The impact of stigma on quality of life and liver disease burden among patients with nonalcoholic fatty liver disease.

Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL. Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p <0.0001). In multivariate analyses, experience with stigmatization or discrimination due to NAFLD was the strongest independent predictor of lower HRQL scores (beta from -5% to -8% of score range size, p <0.02). Experience with stigmatization due to obesity was associated with lower Activity, Emotional Health, Fatigue, and Worry domain scores, and being uncomfortable with the term "fatty liver disease" with lower Emotional Health scores (all p <0.05). In addition to stigma, the greatest disease burden as assessed by LDB was related to patients' self-blame for their liver disease. Conclusions: Stigmatization of patients with NAFLD, whether it is caused by obesity or NAFLD, is strongly and independently associated with a substantial impairment of their HRQL. Self-blame is an important part of disease burden among patients with NAFLD. Impact and implications: Patients with nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), may experience impaired health-related quality of life and stigmatization. Using a specifically designed survey, we found that stigmatization of patients with NAFLD, whether it is caused by obesity or the liver disease per se, is strongly and independently associated with a substantial impairment of their quality of life. Physicians treating patients with NAFLD should be aware of the profound implications of stigma, the high prevalence of self-blame in the context of this disease burden, and that providers' perception may not adequately reflect patients' perspective and experience with the disease.

The Health Care Burden of Hepatic Encephalopathy.

Hepatic encephalopathy-a common and debilitating complication of cirrhosis-results in major health care burden on both patients and caregivers through direct and indirect costs. In addition to risk of falls, inability to work and drive, patients with hepatic encephalopathy often require hospital admission (and often readmission), and many require subacute care following hospitalization. The costs and psychological impact of liver transplantation often ensue. As the prevalence of chronic liver disease increases throughout the United States, the health care burden of hepatic encephalopathy will continue to grow.

African American race does not confer an increased risk of clinical events in patients with primary sclerosing cholangitis.

BACKGROUND: The natural history of primary sclerosing cholangitis (PSC) among African Americans (AA) is not well understood. METHODS: Transplant-free survival and hepatic decompensation-free survival were assessed using a retrospective research registry from 16 centers throughout North America. Patients with PSC alive without liver transplantation after 2008 were included. Diagnostic delay was defined from the first abnormal liver test to the first abnormal cholangiogram/liver biopsy. Socioeconomic status was imputed by the Zip code. RESULTS: Among 850 patients, 661 (77.8%) were non-Hispanic Whites (NHWs), and 85 (10.0%) were AA. There were no significant differences by race in age at diagnosis, sex, or PSC type. Inflammatory bowel disease was more common in NHWs (75.8% vs. 51.8% p=0.0001). The baseline (median, IQR) Amsterdam-Oxford Model score was lower in NHWs (14.3, 13.4-15.2 vs. 15.1, 14.1-15.7, p=0.002), but Mayo risk score (0.03, -0.8 to 1.1 vs. 0.02, -0.7 to 1.0, p=0.83), Model for End-stage Liver Disease (5.9, 2.8-10.7 vs. 6.4, 2.6-10.4, p=0.95), and cirrhosis (27.4% vs. 27.1%, p=0.95) did not differ. Race was not associated with hepatic decompensation, and after adjusting for clinical variables, neither race nor socioeconomic status was associated with transplant-free survival. Variables independently associated with death/liver transplant (HR, 95% CI) included age at diagnosis (1.04, 1.02-1.06, p<0.0001), total bilirubin (1.06, 1.04-1.08, p<0.0001), and albumin (0.44, 0.33-0.61, p<0.0001). AA race did not affect the performance of prognostic models. CONCLUSIONS: AA patients with PSC have a lower rate of inflammatory bowel disease but similar progression to hepatic decompensation and liver transplant/death compared to NHWs.

Real-World Safety and Effectiveness of an 8-Week Regimen of Glecaprevir/Pibrentasvir in Patients with Hepatitis C and Cirrhosis.

