Background and Objectives: Patients who undergo hepatitis virus testing may remain unaware of their results in the absence of clinician feedback, particularly from non-specialists. To address this issue, we introduced patient-directed test result reports and evaluated their effectiveness in promoting physician responses among non-specialists. Materials and Methods: Distribution of hepatitis virus test result reports began on 22 August 2022 at the National Hospital Organization Disaster Medical Center in Japan. The study included all patients who underwent hepatitis testing, excluding those whose tests were ordered by gastroenterologists or screening physicians. The numbers of tests performed and reports distributed were obtained from electronic medical records. Results: Between August 2022 and August 2025, 30,700 patients underwent hepatitis B surface antigen (HBsAg) and/or hepatitis C virus antibody (HCV-Ab) testing, and 11,797 individuals received test result reports. In the most recent one-year period (September 2024–August 2025), the report distribution rate was 49.7%, unaffected by test positivity. Compared with the year before report implementation, the referral rates to gastroenterologists increased significantly for both HBsAg-positive (11.4% to 34.5%) and HCV-Ab-positive cases (7.7% to 25.2%; p < 0.01). Documentation of test results and confirmation of clinical cure or ongoing treatment by the ordering physician both improved. Cases without physician response decreased markedly (from 61.4% to 23.6% in HBsAg-positive patients and from 59.3% to 24.5% in HCV-Ab-positive patients; p < 0.01 for both). Conclusions: Distribution of dedicated hepatitis virus test result reports improved awareness among non-specialist physicians and contributed to better management of test-positive patients.

Background and aims: The enhanced liver fibrosis (ELF) score is a blood test that combines three markers linked to liver fibrosis. The utility of the ELF score has been demonstrated primarily in Western countries, but whether it is useful in areas with a high number of elderly people suffering from chronic liver disease has yet to be determined. Methods: This is a prospective study that included 373 consecutive patients who underwent a liver biopsy and had their ELF score measured on the same day. The diagnostic accuracy of the ELF score for liver fibrosis and the effect of age on the ELF score were investigated. Results: The median (interquartile) ELF scores in F0, F1, F2, F3, and F4 are 8.7 (8.2–9.2), 9.3 (8.8–10.0), 10.1 (9.4–10.7), 10.7 (9.9–11.2), and 12.0 (11.2–12.7), respectively. ELF scores increased with increasing liver fibrosis stage (p < 0.001). The diagnostic accuracy of the ELF score and FIB-4 for significant fibrosis (F2–4) and advanced fibrosis (F3–4) was comparable, but the ELF score had a higher diagnostic accuracy for cirrhosis (F4) than FIB-4. When patients were stratified by age of 60 years, the median ELF score did not differ by age in F2, F3, and F4. However, the median FIB-4 increased in patients with ≥60 years compared to those with <60 years in all fibrosis stages. Conclusions: ELF score has high diagnostic accuracy for liver fibrosis, regardless of age, and it could be used as a primary screening method.

Hepatitis countermeasures are being promoted by governments in Japan. We aimed to develop performance indicators (PIs) to assess the process and outcome of such countermeasures implemented for the prevention of viral hepatitis-related liver cancer at the national and prefectural government levels. We developed 19 PIs for hepatitis countermeasures implemented by local governments, covering the morbidity and mortality of liver cancer, hepatitis testing, subsidy programs for examinations and antiviral treatment, and education on hepatitis patient care to healthcare workers. We analyzed the PIs for each prefecture from Fiscal Year (FY) 2018–2020. The morbidity and mortality of liver cancer significantly decreased in the study period. The percentage of municipalities conducting hepatitis screening was already high at 95% in FY2017. The usage rate of government-subsidized screenings did not change. The subsidy usage rate for periodic viral hepatitis examination significantly increased. Meanwhile, the subsidy usage rate for antiviral treatment of hepatitis B increased, whereas that for hepatitis C decreased. The number of certified healthcare workers providing care for hepatitis patients increased significantly, and these workers were efficiently placed at regional core centers, institutions specialized in liver diseases, health care centers, and municipal governments. Liver cancer mortality was positively correlated with hepatitis screening, subsidies for periodic examinations, and the number of hepatitis medical care coordinators but was negatively correlated with subsidies for anti-HCV therapy, suggesting that rigorous countermeasures were implemented in prefectures with high liver cancer mortality. The developed PIs could be a useful tool for monitoring government efforts and achievements, thereby providing basic data for setting practical goals in liver cancer prevention.

