Chronic liver disease (CLD) entails elevated risk of COVID-19 severity and mortality. The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear. Therefore, we conducted a cross-sectional study involving 237 adult CLD patients and 170 healthy controls (HC) to analyze neutralizing antibodies (NAbs) against SARS-CoV-2 prototype and BA.4/5 variant, anti-receptor binding domain (RBD) IgG, and total anti-SARS-CoV-2 antibodies. Serum levels of the total anti-SARS-CoV-2 antibodies, anti-RBD IgG and inhibition efficacy of NAbs were significantly elevated in CLD patients after the booster dose compared with the pre-booster dose, but were relatively lower than those of HCs. Induced humoral responses decreased over time after booster vaccination. The neutralization efficiency of the serum against BA.4/5 increased but remained below the inhibition threshold. All four SARS-CoV-2 antibodies, including total anti-SARS-CoV-2 antibodies, anti-RBD IgG and NAbs against prototype and BA.4/5, were lower in patients with severe CLD than those with non-severe CLD. After booster shot, age and time after the last vaccine were the risk factors for seropositivity of NAb against BA.4/5 in CLD patients. Additionally, white blood cell counts and hepatitis B core antibodies were the protective factors, and severe liver disease was the risk factor associated with seropositivity of total anti-SARS-CoV-2 antibodies. Overall, our data uncovered that antibody responses were improved in CLD patients and peaked at 120 days after the booster vaccines. All antibodies excepting total anti-SARS-CoV-2 antibodies declined after peak. CLD patients exhibited impaired immunologic responses to vaccination and weakened NAbs against BA.4/5, which hindered the protective effect of the booster shot against Omicron prevalence. Cellular immune responses should be further evaluated to determine the optimal vaccine regimen for CLD patients.

Purpose: To investigate the clinical efficacy of avatrombopag, an oral thrombopoietin receptor agonist, versus subcutaneous recombinant human thrombopoietin (rh-TPO) in the treatment of severe thrombocytopenia (TCP) associated with chronic liver disease (CLD). Methods: Clinical data of 250 patients with severe TCP associated with CLD were collected in a single hospital from January 2019 to January 2022. The main parameters measured were the therapeutic response rate, changes in platelets (PLTs), and adverse events. Propensity score matching (PSM) was used to avoid possible selection bias. Results: After PSM, a total of 154 patients were enrolled in the study: 77 in the avatrombopag group and 77 in the rh-TPO group. There was no statistically significant difference between the two groups in the effect of increasing the PLT count (Waldχ 2 = 1.659, p = 0.198; Waldχ 2 = 0.220, p = 0.639). In addition, no interaction between time and different medications was found (Waldχ 2 = 0.540, p = 0.910; Waldχ 2 = 1.273, p = 0.736). Interestingly, in the subgroup analysis, both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A (88.89% vs. 63.41%, p =0.003; 81.33% vs. 61.76%, p = 0.043). Fewer patients reported dizziness in the avatrombopag group than in the rh-TPO group both before and after PSM (7.8% vs. 25.0%; 7.8% vs. 24.7%, p < 0.05). Conclusion: Both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A and showed a lower incidence of dizziness in all patients.

BACKGROUND: Chronic liver diseases (CLD), including cirrhosis and non-cirrhotic liver diseases, are globally widespread and create a serious disease burden. Platelet count is a clinically accessible and affordable prognostic indicator of liver disease. We investigated the relationship between platelet count and 90-day prognosis in patients with acute-on-chronic liver diseases (AoCLD).
METHODS: A total of 3,970 patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (CATCH-LIFE) study, which included two prospective multi-center cohorts, were included in the study. We grouped the patients according to the platelet count and analyzed the 90-day adverse outcome (death or liver transplantation).
RESULTS: In the final analysis, 3,939 patients with AoCLD were included, of whom 2,802 had definite liver cirrhosis. The cumulative incidence of 90-day adverse outcomes in patients increased with the change of platelet group (log-rank P<0.001). From univariate and multivariate analyses, platelet count was inversely associated with the incidence of 90-day adverse outcomes in patients (P for trend <0.001). The group with platelet count <20×109/L had the highest risk (odds ratio, 3.15; 95% confidence interval, 1.59-6.25), with 21 (36.8%) of these patients having adverse outcomes within 90 days. The risk of a 90-day adverse outcome in patients increased by 5% for every 10×109/L decrease in platelet count below 210×109/L.
CONCLUSIONS: Lower platelet count was associated with a higher incidence of 90-day adverse outcomes in patients with AoCLD. Even within the normal platelet count range, the risk of a 90-day adverse outcome in patients increased with decreases in platelet count.
BACKGROUND: NCT02457637, NCT03641872.

