Search

Primary biliary cholangitis (PBC) is considered to be caused by the interaction between genetic background and environmental triggers. Previous case–control studies have indicated the associations of environmental factors (tobacco smoking, a history of urinary tract infection, and hair dye) use with PBC. Therefore, we conducted a multicenter case–control study to identify the environmental factors associated with the development of PBC in Japan. From 21 participating centers in Japan, we prospectively enrolled 548 patients with PBC (male/female = 78/470, median age 66), and 548 age- and sex-matched controls. These participants completed a questionnaire comprising 121 items with respect to demographic, anthropometric, socioeconomic features, lifestyle, medical/familial history, and reproductive history in female individuals. The association was determined using conditional multivariate logistic regression analysis. The identified factors were vault toilet at home in childhood [odds ratio (OR), 1.63; 95% confidence interval (CI), 1.01–2.62], unpaved roads around the house in childhood (OR, 1.43; 95% CI, 1.07–1.92), ever smoking (OR, 1.70; 95% CI, 1.28–2.25), and hair dye use (OR, 1.57; 95% CI, 1.15–2.14) in the model for lifestyle factors, and a history of any type of autoimmune disease (OR, 8.74; 95% CI, 3.99–19.13), a history of Cesarean section (OR, 0.20; 95% CI, 0.077–0.53), and presence of PBC in first-degree relatives (OR, 21.1; 95% CI, 6.52–68.0) in the model for medical and familial factors. These results suggest that poor environmental hygiene in childhood (vault toilets and unpaved roads) and chronic exposure to chemicals (smoking and hair dye use) are likely to be risk factors for the development of PBC in Japan.

Background: We aimed to investigate the efficacy and safety of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (u-HCC) based on whether they had previously received systemic therapy, as well as the association of atezolizumab plus bevacizumab with early alpha-fetoprotein (AFP) response in real-world practice. Methods: A total of 52 patients with u-HCC were treated with atezolizumab plus bevacizumab between October 2020 and April 2021. The Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST were used to evaluate radiological responses. Results: The patients received atezolizumab plus bevacizumab as 1st-line (n = 23), 2nd-line (n = 16), 3rd-line (n = 6), 4th-line (n = 3), 5th-line (n = 3), or 6th-line (n = 1) therapy. The objective response rate and disease control rate in all patients were 18.4% and 63.2%, respectively. Sixteen patients experienced no adverse events (AEs), whereas 4 patients discontinued therapy due to AEs. The median time to progression (TTP) was significantly longer among patients receiving atezolizumab plus bevacizumab as 1st-line therapy than in patients receiving atezolizumab plus bevacizumab as later-line therapy (P = 0.02). Patients with an AFP response (reduction ≥20% from baseline) at 6 weeks had a significantly longer TTP than those without an AFP response (P = 0.02). Conclusion: Patients who received atezolizumab plus bevacizumab as 1st-line therapy had better clinical outcome than those who received atezolizumab plus bevacizumab in later lines. The AFP response at 6 weeks could be a predictor of disease progression.

Background and Aim Administration of tenofovir alafenamide (TAF) as prevention or treatment of hepatitis B virus (HBV) reactivation is not well known. The aim of this study is to reveal the efficacy and safety of TAF against HBV reactivation. Methods Entecavir (ETV) and TAF were given to 66 and 11 patients, respectively, as prophylaxis against or treatment of HBV reactivation during chemotherapy or immune suppression therapy from January 2010 to June 2020. The antiviral effects and safety were assessed. Results At week 24, the antiviral effects on patients receiving ETV and TAF were similar in terms of reduction of HBV DNA (−2.83 ± 1.45log IU/mL vs −3.05 ± 2.47log IU/mL; P = 0.857) and achieving undetectable levels of HBV DNA (78.8 vs 90.9%; P = 0.681). There was no significant difference in the decrease in the estimated glomerular filtration rate (eGFR) between the two groups (−0.62 ± 11.2 mL/min/1.73 m2 vs −3.67 ± 13.2 mL/min/1.73 m2; P = 0.291). Conclusion TAF is safe and effective against HBV reactivation., The aim of this study is to reveal the efficacy and safety of tenofovir alafenamide (TAF) as prophylaxis against or treatment of hepatitis B virus (HBV) reactivation. The antiviral effects in terms of HBV DNA reduction on patients receiving entecavir and TAF were similar, and there was no significant difference in renal dysfunction between both groups. TAF is safe and effective against HBV reactivation.