INTRODUCTION: In 2019, an 8-week regimen of glecaprevir/ pibrentasvir (GLE/PIB) was FDA-approved for treatment of chronic hepatitis C (HCV) in patients with cirrhosis. We used data from the Chronic Hepatitis Cohort Study (CHeCS) to evaluate treatment response and adverse events among patients with HCV and cirrhosis under routine clinical care. METHODS: Using an intention-to-treat (ITT)/modified ITT (mITT) approach, endpoints were (1) sustained virological response (SVR) at 12 weeks (SVR12) post-treatment; and (2) adverse events (AEs)/serious AEs during treatment. Patients with cirrhosis from two CHeCS sites were included if they were prescribed GLE/PIB from August 2017 to June 2020. Detailed treatment and clinical data were collected. Patient baseline characteristics were described with mean/standard deviation (std) for continuous variables, and proportions for categorical variables. Analyses were propensity score adjusted. The final model retained variables that were significant with p value < 0.05. RESULTS: The ITT sample included 166 patients, with 43, 116, and 7 patients in the 8-week, 12-week, and > 12-week planned treatment groups. Among them, 159 had confirmed SVR (95.8%, LCL 93.2%). The mITT analysis included 160 patients after excluding 6 with unknown HCV RNA results; 159 achieved SVR (99.4%, LCL 98.3%). There were no significant differences in rates of SVR between the 8-week and 12-week regimens in either analysis, nor any association with patient characteristics. SAEs were experienced by 1 patient (2%) in the 8-week group, 7 (5%) in the 12-week group (including one death), and 2 (29%) in the > 12-week group; 4 patients (from the 12-week group) experienced serious AEs or hepatic events that were "likely attributable" to GLE/PIB treatment. CONCLUSION: An 8-week regimen of GLE/PIB is well tolerated and highly effective among US patients with HCV and cirrhosis receiving routine clinical care.

Antiviral Treatment and Response are Associated With Lower Risk of Dementia Among Hepatitis C Virus-Infected Patients.

OBJECTIVE: Eradication of hepatitis C virus (HCV) infection has been linked with improvement in neurocognitive function, but few studies have evaluated the effect of antiviral treatment/ response on risk of dementia. Using data from the Chronic Hepatitis Cohort Study (CHeCS), we investigated how antiviral therapy impacts the risk of developing dementia among patients with HCV. METHODS: A total of 17,485 HCV patients were followed until incidence of dementia, death, or last follow-up. We used an extended landmark modeling approach, which included time-varying covariates and propensity score justification for treatment selection bias, as well as generalized estimating equations (GEE) with a link function as multinominal distribution for a discrete time-to-event data. Death was considered a competing risk. RESULTS: After 15 years of follow-up, 342 patients were diagnosed with incident dementia. Patients who achieved sustained virological response (SVR) had significantly decreased risk of dementia compared to untreated patients, with hazard ratios (HRs) of 0.32 (95% CI 0.22-0.46) among patients who received direct-acting antiviral (DAA) treatment and 0.41 (95% CI 0.26-0.60) for interferon-based (IFN) treatment. Risk reduction remained even when patients failed antiviral treatment (HR 0.38, 95% CI 0.38-0.51). Patients with cirrhosis, Black/African American patients, and those without private insurance were at significantly higher risk of dementia. CONCLUSION: Antiviral treatment independently reduced the risk of dementia among HCV patients, regardless of cirrhosis. Our findings support the importance of initiation antiviral therapy in chronic HCV-infected patients.

Metastatic Neuroendocrine Neoplasms to the Pancreas: Two Unusual Cases and a Review of the Literature.

Neuroendocrine tumor metastases to the pancreas are rare, and they share substantial overlap with the significantly more common primary pancreatic neuroendocrine neoplasms, representing a potential diagnostic pitfall. Elucidating whether a neuroendocrine tumor within the pancreas is a primary neoplasm versus a metastasis has significant prognostic and treatment implications. Correlation with clinical history and imaging as well as incorporating an appropriate immunohistochemical panel are essential to establish the correct diagnosis. Herein, we present 2 rare neuroendocrine tumors that metastasized to the pancreas: a medullary thyroid carcinoma and an atypical carcinoid tumor of lung origin. We also provide a brief review of the literature.

Persistent pruritus associated with worse quality of life in patients with chronic hepatitis.

