Publications by authors named "Takuji Torimura"

217 Publications

Adverse events as potential predictive factors of activity in patients with advanced hepatocellular carcinoma treated with lenvatinib.

Liver Int 2021 Jul 12. Epub 2021 Jul 12.

Department of Gastroenterology, Tokushima Prefectural Central Hospital, Tokushima, Japan.

Background And Aim: Lenvatinib is a standard of care option in first-line therapy of advanced hepatocellular carcinoma (HCC). In the present study, we aim to identify, in patients with HCC treated with lenvatinib, a possible association between occurrence and grading of adverse events (AEs) and outcome.

Methods: We performed a retrospective analysis of 606 Japanese and Italian patients treated with lenvatinib in first-line setting and investigated the possible correlation between the onset of AEs, toxicity grade (G) and outcome measures such as overall survival (OS) and progression-free survival (PFS).

Results: The appearance of arterial hypertension G ≥ 2 independently predicted prolonged OS [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.46-0.93, P = .0188], whereas decreased appetite G ≥ 2 independently predicted decreased OS (HR 1.70, 95% CI 1.25-2.32, P = .0007) by multivariate analysis. Appearance of hand-foot skin reaction independently predicted prolonged PFS (HR 0.72, 95% CI 0.56-0.93, P = .0149), whereas decreased appetite G ≥ 2 predicted decreased PFS (HR 1.36, 95% CI 1.04-1.77, P = .0277).

Conclusions: Our main findings are that the occurrence of arterial hypertension G ≥ 2 is a predictor of longer survival, whereas decreased appetite G ≥ 2 predicts for a poor prognosis. A careful management of AEs under lenvatinib treatment for HCC is required, to improve patients' quality of life, minimize the need for treatment discontinuation and achieve optimal outcome.
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http://dx.doi.org/10.1111/liv.15014DOI Listing
July 2021

Initial Experience of Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice.

Cancers (Basel) 2021 Jun 3;13(11). Epub 2021 Jun 3.

Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan.

Background: Atezolizumab plus bevacizumab was approved for patients with hepatocellular carcinoma (HCC). Although clinical trials have revealed its efficacy, the outcomes in the real-world clinical practice are unclear. We retrospectively evaluated the efficacy and safety of atezolizumab plus bevacizumab for HCC.

Materials And Methods: This is a multicenter study conducted between November 2020 and March 2021. Among the 61 patients, 51 were assessed for progression-free survival (PFS), therapeutic response, and adverse events (AEs).

Results: The median PFS was 5.4 months. The objective response rate (ORR) was 35.3%. The disease control rate (DCR) was 86.3%. The incidence rates of AEs at any grade and grade >3 were 98.0% and 29.4%, respectively. The most frequent AE at any grade and grade >3 was hepatic disorder. In patients with a previous history of molecular targeted agent (MTA) or the degree of albumin-bilirubin (ALBI) grade, there were no significant differences in the PFS, ORR, DCR, and incidence rates of AEs.

Conclusion: The study demonstrated that atezolizumab plus bevacizumab was effective and safe for patients with HCC even in the real-world setting including patients with a previous MTA history or other than ALBI grade 1.
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http://dx.doi.org/10.3390/cancers13112786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199943PMC
June 2021

Effects of Mediterranean Diet in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis of Randomized Controlled Trials.

Semin Liver Dis 2021 Aug 19;41(3):225-234. Epub 2021 Jun 19.

Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.

We conducted a meta-analysis to investigate the effects of the Mediterranean Diet (Med-Diet) on hepatic steatosis and insulin resistance in patients with nonalcoholic fatty liver disease (NAFLD). Six randomized controlled trials were selected for the meta-analysis (sample size: 250 participants). In the meta-analysis, there was no significant difference in body mass index and waist circumference between the Med-Diet and control groups. Med-Diet significantly reduced fatty liver index (FLI) compared with the control diet (standard mean difference [SMD]: -1.06; 95% CI: -1.95 to -0.17;  = 0.02). Med-Diet significantly reduced homeostasis model assessment of insulin resistance (HOMA-IR) compared with the control diet (SMD: -0.34; 95% CI: -0.65 to -0.03;  = 0.03). Similarly, a meta-regression analysis using age showed that Med-Diet significantly reduced FLI and HOMA-IR (95% CI: -0.956 to -0.237,  = 0.001 and 95% CI: -0.713 to -0.003,  = 0.048, respectively). This meta-analysis demonstrated that Med-Diet improved hepatic steatosis and insulin resistance in patients with NAFLD. Thus, Med-Diet is a beneficial pharmaconutritional therapy in patients with NAFLD.
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http://dx.doi.org/10.1055/s-0041-1723751DOI Listing
August 2021

MAFLD better predicts the progression of atherosclerotic cardiovascular risk than NAFLD: Generalized estimating equation approach.

Hepatol Res 2021 Jun 15. Epub 2021 Jun 15.

Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.

Aim: Metabolic associated fatty liver disease (MAFLD) partly overlaps with non-alcoholic fatty liver disease (NAFLD). Thus, using a generalized estimating equation (GEE) approach, we aimed to investigate the difference in worsening of atherosclerotic cardiovascular disease (ASCVD) risk between patients with MAFLD and NAFLD. We also investigated factors related to the difference between the two groups.

Methods: We enrolled 2306 subjects with fatty liver (MAFLD 80.7%, NAFLD 63.4%). Subjects with MAFLD/NAFLD were sub-classified into three groups: NAFLD with no metabolic dysfunction (non-Met NAFLD), overlapping, and MAFLD with moderate alcohol consumption (mod-Alc MAFLD). ASCVD risk was estimated by non-invasive tests, including the Suita score. An event was defined as worsening of these scores from the low-risk to the high-risk group. Independent factors for the event were analyzed by Cox regression analysis with the GEE.