Background and Aims: A retrospective study was to analyze the association of plasma renin activity (PRA) with overall survival and liver disease-related events in decompensated liver cirrhosis with ascites treated by tolvaptan. Methods: We included 196 patients with decompensated cirrhosis treated with tolvaptan and for whom hepatic ascites had remained uncontrolled by conventional diuretics. Factors associated with prognosis and appearance of liver disease-related events were investigated, including vasopressin, sympathetic nervous system hormones (adrenaline, noradrenaline, and dopamine), and the renin-angiotensin system (PRA and aldosterone) at the beginning of tolvaptan treatment. Results: Age, history of hepatocellular carcinoma (HCC), and PRA were identified as independent factors for prognosis after tolvaptan treatment. The median survival time in patients with PRA ≥9.5 ng/mL/h at the beginning of tolvaptan treatment was significantly shorter than in patients with PRA p < 0.001). PRA and a history of HCC were independent factors for the occurrence of liver disease-related events. The median event-free period in patients with PRA ≥3.2 ng/mL/h was significantly shorter than that of patients with PRA p < 0.001). Conclusions: PRA is an independent predictor of prognosis and appearance of liver disease-related events in patients with decompensated cirrhosis who have started tolvaptan treatment.

Background and aim The association between liver fibrosis, fatty liver, and cardiovascular disease (CVD) risk is unknown. Hence, this study aimed to investigate the association of liver fibrosis and fatty liver with CVD risk independent of already known CVD risk comorbidities. Methods This is a prospective study registered with the University Hospital Medical Information Network clinical trial registry (UMIN000036175). Liver fibrosis was assessed by serum fibrosis markers including FIB-4, nonalcoholic fatty liver disease fibrosis score (NFS), and Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+ -M2BP), whereas fatty liver was diagnosed by ultrasonography. CVD risk was evaluated using the Framingham risk score (FRS), and a high CVD risk was defined as an FRS ≥ 20%. Results A total of 3512 subjects were enrolled, and high CVD risk (FRS ≥ 20%) was observed in 17.5%. Advanced fibrosis (FIB-4 ≥ 2.67, NFS ≥ 0.675, and WFA+ -M2BP ≥ 1.0) and the presence of fatty liver were significantly associated with high CVD risk independent of diabetes mellitus, dyslipidemia, and hypertension. When subjects were stratified by liver fibrosis and fatty liver, subjects with advanced fibrosis and fatty liver have the highest odds for high CVD risk (odds ratio [OR]: 5.90-35.6), followed by subjects with advanced fibrosis and without fatty liver (OR: 2.53-9.62) using subjects without advanced fibrosis and fatty liver as a reference. Conclusions Liver fibrosis and fatty liver were associated with CVD risk independent of already known CVD risk comorbidities. The assessment of liver fibrosis and fatty liver may be useful to identify high CVD risk subjects.

Carcinogenesis risk scores for chronic hepatitis B have been proposed, but it remains unclear whether these scores during nucleoside/nucleotide analogue (NA) therapy are useful for risk assessment. In this study, we examined changes of these scores and the predictability during NA treatment. 432 patients with no history of hepatocellular carcinoma (HCC) treated with NA were enrolled. PAGE-B, modified PAGE-B (mPAGE-B), and REACH-B scores were calculated at NA administration, 1 and 2 years after administration. The median follow-up duration was 5.1 years, during which 37 patients (8.6%) developed HCC. Cumulative incidence HCC development in patients with high risk of PAGE at NA administration, and 1 and 2 years after NA administration was significantly higher than those with intermediate and low-risk groups (p

BACKGROUND/AIM Drains are frequently placed at the time of distal pancreatectomy (DP) to evacuate pancreatic juice and intra-abdominal exudate and obtain information on abdominal cavity status. However, the timing of drain removal remains debatable. Meanwhile, prolonged drain placement might increase the risk of postoperative pancreatic fistula (POPF), with a prevalence of 5-40%. Therefore, we examined the effect of removing the drain within postoperative day (POD) 3 on the risk of POPF development. PATIENTS AND METHODS A total of 108 consecutive patients who underwent DP between April 2015 and March 2020 were examined and divided into two groups according to the day of drain removal; hence, for some patients, the drain was removed on POD 1 (POD 1 group) and for others on POD 3 (POD 3 group). Furthermore, risk factors, including drain fluid amylase (DFA) levels, for developing POPF were investigated. RESULTS The overall rate of clinically relevant POPF was 4.6% and did not significantly differ between the POD 1 and POD 3 groups [4.5% and 4.9%, respectively (p=0.924)]. DFA levels on POD 1 did not significantly differ between patients with and without POPF. On POD 3 and POD 5, C-reactive protein (CRP) levels were significantly higher in patients with POPF than in those without (p=0.03 and p

Almost all patients achieved sustained virological response (SVR) by direct-acting antivirals (DAA) therapy, but it is not clear as to what extent DAA therapy affects changes in liver fibrosis after achieving SVR. In this study, we investigated the changes of liver stiffness by magnetic resonance elastogaraphy (MRE) during DAA therapy. A total of 308 patients were enrolled in the study. Liver stiffness was measured twice before and after DAA treatment using MRE and time-course change of liver stiffness was investigated. The median (interquartile range) values for liver stiffness were 4.2 (3.2-6.1) kPa at baseline and 3.3 (2.6-4.8) kPa at SVR, demonstrating a significant improvement (p < 0.01). 44% of patients had no improvement in liver stiffness despite achieving SVR. In patients with advanced fibrosis (lower level of albumin or histological fibrosis stage F4), it was difficult to improve liver stiffness. Except for albumin, there were no blood tests associated with non-improvement in liver stiffness, making these cases difficult to predict. In conclusion, despite obtaining SVR, improvement in liver stiffness could not be obtained in some cases, especially in patients with advanced fibrosis. In these patients, liver stiffness must be followed even if SVR is obtained. This article is protected by copyright. All rights reserved.

