Development and validation of a faecal immunochemical test-based model in the work-up of patients with iron deficiency anaemia.

Objective: In patients with iron deficiency anaemia (IDA), the diagnostic yield of gastroscopy and colonoscopy (bidirectional endoscopy) in detecting neoplastic lesions is low. This study aimed to develop and validate a faecal immunochemical test (FIT)-based model to optimise the work-up of patients with IDA. Methods: Outpatients with IDA were enrolled in a prospective, multicentre study from April 2016 to October 2019. One FIT was performed before bidirectional endoscopy. Significant gastrointestinal lesions were recorded and a combined model developed with variables that were independently associated with significant colorectal lesions in the multivariate analysis. The model cut-off was selected to provide a sensitivity of at least 95% for colorectal cancer (CRC) detection, and its performance was compared to different FIT cut-offs. The data set was randomly split into two groups (developed and validation cohorts). An online calculator was developed for clinical application. Results: The development and validation cohorts included 373 and 160 patients, respectively. The developed model included FIT value, age, and sex. In the development and validation cohorts, a model cut-off of 0.1375 provided a negative predictive value of 98.1 and 96.7% for CRC and 90.7 and 88.3% for significant colorectal lesions, respectively. This combined model reduced the rate of missed significant colorectal lesions compared to FIT alone and could have avoided more than one-fourth of colonoscopies. Conclusion: The FIT-based combined model developed in this study may serve as a useful diagnostic tool to triage IDA patients for early endoscopic referral, resulting in considerable reduction of unnecessary colonoscopies.

An artificial intelligence-generated model predicts 90-day survival in alcohol-associated hepatitis: A global cohort study.

BACKGROUND AND AIMS: Alcohol-associated hepatitis (AH) poses significant short-term mortality. Existing prognostic models lack precision for 90-day mortality. Utilizing artificial intelligence in a global cohort, we sought to derive and validate an enhanced prognostic model. APPROACH AND RESULTS: The Global AlcHep initiative, a retrospective study across 23 centers in 12 countries, enrolled patients with AH per National Institute for Alcohol Abuse and Alcoholism criteria. Centers were partitioned into derivation (11 centers, 860 patients) and validation cohorts (12 centers, 859 patients). Focusing on 30 and 90-day postadmission mortality, 3 artificial intelligence algorithms (Random Forest, Gradient Boosting Machines, and eXtreme Gradient Boosting) informed an ensemble model, subsequently refined through Bayesian updating, integrating the derivation cohort's average 90-day mortality with each center's approximate mortality rate to produce posttest probabilities. The ALCoholic Hepatitis Artificial INtelligence Ensemble score integrated age, gender, cirrhosis, and 9 laboratory values, with center-specific mortality rates. Mortality was 18.7% (30 d) and 27.9% (90 d) in the derivation cohort versus 21.7% and 32.5% in the validation cohort. Validation cohort 30 and 90-day AUCs were 0.811 (0.779-0.844) and 0.799 (0.769-0.830), significantly surpassing legacy models like Maddrey's Discriminant Function, Model for End-Stage Liver Disease variations, age-serum bilirubin-international normalized ratio-serum Creatinine score, Glasgow, and modified Glasgow Scores ( p < 0.001). ALCoholic Hepatitis Artificial INtelligence Ensemble score also showcased superior calibration against MELD and its variants. Steroid use improved 30-day survival for those with an ALCoholic Hepatitis Artificial INtelligence Ensemble score > 0.20 in both derivation and validation cohorts. CONCLUSIONS: Harnessing artificial intelligence within a global consortium, we pioneered a scoring system excelling over traditional models for 30 and 90-day AH mortality predictions. Beneficial for clinical trials, steroid therapy, and transplant indications, it's accessible at: https://aihepatology.shinyapps.io/ALCHAIN/ .

Prevalence and clinical impact of alcohol withdrawal syndrome in alcohol-associated hepatitis and the potential role of prophylaxis: a multinational, retrospective cohort study.