Results: In Cox regression analysis, MAFLD (HR 1.08, 95% CI 1.02-1.15, p = 0.014) and alcohol consumption (20-39 g/day; HR 1.73, 95% CI 1.26-2.36, p = 0.001) were independently associated with worsening of the Suita score. In a subanalysis, the incidence of the event was significantly lower in non-Met NAFLD than in the overlapping group (HR 0.70, 95% CI 0.50-0.98, p = 0.042). However, no significant difference was observed in the incidence between the overlapping and mod-Alc MAFLD group (HR 1.19, 95% CI 0.89-1.58, p = 0.235).

Conclusions: The GEE approach demonstrates that MAFLD better identifies patients with worsening of ASCVD risk than NAFLD. Moreover, the superiority of MAFLD over NAFLD was due to the presence of metabolic dysfunction rather than moderate alcohol consumption.
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http://dx.doi.org/10.1111/hepr.13685DOI Listing
June 2021

Evaluating the therapeutic effect of lenvatinib against advanced hepatocellular carcinoma by measuring blood flow changes using contrast-enhanced ultrasound.

Cancer Rep (Hoboken) 2021 Jun 9:e1471. Epub 2021 Jun 9.

Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.

Background: The antitumor effect of a drug is considered to be associated with a decrease in tumor blood flow.

Aims: We investigated whether the efficacy of lenvatinib (LEN) could be accurately assessed by measuring blood flow in hepatocellular carcinoma (HCC) during early treatment stages.

Methods And Results: Blood flow changes and treatment results of 19 patients who underwent contrast-enhanced ultrasound (CEUS), before and after LEN administration, in Kurume University Hospital from July 2018 to June 2020 were examined. Blood flow was evaluated after the intravenous administration of perflubutane (0.015 ml/kg). The vascular phase was photographed and used as RAW data, and time-intensity curve analysis was used to obtain the region of interest (ROI) on the entire tumor nodule and quantify tumor blood flow. The evaluation was performed before and 1 and 4 weeks after LEN administration. Mean ± standard deviation (SD) values of the brightness of blood flow in the background liver before and 1 and 4 weeks after LEN administration were 2.84 × 10 ± 2.94 × 10 , 3.07 × 10 ± 3.79 × 10 , and 10.0 × 10 ± 20.8 × 10 dB, respectively. Blood flow in the background liver did not significantly decrease at 1 and 4 weeks compared with that before treatment. Mean ± SD values of the brightness of blood flow in HCC before and 1 and 4 weeks after administration were 3.49 × 10 ± 4.58 × 10 , 1.16 × 10 ± 1.57 × 10 , and 6.39 × 10 ± 22.8 × 10 dB, respectively. Blood flow in HCC after 1 week was significantly lower than that before administration (p = .0192). The therapeutic effects were significantly higher in the group with ≥50% blood flow reduction in HCC at 1 week after administration (p = .0038) and the group with reduced blood flow in HCC at 4 weeks after administration (p = .0051) than those before administration.

Conclusion: Early blood flow evaluation by CEUS may be useful in predicting the therapeutic effect of LEN for unresectable advanced HCC.
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http://dx.doi.org/10.1002/cnr2.1471DOI Listing
June 2021

Non-Obese MAFLD Is Associated with Colorectal Adenoma in Health Check Examinees: A Multicenter Retrospective Study.

Int J Mol Sci 2021 May 22;22(11). Epub 2021 May 22.

Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.

Colorectal adenoma is linked to metabolic dysfunction. Metabolic dysfunction-associated fatty liver disease (MAFLD) has a precise definition and three subtypes, including non-obese MAFLD. We aimed to investigate the impact of MAFLD on the prevalence of colorectal adenoma by comparing it to non-alcoholic fatty liver disease (NAFLD) in health check-up examinees. This is a multicenter retrospective study. We enrolled 124 consecutive health check-up examinees who underwent colonoscopy. NAFLD and MAFLD were present in 58 and 63 examinees, respectively. Colorectal adenoma was diagnosed by biopsy. The impact of the MAFLD definition on the prevalence of colorectal adenoma was investigated by logistic regression, decision-tree, and random forest analyses. In logistic regression analysis, MAFLD was identified as the only independent factor associated with the presence of colorectal adenoma (OR 3.191; 95% CI 1.494-7.070; = 0.003). MAFLD was also identified as the most important classifier for the presence of colorectal adenoma in decision-tree and random forest analyses (29 variable importance value). Among the three subtypes of MAFLD, non-obese MAFLD was the sole independent factor associated with the presence of colorectal adenoma (OR 3.351; 95% CI 1.589-7.262; ≤ 0.001). Non-obese MAFLD was also the most important classifier for the presence of colorectal adenoma in decision-tree and random forest analyses (31 variable importance value). MAFLD, particularly non-obese MAFLD, is the most important factor associated with the presence of colorectal adenoma rather than NAFLD. Colonoscopy examination should be considered in patients with MAFLD, especially those who are non-obese.
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http://dx.doi.org/10.3390/ijms22115462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196881PMC
May 2021

Effects of a low-intensity resistance exercise program on serum miR-630, miR-5703, and Fractalkine/CX3CL1 expressions in subjects with No exercise habits: A preliminary study.

Hepatol Res 2021 Jul 2;51(7):823-833. Epub 2021 Jun 2.

Department of Orthopedics, School of Medicine, Kurume University, Kurume, Japan.

Aims: Exercise is effective for the prevention of liver cancer. Exercise exerts biological effects through the regulation of microRNAs (miRNAs) and cytokines/myokines. We aimed to investigate the effects of low-intensity resistance exercise on serum miRNA and cytokine/myokine expressions in subjects with no exercise habits.

Methods: We enrolled seven male subjects with no exercise habits in this prospective before-after study. All subjects performed a low-intensity resistance exercise program (three metabolic equivalents, approximately 20 min/session). Serum miRNA expressions were evaluated using microarrays. We performed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of differentially expressed miRNAs before and after exercise. Serum cytokine/myokine expressions were evaluated using a multiplex panel.