AIM Tyrosine kinase inhibitor (TKI) therapy resulted in better prognosis for patients with hepatocellular carcinoma (HCC). However, some cases with Barcelona Clinic Liver Cancer (BCLC) stage C disease still had poor prognosis. This study aimed to investigate prognosis and characteristics of patients with HCC treated with TKI based on liver function and the extent of portal vein tumor thrombosis (PVTT). METHODS Patients receiving TKI therapy (n = 345) were recruited retrospectively. Child-Pugh score and albumin-bilirubin (ALBI) score were used for assessment of liver function. The extent of PVTT was classified from Vp0 to Vp4. Radiotherapy or hepatic arterial infusion chemotherapy were carried out as additional therapy to TKI. The end-point for this analysis was overall survival (OS). RESULTS A total of 291 and 54 patients received sorafenib and lenvatinib as first-line TKI therapy, respectively. The median OS of patients treated with TKI were significantly stratified by ALBI grade (grade 1, 20.1 months; grade 2a, 16.3 months; grades 2b and 3, 9.8 months; P = 0.0003). The classification of PVTT significantly stratified the prognosis of patients treated with TKI (median OS: Vp0, 18.5 months; Vp1/2, 14.4 months; Vp3/4, 5.5 months; P

Background and Aim Loss of hepatitis B surface antigen (HBsAg) is an important goal in the treatment of chronic hepatitis B. We investigated whether switching from long‐term entecavir (ETV) administration to tenofovir (TFV) (tenofovir alafenamide [TAF] or tenofovir disoproxil fumarate [TDF]) could contribute to the reduction of HBsAg levels. Methods The degree of HBsAg reduction by 48 weeks in 30 patients following switching from ETV to TFV was compared with results from 147 patients who continued ETV as a control. Results TFV group switched to TFV after mean 6.79 years of ETV administration. HBV‐DNA levels remained below 1.0 log IU/mL in all cases in both groups during 48 weeks. Median HBsAg reduction at 48 weeks was 0.075 (−0.05 to 0.38) log/IU/mL in the TFV switch group, and 0.070 (−0.28 to 0.50) in the ETV continuation group, which was not statistically significant (p = 0.5). In a subgroup of hepatitis B e antigen negative patients whose HBsAg had not been reduced (HBsAg reduction ≤0 log IU/mL) in the 48 weeks prior to entry into the study, HBsAg reduction was significantly higher in the TFV switch group than in the ETV continuation group (0.15 [0.07–0.135] in TFV, 0.09 [−0.14 to 0.25] log IU/mL in ETV, p = 0.04). Conclusion Although HBsAg reduction is equivalent with ETV continuation and switching to TFV in all patients at 48 weeks, switching from ETV to TFV could provide an alternative therapeutic strategy toward HBsAg elimination in a specific subpopulation of patients., Hepatitis B surface antigen (HBsAg) reduction is equivalent with entecavir (ETV) continuation and switching to TFV in all patients at 48 weeks. However, a significant reduction in HBsAg was observed in a subgroup of Hepatitis B e‐antigen‐negative patients whose HBsAg was not reduced during ETV therapy. In such cases, HBsAg reduction could be expected following a switch to TFV.

BACKGROUND/PURPOSE Although ursodeoxycholic acid (UDCA) is a first-line treatment for primary biliary cholangitis (PBC), 20%-30% of patients with PBC exhibit an incomplete response to UDCA. Recently, the UDCA Response Score was proposed for predicting response to UDCA using pretreatment parameters in patients with PBC. We aimed to validate the UDCA Response Score in Japanese patients with PBC. METHODS Registry data of Japanese patients (n = 873) were collected. Patients with data on all clinical parameters required for calculating the UDCA Response Score were selected. The endpoint was UDCA response, defined as alkaline phosphatase

Adherence to nucleotide/nucleoside analog therapy is important in improving prognosis in chronic hepatitis B. We aimed to compare medical adherence and satisfaction with entecavir (ETV) and tenofovir alafenamide (TAF) and to assess the effect of switching from ETV to TAF. Patients taking ETV (n = 114) and TAF (n = 35), and who switched from ETV to TAF (n = 15) were included. Medication adherence and satisfaction were assessed using a questionnaire. There was no significant difference in adherence between the ETV and TAF groups, but the medication satisfaction rates (0-10, prefer-dislike) were 1.72 ± 2.2 and 0.69 ± 1.5, respectively (P = .01; significantly higher in the TAF group). In patients who switched from ETV to TAF, medication adherence significantly improved (P = .04) as follows: never forgetting, from 40% to 87%; forgetting once every 2 to 3 months, from 33% to 7%; forgetting once every 2 months, from 20% to 7%, and forgetting once every 4 weeks, from 7% to 0%. Similarly, the medication satisfaction rate significantly improved from 4.53 ± 3.2 to 1.27 ± 2.4 after switching (P = .008). In conclusion, switching from ETV to TAF can be a useful approach to improve medication adherence and satisfaction.

