESULTS: Recipient survival proportions were significantly higher in D-20s compared with all the other groups (P = 0.008, < 0.001, < 0.001, and = 0.006, vs D-30s, -40s, -50s, and -60s, respectively), whereas there was no association between recipient survival and their own age. There are 3 typical relationships between donors and recipients in adult-to-adult LDLT: from child-to-parent, between spouses/siblings, and from parent-to-child. The overall survival in child-to-parent was significantly higher than in spouses/siblings (P = 0.002) and in parent-to-child (P = 0.005), despite significantly higher recipient age in child-to-parent [59 (42-69) years, P < 0.001]. Contrastingly, parent-to-child exhibited the lowest survival, despite the youngest recipient age [26 (20-43) years, P < 0.001]. In addition, younger donor age exhibited significantly better recipient survival both in hepatitis C virus-related and in non-hepatitis C virus diseases. Univariate and multivariate analyses both demonstrated that donor age and graft-type (right-sided livers) are independent prognostic factors for recipient survival. CONCLUSIONS: Donor age is an independent, strong prognostic factor in adult-to-adult LDLT.

Coexistence of Bilirubin ≥10 mg/dL and Prothrombin Time-International Normalized Ratio ≥1.6 on Day 7: A Strong Predictor of Early Graft Loss After Living Donor Liver Transplantation.

BACKGROUND: Early allograft dysfunction (EAD) defined by serum total bilirubin (TB) of 10 mg/dL or greater or prothrombin time-international normalized ratio (PT-INR) of 1.6 or greater on postoperative day 7 (POD 7) or aminotransferase greater than 2000 IU/L within the first week, is associated with early graft loss after deceased-donor liver transplantation. We aimed to determine the prognostic impact of the EAD definition in living-donor liver transplantation (LDLT). METHODS: We analyzed the validity of the EAD definition and its impact on early graft survival in 260 adult recipients who underwent primary LDLT. RESULTS: Eighty-four (32.3%) patients met the EAD criteria; 59 (22.7%) and 46 (17.7%) patients had TB of 10 mg/dL or greater and PT-INR of 1.6 or greater on POD 7, respectively, and 22 (8.5%) patients satisfied both criteria. Graft survival differed significantly when stratified according to TB of 10 mg/dL or greater and PT-INR of 1.6 or greater (P < 0.0001). PT-INR of 1.6 or greater resulted in higher graft mortality (risk ratio [RR], 3.87; P < 0.0001 at 90 days; RR, 2.97; P < 0.0001 at 180 days), as did TB of 10 mg/dL or greater (RR, 1.89; P = 0.027 at 90 days; RR, 1.91; P = 0.006 at 180 days). Coexistence of TB of 10 mg/dL or greater and PT-INR of 1.6 or greater was strongly associated with early graft loss (59.1%, RR, 6.97 at 90 days; 68.2%; RR, 5.75 at 180 days). In Cox regression analysis, PT-INR of 1.6 or greater and TB of 10 mg/dL or greater on POD 7 were significant risk factors for early graft loss (hazard ratio, 4.10; 95% confidence interval, 2.35-7.18; P < 0.0001, and hazard ratio, 2.43; 95% confidence interval, 1.39-4.24; P = 0.0018, respectively). CONCLUSIONS: TB of 10 mg/dL or greater and/or PT-INR of 1.6 or greater on POD 7 predicted early graft loss after LDLT, and their coexistence worsened patient outcomes.