Results: All subjects completed the exercise program with no adverse events. In the microarray analysis, seven miRNAs showed a significant change between before and after exercise. Of these, microRNA (miR)-630 and miR-5703 showed a >1.5-fold increase (miR-630: 40.7 vs. 69.3 signal intensity, p = 0.0133; miR-5703: 30.7 vs. 55.9 signal intensity, p = 0.0051). KEGG pathway enrichment analysis showed that miR-630- and miR-5703-related genes were enriched in 37 and 5 pathways, including transforming growth factor-beta and Wnt signaling pathways, respectively. In the multiplex analysis, 12 cytokines/myokines showed significant alteration after exercise compared to before exercise. Of these, fractalkine/CX3CL1 showed the most significant up-regulation by exercise (94.5 vs. 109.1 pg/ml, p = 0.0017).

Conclusions: A low-intensity resistance exercise program was associated with upregulation of serum miR-630, miR-5703, and fractalkine/CX3CL1 expressions in subjects with no exercise habits. Thus, even low-intensity exercise may alter miRNA and cytokine/myokine expressions in humans.
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http://dx.doi.org/10.1111/hepr.13670DOI Listing
July 2021

A phase II study of gemcitabine plus nab-paclitaxel as first-line therapy for locally advanced pancreatic cancer.

Medicine (Baltimore) 2021 May;100(20):e26052

Division of Gastroenterology, Department of Internal Medicine, Kurume University School of Medicine.

Abstract: Gemcitabine plus nab-paclitaxel (GnP) is widely used in clinical practice, despite a lack of prospective data to validate its efficacy in locally advanced pancreatic cancer (LAPC). We conducted a phase II study of GnP for LAPC to assess its efficacy and safety.We performed a single-arm, single-institution study with GnP in 24 patients with LAPC. The treatment protocol included successive administration of gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2). The primary endpoint was the tumor overall response rate (ORR), and secondary endpoints were overall survival (OS), progression-free survival (PFS), and adverse events (AEs).The median PFS was 11.0 months, median OS was 21.2 months, ORR was 62.5%, and 37.5% of the patients had stable disease. Four (16.7%) of the patients were converted to surgical resection; 3 of these achieved R0 resection. Grade 3 to 4 AEs included hematological (neutropenia, 64%; thrombocytopenia, 12%), nonhematological (cholangitis, 16%), and sensory neuropathy (4%). These AEs were manageable and tolerable.The GnP treatment in patients with LAPC showed favorable tumor shrinkage, good toxicity profile, and enabled conversion to surgical resection in a subset of patients; therefore, GnP is an option for first-line chemotherapy in patients with LAPC.
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http://dx.doi.org/10.1097/MD.0000000000026052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137062PMC
May 2021

Tenofovir Alafenamide Rescues Renal Tubules in Patients with Chronic Hepatitis B.

Life (Basel) 2021 Mar 23;11(3). Epub 2021 Mar 23.

Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.

Nucles(t)ide analogs (NAs) are effective for chronic hepatitis B (CHB). NAs suppress hepatic decompensation and hepatocarcinogenesis, leading to a dramatic improvement of the natural course of patients with CHB. However, renal dysfunction is becoming an important issue for the management of CHB. Renal dysfunction develops in patients with the long-term treatment of NAs including adefovir dipivoxil and tenofovir disoproxil fumarate. Recently, several studies have reported that the newly approved tenofovir alafenamide (TAF) has a safe profile for the kidney due to greater plasma stability. In this mini-review, we discuss the effectiveness of switching to TAF for NAs-related renal tubular dysfunction in patients with CHB.
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http://dx.doi.org/10.3390/life11030263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005189PMC
March 2021

Therapeutic Outcomes and Prognostic Factors of Unresectable Intrahepatic Cholangiocarcinoma: A Data Mining Analysis.

J Clin Med 2021 Mar 2;10(5). Epub 2021 Mar 2.

Division of Gastroenterology, Department of Medicine, School of Medicine, Kurume University, Kurume 830-0011, Japan.

Prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is unsatisfactory. Tumor, host, and treatment factors including hepatic arterial infusion chemotherapy (HAIC) are intricately involved in the progression of ICC. We aimed to identify profiles associated with disease control rate (DCR) and the prognosis of patients with unresectable ICC by decision tree analysis. We analyzed 31 consecutive patients with unresectable ICC (median age, 71 years; the male ratio was 58.1%). Stage IVB occupied 51.6% of patients, and 38.7% and 58.1% of patients were treated with gemcitabine plus cisplatin combination therapy and HAIC, respectively. Profiles associated with prognosis as well as DCR were investigated by decision tree analysis. The median survival time (MST) of the patients was 11.6 months, and the DCR was 70.9%. Multivariate correlation analysis showed that albumin levels and WBC levels were significantly correlated with survival time (albumin, ρ = 0.3572, = 0.0485; WBC, ρ = -0.4008, = 0.0280). In decision tree analysis, WBC level was selected as the initial split variable, and subjects with WBC levels of 6800/μL or less (45.1%) showed a long survival time (MST 476 days). We also demonstrated that the profile associated with the highest DCR was "less than 4.46 mg/dL of CRP levels and treatment with HAIC". We demonstrated a new prognostic profile for ICC patients, which consisted of WBC and CRP levels. Moreover, we demonstrated that HAIC was associated with better disease control in ICC patients with low CPR levels. Thus, these new profiles may be useful for the management of ICC patients.
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http://dx.doi.org/10.3390/jcm10050987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957874PMC
March 2021

Applicability of APRI and FIB-4 as a transition indicator of liver fibrosis in patients with chronic viral hepatitis.

J Gastroenterol 2021 May 31;56(5):470-478. Epub 2021 Mar 31.

Department of Liver Disease, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba, Tokyo, 272-8516, Japan.

Background And Aims: 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.

Methods: 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.

Results: 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.

Conclusion: The APRI and FIB-4 may serve as a transition indicator of liver fibrosis in anti-viral treatment-naïve patients with chronic hepatitis C.
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http://dx.doi.org/10.1007/s00535-021-01782-3DOI Listing
May 2021

Prevalence and profiles of ramucirumab-associated severe ascites in patients with hepatocellular carcinoma.

