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A comparison between atezolizumab plus bevacizumab (ATEZO/BEVA) and lenvatinib (LEN) for the treatment of hepatocellular carcinoma (HCC) remains unclear.This study aimed to compare the therapeutic effects and safety of ATEZO/BEVA and LEN as first-line therapies for HCC.This study was a retrospective analysis of 810 patients with HCC who underwent ATEZO/BEVA (n = 186) or LEN (n = 624) as first-line systemic therapy between March 2018 to March 2022 at 14 facilities. After propensity score matching, 304 patients (ATEZO/BEVA group: n = 152; LEN group: n = 152) were analyzed.After propensity score matching, although there was no significant difference in objective response rates (ORRs) between the ATEZO/BEVA and LEN groups (ORR 44.8% vs. 46.7%, p = 0.644), the median progression-free survival (PFS) and median overall survival (OS) in the ATEZO/BEVA group were significantly higher than those in the LEN group (median PFS: 8.3 months vs. 6.0 months, p = 0.005; median OS: not reached vs. 20.2 months, p = 0.039). The rates of appetite loss, fatigue, and proteinuria of grade 3 or higher in the ATEZO/BEVA group were lower than those in the LEN group. However, the rate of bleeding of grade 3 or higher in the ATEZO/BEVA group was higher than that in the LEN group. The conversion rate was higher in the ATEZO/BEVA group than that in the LEN group (8.6% vs. 1.9%, p = 0.007).ATEZO/BEVA showed superiority to LEN in terms of prognosis and conversion rate as first-line therapy. Moreover, ATEZO/BEVA had a lower rate of severe adverse events, except for bleeding, than LEN.

Adjusting immunosuppression to minimal levels post-adult liver transplantation (LT) is critical; however, graft rejection has been reported in LT recipients with normal liver function evaluated by liver biopsy (LBx). Continual protocol liver biopsy (PLB) is performed regularly in LT recipients with normal liver function in some centers; however, its usefulness remains inadequately evaluated. This study aimed to assess retrospectively the usefulness of late PLB after adult LT.LBx evaluations of LT recipients with normal liver function and hepatitis B and C virus seronegativity were defined as PLB. The cases requiring immunosuppressive therapy for rejection findings based on Banff criteria were extracted from the PLBs, and pathological data collected before and after immunosuppressive dosage adjustment (based on modified histological activity index [HAI] score) were compared.Among 548 LBx cases, 213 LBx in 110 recipients fulfilled the inclusion criteria for PLB. Immunosuppressive therapy after PLB was intensified in 14 LBx (6.6%) recipients (12.7%); of these, nine had late-onset acute rejection, three had isolated perivenular inflammation, one had plasma cell-rich rejection, and one had early chronic rejection. Follow-up LBx after immunosuppressive dose adjustment showed improvement in the modified HAI score grading in 10 of 14 cases (71.4%). No clinical background and blood examination data, including those from the post-LT period, immunosuppressant trough level, or examination for de novo DSA, predicted rejection in PLB. Complications of PLB were found in only three cases.PLB is useful in the management of seemingly stable LT recipients, to discover subclinical rejection and allow for appropriate immunosuppressant dose adjustment.

Aim The course of cryptogenic cirrhosis (CC) after liver transplantation (LT) is unknown. We therefore clarified the natural course post-LT for CC and investigated the etiology of CC. Methods Eighteen patients who underwent LT for CC were included. To rule out the possibility of NASH in patients with CC, those with a history of obesity or liver steatosis found pretransplantation were excluded. A liver biopsy was performed one year after LT and annually thereafter. Results Liver steatosis and steatohepatitis were identified in 61% and 39% of patients after LT, respectively, with a median time to the onset of 12 and 27 months, respectively. There were no other pathological findings such as liver allograft rejection, autoimmune hepatitis, or primary biliary cholangitis. The body mass index after LT (28.5 vs. 22.4 kg/m

