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1.
Dig Dis Sci ; 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34973148

RESUMO

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy is technically difficult. Extensive training is required to develop the ability to perform this procedure. AIMS: To investigate the learning curve of single-balloon-assisted enteroscopy ERCP (SBE-ERCP). METHODS: We conducted a retrospective, observational case series at a single center. We evaluated the SBE-ERCP procedures between April 2011 and February 2021. The main outcomes were the rate of reaching the target site and the success rate of the entire procedure. These parameters were additionally expressed as a learning curve. RESULTS: A total of 687 SBE-ERCP procedures were analyzed. The learning curve was analyzed in blocks of 10 cases. In this study, seven endoscopists, experts in conventional ERCP, were included. The overall SBE-ERCP procedural success rate was 92.2% (634/687 cases). Combining all data from individual endoscopists' evaluation periods, the insertion and success rates of the SBE-ERCP procedures gradually increased with increased experience performing SBE-ERCP. The insertion success rates for the number of SBE-ERCP cases (< 20, 21-30, > 30) were 82.9%, 92.9%, and 94.3%, respectively; the procedure success rates were 74.3%, 81.4%, and 92.9%, respectively. The endoscopists who had performed > 30 SBE-ERCP cases had a success rate of ≥ 90%. CONCLUSIONS: Our results suggest that performing > 30 cases is one of the targets for conventional ERCP experts to become competent in performing SBE-ERCP in patients with a surgically altered anatomy.

2.
Sensors (Basel) ; 22(1)2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35009935

RESUMO

Recently, wet-bulb globe temperature (WBGT) has attracted a lot of attention as a useful index for measuring heat strokes even when core body temperature cannot be available for the prevention. However, because the WBGT is only valid in the vicinity of the WBGT meter, the actual ambient heat could be different even in the same room owing to ventilation, clothes, and body size, especially in hot specific occupational environments. To realize reliable heat stroke prevention in hot working places, we proposed a new personalized vital sign index, which is combined with several types of vital data, including the personalized heat strain temperature (pHST) index based on the temperature/humidity measurement to adjust the WBGT at the individual level. In this study, a wearable device was equipped with the proposed pHST meter, a heart rate monitor, and an accelerometer. Additionally, supervised machine learning based on the proposed personalized vital index was introduced to improve the prevention accuracy. Our developed system with the proposed vital sign index achieved a prevention accuracy of 85.2% in a hot occupational experiment in the summer season, where the true positive rate and true negative rate were 96.3% and 83.7%, respectively.


Assuntos
Transtornos de Estresse por Calor , Golpe de Calor , Temperatura Corporal , Temperatura Alta , Humanos , Aprendizado de Máquina Supervisionado
3.
Metabolism ; 126: 154911, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34648769

RESUMO

BACKGROUND: A significant proportion of the non-alcoholic fatty liver disease (NAFLD) population is non-obese. Prior studies reporting the severity of NAFLD amongst non-obese patients were heterogenous. Our study, using data from the largest biopsy-proven NAFLD international registry within Asia, aims to characterize the demographic, metabolic and histological differences between non-obese and obese NAFLD patients. METHODS: 1812 biopsy-proven NAFLD patients across nine countries in Asia assessed between 2006 and 2019 were pooled into a curated clinical registry. Demographic, metabolic and histological differences between non-obese and obese NAFLD patients were evaluated. The performance of Fibrosis-4 index for liver fibrosis (FIB-4) and NAFLD fibrosis score (NFS) to identify advanced liver disease across the varying obesity subgroups was compared. A random forest analysis was performed to identify novel predictors of fibrosis and steatohepatitis in non-obese patients. FINDINGS: One-fifth (21.6%) of NAFLD patients were non-obese. Non-obese NAFLD patients had lower proportions of NASH (50.5% vs 56.5%, p = 0.033) and advanced fibrosis (14.0% vs 18.7%, p = 0.033). Metabolic syndrome in non-obese individuals was associated with NASH (OR 1.59, 95% CI 1.01-2.54, p = 0.047) and advanced fibrosis (OR 1.88, 95% CI 0.99-3.54, p = 0.051). FIB-4 performed better than the NFS score (AUROC 81.5% vs 73.7%, p < 0.001) when classifying patients with F2-4 fibrosis amongst non-obese NAFLD patients. Haemoglobin, GGT, waist circumference and cholesterol are additional variables found on random forest analysis useful for identifying non-obese NAFLD patients with advanced liver disease. CONCLUSION: A substantial proportion of non-obese NAFLD patients has NASH or advanced fibrosis. FIB-4, compared to NFS better identifies non-obese NAFLD patients with advanced liver disease. Serum GGT, cholesterol, haemoglobin and waist circumference, which are neither components of NFS nor FIB-4, are important biomarkers for advanced liver disease in non-obese patients.


