Chronic alcohol consumption causes increased intestinal permeability and changes in the intestinal microbiota composition, which contribute to the development and progression of alcohol‐related liver ...disease. In this setting, little is known about commensal fungi in the gut. We studied the intestinal mycobiota in a cohort of patients with alcoholic hepatitis, patients with alcohol use disorder, and nonalcoholic controls using fungal‐specific internal transcribed spacer amplicon sequencing of fecal samples. We further measured serum anti–Saccharomyces cerevisiae antibodies (ASCA) as a systemic immune response to fungal products or fungi. Candida was the most abundant genus in the fecal mycobiota of the two alcohol groups, whereas genus Penicillium dominated the mycobiome of nonalcoholic controls. We observed a lower diversity in the alcohol groups compared with controls. Antibiotic or steroid treatment was not associated with a lower diversity. Patients with alcoholic hepatitis had significantly higher ASCA levels compared to patients with alcohol use disorder and to nonalcoholic controls. Within the alcoholic hepatitis cohort, patients with levels of at least 34 IU/mL had a significantly lower 90‐day survival (59%) compared with those with ASCA levels less than 34 IU/mL (80%) with an adjusted hazard ratio of 3.13 (95% CI, 1.11‐8.82; P = 0.031). Conclusion: Patients with alcohol‐associated liver disease have a lower fungal diversity with an overgrowth of Candida compared with controls. Higher serum ASCA was associated with increased mortality in patients with alcoholic hepatitis. Intestinal fungi may serve as a therapeutic target to improve survival, and ASCA may be useful to predict the outcome in patients with alcoholic hepatitis.
Background and aims
Achieving sustained virological response (SVR; cure) in hepatitis C patients using a simple regimen is key to making elimination by 2030 possible. In the largest real‐world ...analysis to date, the effectiveness of pangenotypic, panfibrotic, single‐tablet, sofosbuvir/velpatasvir (SOF/VEL) once‐daily for 12 weeks was assessed in 12 clinical real‐world cohorts from various geographical areas, settings and treatment practices. Factors affecting risk of not achieving SVR were assessed.
Methods
Adults treated with SOF/VEL 400/100 mg, without ribavirin, were included. All HCV patients reaching Week 12 or 24 post‐treatment were assessed for SVR12/24. Factors associated with not achieving SVR12/24 for virological reasons were evaluated using logistic regression analysis.
Results
Overall, 5552 patients were included: 13.3% treatment‐experienced; 20.7% compensated cirrhotic; 30.2% genotype 1; 29.5% genotype 2; 32.9% genotype 3; 4.7% genotype 4; 3.7% HIV coinfection; 13.4% current/former intravenous drug use. Of the 5196 patients evaluated for effectiveness, 98.9% achieved SVR12/24. High SVR12/24 rates occurred in all genotypes including genotype 3 (98.3%; 1649/1677) and in those with compensated cirrhosis (97.9; 1055/1078). Only 55 patients did not achieve SVR12/24 due to a virological reason; the only factor statistically significantly associated with an increased risk of not achieving SVR12/24 was compensated cirrhosis (P = .002). Overall, 6% (332/5552) of patients did not achieve SVR12/24 for non‐virological reasons (67% lost to follow‐up; 26.5% early treatment discontinuation).
Conclusions
In this large cohort, representative of clinical practice, a simple 12‐week regimen of SOF/VEL without ribavirin resulted in high SVR12/24 rates in diverse patient populations, even among those with compensated cirrhosis.
Remdesivir is recommended for certain hospitalized patients with COVID-19. However, these recommendations are based on evidence from small randomized trials, early observational studies, or expert ...opinion. Further investigation is needed to better inform treatment guidelines with regard to the effectiveness of remdesivir among these patients.
We emulated a randomized target trial using chargemaster data from 333 US hospitals from 1 May 2020 to 31 December 2021. We compared three treatment protocols: remdesivir within 2 days of hospital admission, no remdesivir within the first 2 days of admission, and no remdesivir ever. We used baseline comorbidities recorded from encounters up to 12 months before admission and identified the use of in-hospital medications, procedures, and oxygen supplementation from charges. We estimated the cumulative incidence of mortality or mechanical ventilation/extracorporeal membrane oxygenation with an inverse probability of censoring weighted estimator. We conducted analyses in the total population as well as in subgroups stratified by level of oxygen supplementation.
A total of 274,319 adult patients met the eligibility criteria for the study. Thirty-day in-hospital mortality risk differences for patients adhering to the early remdesivir protocol were -3.1% (95% confidence interval = -3.5%, -2.7%) compared to no early remdesivir and -3.7% (95% confidence interval -4.2%, -3.2%) compared to never remdesivir, with the strongest effect in patients needing high-flow oxygen. For mechanical ventilation/extracorporeal membrane oxygenation, risk differences were minimal.
