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.

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.

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.

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.

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.

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.

Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population.

For the identification of susceptibility loci for primary biliary cirrhosis (PBC), a genome-wide association study (GWAS) was performed in 963 Japanese individuals (487 PBC cases and 476 healthy controls) and in a subsequent replication study that included 1,402 other Japanese individuals (787 cases and 615 controls). In addition to the most significant susceptibility region, human leukocyte antigen (HLA), we identified two significant susceptibility loci, TNFSF15 (rs4979462) and POU2AF1 (rs4938534) (combined odds ratio [OR] = 1.56, p = 2.84 × 10(-14) for rs4979462, and combined OR = 1.39, p = 2.38 × 10(-8) for rs4938534). Among 21 non-HLA susceptibility loci for PBC identified in GWASs of individuals of European descent, three loci (IL7R, IKZF3, and CD80) showed significant associations (combined p = 3.66 × 10(-8), 3.66 × 10(-9), and 3.04 × 10(-9), respectively) and STAT4 and NFKB1 loci showed suggestive association with PBC (combined p = 1.11 × 10(-6) and 1.42 × 10(-7), respectively) in the Japanese population. These observations indicated the existence of ethnic differences in genetic susceptibility loci to PBC and the importance of TNF signaling and B cell differentiation for the development of PBC in individuals of European descent and Japanese individuals.

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.

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.

Quality of life after adult living donor liver transplantation: A longitudinal prospective follow-up study.

AIM: Patient survival after living donor liver transplantation (LDLT) has improved, but improvement of the health-related quality of life (HRQOL) of LDLT recipients is also an important issue. The aim of this study was to assess the HRQOL of LDLT recipients from the preoperative period to 18 months following transplantation by prospectively evaluating Short Form-36 Version 2 (SF-36v2) scores. METHODS: Complete longitudinal SF-36v2 scores were collected from 35 consecutive LDLT recipients prior to surgery and at 3, 6, 12 and 18 months after transplantation. RESULTS: HRQOL scores were severely impaired in all dimensions preoperatively. Although the scores improved significantly up to 18 months after transplantation, they remained lower than those of healthy controls in the majority of domains. Impaired scores preoperatively were significantly associated with severity of liver disease represented by a higher Model for End-Stage Liver Disease (MELD) score and Child-Turcotte-Pugh class C, and scores in such patients improved significantly after LDLT in every dimension at 12 months, indicating that the greater the impairment at the pretransplant stage, the greater the improvement in both physical and mental conditions. Preoperative lower HRQOL scores and higher MELD scores were independently associated with significant physical and mental score gains during the first year after LDLT. CONCLUSION: The findings of the present study may facilitate the development of measures aimed at improving recipient's post-transplant life and establishing realistic expectations for LDLT recipients.

Role of 6-month abstinence rule in living donor liver transplantation for patients with alcoholic liver disease.

AIM: Although alcoholic liver disease (ALD) is an accepted indication for liver transplantation (LT), there are several controversial issues. The aim of this study is to examine the applicability of the 6-month abstinence rule prior to LT and to evaluate the results in living donor LT for patients with ALD. METHODS: A retrospective study of 102 patients with ALD referred for LT was performed. Clinical data, including alcohol consumption history, were analyzed. A period of abstinence from drinking alcohol of at least 6 months was strictly required. RESULTS: Among 102 patients, 21 abstained from drinking for at least 6 months. Of these, 13 patients (12%) underwent LT, five patients (5%) recovered without LT and three patients (3%) were listed for deceased donor LT. LT was not indicated for the remaining 81 patients (80%). Eight patients died within 6 months of referral to our program. The Child-Pugh score was higher in these eight patients than in the 21 who achieved 6-month abstinence, although the alcohol consumption history variables did not significantly differ between the two groups. The 5-year overall survival rates after LT in 13 patients with ALD (91%) were similar to those in 387 non-ALD patients (83%). The rate of alcohol consumption relapse after LT was 8% (n = 1/13). CONCLUSION: Living donor LT for patients with ALD who complied with the 6-month abstinence rule provides sufficient survival benefit with good compliance, compensating for the potential risks to the donors.

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.

Lower incidence of biliary carcinoma in patients with primary sclerosing cholangitis and high serum levels of immunoglobulin E.

BACKGROUND & AIMS: High serum levels of immunoglobulin (Ig)E often are detected in patients with primary sclerosing cholangitis (PSC), but the clinical significance is not known. METHODS: We analyzed data from 44 patients with PSC and known serum levels of IgE. They were divided into groups called high IgE (>170 IU/mL; n = 17) or normal IgE (n = 27). We compared occurrence of biliary carcinoma including cholangiocellular and gallbladder carcinoma, liver transplantation, and death between groups. RESULTS: The high IgE group had a later age of onset of PSC than the normal IgE group (54 ± 20 y vs 39 ± 16 y; P = .010); they also had a higher serum level of IgG (2078 ± 638 vs 1517 ± 475 mg/dL; P = .002) and IgG4 (104 ± 102 vs 38 ± 16 mg/dL; P = .002). Association with inflammatory bowel disease did not differ significantly between groups (5 of 17 vs 11 of 27; P = .661). No patient had biliary carcinoma in the high IgE group, but biliary carcinoma was observed during the follow-up period in 8 patients in the normal IgE group (0 of 17 vs 8 of 27; P = .016). The occurrence of biliary carcinoma, liver transplantation, or death did not differ between groups (4 of 17 vs 13 of 27; P = .124). CONCLUSIONS: High serum levels of IgE often are observed in older patients with PSC and are associated with a reduced incidence of biliary carcinoma.