Assuntos
Cirrose Hepática/patologia , Fígado/patologia , Síndrome Metabólica/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/patologia , Adulto , Ásia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos
4.
Sci Rep ; 11(1): 23719, 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34887459

RESUMO

Fusobacterium nucleatum is associated with the progression of colorectal cancer. Thus, the possibility of preventing colorectal cancer or its progression by targeting F. nucleatum has been explored. As F. nucleatum is associated with periodontitis, we analysed whether treating periodontitis could influence F. nucleatum abundance in the colon. Patients with colorectal tumours who underwent colonoscopy were recruited. Patients diagnosed with periodontitis by a dentist were treated for approximately 3 months. Endoscopic resection of colorectal tumours was performed after periodontitis treatment, and resected tumours were pathologically classified as high-(HGD) or low-grade dysplasia (LGD). Saliva and stool samples were collected before and after the treatment. Of the 58 patients with colorectal tumours, 31 were included in the study, 16 showed improvement in periodontitis, and 11 showed no improvement. Stool F. nucleatum levels before treatment were significantly lower in the LGD group than in the HGD group. A significant decrease in faecal F. nucleatum levels was observed in patients who underwent successful treatment but not in those whose treatment failed. Salivary F. nucleatum levels were not altered in patients despite periodontal treatment. Thus, successful periodontitis treatment reduces stool F. nucleatum levels and may aid research on periodontitis and suppression of colorectal cancer development.

5.
Gastroenterol Res Pract ; 2021: 5534687, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34887919

RESUMO

Background: In the 2010s, medications with new mechanisms were introduced in Japan for the treatment of chronic idiopathic constipation (CIC). A few systematic reviews have compared medications' relative efficacy, but the reviews included studies on patients from various races, even though the mechanism of CIC is considered to differ between races. The aim of this study was to use a systematic review and network meta-analysis to compare the relative efficacy of these medications in Japanese patients. Methods: We conducted a meta-analysis and report it here according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We identified studies by searching MEDLINE (via the PubMed interface) and the Cochrane Library and ICHUSHI databases and included randomized clinical trials that compared medications for CIC with placebo in Japanese adults. Two reviewers independently screened and assessed articles, abstracted data, and assessed the risk of bias. We pooled data by random-effects meta-analyses and also performed a Bayesian network meta-analysis to indirectly compare data. Results: The present systematic review and meta-analyses included 1460 patients in 6 randomized clinical trials: 2 on linaclotide, 3 on elobixibat, 2 on lubiprostone, and 1 on lactulose. The results of direct comparisons showed that linaclotide, elobixibat, and lubiprostone were superior to placebo in the change of spontaneous bowel movements (SBMs) within 1 week: linaclotide, 1.95 (95% CI, 1.51-2.39); elobixibat, 5.69 (95% CI, 3.31-8.07); and lubiprostone, 2.41 (95% CI, 0.82-4.01). The Bayesian network meta-analysis showed consistent results. Elobixibat 10 mg was ranked first for the increase in SBMs and complete SBMs within 1 week and the time to first SBM. Lubiprostone 48 µg was ranked first for the proportion of patients with SBM within 24 hours. Conclusion: Our direct and indirect meta-analyses revealed that the new CIC medications available in Japan have equal efficacy but that elobixibat and lubiprostone are highly likely to be more efficacious.