Mol Clin Oncol 2021 Apr 25;14(4):79. Epub 2021 Feb 25.

Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.

Severe ascites is an adverse event of ramucirumab (RAM), a second-line treatment for hepatocellular carcinoma (HCC). Ascites can be associated with various factors, including nutritional status and muscle quality. The aim of the present study was to investigate the prevalence and profiles of RAM-associated severe ascites in patients with HCC. This retrospective study enrolled 14 consecutive patients with HCC treated with RAM (median age, 72 years; Barcelona Clinic Liver Cancer stage B/C, 6/8). Nutritional status and muscle quality were evaluated using the controlling nutritional status (CONUT) score and intramuscular adipose tissue (IMAT) content, respectively. Factors associated with severe ascites were evaluated using decision-tree analysis. The median progression-free survival (PFS) time was 2.1 months, and the overall objective response and disease control rates were 14 and 50%, respectively. Severe ascites developed in 57.1% of the patients, and the median onset was 37.5 days (range, 14-61 days) after initiation of RAM treatment. In the decision-tree analysis, the CONUT score and IMAT content were the first and second splitting variables for the development of severe ascites. In patients with a CONUT score ≥5 and IMAT <-0.54, the prevalence of severe ascites was 80 and 100%, respectively. A high incidence of severe ascites was observed in patients treated with RAM. A CONUT score ≥5 and an IMAT <-0.54 were associated with severe ascites. Thus, caution must be taken for severe ascites in patients with HCC treated with RAM, in particular patients with malnutrition and fat infiltration in muscle.
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http://dx.doi.org/10.3892/mco.2021.2241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947949PMC
April 2021

Gut microbiota composition associated with hepatic fibrosis in non-obese patients with non-alcoholic fatty liver disease.

J Gastroenterol Hepatol 2021 Mar 11. Epub 2021 Mar 11.

Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.

Background And Aim: Gut microbiota composition is associated with the pathogenesis of non-alcoholic fatty liver disease. However, the association between gut microbiota composition and non-alcoholic fatty liver disease in non-obese patients remains unclear. We compared clinical parameters and gut microbiota profiles of healthy controls and non-obese and obese patients with non-alcoholic fatty liver disease.

Methods: We examined the clinical parameters and gut microbiota profiles by 16S rRNA sequences and short-chain fatty acid levels in fecal samples from 51 non-obese patients with non-alcoholic fatty liver disease (body mass index <25 kg/m ) and 51 obese patients with non-alcoholic fatty liver disease (body mass index ≥30 kg/m ) who underwent pathological examination and 87 controls at five hospitals in Japan.

Results: Although no significant differences between the non-obese and other groups were observed in alpha diversity, a significant difference was found in beta diversity. We observed a significant decrease in serum alanine aminotransferase levels, Eubacterium population, and butyric acid levels in non-obese patients with non-alcoholic fatty liver disease compared with those in obese patients with non-alcoholic fatty liver disease. A significant negative correlation was found between the stage of hepatic fibrosis and Eubacterium abundance in non-obese patients with non-alcoholic fatty liver disease.

Conclusions: The decrease in the abundance of Eubacterium that produces butyric acid may play an important role in the development of non-alcoholic fatty liver disease in non-obese individuals. This study was registered at the University Hospital Medical Information Network clinical trial registration system (UMIN000020917).
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http://dx.doi.org/10.1111/jgh.15487DOI Listing
March 2021

Evaluation of Serum Leucine-Rich Alpha-2 Glycoprotein as a New Inflammatory Biomarker of Inflammatory Bowel Disease.

Mediators Inflamm 2021 1;2021:8825374. Epub 2021 Feb 1.

Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.

Studies on serum leucine-rich alpha-2 glycoprotein (LRG) in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are scarce; the methods for estimating disease activity are less established, particularly for CD. This study is aimed at evaluating the utility of serum LRG as a potential inflammatory marker for IBD and to investigate the LRG gene expression in peripheral blood mononuclear cells (PBMCs) as a possible source of serum LRG. Overall, 98 patients with UC and 96 patients with CD were prospectively enrolled and clinically evaluated; 92 age-matched individuals served as the healthy controls. The blood samples were analyzed for serum LRG levels and routine laboratory parameters. Disease activity was assessed clinically and endoscopically. Finally, LRG gene expression in the PBMCs from a different cohort (41 patients with UC, 34 patients with CD, and 30 healthy controls) was examined. The serum LRG levels were higher during active disease than during inactive disease; additionally, serum LRG levels were positively correlated with clinical disease activity, C-reactive protein (CRP) levels, and other laboratory parameters in patients with UC and CD and with endoscopic disease activity in UC. UC and CD showed comparable areas under the curve (AUC) values for determining clinical remission and differentiating between endoscopic remission associated with LRG and CRP. The levels of LRG mRNA were also increased in PBMCs from patients with UC and CD and reflected disease activity. These data suggest that serum LRG, originated partially from PBMCs, is an inflammatory marker in UC and CD. A large-scale well-designed study should be conducted in the future to more accurately reveal the clinical significance of LRG in patients with IBD.
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http://dx.doi.org/10.1155/2021/8825374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874844PMC
February 2021

Therapeutic Potential of a Self-Assembling Peptide Hydrogel to Treat Colonic Injuries Associated with Inflammatory Bowel Disease.

J Crohns Colitis 2021 Feb 17. Epub 2021 Feb 17.

Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.

Background And Aims: The Self-assembling Peptide Hydrogel (SAPH, PuraMatrix TM), a fully synthetic peptide solution designed to replace collagen, has recently been used to promote mucosal regeneration in iatrogenic ulcers following endoscopic submucosal dissection. Herein, we evaluated its utility in ulcer repair using a rat model of topical trinitrobenzene sulfonic acid (TNBS)-induced colonic injuries.