Background/aim The platelet-to-lymphocyte ratio (PLR) has recently been suggested as a new predictor of the prognosis in several carcinoma types. However, the clinical impact remains controversial in patients with ampullary carcinoma. Thus, the aim of this study was to investigate other useful biomarkers for identifying poor prognosis in patients with ampullary carcinoma. Patients and methods Forty-one patients with ampullary carcinoma underwent pancreaticoduodenectomy (PD) with curative resection between April 2000 and April 2017. Various clinicopathological findings of the patients and their tumors were evaluated as potential prognostic factors which might enable better stratification of prognosis. Results Platelet-to-lymphocyte ratio, as well as other markers, was found to be a prognostic factor in patients with ampullary carcinoma. The 2-year disease-free survival percentage was significantly higher in the group with low PLR than in the high PLR group (70.2% vs. 28.6%; p=0.005). Combinational analysis of the PLR and conventional TMs enabled us to stratify prognosis of the patients more clearly than by each marker alone. Conclusion PLR was a useful prognostic factor for patients with ampullary cancer. The combination of preoperative PLR and conventional TMs markers may be powerful predictive factors for postoperative prognosis in patients with ampullary carcinoma following PD.

Nonalcoholic fatty liver disease (NAFLD) has affected more than one-fourth of the global population, thus emerging as a worldwide health and economic burden.1 The common causes of death in patients with NAFLD include cardiovascular disease (CVD), decompensation, and hepatocellular carcinoma (HCC). However, identifying the risk of these complications in patients with NAFLD remains an unmet need in clinical practice.

AIM Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy. However, the characteristics and prognosis of ICC is not well known. This study aims to reveal the relationship between liver function and prognosis of ICC. METHODS A total of 83 ICC patients were recruited retrospectively from March 2009 to August 2020. Child-Pugh (CP) and albumin-bilirubin (ALBI) scores were used to assess liver function. The extent of portal vein tumor thrombosis (PVTT) was classified from Vp0 to Vp4. The end-point for this analysis was overall survival (OS). RESULTS The median age was 72 (44-88) years, 48 patients were male (57.8%), and 70 patients were classified as CP grade A (84.3%). At baseline, chronic liver disease (hepatitis B, 9.6%; hepatitis C, 15.7%; alcoholic liver disease, 9.6%; and nonalcoholic fatty liver disease, 4.8%) were diagnosed. The median OS of all ICC patients was 21.2 months. A total of 27 patients underwent surgical resection; these patients showed a longer median OS compared to those who did not undergo surgery (50.8 months vs. 5.5 months, p

Aim Lenvatinib (LEN) is a newly approved, multikinase inhibitor for treating unresectable hepatocellular carcinoma. In the present study, we investigated the impact of three different criteria for evaluating radiological objective response (OR) on overall survival in real-world data. Methods Consent for LEN therapy was obtained from 51 patients from April 2018 to March 2019. A total of 40 patients who received a minimal cumulative duration of 4 weeks of LEN were included in the analysis. Enhanced computed tomography scan was performed at baseline and every 4-8 weeks after LEN administration. Overall survival and OR were assessed with three different evaluations, as follows: Response Evaluation Criteria in Solid Tumors 1.1, modified Response Evaluation Criteria in Solid Tumors, and Choi criteria. Results The average observation period for all participants after LEN introduction was 209.4 ± 77.5 days. The Response Evaluation Criteria in Solid Tumors 1.1, modified Response Evaluation Criteria in Solid Tumors, and Choi criteria identified 10 of 40 (25.0%), 15 of 40 (37.5%), and 18of 40 (45.0%) patients with OR, respectively. The median overall survival in progressive disease evaluated by each criterion was 227 days. This result was significantly shorter than OR. Furthermore, the cumulative duration of LEN administration (>150 days) represented a significant prognostic factor (HR 0.160. 95% CI 0.039-0.646, P = 0.001). Conclusion The Response Evaluation Criteria in Solid Tumors 1.1, modified Response Evaluation Criteria in Solid Tumors, and Choi criteria were useful therapeutic evaluation methods in LEN therapy for unresectable hepatocellular carcinoma. LEN's appropriate effect evaluation and management might lead to a better prognosis.