6.
Hepatology ; 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34951726

RESUMO

BACKGROUND & AIMS: While hepatic fibrosis often affects the liver globally, the spatial distribution can be heterogeneous. This study aimed to investigate the effect of liver stiffness heterogeneity on concordance between MR elastography (MRE)-based fibrosis staging and biopsy staging in patients with nonalcoholic fatty liver disease (NAFLD). APPROACH & RESULTS: We retrospectively evaluated data from 155 NAFLD patients who underwent liver biopsy and 3T MRE and undertook a retrospective validation study of 169 NAFLD patients at three hepatology centers. Heterogeneity of stiffness was assessed by measuring the range between minimum and maximum MRE-based liver stiffness measurement (LSM). Variability of LSM was defined as the stiffness range divided by the maximum stiffness value. The cohort was divided into two groups (homogenous or heterogeneous), according to whether variability was below or above the average for the training cohort. Based on histopathology and receiver operating characteristic (ROC) analysis, optimum LSM thresholds were determined for MRE-based fibrosis staging of stage 4 (4.43 kPa, AUROC0.89) and stage 3 or greater (3.93 kPa, AUROC0.89). In total, 53 had LSM above the threshold for stage 4. Within this group, 30 had a biopsy stage of less than 4. In 86.7% of these discordant cases, the variability of LSM was classified as heterogeneous. In MRE-based LSM stage ≥ 3, 88.9% of discordant cases were classified as heterogeneous. The results of the validation cohort were similar to those of the training cohort. CONCLUSIONS: Discordance between biopsy-based and MRE-based fibrosis staging is associated with heterogeneity in LSM, as depicted with MRE.

7.
Dig Endosc ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34784076

RESUMO

OBJECTIVES: For suspected common bile duct stone (CBDS) missed on computed tomography (CT), there is no clear evidence on whether endoscopic ultrasound (EUS) or magnetic resonance cholangiopancreatography (MRCP) is the better diagnostic tool. We aimed to compare the diagnostic accuracy of EUS and MRCP for cases of missed CBDS on CT. METHODS: Patients suspected of having CBDS were enrolled and randomly allocated to the EUS or MRCP group. Upon the initial examination, those having CBDS or sludge formation underwent endoscopic retrograde cholangiopancreatography (ERCP), while those who were CBDS-negative underwent a second examination with either MRCP or EUS, which was distinct from the initial diagnostic procedure. The primary outcome was diagnostic accuracy, and the secondary outcomes were diagnostic ability, detection rate and characteristics of CBDS in the second examination, and the frequency of adverse events. RESULTS: Between April 2019 and January 2021, 50 patients were enrolled in the study. The accuracy was 92.3% for EUS and 68.4% for MRCP (P = 0.055). EUS showed 100% sensitivity, 88.2% specificity, 81.8% positive predictive value, and 100% negative predictive value, and MRCP showed 33.3% sensitivity, 84.6% specificity, 50% positive predictive value, and 73.3% negative predictive value. The CBDS detection rate in the second examination was 0% for MRCP after a negative EUS and 35.7% for EUS after a negative MRCP (P = 0.041). No adverse events occurred in any of the patients. CONCLUSIONS: EUS may be a superior diagnostic tool compared to MRCP for the detection of CBDS that are undetected on CT. (UMIN000036357).

8.
Front Endocrinol (Lausanne) ; 12: 770986, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777261

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. It occurs with a prevalence of up to 25%, of which 10-20% cases progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. The histopathology of NASH is characterized by neutrophilic infiltration, and endotoxins from gram-negative rods have been postulated as a contributing factor. Elevations in endotoxin levels in the blood can be classified as intestinal and hepatic factors. In recent years, leaky gut syndrome, which is characterized by impaired intestinal barrier function, has become a significant issue. A leaky gut may prompt intestinal bacteria dysbiosis and increase the amount of endotoxin that enters the liver from the portal vein. These contribute to persistent chronic inflammation and progressive liver damage. In addition, hepatic factors suggest that liver damage can be induced by low-dose endotoxins, which does not occur in healthy individuals. In particular, increased expression of CD14, an endotoxin co-receptor in the liver, may result in leptin-induced endotoxin hyper-responsiveness in obese individuals. Thus, elevated blood endotoxin levels contribute to the progression of NASH. The current therapeutic targets for NASH treat steatosis and liver inflammation and fibrosis. While many clinical trials are underway, no studies have been performed on therapeutic agents that target the intestinal barrier. Recently, a randomized placebo-controlled trial examined the role of the intestinal barrier in patients with NAFLD. To our knowledge, this study was the first of its kind and study suggested that the intestinal barrier may be a novel target in the future treatment of NAFLD.

