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The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japan Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.

BackgroundTo assess the recent real-world changes in the etiologies of liver cirrhosis (LC) in Japan, we conducted a nationwide survey in the annual meeting of the Japan Society of Hepatology (JSH).MethodsWe investigated the etiologies of LC patients accumulated from 68 participants in 79 institutions (N = 48,621). We next assessed changing trends in the etiologies of LC by analyzing cases in which the year of diagnosis was available (N = 45,834). We further evaluated the transition in the real number of newly identified LC patients by assessing data from 36 hospitals with complete datasets for 2008–2016 (N = 18,358).ResultsIn the overall data, HCV infection (48.2%) was the leading cause of LC in Japan, and HBV infection (11.5%) was the third-most common cause. Regarding the transition in the etiologies of LC, the contribution of viral hepatitis-related LC dropped from 73.4 to 49.7%. Among the non-viral etiologies, alcoholic-related disease (ALD) and nonalcoholic steatohepatitis (NASH)-related LC showed a notable increase (from 13.7 to 24.9% and from 2.0 to 9.1%, respectively). Regarding the real numbers of newly diagnosed patients from 2008 to 2016, the numbers of patients with viral hepatitis-related LC decreased, while the numbers of patients with non-viral LC increased.ConclusionsHCV has remained the main cause of LC in Japan; however, the contribution of viral hepatitis as an etiology of LC is suggested to have been decreasing. In addition, non-viral LC, such as ALD-related LC and NASH-related LC, is suggested to have increased as etiologies of LC in Japan.

BackgroundWe recently reported the real-world changes in the etiologies of liver cirrhosis (LC) based on nationwide survey data and assessed the etiologies of LC with hepatocellular carcinoma (HCC).MethodsFifty-five participants from 68 institutions provided data on 23,637 patients with HCC-complicated LC. The changing trends in etiologies were assessed. We further analyzed the data from 29 hospitals that provided the annual number of newly identified HCC-complicated LC patients from 2008 to 2016 (N = 9362) without any missing years and assessed the transition in the real number of newly identified HCC-complicated LC cases.ResultsIn the overall cohort, hepatitis C virus (HCV) infection (60.3%) and hepatitis B virus (HBV) infection (12.9%) were the leading and third-most common causes of HCC-complicated LC in Japan, respectively. HCV infection was found to be the leading cause throughout Japan. The rate of viral hepatitis-related HCC decreased from 85.3 to 64.4%. Among non-viral etiologies, notable increases were observed in nonalcoholic steatohepatitis (NASH)-related HCC (from 1.5 to 7.2%) and alcoholic liver disease (ALD)-related HCC (from 8.5 to 18.6%). Regarding the real number of newly diagnosed patients, the number of patients with viral hepatitis-related HCC decreased, while the number of patients with non-viral HCC, particularly NASH-related HCC, increased.ConclusionsViral hepatitis has remained the main cause of HCC in Japan. However, the decrease in viral hepatitis-related HCC, particularly HCV-related HCC highly contributed to the etiological changes. In addition, the increased incidence of non-viral HCC, particularly NASH-related HCC, was involved in the changing etiologies of HCC-complicated LC in Japan.

Keratoconus (KC) is a progressive corneal disorder resulting in severe visual impairment. We aimed to determine the prevalence and corneal tomographic characteristics of KC and keratoconus suspect (KCS) in a population-based study, and to construct discrimination models with or without corneal tomography. A total of 1,544 eyes (822 participants aged ≥35 years) were evaluated using data from the Yamagata Study (2015–2017). Systemic and ophthalmological examinations including corneal tomography with swept-source anterior segment optical coherence tomography (AS-OCT) were conducted to determine the prevalence and corneal tomographic characteristics of KC and KCS. In addition, data on 766 eyes were used to construct discrimination models with or without corneal tomography. In results, KC was diagnosed in six (0.85%) participants, and KCS was diagnosed in 27 (1.46%) participants. The values including corneal power, keratometric cylinder, corneal central and thinnest thickness, corneal asymmetry, higher-order irregularity, and their inter-eye differences were associated with KC and KCS. The areas under the receiver operating characteristic curves for the three multivariate discrimination models (without corneal tomography, with corneal tomography, and without corneal tomography + inter-eye difference models) for participants with KC or KCS were 0.848, 1.000, and 0.930, respectively. When corneal tomography is unavailable, inter-eye differences in corneal parameters may be useful screening tools for KC and KCS.

