Prevalence of and associated factors for sarcopenia in patients with liver cirrhosis: A systematic review and meta-analysis.

BACKGROUND: Sarcopenia is associated with poor outcomes in patients with cirrhosis. However, the prevalence of and associated factors for developing sarcopenia in this population remain to be determined. OBJECTIVES: This study aimed to summarize the prevalence, characteristics, and associated factors of sarcopenia in patients with cirrhosis. METHODS: Electronic searches were performed from inception to June 9, 2022 to identify the eligible studies. We meta-analyzed the prevalence of sarcopenia in overall patients with cirrhosis and subgroups. Both crude and adjusted odds ratios (ORs) were pooled using the random effects model. RESULTS: A total of 55 studies involving 13,158 patients from 17 countries were included. The overall prevalence of sarcopenia was 40.1 % (95 % CI 35.4%-44.9 %) in patients with cirrhosis. The pooled prevalence was higher in males, Child-Pugh class C cirrhosis, decompensated stage, ascites, subjective global assessment class C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index) at a higher cutoff. In multivariate analysis, older age (adjusted OR 1.04, 95 % CI 1.00-1.07), male (adjusted OR 4.75, 95 % CI 2.72-8.28), lower body mass index (BMI) (adjusted OR 0.78, 95 % CI 0.73-0.83), alcoholic liver disease (ALD) (adjusted OR 1.43, 95 % CI 1.19-1.72), but not ascites and hepatic encephalopathy, were significantly associated with an increased risk of sarcopenia in patients with cirrhosis. CONCLUSION: Sarcopenia is a prevalent complication, and older age, male patients, lower BMI, and patients with ALD are associated with an increased risk of sarcopenia in patients with cirrhosis.

Immune Checkpoint Inhibitors for Child-Pugh Class B Advanced Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Importance: Immune checkpoint inhibitors (ICIs) are increasingly used in patients with advanced hepatocellular carcinoma (HCC). However, data on ICI therapy in patients with advanced HCC and impaired liver function are scarce. Objective: To conduct a systematic review and meta-analysis to determine the efficacy and safety of ICI treatment for advanced HCC with Child-Pugh B liver function. Data Sources: PubMed, Embase, Web of Science, and Cochrane Library were searched for relevant studies from inception through June 15, 2022. Study Selection: Randomized clinical trials, cohort studies, or single-group studies that investigated the efficacy or safety of ICI therapy for Child-Pugh B advanced HCC were included. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline was followed to extract data. A random-effects model was adopted if the heterogeneity was significant (I2 > 50%); otherwise, a fixed-effect model was used. Main Outcomes and Measures: The objective response rate (ORR) and overall survival (OS) were considered to be the primary efficacy outcomes of ICI treatment for Child-Pugh B advanced HCC, and the incidence of treatment-related adverse events (trAEs) was set as the primary measure for the safety outcome. Results: A total of 22 studies including 699 patients with Child-Pugh B and 2114 with Child-Pugh A advanced HCC comprised the analytic sample (median age range, 53-73 years). Upon pooled analysis, patients treated with ICIs in the Child-Pugh B group had an ORR of 14% (95% CI, 11%-17%) and disease control rate (DCR) of 46% (95% CI, 36%-56%), with a median OS of 5.49 (95% CI, 3.57-7.42) months and median progression-free survival of 2.68 (95% CI, 1.85-3.52) months. The rate of any grade trAEs in the Child-Pugh B group was 40% (95% CI, 34%-47%) and of grade 3 or higher trAEs was 12% (95% CI, 6%-23%). Compared with the Child-Pugh A group, the ORR (odds ratio, 0.59; 95% CI, 0.43-0.81; P < .001) and DCR (odds ratio, 0.64; 95% CI, 0.50-0.81; P < .001) were lower in the Child-Pugh B group. Child-Pugh B was independently associated with worse OS in patients with advanced HCC treated with ICIs (hazard ratio, 2.72 [95% CI, 2.34-3.16]; adjusted hazard ratio, 2.33 [95% CI, 1.81-2.99]). However, ICIs were not associated with increased trAEs in the Child-Pugh B group. Conclusions and Relevance: The findings of this systematic review and meta-analysis suggest that although the safety of ICI treatment was comparable between patients with HCC with vs without advanced liver disease and the treatment resulted in a significant number of radiologic responses, survival outcomes are still inferior in patients with worse liver function. More study is needed to determine the effectiveness of ICI treatment in this population.