9.
Dig Dis ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34808618

RESUMO

BACKGROUND: Data regarding the influence of patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism for patients with liver cirrhosis (LC) are scarce. OBJECTIVE: This study assesses the role of the PNPLA3 polymorphism for the development of LC and its complications by the findings of genetic examinations. METHODS: Patients with LC caused by virus (n = 157), alcohol (n = 104), nonalcoholic fatty liver disease (NAFLD) (n = 106), or autoimmune disease (n = 33) and without LC (n = 128) were enrolled. LC were composed of the present and absent of complications, such as variceal bleeding, hepatic ascites, and/or hepatic encephalopathy. To assess the role of the PNPLA3 polymorphism, odds ratio (OR) for the rs738409 variant was calculated for the patients between (i) with LC and without LC in the entire cohort, and (ii) the present and absent of complications in the patients with LC. RESULTS: There was a significant difference among the patients without LC and those with alcohol, NAFLD related LC in the frequency of G alleles (p < 0.001, both). According to complications of LC, the OR for NAFLD related cirrhosis significantly increased in the presence of the two mutated alleles (OR = 3.165; p = 0.046) when the wild type was used as the reference. However, there were no significant risks for the complications in the virus and alcohol related cirrhosis unless there was a presence of G alleles. CONCLUSION: The PNPLA3 polymorphism was associated with the risk of NAFLD related LC and its complications.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34768008

RESUMO

BACKGROUND & AIMS: Ultrasound-guided attenuation parameter (UGAP) is recently developed for noninvasive evaluation of steatosis. However, reports on its usefulness in clinical practice are limited. This prospective multicenter study analyzed the diagnostic accuracy of grading steatosis with reference to magnetic resonance imaging-based proton density fat fraction (MRI-PDFF), a noninvasive method with high accuracy, in a large cohort. METHODS: Altogether, 1010 patients with chronic liver disease who underwent MRI-PDFF and UGAP were recruited and prospectively enrolled from 6 Japanese liver centers. Linearity was evaluated using intraclass correlation coefficients between MRI-PDFF and UGAP values. Bias, defined as the mean difference between MRI-PDFF and UGAP values, was assessed by Bland-Altman analysis. UGAP cutoffs for pairwise MRI-PDFF-based steatosis grade were determined using area under the receiver-operating characteristic curve (AUROC) analyses. RESULTS: UGAP values were shown to be normally distributed. However, because PDFF values were not normally distributed, they were log-transformed (MRI-logPDFF). UGAP values significantly correlated with MRI-logPDFF (intraclass correlation coefficient = 0.768). Additionally, Bland-Altman analysis showed good agreement between MRI-logPDFF and UGAP with a mean bias of 0.0002% and a narrow range of agreement (95% confidence interval [CI], -0.015 to 0.015). The AUROCs for distinguishing steatosis grade ≥1 (MRI-PDFF ≥5.2%), ≥2 (MRI-PDFF ≥11.3%), and 3 (MRI-PDFF ≥17.1%) were 0.910 (95% CI, 0.891-0.928), 0.912 (95% CI, 0.894-0.929), and 0.894 (95% CI, 0.873-0.916), respectively. CONCLUSIONS: UGAP has excellent diagnostic accuracy for grading steatosis with reference to MRI-PDFF. Additionally, UGAP has good linearity and negligible bias, suggesting that UGAP has excellent technical performance characteristics that can be widely used in clinical trials and patient care. (UMIN Clinical Trials Registry, Number: UMIN000041196).

11.
J Gastroenterol ; 56(11): 1022-1032, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34601620

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction associated fatty liver disease (MAFLD) have important associations with cardiovascular disease (CVD). The main objective of this study was to compare the frequency of incidence rate of CVD in the NAFLD or MAFLD patients utilizing a large claims database. METHODS: Using the JMDC database from April 2013 to March 2019, we retrospectively analyzed data for 1,542,688 and 2,452,949 people to estimate the relationship between CVD and NAFLD, MAFLD, respectively. RESULTS: The incidence rates of CVD were 0.97 (95% CI 0.94-1.01) and 2.82 (95% CI 2.64-3.01) per 1000 person-years in the non-NAFLD and NAFLD groups, respectively, and 1.01 (95% CI 0.98-1.03) and 2.69 (95% CI 2.55-2.83) per 1000 person-years in the non-MAFLD and MAFLD groups, respectively. The overall prevalence of hypertriglyceridemia and diabetes mellitus (DM) was 13.1, and 4.2%, respectively, in the non-NAFLD group and 63.6, and 20.2%, respectively, in the NAFLD group. The overall prevalenceof hypertriglyceridemia and DM was 13.6 and 4.3%, respectively, in the non-MAFLD group and 64.1, and 20.6%, respectively, in the MAFLD group. HRs for CVD increased with hypertriglyceridemia and DM. CONCLUSIONS: Results indicated that incident rate of CVD increased with NAFLD/MAFLD; the complication rate of DM and hypertriglyceridemia among NAFLD/MAFLD patients is high and may affect the development of CVD.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34661973