INTRODUCTION: Prevalence and severity of pruritus among US patients with chronic hepatitis B and C (HBV, HCV) are not well-documented. Chronic Hepatitis Cohort Study (CHeCS) patients were surveyed to examine pruritus prevalence and impact on quality of life (QoL). METHODS: Patients who reported experiencing pruritus ≥3 on a Numeric Rating Scale (NRS) within the past 30 days were invited to participate in a 6-month study using the SF-36 questionnaire. General regression (univariate followed by multivariable modelling) was used to analyse pruritus intensity and eight QoL dimensions. RESULTS: Among 1654 patients (HBV = 358, HCV = 1296, HBV/HCV = 6), pruritus prevalence was significantly higher among patients with HCV than those with HBV (44% vs. 35%; p < .05). One hundred and twenty-three patients (21 HBV and 102 HCV) participated in the QoL study (72% ≥60 years; 50% men; 25% Black; 37% with cirrhosis; 66% had BMI > 25). Mean NRS was 4.9-5.3. QoL responses for social functioning and emotional well-being were higher (70-72 points) than responses for energy/fatigue (50-51). Antiviral treatment rates were higher in HCV (92%, SVR 99%) than HBV (71% ever, 43% ongoing). Multivariable analyses showed no significant effect of hepatitis type or antiviral treatments on itch. Antihistamines were associated with severe itch. Higher NRS was associated with significantly reduced QoL. Each unit increase in NRS was associated with a 2-3 unit decline in emotional well-being, general health, physical function, energy/fatigue, social functioning and emotional health. CONCLUSION: Pruritus negatively affects many viral hepatitis patients, regardless of antiviral treatment status. Improved treatment options are needed to address its impact on QoL.

Open-label, clinical trial extension: Two-year safety and efficacy results of seladelpar in patients with primary biliary cholangitis.

BACKGROUND: Seladelpar is a potent and selective peroxisome proliferator-activated receptor-δ agonist that targets multiple cell types involved in primary biliary cholangitis (PBC), leading to anti-cholestatic, anti-inflammatory and anti-pruritic effects. AIMS: To evaluate the long-term safety and efficacy of seladelpar in patients with PBC. METHODS: In an open-label, international, long-term extension study, patients with PBC completing seladelpar lead-in studies continued treatment. Seladelpar was taken orally once daily at doses of 5 or 10 mg with dose adjustment permitted for safety or tolerability. The primary analysis was for safety and the secondary efficacy analysis examined biochemical markers of cholestasis and liver injury. The study was terminated early due to the unexpected histological findings in a concurrent study for non-alcoholic steatohepatitis, which were subsequently found to predate treatment. Safety and efficacy data were analysed through 2 years. RESULTS: There were no serious treatment-related adverse events observed among 106 patients treated with seladelpar for up to 2 years. There were four discontinuations for safety, one possibly related to seladelpar. Among 53 patients who completed 2 years of seladelpar, response rates increased from years 1 to 2 for the composite endpoint (alkaline phosphatase [ALP] <1.67 × ULN, ≥15% decrease in ALP, and total bilirubin ≤ULN) and ALP normalisation from 66% to 79% and from 26% to 42%, respectively. In those with elevated bilirubin at baseline, 43% achieved normalisation at year 2. CONCLUSIONS: Seladelpar was safe, and markedly improved biochemical markers of cholestasis and liver injury in patients with PBC. These effects were maintained or improved throughout the second year. CLINICALTRIALS: gov: NCT03301506; Clinicaltrialsregister.eu: 2017-003910-16.

Snare Tip Soft Coagulation vs Argon Plasma Coagulation vs No Margin Treatment After Large Nonpedunculated Colorectal Polyp Resection: a Randomized Trial.

BACKGROUND & AIMS: Thermal treatment of the defect margin after endoscopic mucosal resection (EMR) of large nonpedunculated colorectal lesions reduces the recurrence rate. Both snare tip soft coagulation (STSC) and argon plasma coagulation (APC) have been used for thermal margin treatment, but there are few data directly comparing STSC with APC for this indication. METHODS: We performed a randomized 3-arm trial in 9 US centers comparing STSC with APC with no margin treatment (control) of defects after EMR of colorectal nonpedunculated lesions ≥15 mm. The primary end point was the presence of residual lesion at first follow-up. RESULTS: There were 384 patients and 414 lesions randomized, and 308 patients (80.2%) with 328 lesions completed ≥1 follow-up. The proportion of lesions with residual polyp at first follow-up was 4.6% with STSC, 9.3% with APC, and 21.4% with control subjects (no margin treatment). The odds of residual polyp at first follow-up were lower for STSC and APC when compared with control subjects (P = .001 and P = .01, respectively). The difference in odds was not significant between STSC and APC. STSC took less time to apply than APC (median, 3.35 vs 4.08 minutes; P = .019). Adverse event rates were low, with no difference between arms. CONCLUSIONS: In a randomized trial STSC and APC were each superior to no thermal margin treatment after EMR. STSC was faster to apply than APC. Because STSC also results in lower cost and plastic waste than APC (APC requires an additional device), our study supports STSC as the preferred thermal margin treatment after colorectal EMR. (Clinicaltrials.gov, Number NCT03654209.).

Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers. METHODS: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey. RESULTS: Surveys were completed by 1,976 patients with NAFLD across 23 countries (51% Middle East/North Africa [MENA], 19% Europe, 17% USA, 8% Southeast Asia, 5% South Asia) and 825 healthcare providers (67% gastroenterologists/hepatologists) across 25 countries (39% MENA, 28% Southeast Asia, 22% USA, 6% South Asia, 3% Europe). Of all patients, 48% ever disclosed having NAFLD/NASH to family/friends; the most commonly used term was "fatty liver" (88% at least sometimes); "metabolic disease" or "MAFLD" were rarely used (never by >84%). Regarding various perceptions of diagnostic terms by patients, there were no substantial differences between "NAFLD", "fatty liver disease (FLD)", "NASH", or "MAFLD". The most popular response was being neither comfortable nor uncomfortable with either term (56%-71%), with slightly greater discomfort with "FLD" among the US and South Asian patients (47-52% uncomfortable). Although 26% of patients reported stigma related to overweight/obesity, only 8% reported a history of stigmatization or discrimination due to NAFLD. Among providers, 38% believed that the term "fatty" was stigmatizing, while 34% believed that "nonalcoholic" was stigmatizing, more commonly in MENA (43%); 42% providers (gastroenterologists/hepatologists 45% vs. 37% other specialties, p = 0.03) believed that the name change to metabolic dysfunction-associated steatotic liver disease (or MASLD) might reduce stigma. Regarding the new nomenclature, the percentage of providers reporting "steatotic liver disease" as stigmatizing was low (14%). CONCLUSIONS: The perception of NAFLD stigma varies among patients, providers, geographic locations and sub-specialties. IMPACT AND IMPLICATIONS: Over the past decades, efforts have been made to change the nomenclature of nonalcoholic fatty liver disease (NAFLD) to better align with its underlying pathogenetic pathways and remove any potential stigma associated with the name. Given the paucity of data related to stigma in NAFLD, we undertook this global comprehensive survey to assess stigma in NAFLD among patients and providers from around the world. We found there is a disconnect between physicians and patients related to stigma and related nomenclature. With this knowledge, educational programs can be developed to better target stigma in NAFLD among all stakeholders and to provide a better opportunity for the new nomenclature to address the issues of stigma.

Alcohol-related hepatitis admissions decline in 2021 after a 2020 surge attributed to the COVID-19 pandemic.

OBJECTIVE: We previously investigated the impact of the COVID-19 pandemic on alcohol-related liver disease (ARLD), finding that admissions for alcoholic hepatitis (AH) increased by 50% in the summer of 2020 compared to the same period in 2016-2019. We have now expanded our analysis to consider full years' data and evaluate how rates changed in 2021. We also sought to identify factors associated with ICU admissions, need for dialysis, liver transplant evaluations, and death. METHODS: Using retrospective data, we identified patients admitted to our four Detroit, Michigan area hospitals for acute ARLD for three periods pre-COVID (2016-February 2020), early COVID (June-December 2020), and late COVID (2021). Clustered logistic regression was performed to study rates of AH admissions across the three eras, where the patient was defined as the cluster and the analysis accounted for multiple encounters per cluster. A similar regression approach, univariate followed by multivariable analysis, was also used to study associations between patient characteristics and outcomes during hospitalization for AH. RESULTS: AH-related admissions declined significantly from the early COVID to late COVID eras (OR 0.68, 95% CL 0.52, 0.88), returning to levels similar to that of the pre- COVID period (OR 1.18, 95% CL 0.96, 1.47). In multivariable analysis, baseline MELD score was associated with ICU admission, initiation of dialysis, transplant evaluation, and death while hospitalized for AH. Female patients were at almost twice the risk of death during admission compared to male patients (aOR 1.81, 95% CL 1.1, 2.98). Increasing age was associated with slightly lower odds of transplant (aOR 0.97, 95% CL 0.94, 1) and higher odds of death (aOR 1.03, 95% CL 1.01. 1.06). CONCLUSION: After a spike in AH-related admissions during the first summer of the COVID-19 pandemic, rates declined significantly in 2021, returning to pre-pandemic levels.

Dynamic risk assessment for hepatocellular carcinoma in patients with chronic hepatitis C.