Methods: Colonic injuries were generated in 7-week-old rats by injecting an ethanol solution (35%, 0.2 mL) containing 0.15 M TNBS into the colonic lumen. At 2- and 4-days post-injury, the rats were subjected to endoscopy, and SAPH (or vehicle) was topically applied to the ulcerative lesion. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used to detect SAPH. Colonic expression of cytokines and wound healing-related factors were assessed using real-time polymerase chain reaction or immunohistochemistry.

Results: SAPH treatment significantly reduced ulcer length (P = 0.0014) and area (P = 0.045), while decreasing colonic weight (P = 0.0375) and histological score (P = 0.0005) 7 days after injury. SAPH treatment also decreased colonic expression of interleukin (IL)-1α (P = 0.0233) and IL-6 (P = 0.0343) and increased that of claudin-1 (P = 0.0486), villin (P = 0.0183), and β-catenin staining (P = 0.0237). TOF-SIMS revealed lesional retention of SAPH on day 7 post-injury. Furthermore, SAPH significantly promoted healing in in vivo mechanical intestinal wound models.

Conclusions: SAPH application effectively suppressed colonic injury, downregulated inflammatory cytokine expression, and upregulated wound healing-related factor expression in the rat model; thus, it may represent a promising therapeutic strategy for IBD-related colonic ulcers.
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http://dx.doi.org/10.1093/ecco-jcc/jjab033DOI Listing
February 2021

Survival Benefit of Hepatic Arterial Infusion Chemotherapy over Sorafenib in the Treatment of Locally Progressed Hepatocellular Carcinoma.

Cancers (Basel) 2021 Feb 5;13(4). Epub 2021 Feb 5.

Department of Gastroenterology, Kurume Central Hospital, Kurume 830-0001, Japan.

Backround: Not all patients with hepatocellular carcinoma (HCC) benefit from treatment with molecular targeted agents such as sorafenib. We investigated whether New-FP (fine-powder cisplatin and 5-fluorouracil), a hepatic arterial infusion chemotherapy regimen, is more favorable than sorafenib as an initial treatment for locally progressed HCC.

Methods: To avoid selection bias, we corrected the data from different facilities that did or did not perform New-FP therapy. In total, 1709 consecutive patients with HCC initially treated with New-FP or sorafenib; 1624 (New-FP, = 644; sorafenib = 980) were assessed. After propensity score matching (PSM), overall survival (OS) and prognostic factors were assessed ( = 344 each). Additionally, the patients were categorized into four groups: cohort-1 [(without macrovascular invasion (MVI) and extrahepatic spread (EHS)], cohort-2 (with MVI), cohort-3 (with EHS), and cohort-4 (with MVI and EHS) to clarify the efficacy of each treatment.

Results: New-FP prolonged OS than sorafenib after PSM (New-FP, 12 months; sorafenib, 7.9 months; < 0.001). Sorafenib treatment, and severe MVI and EHS were poor prognostic factors. In the subgroup analyses, the OS was significantly longer the New-FP group in cohort-2.

Conclusions: Local treatment using New-FP is a potentially superior initial treatment compared with sorafenib as a multidisciplinary treatment in locally progressed HCC without EHS.
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http://dx.doi.org/10.3390/cancers13040646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915251PMC
February 2021

Eradication of hepatitis C virus with direct-acting antivirals improves glycemic control in diabetes: A multicenter study.

JGH Open 2021 Feb 19;5(2):228-234. Epub 2020 Dec 19.

Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan.

Background And Aim: Hepatitis C virus (HCV) infection causes insulin resistance and diabetes as extrahepatic manifestations. We aimed to analyze the effect of HCV eradication by direct-acting antiviral (DAA) agents on glucose tolerance.

Methods: The hemoglobin A1c (HbA1c) of 272 patients with HCV infection who achieved a sustained virologic response (SVR) was analyzed at baseline before DAA treatment, at the end of DAA therapy (ETR), and 12 weeks after therapy (Post12W).

Results: There were no significant differences in HbA1c between baseline, ETR, and Post12W in the overall patients. When the data were stratified according to the presence or absence of diabetes, median HbA1c significantly decreased from baseline (7.2%) to ETR (6.8%) and Post12W (6.8%) in the 55 patients with diabetes, whereas there were no significant changes in the patients without diabetes. Basal HbA1c, fasting plasma glucose, and age were independently associated with the changes in HbA1c according to multivariate analysis, and the predictive formula for changes in HbA1c was found to be ΔHbA1c (%) = 1.449-0.4* HbA1c (%) + 0.012 × Age (year). There were no changes in body mass in diabetic or nondiabetic patients. In diabetic patients taking medication, 63.4% of patients needed less medication.

Conclusions: Eradication of HCV improves glycemic control, indicated by a 0.4% decrease in HbA1c in diabetes.
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http://dx.doi.org/10.1002/jgh3.12474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857302PMC
February 2021

Lenvatinib versus sorafenib in first-line treatment of unresectable hepatocellular carcinoma: An inverse probability of treatment weighting analysis.

Liver Int 2021 06 20;41(6):1389-1397. Epub 2021 Feb 20.

Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Purpose: Data from common clinical practice were used to generate balanced cohorts of patients receiving either sorafenib or lenvatinib, for unresectable hepatocellular carcinoma, with the final aim to investigate their declared equivalence.

Methods: Clinical features of lenvatinib and sorafenib patients were balanced through inverse probability of treatment weighting (IPTW) methodology, which weights patients' characteristics and measured outcomes of each patient in both treatment arms. Overall survival was the primary endpoint and occurrence of adverse events was the secondary.

Results: The analysis included 385 patients who received lenvatinib, and 555 patients who received sorafenib. In the unadjusted cohort, lenvatinib did not show a survival advantage over sorafenib (HR: 0.85, 95% CI 0.70-1.02). After IPTW adjustment, lenvatinib still not returned a survival advantage over sorafenib (HR: 0.82, 95% CI: 0.62-1.07) even in presence of balanced baseline characteristics. Lenvatinib provided longer survival than sorafenib in patients previously submitted to TACE (HR: 0.69), with PS of 0 (HR: 0.73) or without extrahepatic disease (HR: 0.69).