RESUMO

BACKGROUND/PURPOSE: Endoscopic transpapillary re-intervention (ETP-RI) after multiple self-expandable metallic stent (SEMS) placement for unresectable malignant hilar biliary obstruction (MHBO) is challenging, but endoscopic ultrasound-guided biliary drainage (EUS-BD) could be an alternative following failed ETP-RI. We investigated appropriate re-intervention (RI) methods in MHBO after multiple SEMS placement and evaluated RI with EUS-BD (EUS-RI) benefits following ETP-RI failure. METHODS: Patients requiring RI after multiple SEMS placement for MHBO between October 2017 and April 2021 were enrolled. Patients' characteristics, metallic-stent type, stent-placement configuration, overall survival, stent patency, re-intervention results, and re-intervention technical and clinical success rates were reviewed. RESULTS: Forty-nine patients underwent ETP-RI for MHBO. ETP-RI's technical success rate was 69.4%. Of 15 failed ETP-RI cases, all underwent EUS-RI, achieving technical and clinical success rates of 86.7% and 100%, respectively. Time to recurrent biliary obstruction (TRBO) after RI was significantly different between EUS-RI and ETP-RI (212 vs 84 days; P = .01). On multivariate analysis, EUS-RI was the only factor associated with TRBO (odds ratio: 4.48; 95% confidence interval: 1.01-19.91; P = .04). Acute pancreatitis and bile peritonitis were present in 6.1% of ETP-RI and 13.3% of EUS-RI cases, respectively; both improved conservatively. CONCLUSIONS: EUS-RI was effective and safe in difficult ETP-RI cases after multiple SEMS placement for MHBO.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34626833

RESUMO

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence worldwide. NAFLD is associated with excess risk of all-cause mortality, and its progression to nonalcoholic steatohepatitis (NASH) and fibrosis accounts for a growing proportion of cirrhosis and hepatocellular cancer and thus is a leading cause of liver transplant worldwide. Noninvasive precise methods to identify patients with NASH, and NASH with significant disease activity and fibrosis when the disease is still modifiable, are crucial. The aim of this study was to examine the clinical utility of corrected T1 (cT1) vs magnetic resonance imaging (MRI) liver fat for identification of NASH participants with nonalcoholic fatty liver disease activity score ≥4 and fibrosis (F) ≥2 (high-risk NASH). METHODS: Data from 5 clinical studies (n = 543) with participants suspected of NAFLD were pooled or used for individual participant data meta-analysis. The diagnostic accuracy of the MRI biomarkers to stratify NASH patients was determined using the area under the receiver operating characteristic curve (AUROC). RESULTS: A stepwise increase in cT1 and MRI liver fat with increased NAFLD severity was shown, and cT1 was significantly higher in NASH participants with fibrosis grade ≥2 (high-risk NASH). The diagnostic accuracy (AUROC) of cT1 to identify patients with NASH was 0.78 (95% CI, 0.74-0.82), for liver fat was 0.78 (95% CI, 0.73-0.82), and when combined with MRI liver fat was 0.82 (95% CI, 0.78-0.85). The diagnostic accuracy of cT1 to identify patients with high-risk NASH was good (AUROC, 0.78; 95% CI, 0.74-0.82), was superior to MRI liver fat (AUROC, 0.69; 95% CI, 0.64-0.74), and was not substantially improved by combining it with MRI liver fat (AUC, 0.79; 95% CI, 0.75-0.83). The meta-analysis showed similar performance to the pooled analysis for these biomarkers. CONCLUSIONS: This study shows that quantitative MRI-derived biomarkers cT1 and liver fat are suitable for identifying patients with NASH, and cT1 is a better noninvasive technology than liver fat to identify NASH patients at greatest risk of disease progression. MRI cT1 and liver fat therefore have important clinical utility to help guide the appropriate use of interventions in NAFLD and NASH clinical care pathways.