Chronic hepatitis C (HCV) is a primary cause of hepatocellular carcinoma (HCC). Although antiviral treatment reduces risk of HCC, few studies quantify the impact of treatment on long-term risk in the era of direct-acting antivirals (DAA). Using data from the Chronic Hepatitis Cohort Study, we evaluated the impact of treatment type (DAA, interferon-based [IFN], or none) and outcome (sustained virological response [SVR] or treatment failure [TF]) on risk of HCC. We then developed and validated a predictive risk model. 17186 HCV patients were followed until HCC, death or last follow-up. We used extended landmark modelling, with time-varying covariates and propensity score justification and generalized estimating equations with a link function for discrete time-to-event data. Death was considered a competing risk. We observed 586 HCC cases across 104,000 interval-years of follow-up. SVR from DAA or IFN-based treatment reduced risk of HCC (aHR 0.13, 95% CI 0.08-0.20; and aHR 0.45, 95% CI 0.31-0.65); DAA SVR reduced risk more than IFN SVR (aHR 0.29, 95% CI 0.17-0.48). Independent of treatment, cirrhosis was the strongest risk factor for HCC (aHR 3.94, 95% CI 3.17-4.89 vs. no cirrhosis). Other risk factors included male sex, White race and genotype 3. Our six-variable predictive model had 'excellent' accuracy (AUROC 0.94) in independent validation. Our novel landmark interval-based model identified HCC risk factors across antiviral treatment status and interactions with cirrhosis. This model demonstrated excellent predictive accuracy in a large, racially diverse cohort of patients and could be adapted for 'real world' HCC monitoring.

Characteristics associated with receipt of treatment among patients diagnosed with chronic hepatitis C virus.

Although current guidelines recommend that nearly all patients with chronic hepatitis C virus (HCV) infection receive treatment, a substantial proportion remain untreated. We conducted an administrative claims analysis to provide real-world data on treatment patterns and characteristics of treated versus untreated patients among individuals with HCV in the United States. Adults with an HCV diagnosis from 01 July 2016 through 30 September 2020 and continuous health plan enrolment for 12 months before and ≥1 month after the diagnosis date were identified in the Optum Research Database. Descriptive and multivariable analyses were conducted to evaluate the association between patient characteristics and the rate of treatment. Of 24,374 patients identified with HCV, only 30% initiated treatment during follow-up. Factors associated with increased rate of treatment included younger age versus age 75+ (hazard ratio [HR] 1.50-1.83 depending on age group), commercial versus Medicare insurance (HR 1.32), and diagnosis by a specialist versus a primary care physician (HR 2.56 and 2.62 for gastroenterology and infectious disease or hepatology, respectively) (p < .01 for all). Several baseline comorbidities were associated with decreased rate of treatment, including psychiatric disorders (HR 0.87), drug use disorders (HR 0.85) and cirrhosis (HR 0.42) (p < .01 for all). These findings highlight existing HCV treatment inequities, particularly among older patients and those with psychiatric disorders, substance use disorders or chronic comorbidities. Targeted efforts to increase treatment uptake in these populations could mitigate a considerable future burden of HCV-related morbidity, mortality and healthcare costs.

Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study.

BACKGROUND AND AIMS: ENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA). APPROACH AND RESULTS: Patients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) < 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) ( p < 0.0001). ALP normalization occurred in 5.4% ( p =0.08) and 27.3% ( p < 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: -3.14 ( p =0.02); placebo: -1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% ( p =0.0008); 10 mg: 16.7% ( p =0.03); placebo: 4%]. There were no serious treatment-related adverse events. CONCLUSIONS: Patients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated.

Through-the-scope suture closure of nonampullary duodenal endoscopic mucosal resection defects: a retrospective multicenter cohort study.

BACKGROUND: Delayed bleeding is among the most common adverse events associated with endoscopic mucosal resection (EMR) of nonampullary duodenal polyps. We evaluated the rate of delayed bleeding and complete defect closure using a novel through-the-scope (TTS) suturing system for the closure of duodenal EMR defects. METHODS: We reviewed the electronic medical records of patients who underwent EMR for nonampullary duodenal polyps of ≥ 10 mm and prophylactic defect closure with TTS suturing between March 2021 and May 2022 at centers in the USA. We evaluated the rates of delayed bleeding and complete defect closure. RESULTS: 36 nonconsecutive patients (61 % women; mean [SD] age, 65 [12] years) underwent EMR of ≥ 10-mm duodenal polyps followed by attempted defect closure with TTS suturing. The mean (SD) lesion size was 29 (19) mm, defect size was 37 (25) mm; eight polyps (22 %) involved > 50 % of the lumen circumference. Complete closure was achieved in all cases (78 % with TTS suturing alone), using a median of one TTS suturing kit. There were no cases of delayed bleeding and no adverse events attributed to application of the TTS suturing device. CONCLUSION: Prophylactic closure of nonampullary duodenal EMR defects using TTS suturing resulted in a high rate of complete closure and no delayed bleeding events.

