Acute-on-chronic liver failure (ACLF) is a syndrome characterised by acute decompensation of chronic liver disease associated with organ failures and high short-term mortality. Alcohol and chronic ...viral hepatitis are the most common underlying liver diseases. Up to 40%-50% of the cases of ACLF have no identifiable trigger; in the remaining patients, sepsis, active alcoholism and relapse of chronic viral hepatitis are the most common reported precipitating factors. An excessive systemic inflammatory response seems to play a crucial role in the development of ACLF. Using a liver-adapted sequential organ assessment failure score, it is possible to triage and prognosticate the outcome of patients with ACLF. The course of ACLF is dynamic and changes over the course of hospital admission. Most of the patients will have a clear prognosis between day 3 and 7 of hospital admission and clinical decisions such as evaluation for liver transplant or discussion over goals of care could be tailored using clinical scores. Bioartificial liver support systems, granulocyte-colony stimulating factors or stem-cell transplant are in the horizon of medical care of this patient population; however, data are too premature to implement them as standard of care.
Ultrasonography is a widely accessible imaging technique for the detection of fatty liver, but the reported accuracy and reliability have been inconsistent across studies. We aimed to perform a ...systematic review and meta‐analysis of the diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver. We used MEDLINE and Embase from October 1967 to March 2010. Studies that provided cross‐tabulations of ultrasonography versus histology or standard imaging techniques, or that provided reliability data for ultrasonography, were included. Study variables were independently ed by three reviewers and double checked by one reviewer. Forty‐nine (4720 participants) studies were included for the meta‐analysis of diagnostic accuracy. The overall sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of ultrasound for the detection of moderate‐severe fatty liver, compared to histology (gold standard), were 84.8% (95% confidence interval: 79.5‐88.9), 93.6% (87.2‐97.0), 13.3 (6.4‐27.6), and 0.16 (0.12‐0.22), respectively. The area under the summary receiving operating characteristics curve was 0.93 (0.91‐0.95). Reliability of ultrasound for the detection of fatty liver showed kappa statistics ranging from 0.54 to 0.92 for intrarater reliability and from 0.44 to 1.00 for interrater reliability. Sensitivity and specificity of ultrasound was similar to that of other imaging techniques (i.e., computed tomography or magnetic resonance imaging). Statistical heterogeneity was present even after stratification for multiple clinically relevant characteristics. Conclusion: Ultrasonography allows for reliable and accurate detection of moderate‐severe fatty liver, compared to histology. Because of its low cost, safety, and accessibility, ultrasound is likely the imaging technique of choice for screening for fatty liver in clinical and population settings. (HEPATOLOGY 2011; 54:1082–1090)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
INTRODUCTION:
Frailty and sarcopenia are common complications of advanced liver disease. Owing to associated morbidity/mortality, there have been targeted efforts to prevent and/or improve both by ...enrolling these patients in focused exercise programs. This review systematically analyzes the data of randomized clinical trials (RCTs) on anthropometric, physical fitness, quality-of-life, and safety outcomes of exercise interventions in patients with advanced liver disease.
METHODS:
Two authors independently searched trials on PubMed and EMBASE from inception up to November 18, 2021. A third independent arbitrator adjudicated all disagreements. We qualitatively summarized these outcomes as follows: (i) muscular fitness (maximal inspiratory/expiratory pressures, muscle size, muscle strength, and bioimpedance testing), (ii) cardiorespiratory fitness (cardiopulmonary exercise testing and 6-minute walk distance), (iii) quality of life, and (iv) others (safety or frailty indices).
RESULTS:
There were 11 RCTs (4 home-based interventions) with 358 participants. Interventions ranged from 8 to 14 weeks and included cycling, walking, resistance exercises, balance and coordination training, and respiratory exercises. All described outcomes compared preintervention with postintervention measurements. Nine studies showed statistically significant improvements in at least 1 physical fitness variable. Ten studies showed statistically significant improvements in at least 1 muscular fitness variable. Six studies showed statistically significant improvements in at least 1 quality-of-life variable. Attrition rates ranged from 5% to 36%, and adherence rates ranged very widely from 14% to 100%. Only 1 study reported frailty indices. Notably, no complications of portal hypertension were seen in intervention groups in the 9 studies that reported these data.
DISCUSSION:
A review of 11 RCTs with 358 participants with advanced liver disease demonstrates that exercise interventions can have favorable outcomes on muscular/cardiorespiratory fitness and quality of life. Although attrition and adherence varied, these interventions seem to be safe in patients with cirrhosis and are well tolerated.
The risk of nonalcoholic fatty liver disease (NAFLD) and its progression may differ between men and women. We conducted a systematic review and meta-analysis to determine the relationship between sex ...and NAFLD, nonalcoholic steatohepatitis (NASH), and advanced NAFLD fibrosis.