Background: The prevalence and impact of alcohol withdrawal syndrome (AWS) in patients with alcohol-associated hepatitis (AH) are unknown. In this study, we aimed to investigate the prevalence, predictors, management, and clinical impact of AWS in patients hospitalized with AH. Methods: A multinational, retrospective cohort study enrolling patients hospitalized with AH at 5 medical centres in Spain and in the USA was performed between January 1st, 2016 to January 31st, 2021. Data were retrospectively retrieved from electronic health records. Diagnosis of AWS was based on clinical criteria and use of sedatives to control AWS symptoms. The primary outcome was mortality. Multivariable models controlling for demographic variables and disease severity were performed to determine predictors of AWS (adjusted odds ratio [OR]) and the impact of AWS condition and management on clinical outcomes (adjusted hazard ratio [HR]). Findings: In total, 432 patients were included. The median MELD score at admission was 21.9 (18.3-27.3). The overall prevalence of AWS was 32%. Lower platelet levels (OR = 1.61, 95% CI 1.05-2.48) and previous history of AWS (OR = 2.09, 95% CI 1.31-3.33) were associated with a higher rate of incident AWS, whereas the use of prophylaxis decreased the risk (OR = 0.58, 95% CI 0.36-0.93). The use of intravenous benzodiazepines (HR = 2.18, 95% CI 1.02-4.64) and phenobarbital (HR = 2.99, 95% CI 1.07-8.37) for AWS treatment were independently associated with a higher mortality. The development of AWS increased the rate of infections (OR = 2.24, 95% CI 1.44-3.49), the need for mechanical ventilation (OR = 2.49, 95% CI 1.38-4.49), and ICU admission (OR = 1.96, 95% CI 1.19-3.23). Finally, AWS was associated with higher 28-day (HR = 2.31, 95% CI 1.40-3.82), 90-day (HR = 1.78, 95% CI 1.18-2.69), and 180-day mortality (HR = 1.54, 95% CI 1.06-2.24). Interpretation: AWS commonly occurs in patients hospitalized with AH and complicates the hospitalization course. Routine prophylaxis is associated with a lower prevalence of AWS. Prospective studies should determine diagnostic criteria and prophylaxis regimens for AWS management in patients with AH. Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Reengagement strategies for hepatitis C patients lost to follow-up: A randomized clinical trial.

BACKGROUND AND AIMS: To achieve the World Health Organization's goal of eliminating HCV by 2030, reengagement of lost to follow-up cases is mandatory. However, there is lack of evidence concerning the best strategy. Our study evaluated the effectiveness, efficiency, predictive factors, and costs of 2 different strategies. METHODS: We identified patients positive for HCV antibodies without RNA requests from 2005 to 2018. Patients fulfilling trial criteria (NCT04153708) were randomized to (1) phone call or (2) letter of invitation to schedule an appointment, followed by switching strategy. RESULTS: Three hundred forty-five patients among 1167 lost to follow-up were identified. An analysis of the first 270 randomized patients (72% male, 51±13 y) showed a higher contact rate in the mail than in the phone call strategy (84.5% vs. 50.3%). In the intention-to-treat analysis, no differences were found related to appointment attendance (26.5% vs. 28.5%). Regarding efficiency, 3.1 letters and 8 phone calls were needed to successfully link 1 patient (p<0.001) but dropped down to 2.3 phone calls if we only considered the first call attempt (p=0.008). Prior specialist's evaluation and HCV testing in the predirect-acting antiviral era were the only factors associated with no showing up for the appointment. The cost per patient was €621.3 (2.5 quality-adjusted life-years) in the phone call strategy and €611.8 (2.4 quality-adjusted life-years) in the mail letter strategy. CONCLUSIONS: Reengagement of patients with HCV is feasible, and equally effective with similar costs in both strategies. The mail letter was more efficient, except when only 1 phone call was considered. Prior specialist's evaluation and testing in the predirect-acting antiviral era were factors associated with nonattendance to the appointment.