The aims of this study were to identify genetic characteristics of intraductal papillary mucinous neoplasm (IPMN)-associated pancreatic ductal carcinoma (PDC) and to detect these markers using pancreatic juice.From 76 cases, 102 tissues were obtained: 29 cases were noninvasive IPMN, 18 were PDC derived from IPMN (D-PDC; noninvasive part, n = 16; invasive part, n = 18), and 29 were PDC concomitant with IPMN (C-PDC; IPMN part, n = 10; PDC part, n = 29). Moreover, pancreatic juice samples from 28 cases were obtained (noninvasive IPMN, n = 13; D-PDC, n = 7; C-PDC, n = 8). Fifty-one cancer-related genes were analyzed by next-generation sequencing.TP53 mutation rates in D-PDC, C-PDC, and noninvasive IPMN were 67%, 66%, and 10%, respectively. Moreover, KRAS mutational patterns between 2 simultaneous tumors differed in 1 (6.3%) of the 16 D-PDC cases and in 8 (80%) of the 10 C-PDC cases (P = 0.0006). TP53 or multiple KRAS mutations were detected using pancreatic juice more frequently in C-PDC cases than in noninvasive IPMN cases (75% and 23%, respectively, P = 0.03).Multiple KRAS mutations along with TP53 mutation are genetic markers for C-PDC, which could be detected using pancreatic juice preoperatively.

Aim Rescue therapy for patients with genotype 2 (GT2) chronic hepatitis C who failed prior sofosbuvir (SOF) plus ribavirin (RBV) awaits establishment. This study aims to investigate the efficacy and safety of the fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg) (GLE/PIB) for patients with GT2 chronic hepatitis C. Methods In this nationwide observational study undertaken by the Japanese Red Cross Liver Study Group, 28 GT2 patients with prior failure of SOF + RBV were retreated with GLE/PIB for 12 weeks. We evaluated the rate of sustained virologic response (SVR) and adverse events. Results After 4 weeks of therapy, serum hepatitis C virus RNA was below the limit of quantification in all patients. The SVR after 4 and 12 weeks of the end of treatment was validated in 100% (28/28) and 100% (28/28), respectively. The adverse events comprised pruritus (eight patients), fatigue (four patients), and appetite loss (four patients), all of which were mild in severity. Conclusions This study establishes the efficacy of GLE/PIB as retreatment in Japanese patients with GT2 chronic hepatitis C not responding to SOF + RBV.

Postoperative pancreatic fistula (POPF) is one of the most severe complications after pancreatic surgeries. POPF develops as a consequence of pancreatic juice leakage from a surgically exfoliated surface and/or anastomotic stump, which sometimes cause intraperitoneal abscesses and subsequent lethal hemorrhage. In recent years, various surgical and perioperative attempts have been examined to reduce the incidence of POPF. We reviewed several well-designed studies addressing POPF-related factors, such as reconstruction methods, anastomotic techniques, stent usage, prophylactic intra-abdominal drainage, and somatostatin analogs, after pancreaticoduodenectomy and distal pancreatectomy, and we assessed the current status of POPF. In addition, we also discussed the current status of POPF in minimally invasive surgeries, laparoscopic surgeries, and robotic surgeries.

BACKGROUND AND AIM Tenofovir alafenamide (TAF) is a new prodrug of tenofovir, enabling treatment of patients with hepatitis B virus (HBV) infection at a lower dose than tenofovir disoproxil fumarate (TDF), via more efficient delivery of tenofovir to the hepatocytes. We compared the efficacy and safety of TDF and TAF and investigated switching from TDF to TAF therapy. METHODS Consent for TDF and TAF therapy was obtained from 117 and 67 patients from August 2014 to January 2018. In total, 45 and 14 patients were administered with TDF and TAF, respectively, as naive therapy, and 36 patients were switched from TDF to TAF. The antiviral effects and renal function safety were assessed. RESULTS At week 48, the antiviral effects on patients receiving TDF and TAF as naive therapy were similar in terms of reduction of HBV DNA (-5.6 ± 1.8 logIU/ml vs -5.0 ± 1.7 log IU/ml; P = 0.34) and hepatitis B surface antigen (-0.29 ± 0.64 logIU/ml vs -0.15 ± 0.42 logIU/ml; P = 0.71) levels. A significant decrease in the estimated glomerular filtration rate (eGFR) was seen at 48-week TDF treatment (-5.34 ± 7.69 ml/min/1.73 m2 ; P

In Japan, bezafibrate (BF) is a second-line agent for primary biliary cholangitis (PBC) that is refractory to ursodeoxycholic acid (UDCA) treatment. From a retrospective cohort (n = 873) from the Japan PBC Study Group, we enrolled 118 patients who had received UDCA monotherapy for at least 1 year followed by combination therapy with UDCA+BF for at least 1 year. GLOBE and UK-PBC scores after UDCA monotherapy (i.e., immediately before UDCA+BF combination therapy) were compared with those after 1 year of UDCA+BF combination therapy. The real outcomes of enrolled patients estimated by Kaplan-Meier analysis were compared with the predicted outcomes calculated using GLOBE and UK-PBC scores. In addition, the hazard ratio of BF treatment was calculated using propensity score analysis. The mean GLOBE score before the combination therapy was 0.504 ± 0.080, which improved significantly to 0.115 ± 0.085 (P < 0.0001) after 1 year of combination therapy. The real liver transplant-free survival of enrolled patients was significantly better than that predicted by GLOBE score before introducing BF. Combination therapy did not significantly improve the real rates of liver transplantation or liver-related death compared with those predicted by UK-PBC risk score before introducing BF, but the predicted risk was significantly reduced by the addition of BF (P < 0.0001). Cox regression analysis with inverse probability of treatment weighting showed that the addition of BF significantly reduced the hazard of liver transplant or liver-related death in patients who, after 1 year of UDCA monotherapy, had normal serum bilirubin (adjusted hazard ratio 0.09, 95% confidence interval 0.01-0.60, P = 0.013). Conclusion: Addition of BF to UDCA monotherapy improves not only GLOBE and UK-PBC scores but also the long-term prognosis of PBC patients, especially those with early-stage PBC.