Outcomes after living donor liver transplantation for acute liver failure in Japan: results of a nationwide survey.

Nationwide surveys of acute liver failure (ALF) are conducted annually in Japan, and 20% of patients with ALF undergo liver transplantation (LT). We extracted data for 212 patients who underwent LT for ALF from the nationwide survey database of the Intractable Liver Diseases Study Group of Japan. After the exclusion of 3 patients who underwent deceased donor LT, 209 recipients of living donor liver transplantation (LDLT) were analyzed. ALF patients were placed into 3 subgroups according to the time from the onset of the disease to the occurrence of encephalopathy: patients who presented with encephalopathy within 10 days of the disease's onset were classified as having acute ALF, patients who presented within 11 to 56 days were classified as having subacute ALF, and patients who presented within 9 to 24 weeks were classified as having late-onset hepatic failure (LOHF). Long-term follow-up data were obtained from the registry of the Japanese Liver Transplantation Society. The 2 data sets were merged, and descriptive and survival data were analyzed. A Cox regression analysis was performed to define factors predicting overall mortality, short-term mortality (≤90 days after LT), and long-term mortality (>90 days after LT). One hundred ninety of the analyzed patients (91%) were adults (age ≥ 18 years); 70 patients (34%) were diagnosed with acute ALF, 124 (59%) were diagnosed with subacute ALF, and 15 (7%) were diagnosed with LOHF. Hepatitis B virus was the most common cause of acute ALF (61%), whereas autoimmune hepatitis (14%) and drug allergy-induced hepatitis (14%) were more frequent in patients with subacute ALF or LOHF. The cumulative patient survival rates 1, 5, and 10 years after LT were 79%, 74%, and 73%, respectively. Patient age was associated with short- and long-term mortality after LT, whereas ABO incompatibility affected short-term mortality, and donor age affected long-term mortality. In conclusion, the long-term outcomes of LDLT for ALF in this study were excellent, regardless of the etiology or classification. The majority of the donors were living donors. Increasing the deceased donor pool might be an urgent necessity.

Long-term outcome of living donor liver transplantation for primary biliary cirrhosis.

In living donor liver transplantation (LDLT) for primary biliary cirrhosis (PBC), the majority of donors are genetically related to their recipients, leading to concerns of an earlier recurrence of PBC and a poorer prognosis due to genetic susceptibility. Totally 81 patients who underwent LDLT for PBC were the subjects of the present study. Immunosuppressive agents consisted of tacrolimus and methylprednisolone. In the outpatient clinic, when the aspartate and alanine aminotransferase level exceeded the upper limit of the normal range, the dose of methylprednisolone was increased from 4 to 6 mg/day for several months. Blood was examined every 2 weeks for 3 months and a liver biopsy was performed when aminotransferase levels did not decrease to the upper limit of the normal range after more than 3 months. Five-year survival and recurrence rates were estimated and the prognostic factors were analyzed. The mean observation period was 6.2 years. Five years after LDLT for PBC, the biopsy-proven PBC recurrence rate was 1%. The 5-year patient survival rate was 80%. The nonrelated or blood-related donor factor and number of human leukocyte antigen matches did not correlate with prognosis. PBC recurrence rate after LDLT in our series was lower than that in previous studies.

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.

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.

Pre-emptive antiviral therapy in living donor liver transplantation for hepatitis C: observation based on a single-center experience.

Reports of large series in living donor liver transplantation (LDLT) for hepatitis C virus infection (HCV) are scarce. Between 1996 and 2008, 105 LDLTs were performed at the University of Tokyo for HCV. Rapid induction of antiviral treatment with interferon (IFN) and ribavirin (RBV) was attempted per protocol regardless of the clinical presentation of recurrent HCV (pre-emptive treatment approach). Treatment was continued for 12 months after serum HCV-RNA became negative (ETR: end-of-treatment response) and judged as a sustained viral response (SVR) after another 6 months of negative results without treatment. A fixed treatment period was not defined unless an ETR was achieved (no-stopping approach). Flexible dose adjustments were allowed. Ninety-five patients were eligible for pre-emptive therapy. Forty-three (45%) patients experienced an ETR, and 32 (34%) achieved SVR. Nonadherence to full-dose INF and RBV had little impact on the viral response. Evaluation using the Kaplan-Meier method to incorporate the cumulative time-dependent nature of the no-stopping approach estimated SVR rate at 53% by the fifth year. Survival rate at 5 years was 79% for the HCV recipients and did not differ significantly from our non-HCV series. In LDLT for HCV, pre-emptive IFN-RBV-based treatment with the application of no-stopping approach is feasible and effective.