Bariatric Surgery Is Associated with Alcohol-Related Liver Disease and Psychiatric Disorders Associated with AUD.

BACKGROUND/AIMS: Bariatric surgery can increase the risk of addictive disorders and nutritional deficiencies. The aim of this study was to evaluate the association between bariatric surgery and alcohol use disorder (AUD), alcohol-related liver disease (ALD), and psychiatric disorders associated with AUD. The impact of vitamin D deficiency in these associations was also investigated. METHODS: A cross-sectional study was performed using the National Inpatient Sample database and its ICD-9 codes information. Diagnostic and comorbidity data from hospital discharges were obtained from patients with bariatric surgery and other abdominal surgeries between 2005 and 2015. The two groups were then compared for alcohol-related outcomes after propensity-score matching. RESULTS: The final study cohort included 537,757 patients with bariatric surgery and 537,757 with other abdominal surgeries. The bariatric surgery group had an increased risk of AUD [odds ratio (OR): 1.90; 95% CI: 1.85-1.95], ALD [OR: 1.29; 95% CI: 1.22-1.37], cirrhosis [OR, 1.39; 95% CI: 1.37-1.42], and psychiatric disorders associated with AUD [OR, 3.59; 95% CI: 3.37-3.84]. Vitamin D deficiency did not impact in the association between bariatric surgery and AUD, ALD, or psychiatric disorders associated with AUD. CONCLUSIONS: Bariatric surgery is associated with an increased prevalence of AUD, ALD, and psychiatric disorders associated with AUD. These associations appear to be independent from vitamin D deficiency.

A slowdown of hepatitis C diagnosis in high-prevalence groups and with decentralized diagnostic strategies during the COVID-19 pandemic.

INTRODUCTION: the COVID-19 pandemic has had a major impact on hepatitis C virus (HCV) diagnosis by hindering the path to elimination. Albeit, in an uneven manner, depending on the risk group and diagnostic strategy. METHODS: the requests of antibodies/RNA by venipuncture at hospitals and Primary Care centers (centralized) and via venipuncture or dried blood spot tests at prison and drug treatment centers referred for central processing (integrated decentralized) were recorded for one year, before and after the onset of the COVID-19 health crisis. RESULTS: a total of 20,600 tests (51 % male, 47.9 ± 1 5.8 years) were recorded. Among them, 96.5 % of the cases came from centralized and 3.5 % from decentralized settings, with an active infection rate of 0.2 % and 2.3 % (p < 0.001), respectively. There was a 31.3 % decrease in the number of requests during the pandemic compared to the pre-pandemic period, which was more pronounced in the decentralized than centralized diagnosis setting (60 vs 30 %, p < 0.001). In addition, there was a 31.5 % decline in screening and 18.2 % decrease in the diagnosis of new cases of active infection, with a statistically significant decrease in decentralized compared to centralized diagnosis. CONCLUSIONS: during the COVID-19 pandemic, a decline in HCV diagnostic effort was observed, especially in decentralized strategies, with a higher prevalence of infection. Our results suggest a diagnostic delay that will prevent Spain from reaching the elimination target in 2023. Therefore, the reactivation of strategies, particularly targeting the priority groups, is urgently required.

Asynchronous electronic consultation between primary care and specialized care proved effective for continuum of care for viraemic hepatitis C patients.