14.
Free Radic Biol Med ; 177: 391-403, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34715296

RESUMO

Non-alcoholic steatohepatitis (NASH), a severe form of non-alcoholic fatty liver disease (NAFLD), can progress to cirrhosis, hepatocellular carcinoma (HCC), and hepatic failure/liver transplantation. Indeed, NASH will soon be the leading cause of HCC and liver transplantation. Lifestyle intervention represents the cornerstone of NASH treatment, but it is difficult to sustain. However, no pharmacotherapies for NASH have been approved. Oxidative stress has been implicated as one of the key factors in the pathogenesis of NASH. Systematic reviews with meta-analyses have confirmed that vitamin E reduces transaminase activities and may resolve NASH histopathology without improving hepatic fibrosis. However, vitamin E is not recommended for the treatment of NASH in diabetes, NAFLD without liver biopsy, NASH cirrhosis, or cryptogenic cirrhosis. Nevertheless, vitamin E supplementation may improve clinical outcomes in patients with NASH and bridging fibrosis or cirrhosis. Further studies are warranted to confirm such effects of vitamin E and that it would reduce overall mortality/morbidity without increasing the incidence of cardiovascular events. Future clinical trials of the use of vitamin E in combination with other anti-fibrotic agents may demonstrate an additive or synergistic therapeutic effect. Vitamin E is the first-line pharmacotherapy for NASH, according to the consensus of global academic societies.

15.
J Gastroenterol ; 56(12): 1045-1061, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34718870

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver diseases worldwide, including in Japan. The Japanese Society of Gastroenterology (JSGE) and the Japanese Society of Hepatology (JSH) have established the Japanese NAFLD/NASH guidelines in 2014 and revised these guidelines in 2020. As described in these guidelines, weight reduction by diet and/or exercise therapy is important for the treatment of NAFLD patients. The I148M single nucleotide polymorphism (rs738409 C > G) of PNPLA3 (patatin-like phospholipase domain-containing 3 protein) is widely known to be associated with the occurrence and progression of NAFLD. In the Japanese, the ratio of PNPLA3 gene polymorphisms found is approximately 20%, which is higher than that found in Westerners. In addition, the ratio of lean NAFLD patients is also higher in Japan than in Western countries. Therefore, the method for lifestyle guidance for the NAFLD patients in Japan would be different from that for the people in Western countries. The problems in the treatment of NAFLD patients include alcohol consumption and sarcopenia. Therefore, guidelines that can help clinicians treat Japanese patients with NAFLD are needed. In this expert review, we summarize evidence-based interventions for lifestyle modification (diet, exercise, alcohol, and sarcopenia) for the treatment of patients with NAFLD, especially from Japan and Asian countries.

16.
Hepatology ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496054

RESUMO

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) patients with significant hepatic fibrosis (stage ≥ 2) are at increased risk of liver-related morbidity and are candidates for pharmacologic therapies. In this study, we compared the diagnostic accuracy of MEFIB (the combination of magnetic resonance elastography [MRE] and FIB-4) and FAST (FibroScan-AST; combined liver stiffness measurement by vibration-controlled transient elastography, controlled attenuation parameter, and aspartate aminotransferase) for detecting significant fibrosis. APPROACH AND RESULTS: This prospective cohort study included 234 consecutive NAFLD patients who underwent liver biopsy, MRE, and FibroScan at University of California San Diego [UCSD] Cohort, and an independent cohort (N=314) from Yokohama City University, Japan Cohort. The primary outcome was diagnostic accuracy for significant fibrosis (stage ≥ 2). The proportion of significant fibrosis in UCSD and Yokohama cohorts were 29.5% and 66.2%, respectively. Area under the receiver operating characteristic curve (95% confidence interval) of MEFIB (0.860 [0.81-0.91]) was significantly higher than FAST (0.757 [0.69-0.82]) in UCSD cohort (p = 0.005), with consistent results in the Yokohama cohort (AUROC: 0.899 [MEFIB] vs 0.724 [FAST], p < 0.001). When used as the rule-in criteria (MEFIB: MRE ≥ 3.3 kPa and FIB-4 ≥ 1.6, and FAST ≥ 0.67), the positive predictive value for significant fibrosis was 91.2-96.0% for MEFIB, and 74.2-89.2% for FAST. When used as the rule-out criteria (MEFIB: MRE < 3.3 kPa and FIB-4 < 1.6, and FAST ≤ 0.35), negative predictive value for significant fibrosis was 85.6-92.8% for MEFIB, and 57.8-88.3% for FAST. CONCLUSIONS: MEFIB has higher diagnostic accuracy than FAST for significant fibrosis in NAFLD, and our results support the utility of a two-step strategy for detecting significant fibrosis in NAFLD.