Long-term Prognosis and Recurrence of Primary Sclerosing Cholangitis After Liver Transplantation: A Single-Center Experience.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease, with liver transplantation being the sole life-saving treatment for end-stage PSC-related liver disease. However, recurrence of PSC after liver transplantation is a common complication, with the risk factors for recurrence being controversial. METHODS: We conducted a retrospective chart review of 45 patients who had undergone liver transplantation for PSC at our institute. The risk factors for PSC recurrence and graft failure after liver transplantation were analyzed. RESULTS: The graft survival rates were 55.4% at 5 years and 32.8% at 10 years after liver transplantation for PSC. PSC recurrence was diagnosed in 16 (40%) of 40 patients, at a median 30 months (range, 9-70 months) after liver transplantation. The cumulative incidence rate of PSC recurrence was 24.5% at 3 years, 39.3% at 5 years, and 45.8% at 6 years. Among the 16 patients diagnosed with PSC recurrence, the graft survival rate was 56.3% at 5 years, and 21.9% at 10 years after the recurrence. Active inflammatory bowel disease after liver transplantation was identified as an independent risk factor for PSC recurrence. Age younger than 30 years at the time of PSC diagnosis and bacteremia were factors significantly associated with graft failure after liver transplantation on multivariate analysis. CONCLUSIONS: PSC frequently recurred and progressed to graft failure after liver transplantation for PSC. Maintaining an inactive status of inflammatory bowel disease might offer protection against PSC recurrence.

Long-term efficacy of hepatitis B vaccination as post-transplant prophylaxis in hepatitis B surface antigen (HBsAg) positive recipients and HBsAg negative recipients of anti-hepatitis B core positive grafts.

AIM: Hepatitis B virus (HBV) reactivation after liver transplantation in HBV patients, or in HBV negative recipients of anti-hepatitis B core (HBc) positive grafts, has been prevented by prophylactic use of hepatitis B immunoglobulin (HBIG) and/or nucleoside/nucleotide analogs (NA). Vaccination against HBV is an alternative that may provide a chance to discontinue prophylaxis by producing anti-hepatitis B surface (HBs) antibodies. METHODS: We retrospectively reviewed 40 HBV positive recipients (HBV+ group) and 27 HBV negative recipients of anti-HBc positive grafts (HBV-/anti-HBc+ graft group), who were administrated double-dose hepatitis B vaccination. Recipients were regarded as responders when anti-HBs greater than 100 IU/L was maintained for 6 months or more without HBIG. Response rates of vaccine and long-term outcomes were analyzed. RESULTS: Eighteen of the 40 patients in the HBV+ group (45%) and 18 of the 27 patients in the HBV-/anti-HBc+ graft group (67%) responded to vaccination after a median of four and three times, respectively. Younger age was the only independent factor associated with vaccine response in the HBV-/anti-HBc+ graft group (P = 0.03), whereas no factor was found to be an independent predictor for vaccine response in the HBV+ group. Among the 18 responders in the HBV+ group, 17 remained without NA or HBIG 8.2 years after the start of vaccination. Ten of those required periodic booster vaccination. All 18 responders in the HBV-/anti-HBc+ graft group remained free from HBV prophylaxis 6.2 years after the start of vaccination. CONCLUSION: Younger recipients have a greater chance to develop sufficient anti-HBs after double-dose HBV vaccination, leading to discontinue HBV prophylaxis.

Impact of donor and recipient single nucleotide polymorphisms of IL28B rs8099917 in living donor liver transplantation for hepatitis C.

Single nucleotide polymorphisms of interleukin-28B (IL28B) rs8099917 are reported to be associated with virologic clearance in interferon-and ribavirin -based treatment for hepatitis C virus (HCV)-infected patients. We examined virologic response in accordance with IL28B polymorphisms in our living donor liver transplantation series under a preemptive interferon and RBV treatment approach. Adequate DNA samples from both the recipient and donor for the study of single nucleotide polymorphisms of IL28B were available from 96 cases and were the subjects of the present study. Various clinical factors related with virologic response including early virologic response (EVR) and sustained virologic response (SVR) were examined. Totally 51% presented with EVR and 44% achieved SVR. Presence of the major allele (TT) in either the recipient or the donor corresponded to SVR of 53% and 48%. Presence of the minor allele (TG or GG) corresponded to SVR of 26% and 32%. Multivariate analysis revealed that genotype of HCV or EVR, but not IL28B polymorphisms in either the recipient or donor, was an independent factor for achieving SVR. When virologic response to treatment was incorporated into analysis, the impact of IL28B polymorphism on virological clearance remained relative to other factors and was not significantly independent.