Prevalence and Risk Factors of Metabolic Dysfunction-Associated Fatty Liver Disease with Renal Insufficiency in Overweight/Obese Adults.

INTRODUCTION: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) with renal insufficiency in recent years and the association between MAFLD and renal insufficiency are not entirely clear, especially in overweight/obesity. The aim of this study was to analyze the prevalence and risk factors of MAFLD with renal insufficiency in overweight/obese adults. METHODS: Individuals who attended checkup at the Second Affiliated Hospital of Xi'an Jiaotong University from 2016 to 2021 were included. The prevalence of MAFLD with renal insufficiency (estimated glomerular filtration rate ≤90 mL/min/1.73 m2) in overweight/obesity was estimated. Propensity score-matched analysis, univariate and multivariate analyses were used to determine the risk factors for MAFLD with renal insufficiency. RESULTS: From 2016 to 2021, the prevalence of MAFLD in overweight/obesity reached its highest of 44.7% in 2017 and its lowest of 36.9% in 2018; and 33.9% in 2021 and 21.8% in 2019 is the highest and lowest prevalence of MAFLD with renal insufficiency, respectively. MAFLD was more common in men, old individuals, and persons with a higher body mass index (BMI) and was characterized by significant renal insufficiency. MAFLD with renal insufficiency was more common in women, old individuals, and persons with a higher BMI and was characterized by significant metabolic dysfunction and liver fibrosis. Multivariable analysis showed that BMI, uric acid, and fibrosis (evaluated with noninvasive liver fibrosis score [fibrosis-4]) were independent risk factors for MAFLD with renal insufficiency. CONCLUSION: The prevalence of MAFLD with renal insufficiency in overweight/obese adults is quite high in the last 5 years. BMI, uric acid, and fibrosis are independent risk factors for MAFLD with renal insufficiency.

Non-invasive model for predicting high-risk esophageal varices based on liver and spleen stiffness.

BACKGROUND: Acute bleeding due to esophageal varices (EVs) is a life-threatening complication in patients with cirrhosis. The diagnosis of EVs is mainly through upper gastrointestinal endoscopy, but the discomfort, contraindications and complications of gastrointestinal endoscopic screening reduce patient compliance. According to the bleeding risk of EVs, the Baveno VI consensus divides varices into high bleeding risk EVs (HEVs) and low bleeding risk EVs (LEVs). We sought to identify a non-invasive prediction model based on spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) as an alternative to EVs screening. AIM: To develop a safe, simple and non-invasive model to predict HEVs in patients with viral cirrhosis and identify patients who can be exempted from upper gastrointestinal endoscopy. METHODS: Data from 200 patients with viral cirrhosis were included in this study, with 140 patients as the modelling group and 60 patients as the external validation group, and the EVs types of patients were determined by upper gastrointestinal endoscopy and the Baveno VI consensus. Those patients were divided into the HEVs group (66 patients) and the LEVs group (74 patients). The effect of each parameter on HEVs was analyzed by univariate and multivariate analyses, and a non-invasive prediction model was established. Finally, the discrimination ability, calibration ability and clinical efficacy of the new model were verified in the modelling group and the external validation group. RESULTS: Univariate and multivariate analyses showed that SSM and LSM were associated with the occurrence of HEVs in patients with viral cirrhosis. On this basis, logistic regression analysis was used to construct a prediction model: Ln [P/(1-P)] = -8.184 -0.228 × SSM + 0.642 × LSM. The area under the curve of the new model was 0.965. When the cut-off value was 0.27, the sensitivity, specificity, positive predictive value and negative predictive value of the model for predicting HEVs were 100.00%, 82.43%, 83.52%, and 100%, respectively. Compared with the four prediction models of liver stiffness-spleen diameter to platelet ratio score, variceal risk index, aspartate aminotransferase to alanine aminotransferase ratio, and Baveno VI, the established model can better predict HEVs in patients with viral cirrhosis. CONCLUSION: Based on the SSM and LSM measured by transient elastography, we established a non-invasive prediction model for HEVs. The new model is reliable in predicting HEVs and can be used as an alternative to routine upper gastrointestinal endoscopy screening, which is helpful for clinical decision making.

Non-invasive model for predicting esophageal varices based on liver and spleen volume.