Studies reporting sex-stratified NAFLD prevalence among population-based samples and either NASH or advanced fibrosis among patients with biopsy-proven NAFLD were identified from MEDLINE, EMBASE, and Cochrane databases through December 2017. We calculated pooled relative risk ratios comparing women vs men for each outcome.
Our final analysis comprised 54 studies. Samples sizes were 62,239 for the NAFLD analysis, 5428 for the NASH analysis, and 6444 for the advanced fibrosis analysis. Women had a 19% lower risk of NAFLD than men in the general population (pooled risk ratio RR, 0.81; 95% CI, 0.68-0.97; I
= 97.5%). Women had a similar risk of NASH (RR, 1.00; 95% CI, 0.88-1.14; I
= 85.1%), and a 37% higher risk of advanced fibrosis (RR, 1.37; 95% CI, 1.12-1.68; I
= 74.0%) than men. Age modified the effect of sex on NAFLD severity. Risks of NASH (RR, 1.17; 95% CI, 1.01-1.36) and advanced fibrosis (RR, 1.56; 95% CI, 1.36-1.80; I
= 0) were substantially higher in women in study populations with average ages of 50 years and older; sex differences in NASH and advanced fibrosis were attenuated in younger populations.
In a systematic review and meta-analysis, we found women to have a lower risk of NAFLD than men. However, once NAFLD is established, women have a higher risk of advanced fibrosis than men, especially after age 50 years.
Previous estimates of the prevalence of nonalcoholic fatty liver disease (NAFLD) in the US population relied on measures of liver enzymes, potentially underestimating the burden of this disease. We ...used ultrasonography data from 12,454 adults who participated in the Third National Health and Nutrition Examination Survey, conducted in the United States from 1988 to 1994. We defined NAFLD as the presence of hepatic steatosis on ultrasonography in the absence of elevated alcohol consumption. In the US population, the rates of prevalence of hepatic steatosis and NAFLD were 21.4% and 19.0%, respectively, corresponding to estimates of 32.5 (95% confidence interval: 29.9, 35.0) million adults with hepatic steatosis and 28.8 (95% confidence interval: 26.6, 31.2) million adults with NAFLD nationwide. After adjustment for age, income, education, body mass index (weight (kg)/height (m)²), and diabetes status, NAFLD was more common in Mexican Americans (24.1%) compared with non-Hispanic whites (17.8%) and non-Hispanic blacks (13.5%) (P = 0.001) and in men (20.2%) compared with women (15.8%) (P < 0.001). Hepatic steatosis and NAFLD were also independently associated with diabetes, with insulin resistance among people without diabetes, with dyslipidemia, and with obesity. Our results extend previous national estimates of the prevalence of NAFLD in the US population and highlight the burden of this disease. Men, Mexican Americans, and people with diabetes and obesity are the most affected groups.
OBJECTIVE:To examine our pilot to transplant selected patients with acute alcoholic hepatitis, initiated in October 2012.
BACKGROUND:Six months of alcohol abstinence is typically required before ...liver transplant. A Franco-Belgian protocol showed that early transplant in severe alcoholic hepatitis could improve survival with low incidence of alcohol relapse. Application of this controversial indication is growing despite unclear generalizability.
METHODS:Data was collected on all patients with alcohol-related liver disease since initiation of the pilot through June 2015. Patients were stratified into two groupssevere alcoholic hepatitis as first liver decompensation (Group 1), alcoholic cirrhosis with ≥6 months abstinence (Group 2). Alcohol relapse was defined as any evidence of alcohol consumption after transplant, which was assessed for harmful patterns of binge or frequent drinking.
RESULTS:Forty-three patients underwent liver transplant, including 17 patients in Group 1. Six-month survival was 100% versus 89% for Groups 1 and 2, respectively (P = 0.27). Alcohol relapse was similar in Group 1 versus Group 223.5% versus 29.2% (P > 0.99). Harmful drinking was higher in Group 1 versus Group 2, despite lack of statistical significance23.5% versus 11.5% (P = 0.42).
CONCLUSIONS:In this pilot with carefully selected patients, early liver transplant provided excellent short-term survival, and similar rates of alcohol relapse compared with patients with 6 months of abstinence. Harmful patterns of relapse remain challenging in this population, highlighting the need for validated models to predict alcohol relapse, and need for extreme caution in selecting patients for this exceptional indication. Larger prospective studies and longer follow up are necessary.
The variables associated with gastroesophageal reflux (GER) after peroral endoscopic myotomy (POEM) are largely unknown. This study aimed to: 1) identify the prevalence of reflux esophagitis and ...asymptomatic GER in patients who underwent POEM, and 2) evaluate patient and intraprocedural variables associated with post-POEM GER.