Chronologic changes of explanted liver volume and the use of ursodeoxycholic acid in patients with end-stage primary biliary cirrhosis.

AIM: The clinical presentation of Primary biliary cirrhosis (PBC) at the time of liver transplantation (LT) may have changed, due to the long-term use of ursodeoxycholic acid (UDCA). The aim of this retrospective study was to investigate whether the clinical characteristics of LT recipients with PBC have changed over the years. METHODS: Of all 421 adults undergoing LT from 1997 to 2012 at our center, we included 85 recipients with PBC into the present study. The 85 recipients were divided into three groups according to the year LT was performed: group 1 (1997-2001, n = 29), group 2 (2002-2005, n = 29) and group 3 (2006-2012, n = 27). RESULTS: There were no significant differences in sex, recipient age, Model for End-Stage Liver Disease score, updated Mayo risk score for PBC, or liver-related complications except for esophageal varices among the three groups. Patients in group 1 were complicated with esophageal varices less frequently than those in the other two groups. In older cases, the ratio of explanted liver volume to standard liver volume (ELV/SLV) was significantly higher, and the duration of pre-LT UDCA treatment was significantly shorter. The duration of UDCA treatment was significantly correlated with ELV/SLV. CONCLUSION: Recent LT patients were characterized by more frequent portal hypertension and more severe liver atrophy, with longer UDCA therapy prior to LT, which might have prevented the somewhat rapid progression of liver failure characterized by hepatomegaly with insignificant fibrosis or portal hypertension.

Living donor liver transplantation for non-alcoholic steatohepatitis: A single center experience.

AIM: The number of patients referred for liver transplantation (LT) with non-alcoholic steatohepatitis (NASH) continues to increase, but information about living donor liver transplantation (LDLT) for NASH is scarce. We conducted this study to document the details of LDLT for NASH in a Japanese LT center. METHODS: Among all LDLT recipients in our institution from March 1996 to March 2013 (n = 425), we identified seven patients that underwent LDLT for NASH. RESULTS: Of all the seven recipients, most of the patients (86%) were obese. The median follow-up period post-LDLT was 5.3 years. All were alive at the last follow-up. Recurrent NASH was detected in one patient (14%), and no recurrent hepatic steatosis was detected among the remaining six recipients on prospectively performed ultrasonography. No significant comorbidities were observed following donor surgery among the respective living donors during the follow-up period. We also retrospectively reviewed 22 patients with NASH-related end-stage liver disease (ESLD) who were evaluated but rejected for LDLT during the same period. The reasons for rejection for LDLT were presumably associated with the nature of NAFLD/NASH in either potential recipients or donors. CONCLUSION: The post-transplant outcome of LDLT for NASH-related ESLD in our institution was feasible, although the sample size was small. Further studies in a larger patient cohort are warranted to investigate the long-term outcome of LDLT for NASH, both for recipients and living donors.

Changes in risk of immediate adverse reactions to iodinated contrast media by repeated administrations in patients with hepatocellular carcinoma.

BACKGROUND: To elucidate whether repeated exposures to iodinated contrast media increase the risk of adverse reaction. MATERIALS AND METHODS: We retrospectively reviewed 1,861 patients with hepatocellular carcinoma who visited authors' institution, a tertiary referral center, between 2004 and 2008. We analyzed cumulative probability of adverse reactions and risk factors. We categorized all symptoms into hypersensitivity reactions, physiologic reactions, and other reactions, according to the American College of Radiology guidelines, and evaluated each category as an event. We estimated the association between hazard for adverse reactions and the number of cumulative exposures to contrast media. We also evaluated subsequent contrast media injections and adverse reactions. RESULTS: There were 23,684 contrast media injections in 1,729 patients. One hundred and thirty-two patients were excluded because they were given no contrast media during the study period. Adverse reactions occurred in 196 (0.83%) patients. The cumulative incidence at 10(th), 20(th), and 30(th) examination was 7.9%, 15.2%, and 24.1%, respectively. Presence of renal impairment was found to be one of risk factors for adverse reactions. The estimated hazard of overall adverse reaction gradually decreased until around 10(th) exposure and rose with subsequent exposures. The estimated hazard of hypersensitivity showed V-shaped change with cumulative number of exposures. The estimated hazard of physiologic reaction had a tendency toward decreasing and that of other reaction had a tendency toward increasing. Second adverse reaction was more severe than the initial in only one among 130 patients receiving subsequent injections. CONCLUSION: Repeated exposures to iodinated contrast media increase the risk of adverse reaction.