Background and AimHepatocellular carcinoma development can be decreased by achieving and maintaining complete virological response (CVR) in chronic hepatitis B. However, it is unclear whether switching from entecavir (ETV) to tenofovir alafenamide (TAF) could achieve and maintain CVR in patients with low-level viremia (LLV; HBV DNA & LE; 3.3 log IU/mL) or occasional detectable HBV DNA during ETV treatment. Therefore, we aimed to examine whether the switching from ETV to TAF is effective in achieving CVR in patients with LLV or occasional detectable HBV DNA. MethodsThis study comprised 45 patients who switched from ETV to TAF. All patients received ETV and TAF for >2 years, and the HBV DNA levels were measured every 3 months. Maintaining undetectable HBV DNA during 2-year period is defined as CVR. The primary endpoint is the CVR rate during ETV and TAF treatment. ResultsThe CVR rate for each of the 2 years of ETV and TAF therapy was 33.3% (15/45) and 68.9% (31/45, P < 0.01), respectively, and the CVR rate increased by switching from ETV to TAF. In patients with occasional detectable HBV DNA during ETV treatment (22 patients), 15 achieved CVR and 7 maintained occasional detectable HBV DNA. In patients with LLV during ETV treatment (eight patients), three achieved CVR and five had occasional detectable HBV DNA. ConclusionSwitching from ETV to TAF increases the CVR rate in patients with LLV or occasional detectable HBV DNA and could be an alternative treatment option.

Abstract Background/Aim Nab-paclitaxel plus gemcitabine (GnP) is one of the standard chemotherapeutic schemes of treatment of advanced pancreatic cancer (PC). The current study has the aim to outline the predictors of therapeutic effect of GnP in the cases with recurrent PC after pancreatectomy. Patients and Methods We retrospectively evaluated the clinicopathological characteristics of patients with recurrent PC after pancreatectomy who received GnP at our institution from January 2016 to February 2021. We examined various inflammatory markers [neutrophil lymphocyte ratio (NLR), lymphocyte monocyte ratio (LMR), platelet lymphocyte ratio (PLR), C-reactive protein albumin ratio (CAR)] and a nutritional marker [ prognostic nutritional index (PNI) ] in addition to common clinicopathological characteristics as possible predictors of the chemotherapeutic effects of GnP. Results Univariate analysis identified PLR, CAR, and histological differentiation as significant predictors of better chemotherapeutic effects. Meanwhile, multivariate analysis identified only histological differentiation as an independent predictor of better chemotherapeutic effects. Accordingly, patients with well-differentiated adenocarcinoma showed better overall survival after recurrence than those with other histological types. Conclusion Histological differentiation can be a useful predictor of the therapeutic effects of GnP in the clinical cases of recurrent PC after pancreatectomy.

Key Clinical MessageThe liquid CGP was useful for detecting FGFR2 fusion and the patient experienced typical side effects (nail disorders, hyperphosphatemia, and taste disorders) of pemigatinib that required treatment.

AbstractBackgroundTherapeutic strategies for unresectable hepatocellular carcinoma (u‐HCC) in geriatric patients are important for real‐world practice. However, there remain no established biomarkers or therapeutic strategies regarding the best second‐line agent after atezolizumab plus bevacizumab therapy.AimIn this study, we investigated the usefulness of modified Geriatric 8 (mG8) score in examining elderly patients (≥75 years old) with unresectable hepatocellular carcinoma (u‐HCC) using sorafenib or lenvatinib as first‐line therapy.Methods and resultsThis study assessed 101 elderly patients with u‐HCC for their mG8 score (excluding elements of age from 8 items) and classified them into 2 groups according to their mG8 score: ≥11 as the high‐score group and ≤ 10 as the low‐score group. Among those taking sorafenib, no significant differences were noted in overall survival (OS) and progression free survival (PFS) between low and high mG8 score groups. Only modified albumin–bilirubin (ALBI) grade (2b/3 vs. 1/2a: HR 0.34; 95% CI, 0.17–0.69; p = .0029) was significantly associated with OS. Among those taking lenvatinib, patients with a high mG8 score (n = 26) had longer survival than those with a low mG8 score (n = 10) (20.0 months vs. 7.7 months: HR 0.31, 95% CI 0.11–0.89; p = .029). Intrahepatic tumor volume (<50% vs. ≥50%: HR 16.7; 95% CI, 1.71–163; p = .016) and α‐fetoprotein (AFP) (<400 vs. ≥400: HR 3.38; 95% CI 0.84–19.7; p = .031) remained significant factors independently associated with OS.ConclusionsThe mG8 score may contribute to making a decision when considering either sorafenib or lenvatinib as a treatment option for u‐HCC in elderly patients.