This study was conducted to determine the prognosis and risk factors for survival in patients treated with stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC).This retrospective study analyzed 73 patients who underwent SBRT for HCC at Nagasaki University Hospital from December 2012 to July 2019 and examined the relationship between baseline information and prognosis. The Kaplan-Meier analysis and log-rank test were used to estimate the survival rate. Cox regression analysis was performed to determine the factors associated with overall survival (OS) after SBRT.The 1- and 2-year local control rates were 98.6% and 89.9%, respectively. Survival rates at 1, 3, and 5 years were 94.5%, 63.9%, and 45.5%, respectively. In the univariate analysis, baseline modified albumin-bilirubin grade (mALBI grade) [2b/3, hazard ratio (HR)=2.762, p=0.001], tumor size (≥2 cm, HR=2.479, p=0.003), and Barcelona Clinic Liver Cancer stage (BCLC) (B/C, HR=3.284, p0.001) were significantly associated with poor prognosis. In multivariate analysis, baseline mALBI grade (2b/3, HR=2.283, p=0.009) and BCLC stage (B/C, HR=2.330, p=0.013) were significantly associated with poor prognosis. Only three patients (4.1%) developed grade 3 adverse events related to SBRT.SBRT is effective and safe in patients with HCC. The baseline mALBI grade is useful for predicting patient prognosis after SBRT. Patients with an mALBI grade of 1/2a are expected to have a better prognosis than patients with an mALBI grade of 2b/3.

Objective The low-density lipoprotein cholesterol (LDL) level is known to increase following the treatment of hepatitis C virus (HCV) infection using direct-acting antiviral agents (DAAs). This study aimed to investigate the changes in the lipid profiles, including small-dense LDL cholesterol (sdLDL), in HCV patients treated with DAAs. Patients We retrospectively assessed 67 HCV patients who achieved sustained virological response with DAA administration and were observed for more than 2 years, of whom 32 were on daclatasvir/asunaprevir, 14 were on sofosbuvir/ledipasvir, and 21 were on sofosbuvir/ribavirin. Methods We evaluated the lipid profiles, including sdLDL, every 6 months until 2 years after the start of treatment and analyzed the factors related to changes in the sdLDL level. Results The median sdLDL value at baseline was 12.8 mg/dL, which increased to 19.5 mg/dL at 6 months (p

The efficacy of molecular-targeted agents (MTAs) has been demonstrated in recent years. However, the results of multidisciplinary treatment including hepatic resection are still unclear. The present study evaluated the outcomes of MTA treatment for advanced, unresectable hepatocellular carcinoma (HCC), with the goal of achieving liver resection, in our department.Nine patients in whom Lenvatinib had been administered to achieve conversion surgery for unresectable HCC were included in this study. The patient characteristics were as following: median tumor size of 10 cm, vascular invasion in 5 cases, multiple tumors in 2 cases, median treatment duration of 8 weeks, dose reduction due to side effects in 4 patients, and discontinuation of treatment in 1 patient due to tumor growth.The efficacy by modified Response Evaluation Criteria in Solid Tumors (mRECIST) was partial response in 3, sustained disease in 5 and progressive disease in 1, while the liver resection rate was 88%. Four patients (50%) had recurrence after resection, and the median recurrence-free survival was 12.7 months; however, treatment for recurrence was successful and all patients are alive.Lenvatinib may improve the prognosis of HCC with vascular invasion and multiple lesions by achieving radical resection at the appropriate time for patients with tumor shrinkage.

Inferior vena cava (IVC) anomalies, such as the absence of an intra-hepatic IVC or IVC hypoplasia, are rare. Usually, these anomalies are asymptomatic and cause few clinical issues. We herien report a 53-year-old woman with IVC anomalies who demonstrated both azygos and portal vein system continuation. Over time, this resulted in gradually progressive portal hypertension due to abnormal hemodynamics. The increased inflow from the IVC to the portal vein system for an extended time may contribute to the development of portal hypertension without liver cirrhosis.

