Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: An international registry study

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The 2nd edition of consensus statements for the diagnosis and management of intestinal Behçet’s disease: indication of anti-TNFα monoclonal antibodies

Background

Clinical evidence regarding intestinal Behçet’s disease (BD) management is lacking and intestinal lesions are a poor prognostic factor. In 2007, the Japan consensus statement for diagnosis and management of intestinal BD was developed. Recently, the efficacy of anti-tumor necrosis factor (TNF)α monoclonal antibodies (mAbs), and infliximab (IFX) was reported and adalimumab (ADA) was approved for intestinal BD in Japan. This study renewed consensus-based practice guidelines for diagnosis and treatment of intestinal BD focusing on the indication of anti-TNFα mAbs.

Methods

An expert panel of Japanese gastroenterology and rheumatology specialists was involved. Clinical statements for ratings were extracted from the literature, a professional group survey, and by an expert panel discussion, which rated clinical statements on a nine-point scale. After the first round of ratings, a panelist meeting discussed areas of disagreement and clarified areas of uncertainty. The list of clinical statements was revised after the panelist meeting and a second round of ratings was conducted.

Results

Fifteen relevant articles were selected. Based on the first edition consensus statement, improved clinical statements regarding indications for anti-TNFα mAbs use were developed. After a two-round modified Delphi approach, the second edition of consensus statements was finalized.

Conclusions

In addition to standard therapies in the first edition, anti-TNFα mAbs (ADA and IFX) should be considered as a standard therapy for intestinal BD. Colchicines, thalidomide, other pharmacological therapy, endoscopic therapy, and leukocytapheresis were deemed experimental therapies.     

Noninvasive methods to assess liver disease in patients with hepatitis B or C

The prognosis and management of patients with chronic viral hepatitis B and C depend on the amount and progression of liver fibrosis and the risk for cirrhosis. Liver biopsy, traditionally considered to be the reference standard for staging of fibrosis, has been challenged over the past decade by the development of noninvasive methodologies. These methods rely on distinct but complementary approaches: a biologic approach, which quantifies serum levels of biomarkers of fibrosis, and a physical approach, which measures liver stiffness by ultrasound or magnetic resonance elastography. Noninvasive methods were initially studied and validated in patients with chronic hepatitis C but are now used increasingly for patients with hepatitis B, reducing the need for liver biopsy analysis. We review the advantages and limitations of the noninvasive methods used to manage patients with chronic viral hepatitis B or C infection.     

The contribution of physical inactivity and socioeconomic factors to type 2 diabetes in Nepal: A structural equation modelling analysis

Background and aimType 2 diabetes mellitus (T2DM) is emerging as a significant public health challenge in Nepal. Behavioural, social and economic changes are likely to play a part in the rise of this chronic disease, as they are in many developing countries. A better understanding of the relationship between physical activity (PA), socioeconomic factors and T2DM can inform the design of prevention programs. This study aimed to identify the path relationships between PA, socioeconomic position, anthropometric and metabolic variables and T2DM.Methods and resultsThis study analysed data from 1977 Nepalese adults aged 40–69 years from the cross-sectional WHO STEPS survey undertaken in 2013. The latent variable “PA” was created using the information on domains of PA while the latent variable “socioeconomic position” was created using the variables education, occupation and ethnicity. Participants’ fasting blood glucose was used to determine their diabetes status. Structural equation modelling was conducted, and correlations and adjusted regression coefficients are reported.Individuals with higher education, in paid employment and from advantaged ethnic groups were more likely to have T2DM. Waist circumference, triglycerides and hypertension were found to have a statistically significant positive direct effect on T2DM. PA had indirect effects on T2DM, mediated by waist circumference. The indirect effects of socioeconomic position on T2DM were mediated by body mass index, waist circumference, triglycerides and total cholesterol.ConclusionAmong Nepalese adults, higher socioeconomic position had a significant direct effect on T2DM, while both PA and higher socioeconomic position had significant indirect effects. Policies and programs to address T2DM in Nepal should address the factors contributing to unhealthy weight status, particularly among those of higher socioeconomic status.     

Body shape trajectories and mortality in the Seguimiento universidad de Navarra (SUN) cohort

Background and aimThe aim of this study was to assess the association between body shape trajectories and all-cause mortality in a Mediterranean cohort.Methods and resultsUsing a group-based modeling approach to fit body shape trajectories from the age of 5–40 years, among 11,423 participants from the Spanish SUN cohort, we assessed the subsequent risk of all-cause mortality. To create the trajectories, we used a censored normal model as a polynomial function of age. Cox regression models adjusted for sex, age, years of university education, marital status, smoking status, package-years of smoking, and recruitment period were used to estimate the hazard ratios (HR) for mortality according to each assigned trajectory.Overall, five distinct trajectories were identified: “lean-moderate increase,” “medium-moderate increase,” “medium-stable,” “heavy-medium,” and “heavy-moderate increase.” During 106,657 person-years of follow-up, we observed 240 deaths. Compared with those who maintained a medium body shape in early and middle life (“medium-stable” trajectory), those who were heavy and had a moderate increase (“heavy-moderate increase” trajectory) showed higher mortality risk [HR = 1.91 (95% confidence interval: 1.14–3.21)]. In contrast, participants who were heavy in early life, and then decreased their body shape during early adulthood, and maintained a medium body shape throughout middle adulthood (“heavy-medium”), tend to exhibit lower mortality risk [HR = 0.60 (0.34–1.05)], similarly to those who were lean at childhood and had a moderate increase during adulthood (“lean-moderate increase”) [HR = 0.82 (0.58–1.15)].ConclusionA moderate increase in body shape among subjects who were already heavy at early life was associated with higher risk of mortality in a Mediterranean cohort of university graduates.     