17.
Pain Ther ; 10(2): 1635-1648, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34581982

RESUMO

INTRODUCTION: Tapentadol has analgesic effects comparable to those of conventional opioids and is associated with fewer side effects, including gastrointestinal symptoms, drowsiness, and dizziness, than other opioids. However, the safety of tapentadol in the Japanese population remains unclear; the present multicentre study aimed to examine the safety of tapentadol and the characteristics of patients likely to discontinue this treatment owing to adverse events. METHODS: The safety of tapentadol was assessed retrospectively in patients with any type of cancer treated between August 18, 2014 and October 31, 2019 across nine institutions in Japan. Patients were examined at baseline and at the time of opioid discontinuation. Multivariate analysis was performed to identify factors associated with tapentadol discontinuation owing to adverse events. RESULTS: A total of 906 patients were included in this study, and 685 (75.6%) cases were followed up until tapentadol cessation for any reason. Among patients who discontinued treatment, 119 (17.4%) did so because of adverse events. Among adverse events associated with difficulty in taking medication, nausea was the most common cause of treatment discontinuation (4.7%), followed by drowsiness (1.8%). Multivariate analysis showed that those who were prescribed tapentadol by a palliative care physician (odds ratio [OR] 2.60, 95% confidence interval [CI] 1.36-4.99, p = 0.004), patients switching to tapentadol due to side effects from previous opioids (OR 2.19, 95% CI 1.05-4.56, p = 0.037), and patients who did not use naldemedine (OR 5.06, 95% CI 2.47-10.37, p < 0.0001) had an increased risk of treatment discontinuation owing to adverse events. CONCLUSIONS: This study presents the safety profile of tapentadol and the characteristics of patients likely to discontinue this treatment owing to adverse events in the Japanese population. Prospective controlled trials are required to evaluate the safety of tapentadol and validate the present findings. TRIAL REGISTRATION NUMBER: UMIN 000044282 (University Hospital Medical Information Network).

18.
JAMA Netw Open ; 4(9): e2126334, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34546368

RESUMO

Importance: The COVID-19 pandemic has delayed medical consultations, possibly leading to the diagnosis of gastrointestinal cancer at advanced stages. Objective: To evaluate stage at diagnosis among patients with gastrointestinal cancer in Japan before and during the COVID-19 pandemic. Design, Setting, and Participants: This retrospective cohort study included patients in a hospital-based cancer registry who were diagnosed with gastrointestinal cancer (ie, esophageal, gastric, colorectal, pancreatic, liver, and biliary tract cancers) between January 2016 and December 2020 at 2 tertiary Japanese hospitals. Exposures: The pre-COVID-19 period was defined as January 2017 to February 2020, and the COVID-19 period was defined as March 2020 to December 2020. Main Outcome and Measure: Monthly numbers of patients with newly diagnosed cancer were aggregated, classified by stage, and compared. Results: The study evaluated 5167 patients, including 4218 patients (2825 [67.0%] men; mean [SD] age, 71.3 [10.9] years) in the pre-COVID-19 period and 949 patients (607 [64.0%] men; mean [SD] age, 71.8 [10.7] years) in the COVID-19 period. Comparing the pre-COVID-19 period with the COVID-19 period, significant decreases were observed in the mean (SD) number of patients with newly diagnosed gastric cancer (30.63 [6.62] patients/month vs 22.40 [5.85] patients/month; -26.87% change; P < .001) and colorectal cancer (41.61 [6.81] patients/month vs 36.00 [6.72] patients/month; -13.47% change; P = .03). Significant decreases were also observed in the mean (SD) number of cases of stage I gastric cancer (21.55 [5.66] cases/month vs 13.90 [5.99] cases/month; -35.51% change; P < .001), stage 0 colorectal cancer (10.58 [3.36] cases/month vs 7.10 [4.10] cases/month; -32.89% change; P = .008), and stage I colorectal cancer (10.16 [3.14] cases/month vs 6.70 [2.91] cases/month; -34.04% change; P = .003). No significant increases were observed for esophageal, gastric, pancreatic, liver, or biliary tract cancers. A significant decrease was observed in the mean (SD) number of cases per month of stage II colorectal cancer (7.42 [3.06] cases/month vs 4.80 [1.75] cases/month; -35.32% change; P = .01); a significant increase was observed for the mean (SD) number of cases per month of stage III colorectal cancer (7.18 [2.85] cases/month vs 12.10 [2.42] cases/month; 68.42% change; P < .001). Conclusions and Relevance: In this cohort study of patients in a hospital-based cancer registry form Japan, significantly fewer patients were diagnosed with stage I gastric and colorectal cancers during the COVID-19 pandemic. Thus, the number of screening-detected cancers might have decreased, and colorectal cancer may have been diagnosed at more advanced stages.