Objective The influence of interferon (IFN)-free direct-acting antiviral (DAA) on hepatocellular carcinoma (HCC) recurrence remains unclear. Previous retrospective analyses revealed that the time interval between HCC curative treatment and IFN-free DAA induction is the critical factor affecting HCC recurrence. Thus, this study aimed to examine the influence of DAA therapy on HCC recurrence considering this interval. Methods Factors contributing to HCC recurrence were retrospectively analyzed using a landmark time analysis and time-dependent extended Cox proportional hazards model. Patients After screening 620 patients who were diagnosed with primary HCC from January 2001 to December 2016, 76 patients with early-stage (primary and solitary) disease who received curative treatment and were positive for serum hepatitis C virus RNA were included. Results HCC recurrence was observed in 8 of 17 (47.1%) patients who had received IFN-free DAA therapy and 45 of 59 (76.3%) who had not. No significant difference was seen between the IFN-free DAA (-) and IFN-free DAA (+) groups in the landmark time and time-dependent Cox proportional hazards model analyses. However, IFN-free DAA therapy tended to decrease the HCC recurrence rate after curative treatment for primary HCC in patients with chronic hepatitis. In addition, IFN-free DAA therapy tended to decrease the second HCC recurrence rate after treatment for the first HCC recurrence. Conclusion Our results, with a consideration of the time interval between HCC curative treatment and IFN-free DAA induction, showed that IFN-free DAA therapy was not associated with early-stage HCC recurrence after curative treatment.

BACKGROUND: The level and profiles of blood free carnitine and acylcarnitines, obtained by acylcarnitine analysis using tandem mass spectrometry, reflect various metabolic conditions. We aimed to examine the level of free carnitine and acylcarnitines in liver cirrhosis patients by acylcarnitine analysis and determine the clinical and subjective factors associated with blood carnitine fraction levels in liver cirrhosis. METHODS: We compared blood carnitine fractions in 54 liver cirrhotic patients to other laboratory test results and questionnaire answers. RESULTS: In almost all patients, the blood levels of free carnitine (C0) and acetylcarnitine (C2) were within the normal reference range. However, in some patients, the levels of long-chain acylcarnitines, such as C16 and C18:1-acylcarnitine, were higher than the normal reference range. Liver function, assessed by Child-Pugh score, was significantly correlated with the blood level of each carnitine fraction measured (C0, C2, C3, C4, C6, C10, C12, C12:1, C14:1, C16, C18:1, and C18:2-acylcarnitine). Cirrhotic symptom score was significantly correlated with C0, C2, C3, C16, and C18-1-acylcarnitine blood levels. Among the 36-item short-form health survey (SF-36) items, the physical component summary was significantly associated with C0, C2, and C18-1-acylcarnitine blood levels. CONCLUSIONS: Carnitine fraction levels were positively correlated with liver cirrhosis stage, particularly, long-chain acylcarnitines. Moreover, carnitine fraction levels were associated with various subjective physical symptoms in liver cirrhosis patients., BMC gastroenterology, 20(1), art.no.41; 2020

Fibrosis is the most important pathological feature in predicting development of Hepatocellular carcinoma (HCC). However, the incidence rate of HCC in patients with non-alcoholic fatty liver disease (NAFLD) is relatively low. We evaluated phenotypic histological features to differentiate HCC from non-HCC in patients with non-tumor lesions of cirrhotic livers.Seventeen patients with NAFLD who underwent liver transplantation were enrolled. FibroNest was used to quantify histological phenotypes of non-tumor fibrosis lesions. Quantification included collagen content and structure traits, fiber morphometric traits, and fibrosis architecture traits. Each trait was described by up to seven quantitative fibrosis traits (qFTs). Among the qFTs measured in each specimen, those that described most of the variability between consecutive groups were automatically detected and combined into a normalized Phenotypic Composite Fibrosis Score (Ph-CFS). We trained FibroNest to identify the principal traits that differentiate HCC from non-HCC.HCC was found in 8 cases and non-HCC in 9 cases. The Ph-CFS significantly differentiated HCC from non-HCC (4.6 vs. 5.9, p 0.05). Individual qFTs for morphometric features including collagen fiber length, width, perimeter, and area denoted significant differences between HCC and non-HCC. The Ph-CFS could be used to distinguish HCC (Ph-FCS 5.0) from non-HCC (Ph-FCS ≥ 5.0) with 75% sensitivity and 100% specificity.In patients who underwent liver transplantation, fibrotic histological phenotypes in non-tumor lesions appeared to be different between HCC and non-HCC. Phenotypic analysis of collagen in non-tumor lesions might be an effective and automated method to distinguish HCC from non-HCC on histopathology imaging.