Impact of hepatitis C treatment status on risk of Parkinson's disease and secondary parkinsonism in the era of direct-acting antivirals.

Research suggests a possible link between chronic infection with hepatitis C virus (HCV) and the development of Parkinson's Disease (PD) and secondary Parkinsonism (PKM). We investigated the impact of antiviral treatment status (untreated, interferon [IFN] treated, direct-acting antiviral [DAA] treated) and outcome (treatment failure [TF] or sustained virological response [SVR]) on risk of PD/PKM among patients with HCV. Using data from the Chronic Hepatitis Cohort Study (CHeCS), we applied a discrete time-to-event approach with PD/PKM as the outcome. We performed univariate followed by a multivariable modelling that used time-varying covariates, propensity scores to adjust for potential treatment selection bias and death as a competing risk. Among 17,199 confirmed HCV patients, we observed 54 incident cases of PD/PKM during a mean follow-up period of 17 years; 3753 patients died during follow-up. There was no significant association between treatment status/outcome and risk of PD/PKM. Type 2 diabetes tripled risk (hazard ratio [HR] 3.05; 95% CI 1.75-5.32; p < .0001) and presence of cirrhosis doubled risk of PD/PKM (HR 2.13, 95% CI 1.31-3.47). BMI >30 was associated with roughly 50% lower risk of PD/PKM than BMI <25 (HR 0.43; 0.22-0.84; p = .0138). After adjustment for treatment selection bias, we did not observe a significant association between HCV patients' antiviral treatment status/outcome on risk of PD/PKM. Several clinical risk factors-diabetes, cirrhosis and BMI-were associated with PD/PKM.

Novel through-the-scope suture closure of colonic EMR defects (with video).

BACKGROUND AND AIMS: Large colon polyps removed by EMR can be complicated by delayed bleeding. Prophylactic defect clip closure can reduce post-EMR bleeding. Larger defects can be challenging to close using through-the-scope clips (TTSCs), and proximal defects are difficult to reach using over-the-scope techniques. A novel, through-the-scope suturing (TTSS) device allows direct closure of mucosal defects without scope withdrawal. The goal of this study was to evaluate the rate of delayed bleeding after the closure of large colon polyp EMR sites with TTSS. METHODS: A multicenter retrospective cohort study was performed involving 13 centers. All defect closure by TTSS after EMR of colon polyps ≥2 cm from January 2021 to February 2022 were included. The primary outcome was rate of delayed bleeding. RESULTS: A total of 94 patients (52% female; mean age, 65 years) underwent EMR of predominantly right-sided (n = 62 [66%]) colon polyps (median size, 35 mm; interquartile range, 30-40 mm) followed by defect closure with TTSS during the study period. All defects were successfully closed with TTSS alone (n = 62 [66%]) or with TTSS and TTSCs (n = 32 [34%]), using a median of 1 (interquartile range, 1-1) TTSS system. Delayed bleeding occurred in 3 patients (3.2%), with 2 requiring repeated endoscopic evaluation/treatment (moderate). CONCLUSION: TTSS alone or with TTSCs was effective in achieving complete closure of all post-EMR defects, despite a large lesion size. After TTSS closure with or without adjunctive devices, delayed bleeding was seen in 3.2% of cases. Further prospective studies are needed to validate these findings before wider adoption of TTSS for large polypectomy closure.

Hepatic Manifestations of Systemic Diseases.

In addition to being the primary target of infections such as viral hepatitis, the liver may also be affected by systemic disease. These include bacterial, mycotic, and viral infections, as well as autoimmune and infiltrative diseases. These conditions generally manifest as abnormal liver biochemistries, often with a cholestatic profile, and may present with additional signs/symptoms such as jaundice and fever. A high index of suspicion and familiarity with potential causal entities is necessary to guide appropriate testing, diagnosis, and treatment.