INTRODUCTION: It has been proposed that primary care diagnose and treat hepatitis C virus (HCV) infection. However, a care circuit between primary and specialized care based on electronic consultation (EC) can be just as efficient in the micro-elimination of HCV. It is proposed to study characteristics and predictive factors of continuity of care in a circuit between primary and specialized care. METHODS: From February/2018 to December/2019, all EC between primary and specialized care were evaluated and those due to HCV were identified. Variables for regression analysis and to identify predictors of completing the care cascade were recorded. RESULTS: From 8098 EC, 138 were performed by 89 (29%) general practitioners over 118 patients (median 50.8 years; 74.6% men) and were related to HCV (1.9%). Ninety-two patients (78%) were diagnosed>6 months ago, and 26.3% met criteria for late presentation. Overall, 105 patients required assessment by the hepatologist, 82% (n=86) presented for the appointment, of which 67.6% (n=71) were viraemic, 98.6% of known. Finally, 61.9% (n=65) started treatment. Late-presenting status was identified as an independent predictor to complete the care cascade (OR 1.93, CI 1.71-1.99, p<0.001). CONCLUSION: Communication pathway between Primary and Specialized Care based on EC is effective in avoiding significant losses of viraemic patients. However, the referral rate is very low, high in late-stage diagnoses, heterogeneous, and low in new diagnoses. Therefore, early detection strategies for HCV infection in primary care are urgently needed.

Chronic intermittent hypoxia promotes early intrahepatic endothelial impairment in rats with nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a progressive disease that ranges from simple steatosis to cirrhosis. Obstructive sleep apnea syndrome (OSAS) and chronic intermittent hypoxia (CIH) are implicated in the pathogenesis of NAFLD. However, the overlapping consequences of CIH on liver sinusoidal endothelial function over time in NAFLD are largely unknown. We explored endothelial dysfunction in a rat model of NAFLD with a high-fat diet exposed to CIH [12 h/day, every 30 s to fractional concentration of oxygen ([Formula: see text] 8%-10%]. The livers were isolated and perfused, and the endothelial function was determined by testing the vasodilation of the liver circulation to increased concentrations of acetylcholine and von Willebrand factor (vWF) and intercellular adhesion molecule 1 (ICAM-1) expression. Phosphorylated endothelial nitric oxide synthase (p-eNOS), cGMP, and oxidative stress were assessed to determine nitric oxide bioavailability. Inflammation and fibrosis were evaluated by transaminases, myeloperoxidase activity, hydroxyproline, and histological evaluation. Hypoxia-inducible factors (HIFs) were studied as a marker of hypoxia and after a second insult with acetaminophen. CIH exposure provoked typical systemic features of OSAS and provoked a decreased response in vasodilation to acetylcholine. This was associated with increased oxidative stress and reduced p-eNOS and cGMP. The microcirculation impairment due to CIH preceded significant hepatic inflammation and fibrotic changes, despite the presence of HIF expression. In conclusion, CIH exacerbates endothelial dysfunction in NAFLD rats associated with increased oxidative stress and reduced nitric oxide bioavailability. This occurs before inflammation and fibrosis establish. Our results suggest that with CIH endothelial dysfunction should be considered an early target.NEW & NOTEWORTHY We believe the findings are of relevance because we demonstrate that chronic intermittent hypoxia further augments impaired hepatic endothelial dysfunction in nonalcoholic fatty liver disease rats. Because obstructive sleep apnea syndrome is associated with systemic endothelial dysfunction in cardiovascular disorders, and chronic intermittent hypoxia is an independent and reversible risk factor for hypertension and coronary artery disease, we hypothesized that this entity may be of potential relevance in the pathophysiology of nonalcoholic fatty liver disease.

Appropriateness of high-priority criteria and safety of endoscopy procedures during the COVID-19 lockdown.

BACKGROUND: During the coronavirus-19 disease (COVID-19) pandemic, gastroenterology guidelines recommended the suspension or reduction of non-urgent endoscopy. We aimed to assess the appropriateness and safety of endoscopic activity during the pandemic first wave lockdown using European Society of Gastrointestinal Endoscopy (ESGE) recommendations. METHODS: We identified scheduled patients from the onset of the lockdown in Spain since March 16, 2020) to April 14, 2020. Daily hospital COVID-19-related burden was also registered. A similar cohort from a period immediately before the lockdown was studied (pre-lockdown cohort) to compare appropriateness. RESULTS: 454 endoscopy procedures were performed during the studied period, comprising a 49.7% reduction compared to the pre-lockdown cohort (n = 913). There was a significant increase in ESGE high-priority indications (62.1% vs. 45.6%, p<0.001) associated with an increase in relevant endoscopic findings (p = 0.006), advanced neoplasia/cancer (p = 0.004) and cancer detection rate (p = 0.010). There were no differences in the rate of admissions or infection among scheduled patients in the lockdown cohort. None of the staff members tested positive for COVID-19 in the 7 days after the adoption of protective measures. CONCLUSION: A prioritized endoscopic activity is not associated with higher contagion after adopting protective measures. In addition, a triage of procedures that follow the ESGE criteria increases the rate of relevant endoscopic findings. These considerations may reduce the impact of the delays of diagnosis after the pandemic.