Assuntos
Neoplasias do Sistema Biliar/diagnóstico , COVID-19 , Detecção Precoce de Câncer , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Pandemias , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Tardio/tendências , Feminino , Humanos , Japão , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , SARS-CoV-2
19.
Hepatol Commun ; 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34558835

RESUMO

Sodium glucose cotransporter-2 inhibitors (SGLT2is) are now widely used to treat diabetes, but their effects on nonalcoholic fatty liver disease (NAFLD) remain to be determined. We aimed to evaluate the effects of SGLT2is on the pathogenesis of NAFLD. A multicenter, randomized, controlled trial was conducted in patients with type 2 diabetes with NAFLD. The changes in glycemic control, obesity, and liver pathology were compared between participants taking ipragliflozin (50 mg/day for 72 weeks; IPR group) and participants being managed without SGLT2is, pioglitazone, glucagon-like peptide-1 analogs, or insulin (CTR group). In the IPR group (n = 25), there were significant decreases in hemoglobin A1c (HbA1c) and body mass index (BMI) during the study (HbA1c, -0.41%, P < 0.01; BMI, -1.06 kg/m2 , P < 0.01), whereas these did not change in the CTR group (n = 26). Liver pathology was evaluated in 21/25 participants in the IPR/CTR groups, and hepatic fibrosis was found in 17 (81%) and 18 (72%) participants in the IPR and CTR groups at baseline. This was ameliorated in 70.6% (12 of 17) of participants in the IPR group and 22.2 % (4 of 18) of those in the CTR group (P < 0.01). Nonalcoholic steatohepatitis (NASH) resolved in 66.7% of IPR-treated participants and 27.3% of CTR participants. None of the participants in the IPR group developed NASH, whereas 33.3% of the CTR group developed NASH. Conclusion: Long-term ipragliflozin treatment ameliorates hepatic fibrosis in patients with NAFLD. Thus, ipragliflozin might be effective for the treatment and prevention of NASH in patients with diabetes, as well as improving glycemic control and obesity. Therefore, SGLT2is may represent a therapeutic choice for patients with diabetes with NAFLD, but further larger studies are required to confirm these effects.

20.
Aliment Pharmacol Ther ; 54(10): 1263-1277, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34528723

RESUMO

BACKGROUND: Pemafibrate is a novel, selective peroxisome proliferator-activated receptor α modulator (SPPARMα). In mice, Pemafibrate improved the histological features of non-alcoholic steatohepatitis (NASH). In patients with dyslipidaemia, it improved serum alanine aminotransferase (ALT). AIMS: To evaluate the efficacy and safety of Pemafibrate in patients with high-risk, non-alcoholic fatty liver disease (NAFLD). METHODS: This double-blind, placebo-controlled, randomised multicentre, phase 2 trial randomised 118 patients (1:1) to either 0.2 mg Pemafibrate or placebo, orally, twice daily for 72 weeks. The key inclusion criteria included liver fat content of ≥10% by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF); liver stiffness of ≥2.5 kPa, by magnetic resonance elastography (MRE); and elevated ALT levels. The primary endpoint was the percentage change in MRI-PDFF from baseline to week 24. The secondary endpoints included MRE-based liver stiffness, ALT, serum liver fibrosis markers and lipid parameters. RESULTS: There was no significant difference between the groups in the primary endpoint (-5.3% vs -4.2%; treatment difference -1.0%, P = 0.85). However, MRE-based liver stiffness significantly decreased compared to placebo at week 48 (treatment difference -5.7%, P = 0.036), and was maintained at week 72 (treatment difference -6.2%, P = 0.024), with significant reduction in ALT and LDL-C. Adverse events were comparable between the treatment groups and therapy was well tolerated. CONCLUSIONS: Pemafibrate did not decrease liver fat content but had significant reduction in MRE-based liver stiffness. Pemafibrate may be a promising therapeutic agent for NAFLD/NASH, and also be a candidate for combination therapy with agents that reduce liver fat content. ClinicalTrials.gov, number: NCT03350165.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Benzoxazóis/efeitos adversos , Butiratos/uso terapêutico , Método Duplo-Cego , Humanos , Fígado , Camundongos , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , PPAR alfa
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