By putting two harmonic oscillator potentials x2 side by side with a separation 2 d, two exactly solvable piecewise analytic quantum systems with a free parameter d > 0 are obtained. Due to the mirror symmetry, their eigenvalues { E} for the even and odd parity sectors are determined exactly as the zeros of certain combinations of the confluent hypergeometric function [Formula: see text] of d and E, which are common to VD and VS but in two different branches. The eigenfunctions are the piecewise square integrable combinations of [Formula: see text], the so-called U functions. By comparing the eigenvalues and eigenfunctions for various values of the separation d, vivid pictures unfold showing the tunneling effects between the two wells.

Single-nucleotide polymorphisms (SNPs) of patatin-like phospholipase domain-containing 3 (PNPLA3), tolloid-like protein 1 (TLL1) and interleukin-28 (IL28) have been identified as susceptibility factors for liver steatosis, inflammation and fibrosis in patients with hepatitis C virus (HCV) infection. Here, whether these polymorphisms affected predispositions to changes in liver stiffness (LS) and controlled attenuation parameter (CAP) following direct-acting antiviral (DAA) therapy was assessed. The changes in LS and steatosis in 77 HCV-infected patients receiving DAA therapy were compared with PNPLA3, TLL1 and IL28 genotypes, using CAP, FibroScan and Virtual Touch tissue quantification (VTTQ) before treatment and 12 weeks after the end of the treatment. VTTQ results showed that LS significantly decreased in PNPLA3 CC (P=0.035), TLL1 AA (P=0.011) and IL28B TT (P=0.005) genotypes; no significant differences were observed in PNPLA3 CG/GG, TLL1 AT/TT and IL28B TG/GG. FibroScan results showed that LS significantly decreased in TLL1 AA (P=0.028) and IL28B TT (P=0.032), with no significant difference in PNPLA3 CC. No significant differences were observed in PNPLA3 CG/GG, TLL1 AT/TT and IL28B TG/GG groups. CAP was significantly increased in PNPLA3 CG/GG (P=0.039 and P

Background As the diagnosis of non-alcoholic steatohepatitis (NASH) has become more accurate, the number of patients with cryptogenic cirrhosis (CC) has decreased. Despite this, there are patients in the liver transplant registry who are currently listed as having CC. Therefore, knowledge of the natural course of CC after liver transplantation (LT) is important. However, the natural course of CC after LT is unknown. We aimed to clarify the natural course post LT for CC and to infer the etiology of CC. Methods Eighteen patients who underwent LT for CC were included. To rule out the possibility of including NASH patients with CC patients, those with obesity (body mass index [BMI] ≥ 25 kg/m2) and type-2 diabetes mellitus or liver steatosis found on pretransplantation images, were excluded. Liver biopsy was performed 1 year after LT, and annually thereafter. Results Liver steatosis and steatohepatitis were identified in 61% and 39% of the patients after LT, respectively with a median time to onset of 12 and 27 months, respectively. No other pathological findings could identify the etiology of CC. The BMIs after LT were significantly higher in the steatosis group than in the non-steatosis group (28.5 vs. 22.4 kg/m2; P = 0.002). The mean muscle attenuation (MA) at the time of LT was significantly higher and the postoperative hospitalization period was shorter in the steatosis group than in the non-steatosis group (MA: 33.3 vs. 25.8 Hounsfield unit, P = 0.03; hospitalization: 50 vs. 102 days, P = 0.02). Recipients were significantly younger in the steatohepatitis subgroup than in the simple steatosis subgroup (55.0 vs. 63.5 years, P = 0.04). Conclusions Despite excluding patients with a history of obesity from our cohort of patients with CC, we observed that patients with CC had a high prevalence of steatosis after LT. Young patients with a favorable postoperative course were noted to have a high risk of NASH after LT for CC. Patients with CC may represent cases of non-obese NASH.