Hepatitis C virus infection screening reduces mortality and is cost-effective independently of the intervention test.

INTRODUCTION: Chronic infection due to hepatitis C virus (HCV) is frequently asymptomatic even in advanced stages of liver disease. Implementation of a screening program based on different HCV tests may enable an earlier diagnosis of HCV liver disease and subsequent application of highly effective treatment. PATIENTS AND METHODS: A Markov model which compares three different screening strategies for hepatitis C versus no screening in low-risk prevalence (general population) and high-risk prevalence population (people who inject drugs or prison population) was designed, taking into account age at the start of screening and participation. The three strategies were: 1) serological detection of antibodies against the HCV, 2) dried blood spot test (DBS) to detect antibodies against HCV and 3) detection of RNA from HCV. Quality-adjusted life-years (QALY) were taken as a measurement of effectiveness. The incremental cost-effectiveness ratio (ICER) was calculated and a deterministic and probabilistic sensitivity analysis was performed. RESULTS: All three screening strategies were found to be cost-effective with an ICER of €13,633, €12,015 and €12,328/QALY for AntiHCV, DBS-AntiHCV and DBS-RNA HCV, respectively. There was a decrease in mortality due to liver disease in comparison to no screening for AntiHCV (40.7% and 52%), DBS-AntiHCV (45% and 80%) and DBS-RNA HCV (45.2% and 80%) for low-prevalence and high-prevalence populations, respectively. CONCLUSION: All test interventions for HCV screening are cost-effective for the early detection of HCV infection, also achieving a reduction in mortality. Thus, implementation of screening programs for HCV should not be halted by decisions on monetary policy.

Estimated glomerular filtration rate by formulas in patients with cirrhosis: An unreliable procedure.

BACKGROUND & AIMS: In cirrhosis, the reliability of formulas that estimate renal function, either those specifically developed in this population or the classic equations, has not been properly quantified. We studied the agreement between estimated (eGFR) and measured glomerular filtration rate (mGFR) in cirrhosis. METHODS: Renal function was estimated with 56 formulas including specific equations: Glomerular Filtration Rate Assessment in Liver Disease (GRAIL), Royal Free Hospital Cirrhosis (RFHC) and Mindikoglu-eGFR, and measured with a gold standard procedure; plasma clearance of iohexol using dried blood spots sampling in a group of cirrhotics. The agreement eGFR-mGFR was evaluated with specific tests: total deviation index (TDI), concordance correlation coefficient (CCC) and coverage probability (CP). We defined acceptable agreement as values: TDI < 10%, CCC ≥ 0.9 and CP > 90%. RESULTS: A total of 146 patients (age 65 ± 9 years, 81% male) were evaluated; 61 (42%) Child A, 67 (46%) Child B and 18 (12%) Child C. Median MELD-Na was 14 (9-15). The agreement between eGFR and mGFR was poor: TDI averaged was of 73% (90% of the estimations ranged from ±73% of mGFR); CCC averaged was 0.7 indicating low concordance and CP averaged 22% indicating that 78% of the estimations have an error > 10%. Specific formulas showed also poor agreement: TDI was 82%, 70% and 37% for the GRAIL, RFHC and Mindikoglu equations, respectively. CONCLUSIONS: Overall, formulas poorly estimated renal function in cirrhotic patients. Specific formulas designed for cirrhosis did not outperform classic equations. eGFR must be considered with caution in cirrhotic patients.

