Definitions, etiologies and outcomes of acute on chronic liver failure: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a major public health concern. We aimed to assess the definitions, etiological spectrum, organ failure (OF), and outcomes of ACLF globally. METHODS: Three databases were searched for studies on ACLF from 1990 till September 2022. Information regarding definitions, acute precipitants, underlying chronic liver disease (CLD), OF, and mortality were extracted. Meta-analyses were performed for pooled prevalence rates (95% confidence interval, CI) using random effects model for each definition of ACLF. RESULTS: Of the 11,451 studies identified, 114 articles (142 cohorts encompassing 210,239 patients) met the eligibility criteria. Most studies (53.2%) used the European Association for the Study of the Liver (EASL) definition, followed by Asia-Pacific Association for the Study of the Liver (APASL) (33.3%). Systemic infection was the major acute precipitant and alcohol use was the major cause of CLD in EASL-defined studies while alcohol was both, the major acute precipitant and cause of CLD in APASL-defined studies. Liver failure was the major OF in APASL-based studies, while renal failure was predominant in EASL-based studies. Thirty-day mortality varied across definitions: APASL: 38.9% [95%CI 31.2-46.9], EASL: 47.9% [95%CI 42.2-53.5] and NACSELD: 52.2% [95%CI 51.9-52.5]. Diagnostic overlap between definitions ranged from 7.7% to 80.2%. Meta-regression suggested that the WHO region influenced 30-day mortality in studies using EASL definition. CONCLUSION: Heterogeneity in the definition of ACLF proposed by different expert societies and regional preferences in its use result in differences in clinical phenotype and outcomes. A uniform definition would enhance the comparability and interpretation of global data.

Etiological Spectrum of Cirrhosis in India: A Systematic Review and Meta-analysis.

Background: Cirrhosis is a significant cause of morbidity and mortality globally and in India. This systematic review and meta-analysis aimed to ascertain the etiological spectrum and changing trends of cirrhosis in India. Methods: We searched electronic databases, including Pubmed/Medline, Scopus, and Embase. We included original studies that reported the etiology of cirrhosis in the Indian population. Results: We included 158 studies (adults: 147, children: 11). The overall pooled estimate of alcohol as a cause of cirrhosis in adults was 43.2% (95% confidence interval (CI) 39.8-46.6%; I2 = 97.8%), followed by nonalcoholic fatty liver disease (NAFLD)/cryptogenic in 14.4%, 95% CI (11.7-17.3%; I2 = 98.4%), hepatitis B virus (HBV) in 11.5%, 95% CI (9.8-13.3%; I2 = 96.6%), and hepatitis C virus (HCV) in 6.2%, 95% CI (4.8-7.8%; I2 = 97.2%) of the included patients. The most common cause of cirrhosis in all zones was alcohol-related. Comparison of etiologies over time revealed a reduction in the viral hepatitis-related and an increase in the proportion of alcohol-related and NAFLD/cryptogenic-related cirrhosis. The overall pooled estimates of various etiologies in children were: HBV in 10.7%, 95% CI (4.6-18.7%; I2 = 91.0%), NAFLD/Cryptogenic in 22.3%, 95% CI (9.0-39.2%; I2 = 96.7%), and HCV in 2.0%, 95% CI (0.0-8.5%; I2 = 94.6%). Conclusions: Alcohol is the most common etiology of cirrhosis in adults in India. The proportions of alcohol and NAFLD-related cirrhosis are increasing, and those of viral hepatitis-related cirrhosis are reducing. The results of our meta-analysis will help formulate health policies and the allocation of resources.

Comparison of 1-day versus 3-day intravenous terlipressin in cirrhosis patients with variceal bleeding: A pilot randomised controlled trial.