This study aimed to calibrate hepatitis E virus (HEV) serological assays. We optimized the previously developed in-house HEV antibody enzyme-linked immunosorbent assay (ELISA) by setting the cutoff with an in-house serological performance panel consisting of broad HEV antibody titers and subtracting nonspecific background values for anti-HEV IgM, IgA, and IgG. We also compared the assay's performance with that of commercial serological assay kits (four kits for IgM, one for IgA, and two for IgG). Although all serological assays readily detected HEV antibodies at high titers in the symptomatic hepatitis E population, considerable variations between assays were observed in the asymptomatic population. The in-house ELISA showed a higher sensitivity for HEV IgM, IgA, and IgG than the commercial kits and detected the seroconversion of HEV IgM and IgG earlier when testing a commercially available HEV seroconversion panel. The low sensitivity of the commercial kits was due to the high setting of the original cutoff, which was demonstrated by receiver operating characteristic analysis. However, the corrected cutoff value reduced assay specificity. Background subtraction is essential to achieve high specificity because the in-house ELISA without background subtraction reduced its specificity. These results indicate that asymptomatic specimens and background subtraction contribute to the optimization of HEV serological assays. IMPORTANCE Accurate diagnosis of hepatitis E virus (HEV) infection is essential for public health surveillance and for preventing HEV-contaminated blood transfusion. Anti-HEV IgM or IgA is used as a reliable marker of recent HEV infection. However, considerable variability in the sensitivity and specificity of HEV antibody detection is observed among several commercially available assay kits. In addition, none of the HEV antibody detection methods have been approved by the U.S. Food and Drug Administration (FDA). Here, we show that the in-house enzyme-linked immunosorbent assay (ELISA) could detect HEV IgM and IgA more sensitively than commercial kits in the asymptomatic population. We also suggest that the assay performance of commercial kits might be improved by optimizing the cutoff and reducing nonspecific background noise. A sensitive serological (IgM or IgA) assay in addition to HEV RNA testing will contribute to accurate diagnosis of acute HEV infection because HEV RNA-positive duration is relatively short.

Background and aim The long-term prognosis of hepatocellular carcinoma (HCC) treated at a very-early-stage (the Barcelona Clinical Liver Cancer (BCLC) classification stage 0) was unclear, especially in terms of background liver disease. Methods This single-center, retrospective study included 302 patients with BCLC stage 0 HCC treated with radiofrequency ablation (RFA) and followed for at least six months. We examined the impact of background liver disease on overall survival and recurrence. Results The median age was 72 (range; 36–91) years; the median tumor diameter was 15 (range; 8–20) mm. The etiologies of background liver disease were hepatitis B virus infection (HBV) in 24 cases, hepatitis C virus infection (HCV) in 195 cases, and non-viral (NBNC) in 83 cases. Among the patients with HCV, 63 had achieved sustained virological response (SVR) by antiviral therapy (HCV SVR) before developing HCC (n = 37) or after HCC treatment (n = 26), and 132 had active HCV infection (HCV non-SVR). The median overall survival was 85 (95% CI; 72–98) months, and the median recurrence-free survival was 26 (95% CI; 20–30) months. Active infection with hepatitis C virus negatively contributed to overall survival (HR 2.91, 95% CI 1.31–3.60, p = 0.003) and recurrence-free survival (HR 1.47, 95% CI 1.06–2.05, p = 0.011). Conclusions The prognosis of RFA treatment for very early-stage HCC was favorable. Achieving SVR in hepatitis C was important for further prognosis improvement.

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.

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.

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.

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.

Abstract 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.

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.

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-naïve patients with chronic hepatitis C.

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.

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<0.001, respectively). Conclusion: Early drain removal regardless of DFA level may reduce the risk of developing POPF. CRP measured on POD 3 and POD 5 appeared to be a useful predictor of clinically relevant POPF.