Late presentation of chronic HBV and HCV patients seeking first time specialist care in Spain: a 2-year registry review.

Chronic viral hepatitis infection affects an estimated 325 million people globally. People who initiate treatment after significant disease progression face increased risk of severe liver complications and death. Data are scarce on the characteristics and risk factors of people who present late to care in Spain and globally. Data were collected from January 2018 to December 2019 to report late presentation (LP) to specialist care at 11 large university hospitals in Spain to assess related risk factors using a multivariable logistic regression model. 2290 (CHB = 505, CHC = 1785) patients were analysed, with 581 (25.2%) presenting late. Hepatitis C patients more frequently reported LP compared to hepatitis B patients (28.1% vs 15.0%; p < 0.001). Older age (p < 0.001), being male (p < 0.001), being Spanish-born (p < 0.001), and having an unknown origin of referral (p = 0.08) were associated with a higher likelihood of LP. Advanced liver disease was identified in 533 (23%) patients and late-stage liver disease in 124 (5.4%). LP, including with irreversible liver damage, to viral hepatitis specialist care is frequent in Spain, despite being a country with unrestricted treatment access. Initiatives to reduce LP should specifically target men, older individuals, foreign-born populations for CHB, and Spanish nationals for CHC.

Retrieval and treatment of patients with primary biliary cholangitis who are lost in the health system.

INTRODUCTION: hepatitis C patients loss to follow-up in the health care system has been shown to have negative consequences. This study aimed to investigate this issue as regards primary biliary cholangitis. METHODS: the databases (immunology, biochemistry, clinical reports, drug dispensation, appointments) of 4 reference hospitals in Spain (serving a population of 1,450,000 inhabitants) were analyzed. The diagnosis of primary biliary cholangitis was based on an antimitochondrial antibody titer ≥ 1:80, chronically elevated alkaline phosphatase, and the absence of other liver disease. Patients were classified as lost in the absence of reports indicating a diagnosis, specific medical follow-up, and/or treatment with bile salts. RESULTS: a total of 1372 patients with antimitochondrial antibody titers ≥ 1:80 were included between January 2010 and June 2019. A total of 697 (50.8 %) were classified as having primary biliary cholangitis, and 100 patients (14.3 %; 95 % CI: 11.8-17.2) were identified as lost. Of these, 30 were contacted and retrieved. The median age was 70 years, 93 % were female, median alkaline phosphatase was 185 IU/L, 10 % had pruritus, and 27 % had a transient elastography value > 9.5 kPa. The disease was confirmed and ursodeoxycholic acid was started in all 30 patients. Death was liver-related in 6 of the 100 patients classified as lost. CONCLUSION: up to 14.3 % of patients (1 out of 7) with a definitive diagnosis of primary biliary cholangitis remain undiagnosed, thus preventing monitoring and treatment. More than a quarter are at risk of advanced liver disease and its complications. Patients lost in the system must be identified and retrieved, and searching hospital databases is a suitable approach to meet this goal.

Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis: A worldwide study.

