Psychological distress among early medical residents: A 2-year longitudinal cohort study over seven years in Japan.

BACKGROUND: Early medical residents are expected to have a higher prevalence of burnout due to physical and psychological stressors. However psychological distress associated with burnout has not been adequately investigated in a longitudinal manner. We therefore examined the longitudinal trajectory of depression and its associated factors among early medical residents. METHODS: In this cohort study, medical residents (n = 215) who started rotation at the University of Yamanashi Hospital during 2012 to 2018 were recruited and asked to complete the Brief Job Stress Questionnaire (BJSQ), Center for Epidemiologic Studies Depression Scale (CESD), Brief Scale for Coping Profile (BSCP) and Athens Insomnia Scale (AIS) at the time of exit from each clinical department for up to two years over seven years. Factors associated with the CES-D scores were statistically explored, with a cutoff score of 16 to denote depression. RESULTS: The CES-D was completed by 205 residents. The average CES-D score was 10.3 ± 8.0 and the scores were lower in the 2nd versus 1st year of residency (11.3 ± 6.7 versus 9.2 ± 7.0). Multiple regression analysis of BJSQ/BSCP/AIS on CES-D revealed that insomnia had a significant impact on the CES-D scores. Apart from insomnia, avoidance and suppression and peer support had significant effects. Resilient residents, who showed the maximum CES-D score of under 16 consistently throughout the residency, was better in terms of changing a point of view, active solution and changing mood. Women were more likely to express emotions to others, while they reported more job control in the first year. CONCLUSIONS: Our results have high clinical relevance to challenge psychological burnout among early medical residents, offering some possible clues for prevention such as reduced burden, more flexibility during the first year and strengthening coworker support. Insomnia exerted moderate to strong effects on depression and monitoring of sleep appears indispensable in this specific population.

Early experience of atezolizumab plus bevacizumab therapy in Japanese patients with unresectable hepatocellular carcinoma in real-world practice.

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. According to RECIST, the objective response rate (ORR) and disease control rate (DCR) in all patients were 15.4% and 57.7%. In the 1st-line patients, ORR and DCR based on RECIST 1.1 were 27.3% and 81.8%. The median time to progression (TTP) assessed by RECIST 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 < 0.001). Patients with an AFP response (reduction ≥ 20% from baseline) at 6 weeks had a significantly longer TTP assessed by RECIST 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.

Plasma Renin Activity Predicts Prognosis and Liver Disease-Related Events in Liver Cirrhosis Patients with Ascites Treated by Tolvaptan.

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 <9.5 ng/mL/h (193 vs. 893 days, 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 <3.2 ng/mL/h (89 vs. 222 days, 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.

Dynamic evaluation of hepatocellular carcinoma prediction models in patients with chronic hepatitis B receiving nucleotide/nucleoside analogue treatment.

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 < .05 for all time points), whereas HCC incidence in patients with high risk of mPAGE-B and REACH-B at 2 years after NA administration were equivalent to those with intermediate and low-risk groups (p = .2 for mPAGE-B, and p = .1 for REACH-B). The area under the receiver operating characteristic (AUROC) for HCC development of PAGE-B at NA administration, and 1 and 2 years after administration were 0.773, 0.803 and 0.737, respectively. The AUROCs of PAGE-B at each point were continuously higher than those of REACH-B (0.646, 0.725, and 0.653, respectively) and mPAGE-B (0.754, 0.734, and 0.678, respectively).PAGE-B score has a high diagnostic accuracy for HCC development at any time point during NA treatment, indicating its potential use as a real-time monitor of HCC development.

Changes of liver stiffness measured by magnetic resonance elastography during direct-acting antivirals treatment in patients with chronic hepatitis C.

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 < .01). A total of 44% of patients had no improvement in liver stiffness despite achieving SVR. In patients with advanced fibrosis (lower level of albumin [Alb] or histological fibrosis stage F4), it was difficult to improve liver stiffness. Except for Alb, there were no blood tests associated with nonimprovement 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.

Exposure to Blood Components and Inflammation Contribute to Pancreatic Cancer Progression.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Blood components, especially platelets, and inflammation enhance the malignant behaviors of pancreatic cancer cells, potentially contributing to poor prognosis for pancreatic cancer patients.

Prognosis of intrahepatic cholangiocarcinoma stratified by albumin-bilirubin grade.

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 < 0.001). The prognosis of patients with ICC can be stratified by ALBI grade (grade 1, 54.3 months; grade 2a, 8.4 months; grade 2b, 3.9 months; and grade 3, 1.4 months; p < 0.001) and the extent of PVTT (Vp0, 54.3 months; Vp1/2, 8.4 months; and Vp3/4, 3.9 months; p = 0.0039). CONCLUSION: In this study, viral hepatitis (25.3%) was identified as the most prevalent background liver disease of ICC. Assessing liver function using ALBI grade is useful for stratifying the prognosis of patients with ICC.