BACKGROUND: In cirrhosis patients with acute variceal bleeding (AVB), the optimal duration of vasoconstrictor therapy after endoscopic haemostasis is unclear. AIMS: We aimed to compare efficacy of 1-day versus 3-day terlipressin therapy in cirrhosis patients with AVB post-endoscopic intervention. The primary objective was to compare rebleeding at 5 days between the two arms. Secondary objectives included rebleeding and mortality rates at 6 weeks. METHODS: In this open-label, randomised controlled trial, cirrhosis patients with AVB were randomised to either 1-day or 3-day terlipressin therapy. RESULTS: A total of 150 cirrhosis patients with AVB were recruited to receive either 1 day (n = 75) or 3 days (n = 75) of terlipressin therapy. One patient from 1-day arm was excluded. Modified intention-to-treat analysis included 149 patients. Baseline characteristics were comparable between the two groups. Rebleeding at 5 days: 3 (4.1%; 95% confidence interval [CI]: 0.4-9.0) versus 4 (5.3%; 95% CI: 2.0-10.0), risk difference (RD) p = 0.726 and 5-day mortality rates: 1 (1.4%; 95% CI: 0-7.3) versus 1 (1.3%; 95% CI: 0.2-7.0), RD p = 0.960 were similar. Rebleeding at 42 days: 9 (12.2%; 95% CI: 7.0-20.0) versus 10 (13.3%; 95% CI: 7.0-20.0), RD p = 0.842 and mortality at 42 days: 5 (6.8%; 95% CI: 3.0-10.0) versus 4 (5.3%; 95% CI: 2.0-10.0), RD p = 0.704 were also similar. Patients in the 1-day terlipressin therapy arm experienced significantly fewer adverse effects compared with those receiving 3 days of terlipressin therapy: 28 (37.8%) versus 42 (56%), p = 0.026. CONCLUSIONS: Our results suggest that 1 day of terlipressin therapy is associated with similar 5-day and 42-day rebleeding rates, 42-day mortality and an overall superior safety profile compared with 3-day of terlipressin therapy. These findings require to be validated in double-blinded, larger, multiethnic and multicentre studies across the various stages of cirrhosis (CTRI/2019/10/021771).

ABDA Score: A Non-invasive Model to Identify Subjects with Fibrotic Non-alcoholic Steatohepatitis in the Community.

Background: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH) are prevalent in the community, especially among those with metabolic syndrome. Patients with fibrotic NASH are at increased risk of liver-related-events. Currently available non-invasive tests have not been utilized for screening for fibrotic NASH among the community. We aimed to develop a screening tool for fibrotic NASH among community members. Methods: We included two large cohorts aimed at assessing cardiovascular disease among community members. Fibrotic NASH was defined using the FibroScan-aspartate aminotransferase score of ≥0.67 that identifies ≥F2 fibrosis and a non-alcoholic fatty liver disease activity score ≥4 with a specificity of 90%. Metabolic parameters, biochemical tests and anthropometry were used to develop a multivariate model. Results: The derivation cohort (n = 1660) included a population with a median age 45 years, 42.5% males, metabolic syndrome in 66% and 2.7% (n = 45) with fibrotic NASH. Multivariate analysis identified the four significant variables (Age, body mass index , Diabetes and alanine aminotransferas levels) used to derive an ABDA score. The score had high diagnostic accuracy (the area under receiver-operating characteristic curve, 0.952) with adequate internal validity. An ABDA score ≥-3.52 identified fibrotic NASH in the derivation cohort with a sensitivity and specificity of 88.9% and 88.3%. The score was validated in a second cohort (n = 357) that included 21 patients (5.9%) with fibrotic NASH, where it demonstrated a high area under receiver-operating characteristic curve (0.948), sensitivity (81%) and specificity (89.3%). Conclusions: ABDA score utilizes four easily available parameters to identify fibrotic NASH with high accuracy in the community.

Poor Performance of Non-invasive Tests for Advanced Fibrosis in Nonalcoholic Fatty Liver Disease: A Multicentric Asian Study.