CT with hepatic arterioportography as a pretreatment examination for hepatocellular carcinoma patients: a randomized controlled trial.

OBJECTIVES: The combination of computed tomography with hepatic arteriography and arterial portography (CTHA/CTAP) can detect additional hepatocellular carcinoma (HCC) nodules undetected by conventional dynamic CT. METHODS: In this single-center, randomized, open-label, controlled trial, we randomly assigned 280 patients who were diagnosed as having HCC by conventional dynamic CT, and eligible for radiofrequency ablation (RFA), to undergo CTHA/CTAP before treatment, or to the control group. Newly detected HCC nodules by CTHA/CTAP were intended to be ablated completely. The primary end point was recurrence-free survival and the key secondary end point was overall survival. The analysis was conducted on an intention-to-treat basis. Those with nonablated nodules were treated as for recurrence. RESULTS: A total of 75 nodules were newly diagnosed as HCC by CTHA/CTAP in 45 patients. Three patients (one in the CTHA/CTAP group and two in the control group) who refused treatment were excluded from all analyses. The cumulative recurrence-free survival rates at 1, 2, and 3 years were 60.1, 29.0, and 18.9% in the CTHA/CTAP group and 52.2, 29.7, and 23.1% in the control group, respectively (P=0.66 by log-rank test; hazard ratio, 0.94 for CTHA/CTAP vs. control; 95% confidence interval (CI), 0.73-1.22). The cumulative overall survival rates at 3 and 5 years were 79.7 and 56.4% in the CTHA/CTAP group and 86.8 and 60.1% in the control group, respectively (P=0.50; hazard ratio, 1.15, 95% CI, 0.77-1.71). CONCLUSIONS: CTHA/CTAP may detect recurrent lesions earlier. However, CTHA/CTAP before RFA did not improve cumulative recurrence-free survival or overall survival.

De novo malignancies after adult-to-adult living-donor liver transplantation with a malignancy surveillance program: comparison with a Japanese population-based study.

BACKGROUND: Organ transplant recipients have an increased incidence of malignancy. Race differences in a variety of malignancies are observed among the general population, but de novo malignancies after adult-to-adult living-donor liver transplantation (LDLT) have not been compared with those from a Japanese population-based study. METHODS: The subjects were 360 adult LDLT recipients who survived more than 1 year after transplantation. An annual medical checkup and screening examinations were performed as follows: abdominal computed tomography or magnetic resonance imaging, upper gastrointestinal endoscopy, and total colonoscopy and immunochemical fecal occult blood test every 1 to 2 years. Complete blood count, liver function tests, and several tumor markers were checked every 1 to 3 months after LDLT. RESULTS: Mean follow-up period was 7.5±3.4 years. During the follow-up period, 27 de novo malignancies were diagnosed in 26 recipients. Colorectal cancer was the most commonly detected malignancy. The overall mortality of the recipients with de novo malignancies was similar to the findings of the Japanese general population-based study (standardized mortality ratio=0.9). Overall, the incidence of cancer was significantly higher in transplant recipients than in the Japanese general population (standardized incidence ratio=1.8). The 5-year estimated survival rate of recipients with de novo malignancies was 81% and those of recipients without malignancies was 93% (P<0.0001). CONCLUSIONS: Colorectal malignancies predominated in Japanese liver transplant recipients. Although de novo malignancies correlated with a poor prognosis, the standardized mortality ratio was 0.9 compared with that of subjects of a Japanese population-based study.