Hepatitis B core-related antigen predicts disease progression and hepatocellular carcinoma in hepatitis B e antigen-negative chronic hepatitis B patients.

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 < 0.01). In HBeAg-negative patients, higher HBcrAg levels were associated with cirrhosis (119 chronic hepatitis/20 cirrhosis = 3.5/4.7 log U/mL, P = 0.03) and higher serum hepatitis B virus DNA. During a median follow-up of 5.28 (1.03-12.0) years, the 5-year cumulative HCC incidence rate was 5.4% in the HBeAg-negative cohort. In the multivariate Cox regression analysis, higher HBcrAg levels at 1 year were independent predictive factors for HCC development in HBeAg-negative patients who received NA therapy (cutoff value, 4.1 log U/mL; hazard ratio, 6.749; 95% confidence interval, 1.334-34.15, P < 0.01) and even in non-cirrhosis patients. CONCLUSION: Hepatitis B core-related antigen was useful for understanding disease progression in CHB patients and for stratifying the risk for carcinogenesis in HBeAg-negative patients receiving NA therapy.

Liver fibrosis and fatty liver as independent risk factors for cardiovascular disease.

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.

Comparison of medication adherence and satisfaction between entecavir and tenofovir alafenamide therapy in chronic hepatitis B.

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.

Bezafibrate Improves GLOBE and UK-PBC Scores and Long-Term Outcomes in Patients With Primary Biliary Cholangitis.

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.

A validation study of the Ursodeoxycholic Acid Response Score in Japanese patients with primary biliary cholangitis.

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 <1.67 times the upper limit of the normal value after 12 months of UDCA treatment. RESULTS: All parameters were available in 804 patients (male/female = 120/684, age 58.9 [interquartile range 51.1-66.9] years). Bezafibrate was commenced within 12 months of UDCA in 78 patients (9.7%) because of the lack of an early response. We found that the endpoint was not reached in these 78 patients, and the area under the receiver operating characteristic curve (AUROC) of the score was 0.74 (95% confidence interval [CI] 0.70-0.79). The AUROC was 0.77 (95% CI 0.70-0.83) in patients undergoing UDCA monotherapy (n = 726). Finally, the AUROC of the modified UDCA Response Score using only data from the treatment start date was 0.80 (95% CI 0.70-0.90) in patients receiving a combination therapy of UDCA and bezafibrate (n = 160). CONCLUSION: The validity of the UDCA Response Score was acceptable in Japanese patients; this score will be informative in patients treated with a combination therapy of UDCA and bezafibrate.

Validation of albumin, bilirubin, and platelet criteria for avoiding screening endoscopy in patients with advanced fibrosis.

AIM: 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. METHODS: A total of 610 patients with advanced fibrosis were enrolled in the study. ABP criteria are defined as follows: albumin >4.0 g/dL, bilirubin <22 µmol/L, and platelets >114 000/µL. RESULTS: 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 bilirubin <22 µmol/L (HR 2.00, 95% CI 1.2-3.4), albumin >4.0 g/dL (HR 2.56, 95% CI 1.7-3.8), and platelets >114 000/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. CONCLUSIONS: 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.

Strategy for advanced hepatocellular carcinoma based on liver function and portal vein tumor thrombosis.

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 < 0.0001). In the ALBI 2b/3 and Vp3/4 groups, the median OS of patients treated with TKI and additional therapies was significantly longer than those treated with TKI only (9.2 months vs.. 3.6 months; P = 0.0129). CONCLUSION: Liver function and PVTT are useful for stratifying prognosis of HCC patients treated with TKI. The applicative classification could lead to appropriate therapy and better prognosis.

Three criteria for radiological response on survival in patients with hepatocellular carcinoma treated with lenvatinib.

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.

Validation of hepatocellular carcinoma risk scores in Japanese chronic hepatitis B cohort receiving nucleot(s)ide analog.