Conclusion: Present results confirmed randomized controlled trial in the real-life setting, but also suggests that in earlier stages some benefit can be expected.
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http://dx.doi.org/10.1111/liv.14817DOI Listing
June 2021

Prediction of Nonalcoholic Fatty Liver Disease Using Noninvasive and Non-Imaging Procedures in Japanese Health Checkup Examinees.

Diagnostics (Basel) 2021 Jan 16;11(1). Epub 2021 Jan 16.

Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 849-8501, Japan.

Access to imaging is limited for diagnosing nonalcoholic fatty liver disease (NAFLD) in general populations. This study evaluated the diagnostic performance of noninvasive and nonimaging indexes to predict NAFLD in the general Japanese population. Health checkup examinees without hepatitis virus infection or habitual alcohol drinking were included. Fatty liver was diagnosed by ultrasonography. The hepatic steatosis index (HSI), Zhejiang University (ZJU) index, and fatty liver index (FLI) were determined, and risk of advanced liver fibrosis was evaluated by the fibrosis-4 index. NAFLD was diagnosed in 1935 (28.0%) of the 6927 subjects. The area under the receiver operating characteristic (AUROC) curve of the HSI, ZJU index, and FLI was 0.874, 0.886, and 0.884, respectively. The AUROC of the ZJU index ( < 0.001) and FLI ( = 0.002) was significantly greater than that for the HSI. In subjects with a high risk of advanced fibrosis, the sensitivity of the HSI, ZJU index, and FLI were 88.8%, 94.4%, and 83.3% with a low cut-off value and the specificity was 98.5%, 100%, and 100% with a high cut-off value. In conclusion, all indexes were useful to diagnose NAFLD in the general Japanese population and in subjects with potentially advanced liver fibrosis.
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http://dx.doi.org/10.3390/diagnostics11010132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830542PMC
January 2021

Alternating Lenvatinib and Trans-Arterial Therapy Prolongs Overall Survival in Patients with Inter-Mediate Stage HepatoCellular Carcinoma: A Propensity Score Matching Study.

Cancers (Basel) 2021 Jan 5;13(1). Epub 2021 Jan 5.

Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan.

We aimed to evaluate the impact of alternating lenvatinib (LEN) and trans-arterial therapy (AT) in patients with intermediate-stage hepatocellular carcinoma (HCC) after propensity score matching (PSM). This retrospective study enrolled 113 patients with intermediate-stage HCC treated LEN. Patients were classified into the AT ( = 41) or non-AT group ( = 72) according to the post LEN treatment. Overall survival (OS) was calculated using the Kaplan-Meier method and analyzed using a log-rank test after PSM. Factors associated with AT were evaluated using a decision tree analysis. After PSM, there were no significant differences in age, sex, etiology, or albumin-bilirubin (ALBI) score/grade between groups. The survival rate of the AT group was significantly higher than that of the non-AT group (median survival time; not reached vs. 16.3 months, = 0.01). Independent factors associated with OS were AT and ALBI grade 1 in the Cox regression analysis. In the decision tree analysis, age and ALBI were the first and second splitting variables for AT. In this study, we show that AT may improve prognosis in patients with intermediate-stage HCC. Moreover, alternating LEN and trans-arterial therapy may be recommended for patients below 70 years of age with ALBI grade 1.
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http://dx.doi.org/10.3390/cancers13010160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796435PMC
January 2021

Relationship between cervical esophageal squamous cell carcinoma and human papilloma virus infection and gene mutations.

Mol Clin Oncol 2021 Feb 30;14(2):41. Epub 2020 Dec 30.

Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan.

Cervical esophageal squamous cell carcinoma (CESCC) is rare, accounting for 5% of all esophageal carcinomas. Several diagnostic and predictive markers have been studied. However, to the best of our knowledge, no biomarker is known to determine patient management except the clinical stage. The present study aimed to evaluate whether human papilloma virus (HPV) infection, epidermal growth factor receptor (EGFR) and its pathway-related gene mutations, known to be sensitive biomarkers of oropharyngeal carcinomas, could be used as biomarkers for the prediction of the prognosis of patients with CESCC. The present retrospective study included patients with CESCC who received chemoradiotherapy or surgery. HPV infection and the genomic status of , , , and of each tumor sample from patients with CESCC were analyzed by hybridizations (ISH) and PCR methods, respectively. The present study included 33 patients with CESCC (male/female, 29/4; median age, 62 years; age range, 41-86 years; clinical stage I/II/III/IV, 2/6/10/15). The present study detected HPV in one patient (3.0%) by ISH and PCR. Concerning the investigation of and its pathway-related gene mutations, the present study detected 15.1% of , 6.0% of , 3.5% of , 3.0% of and 3.0% for mutations, with no significant relationship between any gene mutations and the clinical prognostic factors. The HPV-infected patient did not exhibit any gene mutations. The present study indicated that HPV infection, EGFR and its pathway-related gene mutations rarely exist in patients with CESCC. The relationship between these biomarkers and the prognosis in patients with CESCC is still unclear.
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http://dx.doi.org/10.3892/mco.2020.2205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788557PMC
February 2021

Effects of In-Hospital Exercise on Frailty in Patients with Hepatocellular Carcinoma.

Cancers (Basel) 2021 Jan 7;13(2). Epub 2021 Jan 7.

Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan.