Background: While the proportion of hepatocellular carcinoma (HCC) cases with non-viral etiology continues to increase in Japan, the epidemiological trends in the sex and age distribution of new HCC cases remain unclear. This study examines the epidemiological trends, including the distribution of sex, age, and disease etiology, in HCC incidence over 24 years.Methods: Data of 20,547 newly diagnosed HCC patients in 1996–2019 at 19 institutions participating in the Liver Cancer Study Group of Kyushu were analyzed in this prospective study. We divided the study period into four 6-year quarters. HCC etiology was categorized as hepatitis B virus (HBV) infection, HBV+hepatitis C virus (HCV) infection, HCV infection, and both negative (non-BC). Results: The incidences of HCC per quarter of the study period were 4,311 (21.0%), 5,505 (26.8%), 5,776 (28.1%), and 4,955 (24.1%) cases, sequentially. Overall, 14,020 (68.2%) patients were male. The number of HCC cases in patients ≤50 years, 60–69 years, 70–79 years, and ≥80 years were 3,711 (18.1%), 6,652 (32.4%), 7,448 (36.2%), and 2,736 (13.3%), respectively. The average age of newly diagnosed patients increased in each quarter. HCC was associated with HBV, HBV+HCV, and HCV infections and non-BC in 2,997 (14.6%), 187 (0.9%), and 12,019 (58.5%), and 5,344 (26.0%) cases, respectively. The number of HCV-associated cases decreased in each quarter, while that of non-BC-associated cases increased.Conclusions: HCC incidence tends to increase in the elderly and in non-BC patients; in contrast, HCC incidence due to HCV tends to decrease. In countries where HCV infection is likely the predominant cause of HCC, similar trends in HCC incidence are anticipated in the future.

Objective: Sodium glucose co-transporter 2 inhibitor (SGLT-2i), recommended for patients with type 2 diabetes, has been reported to improve the liver function test results in non-alcoholic fatty liver disease (NAFLD). However, the long-term effects of SGLT-2i on the liver function and body weight in NAFLD patients have not been fully elucidated. In this study, we investigated the long-term effects of SGLT-2i in NAFLD patients. Methods: Twenty-two diabetic patients with NAFLD were enrolled in this study. We assessed the body weight, liver enzyme levels, metabolism, and glucose levels at 12 months (22 cases) and 24 months (15 cases) after the initiation of SGLT-2i. The changes in controlled attenuation parameter (CAP) and liver stiffness in 20 of the 22 patients were evaluated using transient elastography (TE) and acoustic radiation force impulse (ARFI) elastography before the initiation of treatment and 1 year later. Results: Body weight and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were significantly decreased at 12 and 24 months after SGLT-2i treatment. The decrease in the levels of ALT at 12 and 24 months was significantly correlated with the level of ALT at the initiation of SGLT-2i (r=0.813, p=0.001 and r=0.867, p=0.0001,respectively). SGLT-2i also reduced the CAP and velocity of shear wave (Vs) values at 12 months (CAP 315.1±43.4 db/mL→293.1±27.2 db/mL, p=0.027; Vs 1.87±0.8 m/s→ 1.48±0.6 m/s, p=0.011). Conclusion: SGLT-2i treatment improved the liver function test results and reduced the body weight in NAFLD patients over a period of 12-24 months. This improvement was greater in patients with higher ALT values at baseline than in those with lower values., Internal medicine, 58(14), pp.1987-1992; 2019

Posttransplant liver steatosis occurs frequently and can affect patient outcome. Our aim was to clarify the risk factors for steatosis or steatohepatitis after living donor liver transplantation (LT) through a retrospective examination of recent 100 living donor LT recipients and their liver donors.Liver biopsy was performed at 1 year after LT and each year, thereafter, or as needed due to abnormal liver enzyme levels, with a median follow-up of 4 years (2-10 years).Liver steatosis (≥5%) was identified in 33 cases, with steatohepatitis identified in 9 of 33 patients with liver steatosis. Recipients with liver steatosis were younger than those without steatosis (53.4 ± 9.5 years vs 57.6 ± 9.9 years, respectively; P = 0.045). Of note, the prevalence of steatosis was significantly higher among LT recipients who received a graft from a donor with steatosis than without (60% vs 23%, respectively; P = 0.001). Donor steatosis was also associated with steatohepatitis in recipients after LT (steatohepatitis/simple steatosis, 88%:50%). On multivariate analysis, younger recipient age (P = 0.023) and donor steatosis (P = 0.005) were independent risk factors of liver steatosis after LT. Among the 33 recipients in our study group, 26 were assessed by serial liver biopsies, with 6 showing progression of the nonalcoholic fatty liver disease activity score. An increase in body weight was predictive of steatosis progression after LT (P = 0.005).Age and donor steatosis influence the risk of liver steatosis and steatohepatitis in recipients after LT. The clinical course of steatosis is relatively benign, with only 19% developing nonalcoholic fatty liver disease activity score and 7.6% significant fibrosis.