BACKGROUND & AIMS: Corticosteroids are the only effective therapy for severe alcohol-associated hepatitis (AH), defined by a model for end-stage liver disease (MELD) score >20. However, there are patients who may be too sick to benefit from therapy. Herein, we aimed to identify the range of MELD scores within which steroids are effective for AH. METHODS: We performed a retrospective, international multicenter cohort study across 4 continents, including 3,380 adults with a clinical and/or histological diagnosis of AH. The main outcome was mortality at 30 days. We used a discrete-time survival analysis model, and MELD cut-offs were established using the transform-the-endpoints method. RESULTS: In our cohort, median age was 49 (40-56) years, 76.5% were male, and 79% had underlying cirrhosis. Median MELD at admission was 24 (19-29). Survival was 88% (87-89) at 30 days, 77% (76-78) at 90 days, and 72% (72-74) at 180 days. A total of 1,225 patients received corticosteroids. In an adjusted-survival-model, corticosteroid use decreased 30-day mortality by 41% (hazard ratio [HR] 0.59; 0.47-0.74; p <0.001). Steroids only improved survival in patients with MELD scores between 21 (HR 0.61; 0.39-0.95; p = 0.027) and 51 (HR 0.72; 0.52-0.99; p = 0.041). The maximum effect of corticosteroid treatment (21-30% survival benefit) was observed with MELD scores between 25 (HR 0.58; 0.42-0.77; p <0.001) and 39 (HR 0.57; 0.41-0.79; p <0.001). No corticosteroid benefit was seen in patients with MELD >51. The type of corticosteroids used (prednisone, prednisolone, or methylprednisolone) was not associated with survival benefit (p = 0.247). CONCLUSION: Corticosteroids improve 30-day survival only among patients with severe AH, especially with MELD scores between 25 and 39. LAY SUMMARY: Alcohol-associated hepatitis is a condition where the liver is severely inflamed as a result of excess alcohol use. It is associated with high mortality and it is not clear whether the most commonly used treatments (corticosteroids) are effective, particularly in patients with very severe liver disease. In this worldwide study, the use of corticosteroids was associated with increased 30-day, but not 90- or 180-day, survival. The maximal benefit was observed in patients with an MELD score (a marker of severity of liver disease; higher scores signify worse disease) between 25-39. However, this benefit was lost in patients with the most severe liver disease (MELD score higher than 51).

Hepatitis C-treated patients as a potential source for referral of new cases. / El paciente tratado de hepatitis C como fuente potencial de derivación de nuevos casos.

INTRODUCTION: Direct-acting antivirals (DAAs) are an opportunity for hepatitis C virus (HCV) elimination. Strategies are needed to diagnose new patients and to attract those diagnosed without evaluation. Patients with other chronic viral diseases who receive satisfactory treatment promote referral of other patients for evaluation. Our aim was to evaluate whether patients who have been treated with DAAs would recommend follow-up and treatment to other patients as well as the characteristics that influence this decision. PATIENTS AND METHODS: Two-hundred and 2HCV-infected patients treated with DAAs were included. Patients were asked about whether they knew other infected people and their willingness to share their experience. A general satisfaction survey and a specific HCV satisfaction survey were carried out. Demographic, socioeconomic and HCV infection variables were recorded. RESULTS: Despite the fact that 54.4% of the patients reported knowing others infected, 34.2% would not fully agree to share their experience. The analysis of general and specific satisfaction showed that patients who shared their experience mentioned a perception of greater care from the specialist (4.7±0.4 vs. 4.3±0.6, P=.001) and had more information on treatment expectations (4.6±0.5 vs. 4.0±0.7, P=.001) and social support (4.5±0.7 vs. 4.0±0.8, P=.001). CONCLUSIONS: The perception by treated patients of general satisfaction with the healthcare process and information about benefits influences the degree of recommendation to other infected people. Knowledge about treatment and perception of improvement in health of treated patients should be enhanced as it can contribute to increasing referrals to specialized consultation.

Telemedicine and decentralized hepatitis C treatment as a strategy to enhance retention in care among people attending drug treatment centres.