Frailty including physical inactivity is associated with the survival of patients with hepatocellular carcinoma (HCC). We aimed to investigate the effects of in-hospital exercise on frailty in patients with HCC. This was a multi-center observational study. Patients with HCC were classified into exercise ( = 114) and non-exercise ( = 67) groups. The exercise group was treated with a mixture of aerobic and resistance exercises (20-40 min/day, median four days). Frailty was assessed using the liver frailty index (LFI). Factors for changes in LFI were examined by multivariate and decision-tree analyses. The factors were also examined after propensity score matching. During hospitalization, LFI was significantly improved in the exercise group compared to the non-exercise group (ΔLFI -0.17 vs. -0.02, = 0.0119). In multivariate analysis, exercise (odds ratio (OR) 2.38, 95% confidence interval (CI) 1.240-4.570, = 0.0091) and females (OR 2.09; 95%CI, 1.062-4.109; = 0.0328) were identified as independent factors for the improvement of LFI. In the decision-tree analysis, exercise was identified as an initial classifier associated with the improvement of LFI. Similar findings were also seen in the propensity score matching analyses. We demonstrated that in-hospital exercise improved frailty in patients with HCC. Thus, in-hospital exercise may be beneficial for improving physical function in patients with HCC.
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http://dx.doi.org/10.3390/cancers13020194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826707PMC
January 2021

Efficacy of a Glass Membrane Emulsification Device to Form Mixture of Cisplatin Powder with Lipiodol on Transarterial Therapy for Hepatocellular Carcinoma.

Cardiovasc Intervent Radiol 2021 May 7;44(5):766-773. Epub 2021 Jan 7.

Department of Radiology, IVR Center, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan.

Purpose: To examine physiochemical characteristics and drug release properties of cisplatin powder and lipiodol mixtures formed by a glass membrane emulsification device compared with a 3-way stopcock.

Materials And Methods: Seven different types of mixtures were evaluated: cisplatin powder and lipiodol directly mixed (suspension), complete cisplatin solution and lipiodol mixed by a 3-way stopcock or the device (emulsion), incomplete cisplatin solution and lipiodol mixed by a 3-way stopcock or the device (solid-in-water emulsion), and contrast material and cisplatin suspension mixed by a 3-way stopcock or the device (solid-in-oil emulsion).

Result: The percentages of water-in-oil were 98.08 ± 0.27% in the emulsion formed by the device, while 70.3 ± 4.63% in the emulsion formed by a 3-way stopcock (P = 0.037). Solid-in-water and solid-in-oil emulsions formed by the device showed 98.09 ± 0.38% and 98.70 ± 0.40% of water-in-oil, respectively, whereas both solid-in-water and solid-in-oil emulsions formed by a 3-way stopcock showed 0.00%. Homogenous droplet sizes were shown by using the device. The half release times of cisplatin in the emulsions formed by the device were 197 ± 19, 244 ± 24 and 478 ± 52 min, respectively, which were significantly longer than the emulsion formed by a 3-way stopcock of 8 ± 8 min (P = 0.046-0.050). Suspension showed the longest release time; however, the viscosity was lowest.

Conclusion: The glass membrane emulsification device formed almost 100% water-in-oil, whereas 3-way stopcock produced 100% oil-in-water when incomplete solution or suspension was mixed. Slower cisplatin release was shown in the emulsions formed by the device.
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http://dx.doi.org/10.1007/s00270-020-02757-2DOI Listing
May 2021

Optimizing the management of intermediate-stage hepatocellular carcinoma: Current trends and prospects.

Clin Mol Hepatol 2021 Apr 3;27(2):236-245. Epub 2020 Dec 3.

Division of gastroenterology, Department of Medicine, Kurume University School of Medicine, Research Center for Innovative Cancer Therapy Kurume University, Kurume, Japan.

Hepatocellular carcinoma (HCC) is usually accompanied by chronic liver damage, which sometimes influences the selection of HCC treatment. The Barcelona Clinic Liver Cancer (BCLC) staging system, which was first introduced in 1999, is the most commonly used worldwide. Although the intermediate-stage (BCLC stage B) includes the largest number and heterogeneous HCC patients, the recommended treatment option is transarterial chemoembolization (TACE) only. However, recent progress in radical treatments such as hepatic resection, liver transplantation, radiation therapy, and percutaneous therapy has made it possible to treat selected patients with BCLC stage B HCC. Radical treatments are expected to prolong survival time. To-date, TACE has also progressed. In addition to conventional TACE, balloon-occluded TACE and drug-eluting beads TACE are available. These new modalities of TACE will improve therapeutic efficacy and reduce adverse events. One of the most serious concerns of TACE is that repeated TACE reduces the treatment effect and induces liver function impairment. The decision on when TACE should be interrupted is complex. Many molecular targeted agents are now available, and immune checkpoint inhibitors will soon be available for HCC patients with Child-Pugh class A worldwide. Under these circumstances, in patients with TACE unsuitability, switching to molecular targeted agents before deterioration of liver function might improve the prognosis compared to repeated TACE. We should pay attention to stop TACE in TACE-unsuitable HCC patients as it can induce the deterioration of liver function.
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http://dx.doi.org/10.3350/cmh.2020.0204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046626PMC
April 2021

Effects of In-Hospital Physical Therapy on Activities of Daily Living in Patients with Hepatocellular Carcinoma.

Int J Environ Res Public Health 2020 12 6;17(23). Epub 2020 Dec 6.

Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan.

Activities of daily living (ADL) are frequently impaired in patients with hepatocellular carcinoma (HCC). In this retrospective study, we aimed to investigate the effects of physical therapy on ADLs in patients with HCC during hospitalization for cancer treatment. Nineteen patients with HCC were enrolled. During hospitalization, patients performed a combination of resistance training, stretching, and aerobic exercise (20-60 min/day). ADLs were assessed using the functional independence measure (FIM). Changes in FIM were evaluated by before-after analysis. No significant difference was seen in Child-Pugh class before and after physical therapy. The bilateral knee extension strength and chair stand test were significantly increased after physical therapy compared with before physical therapy ( = 0.001 and = 0.008, respectively). The total FIM score was significantly increased after physical therapy compared with that before physical therapy ( = 0.0156). Among the 18 indexes of FIM, the stairs index was significantly improved after physical therapy compared with that before physical therapy (5.9 vs. 6.4 points, = 0.0241). We demonstrated that physical therapy improved muscle strength without worsening liver function. Furthermore, physical therapy improved FIM, especially in the stairs index, in patients with HCC. Thus, physical therapy may be beneficial in patients with HCC during cancer treatment.
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http://dx.doi.org/10.3390/ijerph17239098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730642PMC
December 2020

Short-term efficacy after switching from adefovir dipivoxil and tenofovir disoproxil fumarate therapy to tenofovir alaferamide for chronic hepatitis B.