BACKGROUND: Upper endoscopy is the gold standard for predicting esophageal varices in China. Guidelines and consensus suggest that patients with liver cirrhosis should undergo periodic upper endoscopy, most patients undergo their first upper endoscopy when esophageal variceal bleeds. Therefore, it is important to develop a non-invasive model to early diagnose esophageal varices. AIM: To develop a non-invasive predictive model for esophageal varices based on liver and spleen volume in viral cirrhosis patients. METHODS: We conducted a cross-sectional study based on viral cirrhosis crowd in the Second Affiliated Hospital of Xi'an Jiaotong University. By collecting the basic information and clinical data of the participants, we derived the independent risk factors and established the prediction model of esophageal varices. The established model was compared with other models. Area under the receiver operating characteristic curve, calibration plot and decision curve analysis were used to test the discriminating ability, calibration ability and clinical practicability in both the internal and external validation. RESULTS: The portal vein diameter, the liver and spleen volume, and volume change rate were the independent risk factors of esophageal varices. We successfully used the factors to establish the predictive model [area under the curve (AUC) 0.87, 95%CI: 0.80-0.95], which showed better predictive value than other models. The model showed good discriminating ability, calibration ability and the clinical practicability in both modelling group and external validation group. CONCLUSION: The developed non-invasive predictive model can be used as an effective tool for predicting esophageal varices in viral cirrhosis patients.

The Effects of Psychological Interventions on Symptoms and Psychology of Functional Dyspepsia: A Systematic Review and Meta-Analysis.

Background: The effects of psychological interventions on symptoms and psychology of functional dyspepsia (FD) remain unclear. We aimed to comprehensively evaluate the effects of psychological interventions on symptoms and psychology of FD. Methods: We searched the PubMed, Cochrane Library, and Embase electronic databases for randomized controlled trials (RCTs) evaluating the role of psychological interventions in FD patients published before July 2021. Standardized mean differences (SMDs), risk ratios (RRs) and 95% confidence intervals (CIs) were calculated by a random effects model. Subgroup analyses and sensitivity analyses were also performed. Results: Fourteen RCTs with a total of 1,434 FD patients were included. Compared with the control group, psychological interventions were significantly more likely to symptom improvement [RR = 1.74, 95% CI (1.12, 2.72), p = 0.01], relieve gastrointestinal symptoms scores at follow up [SMD = -1.06, 95% CI (-1.55, -0.57), p < 0.0001], relieve gastrointestinal symptoms scores at end of treatment [SMD = -0.98, 95% CI (-1.29, -0.67), p < 0.001], decrease anxiety [SMD = -0.8, 95% CI (-1.38, -0.22), p = 0.006] and depression levels [SMD = -1.11, 95% CI (-1.62, -0.61), p < 0.001]. The results of the subgroup analysis showed that psychotherapy was more likely to symptom improvement, relieve gastrointestinal symptoms scores and decreased depression levels compared to the control. Conclusions: Psychological interventions may be effective in alleviating the symptoms and psychology of FD, but the effect appears to be limited to psychotherapy with fewer trials for other psychological interventions. More data from high-quality RCTs are needed to confirm their use in the treatment of FD.

Predictive value of alarm symptoms in Rome IV irritable bowel syndrome: A multicenter cross-sectional study.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional bowel disease that shares features with many organic diseases and cannot be accurately diagnosed by symptom-based criteria. Alarm symptoms have long been applied in the clinical diagnosis of IBS. However, no study has explored the predictive value of alarm symptoms in suspected IBS patients based on the latest Rome IV criteria. AIM: To investigate the predictive value of alarm symptoms in suspected IBS patients based on the Rome IV criteria. METHODS: In this multicenter cross-sectional study, we collected data from 730 suspected IBS patients evaluated at 3 tertiary care centers from August 2018 to August 2019. Patients with IBS-like symptoms who completed colonoscopy during the study period were initially identified by investigators through medical records. Eligible patients completed questionnaires, underwent laboratory tests, and were assigned to the IBS or organic disease group according to colonoscopy findings and pathology results (if a biopsy was taken). Independent risk factors for organic disease were explored by logistic regression analysis, and the positive predictive value (PPV) and missed diagnosis rate were calculated. RESULTS: The incidence of alarm symptoms in suspected IBS patients was 75.34%. Anemia [odds ratio (OR) = 2.825, 95% confidence interval (CI): 1.273-6.267, P = 0.011], fecal occult blood [OR = 1.940 (95%CI: 1.041-3.613), P = 0.037], unintended weight loss (P = 0.009), female sex [OR = 0.560 (95%CI: 0.330-0.949), P = 0.031] and marital status (P = 0.030) were independently correlated with organic disease. The prevalence of organic disease was 10.41% in suspected IBS patients. The PPV of alarm symptoms for organic disease was highest for anemia (22.92%), fecal occult blood (19.35%) and unintended weight loss (16.48%), and it was 100% when these three factors were combined. The PPV and missed diagnosis rate for diagnosing IBS were 91.67% and 74.77% when all alarm symptoms were combined with Rome IV and 92.09% and 34.10% when only fecal occult blood, unintended weight loss and anemia were combined with Rome IV, respectively. CONCLUSION: Anemia, fecal occult blood and unintended weight loss have high predictive value for organic disease in suspected IBS patients and can help identify patients requiring further examination but are not recommended as exclusion criteria for IBS.

