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.

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.

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.

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.

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.