BACKGROUND: Non-invasive tests (NITs) are useful to assess advanced fibrosis (AF) in nonalcoholic fatty liver disease (NAFLD). Data from Asian countries suggest that these tests have poor performance. We aimed to assess diagnostic accuracy of established thresholds of biomarker-based NITs and Transient Elastography (TE) in identifying AF and evaluated the utility of a two-step test approach. METHODS: Biopsy-proven 641 NAFLD patients (55.2% males, median age 42 years) were included from three different centers of Asia. AF (≥ F3) was identified as per histological staging (24.8%). RESULTS: TE had the highest area under the receiver operating characteristic curve (AUROC) 0.82 (0.79-0.86), and all other biomarker-based NITs had low AUROC (< 0.7). NITs performed poorly at established thresholds. The combination of NITs utilizing liver stiffness measurement (LSM) and biomarkers, Agile 3+ and FAST, demonstrated acceptable diagnostic accuracy (AUROC 0.82 and 0.78, respectively), but none were superior to LSM alone. LSM measured using appropriate M and XL probes remained accurate regardless of body mass index (BMI); NFS and APRI scores were less accurate at higher BMI ranges. A two-step approach using NFS rule-out criteria (< - 2.97 to rule out) followed by LSM (< 7.3 kPa to rule out and ≥ 12.7 kPa to rule in) correctly classified 62.4% of patients, with only 10.2% of patients incorrectly classified. CONCLUSION: NITs have not been validated to identify AF in the Asian NAFLD population, and internationally accepted thresholds yield high false-negative rates. LSM and LSM-based combination tests remain the most accurate.

Hepatic Venous Pressure Gradient Predicts Further Decompensation in Cirrhosis Patients with Acute Esophageal Variceal Bleeding.

BACKGROUND: The role of hepatic venous pressure gradient (HVPG) in predicting further decompensation in cirrhosis patients with acute variceal bleeding (AVB) is not known. We aimed to evaluate the role of HVPG in predicting further decompensation in cirrhosis patients with AVB Methods: In this prospective study, 145 patients with cirrhosis with esophageal or gastric AVB were included. HVPG was measured on the day of the AVB. Decompensating events occurring after 42-days of AVB were considered further decompensation. RESULTS: The median age of the study cohort was 44 years; 88.3% males. The predominant etiology of cirrhosis was alcohol (46.2%). Overall, 40 (27.6%) patients developed further decompensation during median follow-up of 296 days following AVB. Gastro intestinal bleeding n = 27 (18.6%) and new-onset/worsening ascites n = 20 (13.8%) were the most common decompensating events. According to the multivariate model, HVPG was an independent predictor of any further decompensation in esophageal AVB patients but not in gastric variceal bleeding patients. HVPG cut-off of ≥16 mmHg predicted further decompensation in the esophageal AVB. However, HVPG was not an independent predictor of mortality. CONCLUSION: HVPG measured during an episode of acute variceal hemorrhage from esophageal varices predicts further decompensating events in cirrhosis patients.

Impact of body mass index on disease progression and outcomes in patients with nonalcoholic fatty liver disease.

BACKGROUND: The relationship between body mass index (BMI) and outcomes in patients with nonalcoholic fatty liver disease (NAFLD) is not well defined. This study aimed to assess the presentations, outcomes, and development of liver-related events (LREs) and non-LREs in patients with NAFLD stratified by BMI. METHODS: Records of NAFLD patients from 2000-2022 were reviewed. Patients were categorized as lean (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2), and obese (>25 kg/m2) based on BMI. Stage of steatosis, fibrosis, and NAFLD activity score were noted in the patients undergoing liver biopsy in each group. RESULTS: Out of 1051 NAFLD patients, 127 (12.1%) had normal BMI, 177 (16.8%) and 747 (71.1%) were overweight and obese, respectively. Median [interquartile range] BMI was 21.9 [20.6-22.5], 24.2 [23.7-24.6], and 28.3 [26.6-30.6] kg/m2 in each group, respectively. Prevalence of metabolic syndrome and dyslipidemia were significantly higher in the obese. Obese patients had significantly higher median [interquartile range] liver stiffness (6.4 [4.9-9.4] kPa) than overweight and lean subjects. A higher proportion of obese patients had significant and advanced liver fibrosis. At follow-up, there were no significant differences in the progression of liver disease, new LREs, coronary artery disease, or hypertension across the BMI groups. Overweight and obese patients were more likely to develop new-onset diabetes by follow-up. The mortality rates in the three groups were comparable (0.47, 0.68, and 0.49 per 100 person-years, respectively), with similar causes of death (liver-related vs non-liver-related). CONCLUSIONS: Patients with lean NAFLD have similar disease severity and rates of progression as the obese. BMI is not a reliable determinant of outcomes in NAFLD patients.