Effect of sarcopenia on survival in patients with cirrhosis: A meta-analysis.

BACKGROUND & AIMS: The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, stratified by sex, underlying liver disease etiology, and severity of hepatic dysfunction. METHODS: PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with an additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included. RESULTS: Twenty-two studies involving 6,965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), and was higher in male patients, those with alcohol-associated liver disease, those with Child-Pugh grade C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index). Sarcopenia was associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in a sensitivity analysis of patients with cirrhosis without hepatocellular carcinoma (aHR 2.35, 95% CI 1.95-2.83) and in subgroups stratified by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the association between sarcopenia and poor prognosis (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in any of our analyses. CONCLUSIONS: Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis. LAY SUMMARY: The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% of patients with alcohol-related liver disease or Child-Pugh class C cirrhosis. Sarcopenia was independently associated with an ∼2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer durations of sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.

Feasibility of salvage colonoscopy by water exchange for failed air-insufflated patients: a prospective, randomized, controlled trial.

BACKGROUND: A complete colonoscopy is crucial for screening colorectal diseases and colorectal cancer. However, a failure rate of up to 43% still exists. Several studies have indicated that the water exchange method can enhance the cecal intubation rate while reducing discomfort of the patient. Water exchange colonoscopy (WEC) might be a salvage treatment for the patients who failed from air insufflation colonoscopy (AIC). We aimed to assess the feasibility of WEC as a salvage measure following the failure of conventional AIC. METHODS: Patients willing to undergo unsedated colonoscopy at a tertiary-care referral center in China were randomly assigned 1:1 to WEC or AIC group for salvage after the initial AIC attempt failed. Patients were blinded to group assignment. The primary outcome was cecal intubation rate, the secondary outcomes included time to the cecum, maximum pain scores, and technical difficulty level. RESULTS: Recruited 104 patients were randomized to the WEC (n = 52) or AIC (n = 52) group. WEC significantly increased the cecal intubation rate (92.3% vs 73.1%; p = .02). The maximum pain scores and technical difficulty level in the WEC group were significantly lower than the AIC group during salvage procedure (p < .001). CONCLUSIONS: This randomized, controlled trial confirms that the WEC significantly enhanced cecal intubation rate in difficult colonoscopy in unsedated patients after the failure of standard AIC. The increased cecal intubation rate, lower pain scores and technical difficulty level suggest WEC is a good alternative for incomplete unsedated colonoscopy. Clinical trial registration number: ChiCTR2100051483.

Predictive value of alarm symptoms in patients with Rome IV dyspepsia: A cross-sectional study.