Until recently, interferon-free anti-hepatitis C virus (HCV) therapy for genotype 2 (GT2) HCV-infected hemodialysis patients was an unfulfilled medical need. Recent clinical trials of glecaprevir and pibrentasvir (G/P) for hemodialysis patients showed high efficacy and safety; however, the number of GT2 HCV-infected patients, especially Asian patients, was limited and most of them were treated with a 12-week regimen. In this prospective multicenter study, we aimed to investigate the efficacy and safety of G/P in Japanese hemodialysis patients with GT2 HCV infection. Twenty-seven Japanese hemodialysis patients with GT2 HCV infection who were started on with 8- or 12-week G/P regimen between November 2017 and June 2018 were included and followed up for around 12 weeks after treatment completion. Among the 27 included patients, 13 non-liver cirrhosis (LC) and direct-acting antivirals (DAAs)-naive patients were treated with 8 weeks of G/P and 14 patients with LC (n = 13) or history of failure of DAAs (n = 1) were treated with a 12-week regimen. The overall sustained virological response at 12 weeks after treatment completion (SVR 12) was 96.3% (26/27). All patients with 8 weeks of treatment achieved SVR12. Two patients discontinued the therapy at 2 and 11 weeks after treatment initiation. The patient who discontinued at 2 weeks due to pruritus alone failed to respond to G/P. No patients experienced lethal adverse events during the therapy, and the most common adverse event was pruritus. An 8- or 12-week G/P regimen is highly effective and safe in GT2 HCV-infected hemodialysis patients.

Background/aim Although perioperative management and operative techniques for pancreatic surgery have improved, postoperative pancreatic fistula (POPF) remains the major cause of morbidity and mortality following distal pancreatectomy (DP). The purpose of this study was to evaluate the superiority of the reinforced stapler compared to the bare triple row stapler. Patients and methods A total of 93 patients who underwent DP at the First Department of Surgery at Yamanashi University were examined. The patients were divided into two groups according to the closure method for the pancreatic stump; the bare triple-row stapler (BTRS) group and the reinforced triple-row stapler (RTRS) group. The postoperative outcomes were then compared in terms of several clinicopathological factors between the two groups. Results Seven patients were diagnosed with Grade B/C POPF in this series. The incidence of POPF in the RTRS group was lower than that in the BTRS group (3.6% vs. 13.5%), although there was no significant difference (p=0.077). Further detailed analysis demonstrated that RTRS significantly reduced POPF compared to BTRS in obese patients with a BMI >25.0 kg/m2 (p=0.038). Conclusion Reinforced triple-row staplers may reduce the incidence of severe POPF, especially in obese patients with a BMI >25 kg/m2.

BACKGROUND AND AIM The serum hepatitis B core-related antigen (HBcrAg) is considered a surrogate marker of the amount and activity of intrahepatic covalently closed circular DNA. This study aims to investigate the virological characteristics of HBcrAg in chronic hepatitis B (CHB) patients and to reveal the hepatocellular carcinoma (HCC) risk factors of hepatitis B e antigen (HBeAg)-negative patients. METHODS Hepatitis B core-related antigen was measured in 245 naive CHB patients before receiving nucleoside/nucleotide analog (NA) therapy. All patients were receiving NA (entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide) continuously for more than 1 year until the end of follow-up, and they did not have a history of HCC. Hepatitis B viral status was compared between 106 HBeAg-positive and 139 HBeAg-negative patients. RESULTS Median HBcrAg levels were significantly higher in HBeAg-positive patients than in HBeAg-negative patients (> 6.8 vs 3.7 log U/mL, P

Pancreatectomy is a highly invasive procedure with extensive intraoperative blood loss (IBL) and high risk of postoperative pancreatic fistula (POPF). We conducted an experimental and retrospective clinical study to determine whether the malignant behaviors of pancreatic cancer cells were enhanced by exposure to blood components in vitro and to evaluate the oncological significance of high IBL and POPF in pancreatic cancer. This study included 107 patients undergoing radical pancreatectomy in the University of Yamanashi Hospital between 2011 and 2017, classified into high (n = 29) and low (n = 78) IBL groups. In vitro experiments included functional analyses of Panc-1 pancreatic cancer and normal mesothelial cells exposed to patient blood components, and clinical data were used to assess the contribution of IBL and POPF to patient outcomes. The migration (p = 0.007), invasion (p < 0.001), and proliferation (p < 0.01) of Panc-1 cells were enhanced with platelet coculture. The ability of Panc-1 cells to adhere mesothelial cells was enhanced by plasma coincubation, especially in the presence of inflammation (p < 0.001). High IBL was associated with worse overall survival (p = 0.007) and increased locoregional recurrence (p = 0.003) in patients. POPF enhanced the negative prognostic significance of high IBL (p < 0.001 for overall survival, p = 0.001 for locoregional recurrence), indicating the oncological negative effects of high IBL and POPF. Blood components, especially platelets, and inflammation enhance the malignant behaviors of pancreatic cancer cells, potentially contributing to poor prognosis for pancreatic cancer patients.