Pregnancy outcomes in patients with Budd-Chiari syndrome: A tertiary care experience.

BACKGROUND: Budd-Chiari syndrome (BCS) is associated with infertility and adverse pregnancy outcomes in affected females. Scant literature is available on the effect of an endovascular intervention on fertility and the outcome of future pregnancies in these patients. AIMS: To assess the infertility rates, maternal and fetal outcomes of pregnancy and effect of endovascular intervention in women with BCS. METHODS: In this retrospective analysis, 121 female patients with BCS attending our liver clinic from 2017 to 2020 were included. Demographic details, intervention details, pregnancies - pre- and post-intervention - and fetal outcomes were noted. RESULTS: BCS was diagnosed pre-conception in 58 women (group 1; median age: 22 years), during/after pregnancy, but before completion of family in 39 (group 2; median age: 27 years), and after completion of family in 24 (group 3; median age: 34 years). Median Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD) scores were 7 and 12, respectively. The primary infertility rate was 19.8% (24/121). In group 1, 15 women with primary infertility underwent endovascular intervention with 5/15 (33%) women conceiving subsequently, resulting in four live births and seven abortions. In group 2, five women developed BCS during pregnancy and 11 postpartum; 11/39 had a history of one or more abortions. Overall, 8/34 (23.5%) who underwent endovascular intervention had 4/8 (50%) successful pregnancies. In group 3, no patient had any major complications during past pregnancies. The mode of delivery was vaginal in 88% of cases. No congenital anomaly/major bleeding episodes/decompensation/maternal mortality occurred. CONCLUSIONS: Infertility is common in patients with BCS. Pregnancy is well-tolerated in those with compensated liver disease.

Incidence and Predictors of Liver-Related Events in Patients With Nonalcoholic Fatty Liver Disease.

Background: Nonalcoholic fatty liver disease (NAFLD) is the commonest type of liver disease worldwide. We aimed to assess the incidence and predictors of liver-related events (LREs) and mortality in NAFLD patients. Methods: NAFLD patients (n = 957) evaluated between January 2000 and November 2021 were included. Patients were categorised as noncirrhosis (NC), compensated cirrhosis (CC) and decompensated cirrhosis (DC), and the incidence of LRE and mortality were estimated and compared. Results: The proportions of NC, CC and DC were 87.8% (n = 840), 8.8% (n = 84) and 3.4% (n = 33), respectively. The median follow-up duration was 3.9 (3.0-5.7) years, and the total cumulative duration was 4633 person-years. The incidence of LRE per 100 person-years was 0.14, 2.72 and 10.24 in patients with NC, CC and DC, respectively. The incidence of mortality was 0.12, 1.05 and 4.24 per 100 person-years, respectively, in the 3 groups. The causes of mortality in the 3 groups were liver related in 1/5 (20%), 3/4 (75%) and 6/9 (66.7%), respectively. Overall, the mortality rate was higher in those with diabetes than those without diabetes (log-rank P value = 0.005). On further analysis, diabetes was associated with poor outcomes only in NC group (log-rank P value = 0.036), and not in CC (log-rank P value = 0.353) or DC groups (log-rank P value = 0.771). On multivariate Cox proportional hazard analysis, age (hazard ratio [HR] 1.070), hypertension (HR 4.361) and DC (HR 15.036) were independent predictors of poor outcomes. Liver stiffness measurement, bilirubin, CC and DC were independent predictors of LRE. Conclusion: In our study of NAFLD from India, the incidence of LRE was found to be similar to that seen in Western studies. In NC NAFLD, diabetes was associated with poor outcomes.