Background: Positive and negative psychological factors are associated with mortality and cardiovascular disease. This study prospectively investigated associations of daily frequency of laughter with mortality and cardiovascular disease in a community-based population. Methods: This study included 17,152 subjects ≥40 years old who participated in an annual health check in Yamagata Prefecture. Self-reported daily frequency of laughter was grouped into three categories (≥1/week; ≥1/month but <1/week; <1/month). Associations of daily frequency of laughter with increase in all-cause mortality and cardiovascular disease incidence were determined using Cox proportional hazards modeling. Results: During follow-up (median, 5.4 years), 257 subjects died and 138 subjects experienced cardiovascular events. Kaplan-Meier analysis revealed that all-cause mortality and cardiovascular disease incidence were significantly higher among subjects with a low frequency of laughter (log-rank P < 0.01). Cox proportional hazard model analysis adjusted for age, gender, hypertension, smoking, and alcohol drinking status showed that risk of all-cause mortality was significantly higher in subjects who laughed <1/month than in subjects who laughed ≥1/week (hazard ratio [HR] 1.95; 95% confidence interval [CI], 1.16–3.09). Similarly, risk of cardiovascular events was higher in subjects who laughed ≥1/month but <1/week than in subjects who laughed ≥1/week (HR 1.62; 95% CI, 1.07–2.40). Conclusion: Daily frequency of laughter represents an independent risk factor for all-cause mortality and cardiovascular disease in a Japanese general population.

BackgroundIntraductal papillary mucinous neoplasm (IPMN) of the pancreas is categorized into four distinct types: the gastric, intestinal, pancreatobiliary, and oncocytic. Each type is associated with specific clinicopathological features. We aimed to uncover the molecular mechanisms underlying the development of these types of IPMN.MethodsWe obtained 103 lesions of various types, including 49 gastric, 26 intestinal, 22 pancreatobiliary, and 6 oncocytic lesions, from 43 IPMNs, including 36 with multiple types. Comparative analysis was performed by targeted sequencing of 37 genes in different lesion types within each pancreas.ResultsGastric-type low-grade lesions were observed in all 36 tumors with multiple types, with 245 mutations identified across all samples. The average number of mutations was significantly different between different lesion grades and types: 1.88 for low-grade lesions, 2.77 for high-grade lesions, and 2.38 for invasive lesions (p = 0.0067); and 1.96 for gastric-type lesion, 2.92 for intestinal-type lesion, 2.73 for pancreatobiliary-type lesion, and 2.17 for oncocytic-type lesion (p = 0.0163). Tracing of mutations between lesions containing multiple types in the same pancreas suggested three developmental pathways, denoted as “progressive”, “divergent”, and “independent”. The progressive and divergent pathways indicate an ancestral lesion that was mostly gastric-type and low-grade may progress or diversify into lesions of other types and/or higher grades. The independent pathway suggests that some high-grade lesions of any type may develop independently.ConclusionThese findings suggest that gastric-type low-grade lesions have a risk of progression into high-grade lesions of other types. Therefore, low-grade gastric-type IPMNs should be under constant surveillance.

[...]primary treatment is associated with acute bleeding from esophageal varices EBL is often the first choice for primary treatment. [...]EBL is often the primary treatment of choice because of acute bleeding from esophageal varices. Because of the safety and simplicity of the procedure, it has been accepted worldwide as a treatment for esophageal varices. Comparison of rebleeding and recurrence rates in EBL and EIS EBL EIS EBL treatment timing Rebleeding rate (%) Recurrence rate (%) Rebleeding rate (%) Recurrence rate (%) Reference Primary 13 36 [5] Primary 31 47 50 23 [6] Primary 24 18 [7] Secondary 16 30 19 13 [8] Secondary 20 56 16 [9] Secondary 29 31 20 11 [10] Pfisterer et al. showed that PRB occurred in 3.1% of patients with large varices and 2.6% of patients with small varices in the first 30 days after EBL, but there was no significant difference in the incidence of PRB. Especially in cases of prophylactic or wait-and-see treatment, EBL should be performed after careful evaluation of the patient's nutritional status, blood coagulation capacity, and overall portal venous circulation, and after careful consideration of whether EBL can completely block variceal blood flow.

Background and AimsThe 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.MethodsThis 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.ResultsThe 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.ConclusionThe APRI and FIB-4 may serve as a transition indicator of liver fibrosis in anti-viral treatment-naïve patients with chronic hepatitis C.

Health intentions and behaviours are essential for improving the health of individuals and society. This study used cross-sectional data from 20,155 health checkup participants in the Yamagata study to identify factors associated with health intentions and behaviours. Information regarding the current level of health intentions and behaviours was collected using a baseline survey questionnaire. Participants were categorised into three groups: having no intention (no intention), having intentions to improve but not acting on them (intention), and already active (action). The associations between background factors and the presence/absence of health intentions and behaviours were assessed using logistic regression analysis. Of the participants, 35.4%, 37.7%, and 26.9% belonged to the no intention, intention, and action groups, respectively. Multivariate analysis revealed that the factors associated with health intentions were being young, being female, longer duration of education, higher body mass index and abdominal circumference, diabetes, and dyslipidaemia. The factors associated with health behaviours were being older and male, not consuming alcohol, not smoking, performing daily exercise, and having diabetes. These results indicate that health guidance considering background factors, including age, gender, education, and comorbidities, may be useful for effectively promoting health intentions and health behaviours in the Japanese population.