Triglyceride to high-density lipoprotein cholesterol ratio and risk of atherosclerotic cardiovascular disease in a Chinese population

Background and aimsTriglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio may play a role in predicting cardiovascular events. We aimed to prospectively explore the association between the TG/HDL-C ratio and atherosclerotic cardiovascular disease (ASCVD), ischemic stroke, as well as coronary heart disease (CHD) in a Chinese population.Methods and resultsThis prospective cohort study included 9368 participants from four Chinese populations in the People's Republic of China–United States of America (PRC-USA) Collaborative Study of Cardiovascular and Cardiopulmonary Epidemiology. Over a follow-up period of 20 years, 624 cases of ASCVD events including 458 ischemic stroke events and 166 CHD events were recorded. The relationship between the TG/HDL-C ratio and the endpoints was evaluated through multivariate Cox proportional hazard models adjusted for potential confounding variables, including age, sex, urban or rural residence, northern or southern China, occupational type, education, physical exercise, smoking status, drinking status, body mass index, hypertension, high low-density lipoprotein cholesterol, diabetes, and antihypertensive medication use at baseline. With the lowest TG/HDL-C tertile as the reference, the middle and highest tertiles had the hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.13 (0.91, 1.40), 1.36 (1.10, 1.67) respectively for ASCVD (p for trend = 0.0028), and 1.19 (0.93, 1.54),1.47 (1.15, 1.87) respectively for ischemic stroke (p for trend = 0.0016). However, no significant association was found for CHD events.ConclusionTG/HDL-C ratio was positively associated with the risk of ASCVD and ischemic stroke events in the Chinese population.     

肝移植急性排异患者外周血Th17及调节性T细胞的特征及意义

目的 探讨肝移植术后急性排异患者外周血中Th17细胞、CD4+CD25+Foxp3+调节性T细胞(Treg)的变化特征及临床意义.方法 2011年1-9月解放军302医院肝移植研究中心收治的肝移植术后患者25例,根据移植组织穿刺活检病理结果分为急性排异组(排异组,12例)和非排斥稳定组(稳定组,13例),另选取13名健康体检者作为对照.采用流式细胞分析法检测外周血中Th17、Treg细胞占CD4+T细胞的比例,观察Th17/Treg比值变化及其与肝脏损伤的关系.结果移植术后排异组外周血中Th17占CD4+T细胞的比例(3.50％±0.86％)明显高于稳定组(2.10％±0.52％)和对照组(1.79％±0.42％,P＜0.01),稳定组和对照组比较无统计学差异(P＞0.05).排异组和稳定组患者外周血中Treg占CD4+T细胞的比例(分别为0.90％±0.25％、1.51％±0.23％)明显低于对照组(2.57％±0.79％,P＜0.01),且排异组明显低于稳定组(P＜0.05).排异组Th17/Treg比值(4.20±1.69)明显高于稳定组(1.43±0.47)及对照组(0.75±0.28,P＜0.01),且稳定组明显高于对照组(P＜0.01).Th17/Treg比值与丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、谷氨酸转氨酶(GGT)水平呈正相关(分别为r=0.5023,P=0.0105; r=0.4561,P=0.0219;r=0.4393,P=0.0280; r=0.5516,P=0.0043).结论 肝移植术后急性排异反应患者外周血中存在Th17/Treg失衡,且与肝脏损伤有一定关系.Th17/Treg失衡可能参与了肝移植术后急性排异反应的发生发展过程.     

Hepatic Phosphatidylethanolamine Methyltransferase Activity Is Decreased by Ethanol and Increased by Phosphatidylcholine

Phosphatidylethanolamine N-methyltransferase participates in the synthesis of membrane phosphatidylcholine. Its activity was reported to be decreased in patients with alcoholic cirrhosis, but it is not known whether this is a consequence of the cirrhosis or precedes it. This question was studied in a baboon model of alcohol-induced fibrosis. Phosphatidylethanolamine N-methyltransferase activity was measured in sequential percutaneous needle liver biopsies by the conversion of phosphatidylethanolamine to phosphatidylcholine, using radioactive S-adenosylmethionine as a methyl donor. Chronic alcohol consumption (1–6 years) significantly decreased hepatic phospholipid and phosphatidylcholine levels and reduced phosphatidyl-ethanolamine N-methyltransferase activity even before the development of fibrosis. These effects were prevented or attenuated by supplementing the diet with 2.8 g/1000 kcal of a preparation rich in dilinoleoyl phosphatidylcholine, a highly bioavailable phosphatidylcholine species. There were significant ( p < 0.001) correlations between phosphatidylethanolamine N-methyltransferase activity and both hepatic phosphatidylcholine ( r = 0.678) and total phospholipid ( r = 0.662).
Conclusions:

• 1. 

  Alcohol consumption diminishes phosphatidylethanolamine N-methyltransferase activity prior to the development of cirrhosis and decreases the hepatic content of its product, namely phosphatidylcholine, a key component of cell membranes. This may promote hepatic injury and possibly trigger fibrosis.
• 2. 

  Phosphatidylcholine administration ameliorates the ethanol-induced decrease in phosphatidylethanolamine N-methyltransferase activity and corrects phospholipid and phosphatidylcholine depletions, thereby possibly contributing to the protection against alcoholic liver injury.