Compensated Advanced Chronic Liver Disease in Nonalcoholic Fatty Liver Disease: Two-Step Strategy is Better than Baveno Criteria.

BACKGROUND: Advanced fibrosis and cirrhosis (compensated advanced chronic liver disease [cACLD]) are clinically indistinguishable and increase risk of developing clinically significant portal hypertension. Baveno VII recommends using elastography to rule out and diagnose cACLD with liver stiffness measurement (LSM) cut-offs of 10/15 kPa. METHODS: In a retrospective analysis of 330 nonalcoholic fatty liver disease (NAFLD) patients, performance of the Baveno VII cut-offs for diagnosing cACLD was compared with newly suggested lower cut-offs (8/12 kPa). A model for detecting cACLD among those with LSM between 8 and 12 kPa was developed and compared with recently published models. RESULTS: Seventy (21.2%) of the 330 NAFLD patients had biopsy-proven cACLD. The Baveno VII cut-offs (10/15 kPa) had a lower sensitivity of 72.8% (60.9-82.8%) and a specificity of 93.4% (89.7-96.1%). Sensitivity and specificity of lower cut-offs (8/12 kPa) were 91.4% (82.3-96.8%) and 88.5% (83.9-92.1%), respectively. Modeling based on the presence of diabetes (odds ratio [OR] 3.625[1.161-11.320], p = 0.027) and serum aspartate aminotransferase (AST) levels (OR 1.636[1.098-2.436], p = 0.015) correctly identified 75.7% of patients with LSM between 8 and 12 kPa. Our model performed best with an area under receiver operator curve (AUROC) of 0.725 (95%CI 0.609-0.822), compared to Papatheodoridi (AUROC 0.626, CI 0.506-.736) and Zhou (AUROC 0.523, CI 0.403-0.640) models. A two-step strategy comprising application of lower LSM cut-offs followed by the predictive model correctly identified the presence of cACLD in 83% of the patients as compared to 75% by the Baveno VII cut-offs. CONCLUSION: A two-step strategy employing lower LSM cut-offs and modeling based on diabetes and AST levels outperforms Baveno VII cut-offs for identifying cACLD in NAFLD patients.

Therapeutic plasma-exchange improves short-term, but not long-term, outcomes in patients with acute-on-chronic liver failure: A propensity score-matched analysis.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is associated with a high short-term mortality rate in the absence of liver transplantation. The role of therapeutic plasma exchange (TPE) in improving the outcomes of ACLF and acute decompensation (AD) is unclear. In this retrospective analysis, we aimed to determine the impact of TPE on mortality in patients with ACLF. METHODS: ACLF patients receiving TPE with standard medical treatment (SMT) were propensity score matched (PSM) with those receiving SMT alone (1:1) for sex, grades of ACLF, CLIF C ACLF scores, and the presence of hepatic encephalopathy. The primary outcomes assessed were mortality at 30 and 90 days. Survival analysis was performed using Kaplan Meier survival curves. RESULTS: A total of 1151 patients (ACLF n = 864 [75%], AD [without organ failure] n = 287 [25%]) were included. Of the patients with ACLF (n = 864), grade 1, 2, and 3 ACLF was present in 167 (19.3%), 325 (37.6%), and 372 (43.0%) patients, respectively. Thirty-nine patients received TPE and SMT, and 1112 patients received only SMT. On PSM analysis, there were 38 patients in each group (SMT plus TPE vs SMT alone). In the matched cohort, the 30-days mortality was lower in the TPE arm compared to SMT (21% vs 50%, P = .008), however, the 90-day mortality was not significantly different between the two groups (36.8% vs 52.6%, P = .166); HR, 0.82 (0.44-1.52), P = .549. CONCLUSION: TPE improves short-term survival in patients with ACLF, but has no significant impact on long-term outcomes. Randomized control trials are needed to obtain a robust conclusion in this regard.