BACKGROUND: No studies have evaluated the predictive value of alarm symptoms for organic dyspepsia and organic upper gastrointestinal (GI) diseases based on Rome IV criteria in the Chinese population. AIM: To evaluate the predictive value of alarm symptoms for dyspeptic patients based on Rome IV criteria. METHODS: We performed a cross-sectional study of dyspepsia patients who met the inclusion and exclusion criteria at two academic urban tertiary-care centers from March 2018 to January 2019. Basic demographic data, dyspeptic information, alarm symptoms, lifestyle, examination results, family history and outpatient cost information were collected. Dyspepsia patients with normal findings on upper GI endoscopy, epigastric ultrasound and laboratory examination and without Helicobacter pylori-associated dyspepsia were classified as functional dyspepsia. RESULTS: A total of 381 patients were enrolled in the study, including 266 functional dyspepsia patients and 115 organic dyspepsia patients. There were 24 patients with organic upper GI disease among patients with organic dyspepsia. We found that based on the Rome IV criteria, alarm symptoms were of limited value in differentiating organic dyspepsia and organic upper GI diseases from functional dyspepsia. Age (odds ratio (OR) = 1.056, P = 0.012), smoking (OR = 4.714, P = 0.006) and anemia (OR = 88.270, P < 0.001) were independent predictors for organic upper GI diseases. For the comparison of epigastric pain syndrome, postprandial distress syndrome and epigastric pain syndrome combined with postprandial distress syndrome, the results showed that there were statistically significant differences in anorexia (P = 0.021) and previous visits (P = 0.012). The ClinicalTrials.gov number is NCT03479528. CONCLUSION: Most alarm symptoms had poor predictive value for organic dyspepsia and organic upper GI diseases based on Rome IV criteria. Gastroscopic screening should not be based solely on alarm symptoms.

Non-invasive prediction model for high-risk esophageal varices in the Chinese population.

BACKGROUND: There are two types of esophageal varices (EVs): high-risk EVs (HEVs) and low-risk EVs, and HEVs pose a greater threat to patient life than low-risk EVs. The diagnosis of EVs is mainly conducted by gastroscopy, which can cause discomfort to patients, or by non-invasive prediction models. A number of non-invasive models for predicting EVs have been reported; however, those that are based on the formula for calculation of liver and spleen volume in HEVs have not been reported. AIM: To establish a non-invasive prediction model based on the formula for liver and spleen volume for predicting HEVs in patients with viral cirrhosis. METHODS: Data from 86 EV patients with viral cirrhosis were collected. Actual liver and spleen volumes of the patients were determined by computed tomography, and their calculated liver and spleen volumes were calculated by standard formulas. Other imaging and biochemical data were determined. The impact of each parameter on HEVs was analyzed by univariate and multivariate analyses, the data from which were employed to establish a non-invasive prediction model. Then the established prediction model was compared with other previous prediction models. Finally, the discriminating ability, calibration ability, and clinical efficacy of the new model was verified in both the modeling group and the external validation group. RESULTS: Data from univariate and multivariate analyses indicated that the liver-spleen volume ratio, spleen volume change rate, and aspartate aminotransferase were correlated with HEVs. These indexes were successfully used to establish the non-invasive prediction model. The comparison of the models showed that the established model could better predict HEVs compared with previous models. The discriminating ability, calibration ability, and clinical efficacy of the new model were affirmed. CONCLUSION: The non-invasive prediction model for predicting HEVs in patients with viral cirrhosis was successfully established. The new model is reliable for predicting HEVs and has clinical applicability.

Rome III, Rome IV, and Potential Asia Symptom Criteria for Functional Dyspepsia Do Not Reliably Distinguish Functional From Organic Disease.

INTRODUCTION: Although the Rome criteria were created primarily for research purposes, it was an important question whether the Rome criteria can distinguish organic dyspepsia from functional dyspepsia (FD). We evaluated the accuracy of the Rome IV criteria in identifying patients with FD and compared the differences between the Rome IV, Rome III, and potential Asia criteria in identifying patients with FD. METHODS: In this cross-sectional study, we analyzed data from patients who met the inclusion and exclusion criteria from March 2018 to January 2019 at 2 tertiary hospitals. RESULTS: A total of 600 patients were enrolled in this study, including 381 individuals met the Rome IV criteria for FD, 438 individuals met the Rome III criteria for FD, and 525 individuals met the potential Asia criteria for FD. The Rome IV criteria identified patients with FD with 67.3% sensitivity and 38.4% specificity, and the positive and negative likelihood ratios of FD identified by Rome IV criteria were 1.09 (95% confidence interval 0.97-1.24) and 0.85 (95% confidence interval 0.67-1.08), respectively. There was no significant difference in the area under Rome IV, Rome III, or potential Asia criteria receiver operating characteristic curves in identifying FD (P > 0.05). DISCUSSION: The Rome IV criteria were no better than the Rome III or potential Asia criteria in identifying FD and were not helpful in identifying patients with FD. Hence, although the Rome criteria remain useful for defining patients with FD for inclusion into clinical treatment trials, they should not be used for diagnosing FD.