We present 15 explicit examples of discrete time Birth and Death processes which are exactly solvable. They are related to the hypergeometric orthogonal polynomials of Askey scheme having discrete orthogonality measures. Namely, they are the Krawtchouk, three different kinds of q-Krawtchouk, (dual, q)-Hahn, (q)-Racah, Al-Salam-Carlitz II, q-Meixner, q-Charlier, dual big q-Jacobi and dual big q-Laguerre polynomials. The birth and death rates are determined by the difference equations governing the polynomials. The stationary distributions are the normalised orthogonality measures of the polynomials. The transition probabilities are neatly expressed by the normalised polynomials and the corresponding eigenvalues. This paper is simply the discrete time versions of the known solutions of the continuous time birth and death processes., 29 pages, no figure

Background The age of patients with advanced hepatocellular carcinoma (HCC) eligible for molecular-targeted drug treatment is increasing. We assessed liver function after lenvatinib administration according to age in patients with advanced HCC. Patients and methods In this retrospective, multicenter, observational study, we reviewed the records of patients with HCC who received lenvatinib treatment (March 2018-March 2020). Liver function was measured using the Albumin-Bilirubin Index (ALBI). Results Of 119 patients, with a median age of 72.0 years, median overall survival was 15.3 months. Overall survival was significantly better in the group which maintained liver function (p=0.02). Older age (≥72 years) was associated with liver-function deterioration within 8 weeks (odds ratio=2.47, 95% confidence interval=1.06-5.75, p=0.035). The ALBI score was significantly higher in the older group at 4 and 8 weeks after lenvatinib administration. Conclusion Lenvatinib administration was more likely to adversely affect liver function in older patients; dose adjustment should be considered in such patients.

About two dozens of exactly solvable Markov chains on one-dimensional finite and semi-infinite integer lattices are constructed in terms of convolutions of orthogonality measures of the Krawtchouk, Hahn, Meixner, Charlier, $q$-Hahn, $q$-Meixner and little $q$-Jacobi polynomials. By construction, the stationary probability distributions, the complete sets of eigenvalues and eigenvectors are provided by the polynomials and the orthogonality measures. An interesting property possessed by these stationary probability distributions, called `convolutional self-similarity,' is demonstrated., Comment: 46 pages. Comments added, some repeated results deleted. To appear in J.Phys.A

INTRODUCTION Non-invasive assessment of graft fibrosis is important in liver transplantation. Mac-2 binding protein glycosylation isomer (M2BPGi) has been reported as a diagnostic marker for this purpose, and thus, this predictive ability of M2BPGi was assessed in this study. PATIENTS AND METHODS In this retrospective study, 236 patients who received living donor liver transplantation (LDLT) from August 1997 to March 2017 were enrolled. Among them, 94 biopsy patients were analyzed. Further, the predictive ability of fibrotic biopsy using M2BPGi, Fibroscan, and Fib-4 index was compared. RESULTS Of 94 LDLT patients (53 men, 41 women), the median ages of recipients and donors were 57.5 and 33.0 years, respectively. The median M2BPGi values in patients with F0 (n = 11), F1 (n = 38), F2 (n = 35), and F3/4 (n = 10) were 0.680, 0.760, 1.240, and 4.110 COI, respectively. There were significant correlations between the fibrotic stage and M2BPGi levels (Kruskal-Wallis test, P