We estimate that, among hospitalized patients with COVID-19, remdesivir treatment within 2 days of admission reduced 30-day in-hospital mortality, particularly for patients receiving supplemental oxygen on the day of admission.
The 2019 novel coronavirus disease (COVID-19) has created unprecedented medical challenges. There remains a need for validated risk prediction models to assess short-term mortality risk among ...hospitalized patients with COVID-19. The objective of this study was to develop and validate a 7-day and 14-day mortality risk prediction model for patients hospitalized with COVID-19.
We performed a multicenter retrospective cohort study with a separate multicenter cohort for external validation using two hospitals in New York, NY, and 9 hospitals in Massachusetts, respectively. A total of 664 patients in NY and 265 patients with COVID-19 in Massachusetts, hospitalized from March to April 2020.
We developed a risk model consisting of patient age, hypoxia severity, mean arterial pressure and presence of kidney dysfunction at hospital presentation. Multivariable regression model was based on risk factors selected from univariable and Chi-squared automatic interaction detection analyses. Validation was by receiver operating characteristic curve (discrimination) and Hosmer-Lemeshow goodness of fit (GOF) test (calibration). In internal cross-validation, prediction of 7-day mortality had an AUC of 0.86 (95%CI 0.74-0.98; GOF p = 0.744); while 14-day had an AUC of 0.83 (95%CI 0.69-0.97; GOF p = 0.588). External validation was achieved using 265 patients from an outside cohort and confirmed 7- and 14-day mortality prediction performance with an AUC of 0.85 (95%CI 0.78-0.92; GOF p = 0.340) and 0.83 (95%CI 0.76-0.89; GOF p = 0.471) respectively, along with excellent calibration. Retrospective data collection, short follow-up time, and development in COVID-19 epicenter may limit model generalizability.
The COVID-AID risk tool is a well-calibrated model that demonstrates accuracy in the prediction of both 7-day and 14-day mortality risk among patients hospitalized with COVID-19. This prediction score could assist with resource utilization, patient and caregiver education, and provide a risk stratification instrument for future research trials.
Display omitted
•343 treatment-naïve patients with chronic HCV genotypes 1–6 and compensated cirrhosis.•Glecaprevir/pibrentasvir for 8 weeks achieved 99.7% virologic cure.•One patient experienced ...relapse at post-treatment week 4.•Efficacy did not depend on any pre-treatment patient or viral characteristics.•No drug-related serious adverse events or discontinuations due to adverse events occurred.
Eight-week glecaprevir/pibrentasvir leads to high rates of sustained virological response at post-treatment week 12 (SVR12) across HCV genotypes (GT) 1–6 in treatment-naïve patients without cirrhosis. We evaluated glecaprevir/pibrentasvir once daily for 8 weeks in treatment-naïve patients with compensated cirrhosis.
EXPEDITION-8 was a single-arm, multicenter, phase IIIb trial. The primary and key secondary efficacy analyses were to compare the lower bound of the 95% CI of the SVR12 rate in i) patients with GT1,2,4–6 in the per protocol (PP) population, ii) patients with GT1,2,4–6 in the intention-to-treat (ITT) population, iii) patients with GT1–6 in the PP population, and iv) patients with GT1–6 in the ITT population, to pre-defined efficacy thresholds based on historical SVR12 rates for 12 weeks of glecaprevir/pibrentasvir in the same populations. Safety was also assessed.
A total of 343 patients were enrolled. Most patients were male (63%), white (83%), and had GT1 (67%). The SVR12 rate in patients with GT1–6 was 99.7% (n/N = 334/335; 95%CI 98.3–99.9) in the PP population and 97.7% (n/N = 335/343; 95% CI 96.1–99.3) in the ITT population. All primary and key secondary efficacy analyses were achieved. One patient (GT3a) experienced relapse (0.3%) at post-treatment week 4. Common adverse events (≥5%) were fatigue (9%), pruritus (8%), headache (8%), and nausea (6%). Serious adverse events (none related) occurred in 2% of patients. No adverse event led to study drug discontinuation. Clinically significant laboratory abnormalities were infrequent.
Eight-week glecaprevir/pibrentasvir was well tolerated and led to a similarly high SVR12 rate as the 12-week regimen in treatment-naïve patients with chronic HCV GT1–6 infection and compensated cirrhosis.
Trial registration: ClinicalTrials.gov, NCT03089944.
This study was the first to evaluate an 8-week direct-acting antiviral (DAA) regimen active against all major types of hepatitis C virus (HCV) in untreated patients with compensated cirrhosis. High virological cure rates were achieved with glecaprevir/pibrentasvir across HCV genotypes 1–6, and these high cure rates did not depend on any patient or viral characteristics present before treatment. This may simplify care and allow non-specialist healthcare professionals to treat these patients, contributing to global efforts to eliminate HCV.