Serological Immune Response Following ChAdOx1 nCoV-19 Vaccine (Covishield®) in Patients with Liver Cirrhosis.

Introduction: Data are limited on antibody response to the ChAdOx1 nCoV-19 vaccine (AZD1222; Covishield®) in cirrhosis. We studied the antibody response following two doses of the ChAdOx1 vaccine, given 4−12 weeks apart, in cirrhosis. Methods: Prospectively enrolled, 131 participants (71% males; age 50 (43−58); alcohol-related etiology 14, hepatitis B 33, hepatitis C 46, cryptogenic 21, autoimmune 9, others 8; Child−Turcott−Pugh class A/B/C 52/63/16). According to dose intervals, the participants were grouped as ≤6 weeks (group I), 7−12 weeks (group II), and 13−36 weeks (group III). Blood specimens collected at ≥4 weeks after the second dose were tested for anti-spike antibody titre (ASAb; positive ≥ 0.80 U/mL) and neutralizing antibody (NAb; positive ≥20% neutralization) using Elecsys Anti-SARS-CoV-2 S (Roche) and SARS-CoV-2 NAb ELISA Kit (Invitrogen), respectively. Data are expressed as number (proportion) and median (interquartile range) and compared using non-parametric tests. Results: Overall, 99.2% and 84% patients developed ASAb (titre 5440 (1719−9980 U/mL)) and NAb (92 (49.1−97.6%)), respectively. When comparing between the study groups, the ASAb titres were significantly higher in group II than in group I (2613 (310−7518) versus 6365 (2968−9463), p = 0.027) but were comparable between group II and III (6365 (2968−9463) versus 5267 (1739−11,653), p = 0.999). Similarly, NAb was higher in group II than in group I (95.5 (57.6−98.0) versus 45.9 (15.4−92.0); p < 0.001), but not between the groups II and III (95.5 (57.6−98.0) versus 92.4 (73.8−97.5); p = 0.386). Conclusion: Covishield® induces high titres of ASAb and NAb in cirrhosis. A higher titre is achieved if two doses are given at an interval of more than six weeks.

Effect of thrombocytopenia and platelet transfusion on outcomes of acute variceal bleeding in patients with chronic liver disease.

BACKGROUND: Platelet transfusion in acute variceal bleeding (AVB) is recommended by few guidelines and is common in routine clinical practice, even though the effect of thrombocytopenia and platelet transfusion on the outcomes of AVB is unclear. AIM: To determine how platelet counts, platelets transfusions, and fresh frozen plasma transfusions affect the outcomes of AVB in cirrhosis patients in terms of bleeding control, rebleeding, and mortality. METHODS: Prospectively maintained database was used to analyze the outcomes of cirrhosis patients who presented with AVB. The outcomes were assessed as the risk of rebleeding at days 5 and 42, and risk of death at day 42, considering the platelet counts and platelet transfusion. Propensity score matching (PSM) was used to compare the outcomes in those who received platelet transfusion. Statistical comparisons were done using Kaplan-Meier curves with log-rank tests and Cox-proportional hazard model for rebleeding and for 42-d mortality. RESULTS: The study included 913 patients, with 83.5% men, median age 45 years, and Model for End-stage Liver Disease score 14.7. Platelet count < 20 × 109/L, 20-50 × 109/L, and > 50 × 109/L were found in 23 (2.5%), 168 (18.4%), and 722 (79.1%) patients, respectively. Rebleeding rates were similar between the three platelet groups on days 5 and 42 (13%, 6.5%, and 4.7%, respectively, on days 5, P = 0.150; and 21.7%, 17.3%, and 14.4%, respectively, on days 42, P = 0.433). At day 42, the mortality rates for the three platelet groups were also similar (13.0%, 23.2%, and 17.2%, respectively, P = 0.153). On PSM analysis patients receiving platelets transfusions (n = 89) had significantly higher rebleeding rates on day 5 (14.6% vs 4.5%; P = 0.039) and day 42 (32.6% vs 15.7%; P = 0.014), compared to those who didn't. The mortality rates were also higher among patients receiving platelets (25.8% vs 23.6%; P = 0.862), although the difference was not significant. On multivariate analysis, platelet transfusion and not platelet count, was independently associated with 42-d rebleeding. Hepatic encephalopathy was independently associated with 42-d mortality. CONCLUSION: Thrombocytopenia had no effect on rebleeding rates or mortality in cirrhosis patients with AVB; however, platelet transfusion increased rebleeding on days 5 and 42, with a higher but non-significant effect on mortality.