BACKGROUND AND AIM: The prediction of hepatocellular carcinoma (HCC) development during nucleotide/nucleoside analog (NA) therapy is clinically important in patients with chronic hepatitis B. Although several useful models for HCC prediction have been previously reported, their usefulness in the Japanese population is unclear. Therefore, this study examines the applicability of these models in Japanese patients. METHODS: Four hundred forty-three patients with no history of HCC who were treated with entecavir, tenofovir alafenamide, or tenofovir disoproxil fumarate were enrolled. PAGE-B, modified-PAGE-B, and REACH-B scores were calculated, and subsequent HCC development was investigated. RESULTS: The mean follow-up duration was 5.1 years, and a total of 33 patients (7.4%) developed HCC during the follow-up period. Multivariate analysis revealed that old age (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.01-1.09, P = 0.011), male gender (HR 2.62, 95% CI 1.06-6.49, P = 0.037), and low platelet count (HR 0.83, 95% CI 0.77-0.91, P < 0.001) were independent predictors of HCC development. These factors are the same as the factors identified in the PAGE-B model. Time-dependent area under the receiver operating characteristic (AUROC) curve revealed that the AUROCs for 3 and 7 years of PAGE-B (AUROC: 0.786 and 0.744 at 3 and 7 years, respectively) were continuously higher than those of REACH-B (0.658 and 0.543) and modified PAGE-B AUROC (0.772 and 0.731). CONCLUSIONS: PAGE-B, which can easily identify high-risk cases, can be useful for predicting HCC development in Japanese patients treated with NA therapy.

Anastomosis technique for pancreatojejunostomy and early removal of drainage tubes may reduce postoperative pancreatic fistula.

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 < 0.001), with there being only one case of POPF in the modified group. There were no cases of POPF-related hemorrhaging in the modified group. On the third day after the operation, the amylase levels in the drainage fluid for the modified group became less than half (1696 vs 650 U/L). Multivariate analysis showed that the modified method was the independent predictors to prevent clinical POPF (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.

Wisteria floribunda Agglutinin-Positive Mac-2 Binding Protein as a Screening Tool for Significant Liver Fibrosis in Health Checkup.

Chronic liver disease is generally widespread, and a test for screening fibrotic subjects in a large population is needed. The ability of Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA+-M2BP) to detect significant fibrosis was investigated in health checkup subjects in this research. Of 2021 health checkup subjects enrolled in this prospective cross-sectional study, those with WFA+-M2BP ≥ 1.0 were defined as high risk. Liver fibrosis was evaluated using magnetic resonance elastography (MRE) in subjects with high risk. The primary outcome was the positive predictive value (PPV) of WFA+-M2BP for significant fibrosis (liver stiffness ≥ 2.97 kPa by MRE). This trial was registered with the UMIN clinical trial registry, UMIN000036175. WFA+-M2BP ≥ 1.0 was observed in 5.3% of the 2021 subjects. The PPV for significant fibrosis with the threshold of WFA+-M2BP at ≥1.0, ≥1.1, ≥1.2, ≥1.3, ≥1.4, and ≥1.5 was 29.2%, 36.4%, 43.5%, 42.9%, 62.5%, and 71.4%, respectively. A WFA+-M2BP of 1.2 was selected as the optimal threshold for significant fibrosis among high-risk subjects, and the PPV, negative predictive value, sensitivity, and specificity for significant fibrosis were 43.5%, 84.0%, 71.4%, and 61.8%, respectively. WFA+-M2BP ≥ 1.2 was significantly associated with significant fibrosis, with an odds ratio (OR) of 4.04 (95% confidence interval (CI): 1.1-16, p = 0.04), but not FIB-4 ≥ 2.67 (OR: 2.40, 95%CI: 0.7-8.6, p-value = 0.2). In conclusion, WFA+-M2BP is associated with significant fibrosis and could narrow down potential subjects with liver fibrosis. The strategy of narrowing down fibrosis subjects using WFA+-M2BP may be used to screen for fibrotic subjects in a large population.

Wisteria floribunda Agglutinin-Positive Mac-2 Binding Protein but not α-fetoprotein as a Long-Term Hepatocellular Carcinoma Predictor.

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 ± 10 months, 24 patients developed HCC. At SVR24, Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA±M2BP) ≥ 1.85 and α-fetoprotein (AFP) ≥ 6.0 ng/mL were independent factors of HCC development. However, at 1 year after SVR24, WFA±M2BP ≥ 1.85 was associated with subsequent HCC development (hazard ratio: 23.5, 95% confidence interval: 2.68-205) but not AFP. Among patients with WFA±M2BP ≥ 1.85 at SVR24, 42% had WFA±M2BP < 1.85 at 1 year after SVR24 (WFA±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±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.

Prediction of Hepatocellular Carcinoma After Sustained Virological Responses Using Magnetic Resonance Elastography.

Direct acting antivirals (DAAs) have made it possible for most patients to achieve sustained virologic responses (SVR).1 However, some patients developed hepatocellular carcinoma (HCC) even after the eradication of hepatitis C virus2; therefore, it is clinically important to identify patients with a high risk of HCC development after SVR.