BACKGROUND: People attending drug treatment centres have a high burden of hepatitis C virus (HCV) and face barriers to diagnosis and treatment. Dried blood spot (DBS) testing has been proposed to simplify diagnosis, but many patients remain untreated. In this retrospective study, we evaluated the reasons for non-retention in care in an intervention using on-site DBS testing and the effect of telemedicine and decentralized care compared to standard of care among people attending drug treatment centres who were lost to follow-up. METHODS: In a first phase, retention in care, adherence to treatment, and predictive factors in the DBS testing program of patients in drug treatment centres were analyzed and compared to a cohort of patients treated at the hospital outpatient clinic. Subsequently, in a second phase we evaluated in patients lost to follow-up from drug treatment centres the efficacy of one-step testing and telemedicine linked to a decentralized dispensation of HCV treatment or standard of care. RESULTS: Among 512 patients attending drug treatment centres, 467 (91.2%) agreed to be tested and 53.4% (237 patients/444 valid tests) tested positive (46 ± 9 years, 87.3% male) for HCV antibodies. After excluding patients negative for RNA or under surveillance, 178 patients were scheduled to meet with a specialist. Overall, 44 patients did not attend and 25 did not complete the pre-treatment evaluation. The only factor associated with retention in care was patient's knowledge of HCV infection. Treated patients attending drug treatment centres (n = 68) compared to the hospital outpatient clinic cohort (n = 135) had lower rates of treatment adherence. Among the patients who attended drug treatment centres that were lost to follow-up (n = 69), the proportion of patients who completed the program was significantly higher among those assisted by telemedicine than by standard of care (62.5% vs. 24.3%, p = 0.002). CONCLUSION: Although there was a high participation rate in a DBS testing program in drug treatment centres, non-retention in care is a challenge. Importantly, telemedicine linked to a decentralized dispensation of HCV treatment re-engages patients and may be effective for HCV microelimination.

Comparison of flipped learning and traditional lecture method for teaching digestive system diseases in undergraduate medicine: A prospective non-randomized controlled trial.

INTRODUCTION: This study examined the effects of a large-scale flipped learning (FL) approach in an undergraduate course of Digestive System Diseases. METHODS: This prospective non-randomized trial recruited 404 students over three academic years. In 2016, the course was taught entirely in a Traditional Lecture (TL) style, in 2017 half of the course (Medical topics) was replaced by FL while the remaining half (Surgical topics) was taught by TL and in 2018, the whole course was taught entirely by FL. Academic performance, class attendance and student's satisfaction surveys were compared between cohorts. RESULTS: Test scores were higher in the FL module (Medical) than in the TL module (Surgical) in the 2017 cohort but were not different when both components were taught entirely by TL (2016) or by FL (2018). Also, FL increased the probability of reaching superior grades (scores >7.0) and improved class attendance and students' satisfaction. CONCLUSION: The holistic FL model is more effective for teaching undergraduate clinical gastroenterology compared to traditional teaching methods and has a positive impact on classroom attendances.

Integrated Multiomics Reveals Glucose Use Reprogramming and Identifies a Novel Hexokinase in Alcoholic Hepatitis.

BACKGROUND & AIMS: We recently showed that alcoholic hepatitis (AH) is characterized by dedifferentiation of hepatocytes and loss of mature functions. Glucose metabolism is tightly regulated in healthy hepatocytes. We hypothesize that AH may lead to metabolic reprogramming of the liver, including dysregulation of glucose metabolism. METHODS: We performed integrated metabolomic and transcriptomic analyses of liver tissue from patients with AH or alcoholic cirrhosis or normal liver tissue from hepatic resection. Focused analyses of chromatin immunoprecipitation coupled to DNA sequencing was performed. Functional in vitro studies were performed in primary rat and human hepatocytes and HepG2 cells. RESULTS: Patients with AH exhibited specific changes in the levels of intermediates of glycolysis/gluconeogenesis, the tricarboxylic acid cycle, and monosaccharide and disaccharide metabolism. Integrated analysis of the transcriptome and metabolome showed the used of alternate energetic pathways, metabolite sinks and bottlenecks, and dysregulated glucose storage in patients with AH. Among genes involved in glucose metabolism, hexokinase domain containing 1 (HKDC1) was identified as the most up-regulated kinase in patients with AH. Histone active promoter and enhancer markers were increased in the HKDC1 genomic region. High HKDC1 levels were associated with the development of acute kidney injury and decreased survival. Increased HKDC1 activity contributed to the accumulation of glucose-6-P and glycogen in primary rat hepatocytes. CONCLUSIONS: Altered metabolite levels and messenger RNA expression of metabolic enzymes suggest the existence of extensive reprogramming of glucose metabolism in AH. Increased HKDC1 expression may contribute to dysregulated glucose metabolism and represents a novel biomarker and therapeutic target for AH.