Prevalence and Predictors of Nonalcoholic Fatty Liver Disease in Family Members of Patients With Nonalcoholic Fatty Liver Disease.

Background and aims: Nonalcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease worldwide. Despite the high prevalence, no screening recommendations yet exist. We designed a prospective observational study to estimate the prevalence of NAFLD in the family of patients with NAFLD and develop a predictive model for identifying it. Methodology: The prevalence of NAFLD in patients' family members was estimated using ultrasonography, and univariate and multivariate odds were calculated for its predictors. A model was created using the significant parameters on multivariate odds, and its performance was tested using the area under the receiver operating characteristic (AUROC). Results: Among 447 family members of 191 patients with NAFLD, the prevalence of NAFLD was 55.9%. Family members with NAFLD were younger and had lower serum levels of aspartate aminotransferase, alanine aminotransferase (ALT), triglycerides. The liver stiffness measurement and controlled attenuation parameter values were also lesser in family members compared to the index cases. Age, body mass index (BMI), and ALT were independent predictors of NAFLD in the family members. A model combining age and BMI had an AUROC of 0.838 [95% confidence interval (CI) 0.800-0.876, P < 0.001]. Age ≥30 years and BMI ≥25 kg/m2 had an odds ratio of 33.5 (95% CI 17.0-66.0, P < 0.001) for prediction of NAFLD, in comparison to BMI <25 kg/m2 and age <30 years. Conclusion: Family members of patients with NAFLD are at increased risk of NAFLD. Screening strategies using BMI and age ensure early identification and could be beneficial in clinical practice.

Predictors of in-hospital Outcomes in Patients With Cirrhosis and Coronavirus Disease-2019.

Background: Coronavirus disease-2019 (COVID-19) cases continue to increase globally. Poor outcomes in patients with COVID-19 and cirrhosis have been reported; predictors of outcome are unclear. The existing data is from the early part of the pandemic when variants of concern (VOC) were not reported. Aims: We aimed to assess the outcomes and predictors in patients with cirrhosis and COVID-19. We also compared the differences in outcomes between the first wave of pandemic and the second wave. Methods: In this retrospective analysis of a prospectively maintained database, data on consecutive cirrhosis patients (n = 221) admitted to the COVID-19 care facility of a tertiary care center in India were evaluated for presentation, the severity of liver disease, the severity of COVID-19, and outcomes. Results: The clinical presentation included: 18 (8.1%) patients had compensated cirrhosis, 139 (62.9%) acute decompensation (AD), and 64 (29.0%) had an acute-on-chronic liver failure (ACLF). Patients with ACLF had more severe COVID-19 infection than those with compensated cirrhosis and AD (54.7% vs. 16.5% and 33.3%, P < 0.001). The overall mortality was 90 (40.7%), the highest among ACLF (72.0%). On multivariate analysis, independent predictors of mortality were high leukocyte count, alkaline phosphatase, creatinine, child class, model for end-stage liver disease (MELD) score, and COVID-19 severity. The second wave had more cases of severe COVID-19 as compared to the first wave, with a similar MELD score and Child score. The overall mortality was similar between the two waves. Conclusion: Patients with COVID-19 and cirrhosis have high mortality (40%), particularly those with ACLF (72%). A higher leukocyte count, creatinine, alkaline phosphatase, Child class, and MELD score are predictors of mortality.

The Outcome in Cirrhosis after Hospital Discharge is Not Worsened with COVID-19 Infection: A Propensity Score-matched Analysis.