All patients who underwent POEM and subsequent objective testing for GER (pH study with or without upper gastrointestinal GI endoscopy) at seven tertiary academic centers (one Asian, two US, four European) were included. Patients were divided into two groups: 1) DeMeester score ≥ 14.72 (cases) and 2) DeMeester score of < 14.72 (controls). Asymptomatic GER was defined as a patient with a DeMeester score ≥ 14.72 who was not consuming proton pump inhibitor (PPI).
A total of 282 patients (female 48.2 %, Caucasian 84.8 %; mean body mass index 24.1 kg/m
) were included. Clinical success was achieved in 94.3 % of patients. GER evaluation was completed after a median follow-up of 12 months (interquartile range 10 - 24 months). A DeMeester score of ≥ 14.72 was seen in 57.8 % of patients. Multivariable analysis revealed female sex to be the only independent association (odds ratio 1.69, 95 % confidence interval 1.04 - 2.74) with post-POEM GER. No intraprocedural variables were associated with GER. Upper GI endoscopy was available in 233 patients, 54 (23.2 %) of whom were noted to have reflux esophagitis (majority Los Angeles Grade A or B). GER was asymptomatic in 60.1 %.
Post-POEM GER was seen in the majority of patients. No intraprocedural variables were identified to allow for potential alteration in procedural technique.
Despite tremendous interest in modulating the microbiome to improve health, the association between diet and the colonic mucosa–associated gut microbiome in healthy individuals has not been examined.
...To investigate the associations between Healthy Eating Index (HEI)–2005 and the colonic mucosa–associated microbiota.
In this cross-sectional observational study, we analyzed bacterial community composition and structure using 16S rRNA gene (V4 region) sequencing of 97 colonic mucosal biopsies obtained endoscopically from different colon segments of 34 polyp-free participants. Dietary consumption was ascertained using an FFQ. Differences in α- and β-diversity and taxonomic relative abundances between the higher and lower score of total HEI and its components were compared, followed by multivariable analyses.
The structure of the microbiota significantly differed by the scores for total HEI, total and whole fruits (HEI 1 and HEI 2), whole grains (HEI 6), milk products and soy beverages (HEI 7), and solid fat, alcohol, and added sugar (HEI 12). A lower score for total HEI and HEIs 2, 7, and 12 was associated with significantly lower richness. A lower score for total HEI was associated with significantly reduced relative abundance of Parabacteroides, Roseburia, and Subdoligranulum but higher Fusobacterium. A lower score for HEI 2 was associated with lower Roseburia but higher Bacteroides. A lower score for HEI 7 was associated with lower Faecalibacterium and Fusobacterium but higher Bacteroides. A lower score for HEI 12 was associated with lower Subdoligranulum but higher Escherichia and Fusobacterium (false discovery rate–adjusted P values <0.05). The findings were confirmed by multivariate analysis. Less abundant bacteria such as Alistipes, Odoribacter, Bilophila, and Tyzzerella were also associated with dietary quality.
A lower score for total HEI–2005 was significantly associated with reduced relative abundance of potentially beneficial bacteria but increased potentially harmful bacteria in the colonic mucosa of endoscopically normal individuals.
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CMK, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background & Aims
Cirrhosis disrupts the hypothalamic–pituitary–gonadal axis causing low testosterone. Testosterone deficiency is associated with sarcopenia and osteopenia, leading to a state of ...frailty and worse clinical outcomes, morbidity and mortality. We aimed to conduct a systematic review on the relationship between serum testosterone and laboratory, anthropometric and clinical outcomes in observational and interventional studies in cirrhosis.
Methods
PubMed and EMBASE were searched from inception through 27 August 2020 and reviewed independently by two investigators; a third reviewer solved disagreement. A qualitative summary of relevant findings was done. Methodological quality was assessed using the Newcastle Ottawa Scale for non‐interventional studies and the Cochrane Risk of Bias for interventional studies.
Results
Out of 3569 articles, 15 met inclusion criteria with six observational studies of 1267 patients and nine interventional studies of 580 patients. In observational studies, low serum testosterone level was associated with sarcopenia, shorter median time to hepatic decompensation, transplant requirement, higher model for end‐stage liver disease (MELD) scores, and death in cirrhotic patients. Nine interventional studies (361 treated with testosterone vs 219 placebo, 1‐36 months) showed that testosterone supplementation improved serum testosterone, appendicular mass and bone mineral density. However, no trial reported improvement in liver‐related scores, complications, readmission rates or death.
Conclusions
Low serum testosterone is associated with increased morbidity and mortality in cirrhosis patients. Testosterone supplementation improved intermediate endpoints, but there was no conclusive data on clinical outcomes. Testosterone supplementation may be a promising strategy to improve frailty and decrease significant clinical complications in cirrhosis.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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