The usefulness of APRI or FIB-4 is well established as a non-invasive liver fibrosis marker at a point of diagnosis in patients with chronic liver disease. However, their applicability for the monitoring of progression of liver fibrosis over time is yet to be determined. We aimed to clarify the feasibility of APRI and FIB-4 for the longitudinal evaluation of liver fibrosis in patients with chronic hepatitis B and C. This is a multi-center retrospective and prospective cohort study, enrolling 1029 patients with HCV and 384 patients with HBV who were histologically diagnosed by liver biopsy. The observation period of retrospective and prospective study was 14 and 12 years, respectively. The APRI and FIB-4 were traced back in cases of histologically diagnosed cirrhosis, and those were prospectively analyzed after biopsy in cases diagnosed as F3 of METAVIR score, respectively. The averaged APRI and FIB-4 exhibited time-dependent increase in the retrospective study of hepatitis C patients (increase by 0.09/year in APRI and 0.29/year in FIB-4). In the prospective study of untreated hepatitis C patients, such increases were 0.14/year in APRI and 0.40/year in FIB-4, respectively. Neither the average of APRI nor FIB-4 showed a specific tendency with hepatitis B patients and treatment-experienced hepatitis C patients. The APRI and FIB-4 may serve as a transition indicator of liver fibrosis in anti-viral treatment-naive patients with chronic hepatitis C.

BackgroundWe aimed to investigate the efficacy and safety of ramucirumab therapy in Japanese patients with unresectable hepatocellular carcinoma (u-HCC) in real-world practice.MethodsA total of 16 patients with u-HCC were treated with ramucirumab of ≥2 cycles between July 2019 and April 2020. Modified response evaluation criteria in solid tumors (RECIST) and RECIST version 1.1 were used to evaluate radiological responses.ResultsThe patients received ramucirumab as second-line (n = 4), third-line (n = 2), and fourth-line (n = 10). Median observation period was 3.7 months and 3 patients treated as fourth-line died from HCC progression. According to modified RECIST, the objective response rate (ORR) and disease control rate (DCR) were 27.2% and 81.8%, respectively. ORR and DCR by RECIST version 1.1 were 9.1 % and 72.7%, respectively. PFS at 3 months was 68.2%. Drug discontinuation caused by adverse events (AEs) was reported in 7 patients treated as fourth-line and 1 patient as third-line. Pretreatment creatinine (Cr) and estimated glomerular filtration rate (eGFR) were significantly higher in patients with discontinuation owing to AEs (P = 0.01 and P = 0.02). Urine protein-to-creatine ratio after 4 weeks was significantly higher in patients with impaired renal function than patients with preserved renal function (0.93 vs. 0.14; P = 0.017).ConclusionRamucirumab therapy was found to have similar radiological responses between u-HCC patients with single and multiple experiences of TKI therapies. The pretreatment factors would be associated with the incidence of AEs during the therapy.

Background Postoperative pancreatic fistula (POPF) is one of the most serious complications after pancreaticoduodenectomy (PD). Various factors have been reported as POPF risks, but the most serious of these is soft pancreas. To reduce POPF occurrences, many changes to the PD process have been proposed. This study evaluates short-term results of anastomosis technique for PD. Methods In total, 123 patients with soft pancreases who had undergone PD at Yamanashi University between January 2012 and August 2020 were retrospectively analyzed. We divided these patients into two groups depending on the time PD was performed: a conventional group (n = 67) and a modified group (n = 56). Results The rate of clinically relevant POPF was significantly lower in the modified group than that in the conventional group (5.4% vs 22.4%, p value p value = 0.002). Conclusions Our novel anastomosis technique for pancreatojejunostomy reduced POPF in PD, especially in cases where the patient had a soft pancreas.