Biomed Rep 2021 Jan 12;14(1):12. Epub 2020 Nov 12.

Division of Gastroenterology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.

The aim of the present study was to evaluate the effects of switching to tenofovir alafenamide (TAF) in patients who had received a nucleos(t)ide analog (NA) for the treatment of chronic hepatitis B (CHB). The data from 33 Japanese patients with CHB who received TAF therapy after using NA [adefovir dipivoxil (ADV) and/or tenofovir disoproxil fumarate (TDF)] were retrospectively analyzed. Specifically, the biochemical and virological markers from the start of the TAF treatment to 6 months later were assessed. Comparative evaluation was performed by dividing patients into two groups: Long-term (n=19) and short-term administration groups (n=14), with a cutoff administration duration of 10 years. In all 33 patients, the levels of serum hepatitis B surface antigen (HBsAg; 1,126±1,724 to 1,001±1,591 IU/ml; P<0.0001), serum alkaline phosphatase (ALP) (320±126 to 283±124 U/l; P=0.028), serum bone specific alkaline phosphatase (19.7±9.0 to 17.7±8.0 µg/l; P=0.0006) and urine β2-microglobulin-creatinine ratio (U-BMG/Cr; 5,224±17,471 to 3,547±14,652 µg/g·Cre; P=0.002) significantly decreased from baseline after 6 months. Serum HBsAg, serum ALP and U-BMG/Cr showed a significant reduction in both groups. In conclusion, switching from ADV or TDF to TAF resulted in a decrease in serum HBsAg and improvement in serum ALP and U-BMG/Cr after 6 months of treatment in patients regardless of history of treatment with NA.
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http://dx.doi.org/10.3892/br.2020.1388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678628PMC
January 2021

Quality of life among patients with autoimmune hepatitis in remission: A comparative study.

Medicine (Baltimore) 2020 Oct;99(43):e22764

Department of Gastroenterology, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima.

Health-related quality of life (HRQOL) is lower in individuals with autoimmune hepatitis (AIH) than in the general population. However, previous evaluations of HRQOL for AIH have included a broad range of disease activities. The aim of this study was to clarify HRQOL among patients with AIH in remission.We assessed HRQOL in patients with AIH in remission, patients with chronic hepatitis C (CHC) with eradicated hepatitis C virus (HCV) and patients with primary biliary cholangitis (PBC) using the Japanese version of the Chronic Liver Disease Questionnaire (CLDQ).Participants comprised 62 patients with AIH in remission, 39 patients with CHC with eradicated HCV and 66 patients with PBC. Median ages of patients were 63, 69, and 64 years, respectively. Overall score (5.6 vs 5.9, P = .02) and fatigue (5.2 vs 5.6, P = .01) and worry (5.6 vs 6.0, P = .01) domain scores of the CLDQ were significantly lower in patients with AIH in remission than in CHC with eradicated HCV, and similar to scores except for the systemic symptoms domain in patients with PBC. Disease duration was associated with lower scores on systemic symptoms and activity domains of the CLDQ in patients with AIH in remission.Patients with AIH in remission show impaired HRQOL associated with disease duration.
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http://dx.doi.org/10.1097/MD.0000000000022764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581115PMC
October 2020

Predictive model of bleeding following endoscopic sphincterotomy for the treatment of choledocholithiasis in hemodialysis patients: A retrospective multicenter study.

JGH Open 2020 Oct 17;4(5):915-922. Epub 2020 May 17.

Department of Gastroenterology Kameda Medical Center Chiba Japan.

Background And Aim: Although hemodialysis (HD) is a strong risk factor for postendoscopic sphincterotomy (ES) bleeding, additional risk factors in HD patients remain unclear. There is no model for predicting post-ES bleeding risk in HD patients. Therefore, we conducted a retrospective multicenter study to reveal these risk factors and develop a predictive model of post-ES bleeding in HD patients.

Methods: We retrospectively reviewed the medical records of HD patients who underwent ES at eight hospitals between January 2006 and December 2016, with post-ES bleeding as the main outcome measure. Univariate analyses were performed to extract possible risk factors for post-ES bleeding. Factors that were clinically important and statistically significant in our univariate analyses were then included in our logistic regression analysis for the development of a multivariate predictive model of post-ES bleeding. This predictive model was visualized using a predictive nomogram.

Results: Post-ES bleeding occurred in 20 (16.3%) of 123 HD patients. Based on clinically important factors and the results of our univariate analyses, platelet count, prothrombin time (international normalized ratio), and HD duration were included in our predictive model of post-ES bleeding. Receiver operating characteristic analysis found that this model had an area under the curve of 0.715 (95% confidence interval, 0.609-0.822). We developed a predictive nomogram based on these results.

Conclusions: We demonstrated that post-ES bleeding is more common in HD patients than in the general population and succeeded in constructing a predictive model that can effectively identify HD patients at risk of post-ES bleeding.
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http://dx.doi.org/10.1002/jgh3.12363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578281PMC
October 2020

Prednisolone-responsive primary sclerosing cholangitis with autoimmune hemolytic anemia: a case report and review of the literature.

Clin J Gastroenterol 2021 Feb 10;14(1):330-335. Epub 2020 Oct 10.

Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67, Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.

We report a case of primary sclerosing cholangitis (PSC) with autoimmune hemolytic anemia (AIHA). A 47-year-old woman was diagnosed with PSC. One year later, she was admitted to our hospital for jaundice and fatigue. Magnetic resonance cholangiopancreatography (MRCP) showed worsening of the biliary stricture, and rapidly progressive anemia developed simultaneously. Based on the various laboratory findings, she was diagnosed with AIHA. The administration of prednisolone improved not only the anemia but also the biliary stricture. This case is impactful, as there are few case reports of PSC with AIHA. In addition, we were able to observe the changes in imaging findings using MRCP over time.
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http://dx.doi.org/10.1007/s12328-020-01256-8DOI Listing
February 2021
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