HCV therapy is highly effective but underutilized in the transplant setting, likely due to a combination of insurance barriers and lack of adherence to treatment guidelines by transplant ...professionals. See the article from Axelrod et al on page 2473.
Living donor liver transplantation (LDLT) remains underutilized in the United States. Barriers to LDLT and acceptance of nondirected living liver donation (ND‐LLD) and liver paired exchange (LPE) are ...unclear. The medical and surgical directors of 99 unique transplantation programs (56 LDLT programs and 43 non‐LDLT programs) were surveyed to gain insight into perceptions and practices of LDLT and types of donors utilized. The response rate was 84%. Most LDLT programs (65%) reported performing ND‐LLD, though opinions regarding allocation and the need for additional evaluation of these donors were mixed. Only a minority of LDLT programs reported performing LPE (12%), but most programs (78%) would be open to cross‐institutional LPE barring logistical barriers. There were significant differences between LDLT and non‐LDLT programs with regard to perceived barriers to LDLT, with LDLT programs reporting mainly donor and recipient factors and non‐LDLT programs reporting institutional factors (P < 0.001). Understanding perceptions and practices of LDLT, ND‐LLD, and LPE is important to aid in the growth of LDLT.
Despite improvement in the care of patients with end‐stage liver disease (ESLD), mortality is rising. In the United States, patients are increasingly choosing to die at hospice and home, but data in ...patients with ESLD are lacking. Therefore, this study aimed to describe the trends in location of death in patients with ESLD. We conducted a retrospective cross‐sectional analysis using the Centers for Disease Control and Prevention Wide‐Ranging OnLine Data for Epidemiologic Research from 2003 to 2018. Death location was categorized as hospice, home, inpatient facility, nursing home, or other. Comparisons were made between sex, age, ethnicity, race, region, and other causes of death. Comparisons were also made between rates of change (calculated as annual percent change), proportion of deaths in 2018, and multivariable logistic regression. A total of 535,261 deaths were attributed to ESLD—most were male, non‐Hispanic, and White. The proportion of deaths at hospice and home increased during the study period from 0.2% to 10.6% and 20.3% to 25.7%, respectively. Whites had the highest proportion of deaths in hospice and home. In multivariable analysis, elderly patients were more likely to die in hospice or home (odds ratio OR, 1.20; 95% confidence interval CI, 1.07‐1.35), whereas Black patients were less likely (OR, 0.58; 95% CI, 0.46‐0.73). Compared with other causes of death, ESLD had the second highest proportion of deaths in hospice but lagged behind non–hepatocellular carcinoma malignancy. Deaths in patients with ESLD are increasingly common at hospice and home overall, and although the rates have been increasing among Black patients, they are still less likely to die at hospice or home. Efforts to improve this disparity, promote end‐of‐life care planning, and enhance access to death at hospice and home are needed.
https://www.wileyhealthlearning.com/Activity2/7249870/Activity.aspx?parentActivityId=0
Data outside of clinical trials with direct‐acting antiviral regimens with or without ribavirin as treatment of chronic hepatitis C virus in solid organ transplant recipients are limited. Liver ...transplant (LT), kidney transplant (KT), and dual liver kidney (DLK) transplant recipients from the Hepatitis C Therapeutic Registry and Research Network database, a multicenter, longitudinal clinical care treatment cohort, treated with direct‐acting antiviral regimens between January 1, 2014, and February 15, 2016, were included to assess safety and efficacy. Included were 443 posttransplant patients (KT = 60, LT = 347, DLK = 36); 42% had cirrhosis, and 54% had failed prior antiviral therapy. Most had genotype (GT) 1 (87% with 52% GT1a, 27% GT1b, and 8% GT1 no subtype) and were treated with sofosbuvir (SOF)/ledipasvir ± ribavirin (85%) followed by SOF + daclatasvir ± ribavirin (9%) and ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (6%). Rates of sustained virologic response (SVR) at 12 weeks were available on 412 patients, and 395 patients (95.9%) achieved SVR at 12 weeks: 96.6%, 94.5%, and 90.9% among LT, KT, and DLK transplant recipients, respectively. Ribavirin did not influence SVR rates and was more often used in those with higher BMI, higher estimated glomerular filtration rate and lower creatinine. Female gender, baseline albumin ≥3.5 g/dL, baseline total bilirubin ≤1.2 mg/dL, absence of cirrhosis, and hepatic decompensation predicted SVR at 12 weeks. Six episodes of acute rejection (n = 2 KT, 4 LT) occurred, during hepatitis C virus treatment in 4 and after cessation of treatment in 2. Conclusion: In a large prospective observational cohort study, direct‐acting antiviral therapy with SOF/ledipasvir, ombitasvir/paritaprevir/ritonavir + dasabuvir, and SOF plus daclatasvir was efficacious and safe in LT, KT, and DLK transplant recipients; ribavirin did not influence SVR, and graft rejection was rare. (Hepatology 2017;66:1090‐1101).
PDF