Background and Aim Lenvatinib (LEN) has an antitumor effect with an early reduction in contrast enhancement for unresectable hepatocellular carcinoma (HCC). The aim of this study was to reveal the most useful radiological response evaluation for overall survival (OS) in patients treated with LEN. Methods Patients receiving LEN therapy (n = 80) were retrospectively recruited from April 2018 to January 2020. Enhanced computed tomography scans were performed at baseline and every 4–8 weeks. OS and radiological response were evaluated using response evaluation criteria in solid tumors (RECIST 1.1), modified RECIST (mRECIST), and Choi criteria. To be eligible for study, a minimal cumulative duration of LEN was 4 weeks. A total of 62 patients were included in the analysis. Results The median OS was 469 days. The RECIST 1.1, mRECIST, and Choi criteria identified 14 (22.5%), 30 (48.3%), and 33 (53.2%) patients with an objective response, respectively. In the univariate analysis, Child–Pugh class B, major vascular invasion, and high alpha‐fetoprotein (>200) were statistically significant poor prognostic factors. Radiological response was a significantly better prognostic factor in each criterion (RECIST, mRECIST, and Choi). In the multivariate analysis, radiological response evaluated by RECIST (hazard ratio, 0.259; 95% confidence interval, 0.0723–0.928; P = 0.038) was an independent factor. Furthermore, only RECIST significantly stratified prognosis (P = 0.041) when limited to the first evaluation. Conclusion RECIST 1.1 was useful even as early therapeutic evaluation for HCC patients treated with LEN. Understanding the characteristics of radiological response over time may contribute to improving the prognosis of patients with HCC., The RECIST 1.1 was a useful, even early, therapeutic evaluation for hepatocellular carcinoma patients treated with lenvatinib. Maintaining relative dose intensity of lenvatinib is crucial after the first evaluation, especially with the mRECIST and Choi criteria, which evaluate staining, in Barcelona Clinic Liver Cancer stage B patients.

Background Postoperative pancreatic fistula (POPF) is one of the most serious complications after pancreaticoduodenectomy (PD). Various factors have been reported as POPF risks, but the most serious of these is soft pancreas. To reduce POPF occurrences, many changes to the PD process have been proposed. This study evaluates short-term results of anastomosis technique for PD.Methods In total, 120 patients with soft pancreases who had undergone PD at Yamanashi University between January 2012 and December 2019 were analyzed. We divided these patients into two groups: a conventional group (n = 67) and a modified group (n = 53).Results The rate of clinically relevant POPF was significantly lower in the modified group than that in the conventional group (1.9% vs 22.4%, p

Identification of high-risk patients for hepatocellular carcinoma (HCC) after sustained virological responses (SVR) is necessary to define candidates for long-term surveillance. In this study, we examined whether serum markers after 1 year of SVR could predict subsequent HCC development. Total 734 chronic hepatitis C patients without a history of HCC who achieved SVR with direct-acting antivirals were included. The regular surveillance for HCC started from 24 weeks after the end of treatment (SVR24). Factors at SVR24 and 1 year after SVR24 were analyzed for predicting HCC development. During the mean observation period of 19.7 &plusmn, 10 months, 24 patients developed HCC. At SVR24, Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA&plusmn, M2BP) &ge, 1.85 and &alpha, fetoprotein (AFP) &ge, 6.0 ng/mL were independent factors of HCC development. However, at 1 year after SVR24, WFA&plusmn, M2BP &ge, 1.85 was associated with subsequent HCC development (hazard ratio: 23.5, 95% confidence interval: 2.68&ndash, 205) but not AFP. Among patients with WFA&plusmn, 1.85 at SVR24, 42% had WFA&plusmn, M2BP &lt, 1.85 at 1 year after SVR24 (WFA&plusmn, M2BP declined group). Subsequent HCC development was significantly lower in the declined group than in the non-declined group (1 year HCC rate: 0% vs. 9.4%, p = 0.04). In conclusion, WFA&plusmn, M2BP but not AFP could identify high and no-risk cases of HCC at 1 year after SVR. Therefore, it was useful as a real-time monitoring tool to identify the candidates for continuous surveillance for HCC.

The albumin, bilirubin, and platelet (ABP) criteria was proposed to avoid screening endoscopy for detecting high-risk varices (HRV) and it has high diagnostic accuracy. We carried out a retrospective cross-sectional study to verify the diagnostic accuracy.A total of 610 patients with advanced fibrosis were enrolled in the study. ABP criteria are defined as follows: albumin4.0 g/dL, bilirubin22 μmol/L, and platelets114 000/μL.Background liver disease were hepatitis C/hepatitis B/non-alcoholic fatty liver disease/others:405 (66.4%)/67 (10.5%)/78 (12.8%)/60 (10.3%). A total of 105 patients (17.2%) had HRV. In multivariate analysis, serum bilirubin22 μmol/L (HR 2.00, 95% CI 1.2-3.4), albumin4.0 g/dL (HR 2.56, 95% CI 1.7-3.8), and platelets114 000/μL (HR 3.52, 95% CI 2.1-5.8) levels were independently associated with no presence of HRV. When the ABP criteria were examined, 200 patients (32.8%) fulfilled the criteria, and 194 patients had no HRV (positive predictive value 97.0%) When classified by etiologies (hepatitis C/hepatitis B/non-alcoholic fatty liver disease), positive predictive value were 97.7/100/92.0%, respectively.The ABP criteria are easy to examine, because they use only standard laboratory tests, and they are available for screening patients who might avoid endoscopy regardless of etiologies.