Background: Patients with cirrhosis and coronavirus disease-2019 (COVID-19) have high in-hospital mortality. The information on the outcome of cirrhosis patients in the posthospitalization period is limited. Aims: We aimed to study the outcome of cirrhosis patients with COVID-19 after hospital discharge. Methods: The records of the cirrhosis patients discharged after COVID-19 were reviewed. Their data were compared with a similar number of cirrhosis patients without COVID-19 after propensity score matching for age, sex, etiology of cirrhosis, and model for end-stage liver disease (MELD) score. Results: Cirrhosis patients with (n = 92) or without (n = 92) COVID-19 were included in 1:1 ratio. The mortality among COVID-19 (22; 23.9%) and non-COVID-19 (19; 20.7%) were comparable (HR 1.224; 95% CI 0.663-2.263, P = 0.520), over a similar duration of follow-up [186 (86-271) vs. 183 (103-274)]. Among COVID-19 patients, 45; 48.9% developed a new acute decompensation-increased ascites (40; 43.5%), hepatic encephalopathy (20; 21.7%), or variceal bleeding (8; 8.7%) whereas 25 (27.2%) patients needed rehospitalization. A proportion of participants continued to have either fatigue/weakness (24/80; 30.0%), sleep disturbances (11/80; 13.7%), or joint pains (16/80; 20.0%). The most common causes of death in patients of both groups were end-stage liver disease: 16 (72.7%) vs. 9 (47.4%), followed by multiorgan dysfunction: 4 (18.2%) vs. 6 (31.6%), GI bleeding: 2 (9.1%) vs. 4 (21.0%), P = 0.484. A lower albumin level, higher international normalized ratio, bilirubin, Child-Turcotte-Pugh, and MELD scores at discharge predicted mortality in the COVID-19 group. Conclusion: Short-term outcomes of patients with cirrhosis who survive the initial insult of COVID-19 are not different from patients without COVID-19, and survival is determined by the severity of liver disease at discharge.

Clinical Utility of Transient Elastography in the Management of Patients with Budd-Chiari Syndrome Undergoing Endovascular Intervention.

PURPOSE: To quantify liver stiffness measurement (LSM) changes after endovascular intervention for Budd-Chiari syndrome (BCS) and evaluate whether LSM changes predict restenosis after endovascular intervention. MATERIALS AND METHODS: Patients with BCS who underwent endovascular intervention and had at least 2 LSM values available after the intervention were included. ΔLSM was the difference between LSMs estimated at the last and second last hospital visits. In patients with restenosis, 2 LSM values before restenosis were included. ΔLSM% was calculated as the ratio of ΔLSM to the LSM at the second last visit and expressed as a percentage. Odds ratio (OR) with confidence interval (CI) and area under the receiver operating characteristic curves (AUROCs) were calculated for the predictors of restenosis. RESULTS: The median baseline and postinterventional 1-week, 3-month, 6-month, and 12-month LSM values were 47.2 kPa (33.8-68.4 kPa), 29.2 kPa (24.5-43.0 kPa), 26.2 kPa (18.6-38.9 kPa), 20.9 kPa (13.3-29.8 kPa), and 17.3 kPa (11.8-25.4 kPa), respectively. Of the 118 patients, including 67 men, restenosis developed in 10 patients after a median (interquartile range) duration of 19 months (11-46 months). ΔLSM% was higher (more positive) in patients with restenosis than in those without restenosis (44.7 [8.3-134.3] vs -6.6 [-19.4 to 14.9], P = .001). ΔLSM% was a significant predictor of restenosis with an OR of 1.032 (95% CI, 1.015-1.050; P < .001). The AUROC for ΔLSM% was 0.831 (95% CI, 0.750-0.893; P = .001), and a ΔLSM% increment of 13.2% predicted restenosis with a sensitivity and specificity of 80.0% and 74.1%, respectively. CONCLUSIONS: LSM gradually decreases after endovascular intervention, and transient elastography is a promising test for detecting restenosis after the endovascular treatment of patients with BCS.