Background and aim Elimination of hepatitis B virus (HBV) is infrequently achieved with current therapies. Therefore, more effective anti-HBV therapy is needed. We previously reported that geranylgeranylacetone (GGA) showed anti-hepatitis C virus activity in human hepatoma cells. In this study, we examined the anti-HBV activity of GGA. Methods We used HepG2.2.15.7 cells, PXB cells infected with HBV, Huh7 cells transfected with linear HBV, and PLC/PRF/5 cells as HBV-infected hepatocyte models. After GGA treatment, HBV-related antigen was measured by chemiluminescent immunoassay. HBV-related mRNA was examined by Northern blot. cccDNA and endoplasmic reticulum stress markers were measured by real-time polymerase chain reaction. The activities of HBV promoters and enhancer regions were examined using luciferase vectors. Results After GGA treatment, hepatitis B surface antigen and hepatitis B e antigen secretion was decreased in all HBV-infected hepatocyte models. HBV-related mRNA was also decreased by GGA treatment, although cccDNA levels were not affected. Additionally, the activity of HBV S1 and S2 promoter region and Enhancer 1/Enhancer 2/core promoter region was reduced by GGA treatment. The mRNA expression of the main transcription factors, hepatocyte nuclear factor 3 and 4 and CCAAT/enhancer binding protein, was also decreased. Further, the expression levels of endoplasmic reticulum stress markers were increased by GGA treatment, which reflected the change in HBV-related antigen secretion. Conclusions Geranylgeranylacetone treatment reduces HBV-related protein levels by suppressing comprehensive downregulation of HBV promoter and enhancer activity, which might be caused by decreased hepatic transcription factor expression. GGA treatment may enhance anti-HBV effects in combination with other therapies.

Background: Some patients with liver cirrhosis have sleep-wake disturbance and reduced quality of life (QOL). However, the effects of L-carnitine on QOL and sleep-wake disturbance have not been extensively studied. Thus, we aimed to examine the effects of L-carnitine on the sleep quality and QOL in cirrhotic patients.Methods: We investigated 19 cirrhotic patients (age: 65.0±10.2 years, male:female=10:9, Child-Pugh score: 6.5±1.8) treated with 1500-mg L-carnitine at Nagasaki University Hospital and its associated hospitals. We used questionnaires to evaluate the patients’ sleep-wake disturbance and QOL at the time of entry and 8 weeks. Results: Cirrhosis-related symptom scores (CSSs), Pittsburgh Sleep Quality Index (PSQI) and General Health (GH) of QOL score improved with L-carnitine treatment (CSS: from 11.5±9.4 to 9.4±3.7, p=0.015; PSQI: from 9.6±5.8 to 7.4±3.3, p=0.035; GH: from 33.5±8.2 to 38.3±9.8, p=0.05). L-carnitine treatment reduced PSQI in 12 out of 14 patients with sleep disturbance (PSQI>5). CSS was improved in 12 cases (63%), and PSQI was improved in 13 cases (68%). However, L-carnitine treatment did not improve daytime hypersomnolence, as evaluated by the Epworth Sleepiness Scale. None of patients had any adverse events related to the L-carnitine treatment.Conclusions: L-carnitine is a safe and useful treatment for cirrhotic patients with reduced sleep quality and QOL.

The meaning of participation in care prevention group activities may encourage continuous participation, making older adults active and healthy throughout their lives. This study developed a scale to assess the meaning of participation in care prevention group activities. It involved 427 participants in care prevention group activities (CPGAs) in Japan who filled out a self-administered questionnaire between October 2017 and February 2018. The meaning of participation was assessed using 15 items. In total, there were 379 valid responses. A factor analysis yielded two factors: &ldquo, promotion of self-growth&rdquo, and &ldquo, enrichment of daily life&rdquo, The goodness of fit index (GFI), comparative fit index (CFI), and root mean square error of approximation (RMSEA) were satisfactory (GFI = 0.923, CFI = 0.960, RMSEA = 0.073). Cronbach&rsquo, s &alpha, was 0.939 for the entire scale. The scale scores were significantly correlated with scores of the social activity-related daily life satisfaction scale and Ikigai-9. The scale&rsquo, s reliability and validity were confirmed, indicating its usability for promoting care prevention efforts.