UNASSIGNED: Noninvasive methods for the early diagnosis and staging of hepatic fibrosis are needed. The present study aimed to investigate the alteration of magnetic susceptibility in the liver of patients with various fibrosis stages and to evaluate the feasibility of using susceptibility to stage hepatic fibrosis.
UNASSIGNED: A total of 30 consecutive patients with chronic liver diseases (CLDs) underwent magnetic resonance imaging (MRI) and liver biopsy evaluation of hepatic fibrosis, necroinflammatory activity, iron load, and steatosis. Quantitative susceptibility mapping (QSM), R2* and proton density fat fraction (PDFF) images were postprocessed from the same gradient-echo data for quantitative tissue characterization using region of interest (ROI) analysis. The differences for MRI measurements between cohorts of non-significant (Ishak-F <3) and significant fibrosis (Ishak-F ≥3) and the correlation of MRI measurements with fibrosis stages and necroinflammatory activity grades were tested. Receiver operating characteristic (ROC) analysis was also performed.
UNASSIGNED: There was a significant difference in liver susceptibility between the cohorts of significant and non-significant fibrosis (Z=-2.880, P=0.004). A moderate negative correlation between the stages of liver fibrosis and liver susceptibility was observed (r=-0.471, P=0.015). Liver magnetic susceptibility differentiated non-significant from significant hepatic fibrosis with an area under the receiver operating curve (AUC) of 0.836 (P=0.004). A highly sensitive diagnostic performance with an AUC of 0.933 was obtained using magnetic susceptibility and PDFF together (P<0.001).
UNASSIGNED: A noninvasive liver QSM-based evaluation promises an accurate assessment of significant fibrosis in patients with CLDs.

UNASSIGNED: Patients with chronic liver diseases (CLDs) often suffer from lipidosis or siderosis. Proton density fat fraction (PDFF) and R2* can be used as quantitative parameters to assess the fat/iron content of the liver. The aim of this study was to evaluate the influence of liver fibrosis and inflammation on the 3D Multi-echo Dixon (3D ME Dixon) parameters (MRI-PDFF and R2*) in patients with CLDs and to determine the feasibility of 3D ME Dixon technique for the simultaneous assessment of liver steatosis and iron overload using histopathologic findings as the reference standard.
UNASSIGNED: Ninety-nine consecutive patients with CLDs underwent T1-independent, T2*-corrected 3D ME Dixon sequence with reconstruction using multipeak spectral modeling on a 3T MR scanner. Liver specimen was reviewed in all cases, grading liver steatosis, siderosis, fibrosis, and inflammation. Spearman correlation analysis was performed to determine the relationship between 3D ME Dixon parameters (MRI-PDFF and R2*) and histopathological and biochemical features [liver steatosis, iron overload, liver fibrosis, inflammation, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL)]. Multiple regression analysis was applied to identify variables associated with 3D ME Dixon parameters. Receiver operating characteristic (ROC) analysis was performed to determine the diagnostic performance of these parameters to differentiate liver steatosis or iron overload.
UNASSIGNED: In multivariate analysis, only liver steatosis independently influenced PDFF values (R2=0.803, P<0.001), liver iron overload and fibrosis influenced R2* values (R2=0.647, P<0.001). The Spearman analyses showed that R2* values were moderately correlated with fibrosis stages (r=0.542, P<0.001) in the subgroup with the absence of iron overload. The area under the ROC curve of PDFF was 0.989 for the diagnosis of steatosis grade 1 or greater, and 0.986 for steatosis grade 2 or greater. The area under the ROC curve of R2* was 0.815 for identifying iron overload grade 1 or greater, and 0.876 for iron overload grade 2 or greater.
UNASSIGNED: 3D Multi-Echo Dixon can be used to simultaneously evaluate liver steatosis and iron overload in patients with CLDs, especially for quantification of liver steatosis. However, liver R2* value may be affected by the liver fibrosis in the setting of CLDs with absence of iron overload.

The occurrence of depression is higher in patients with chronic liver disease (CLD) than that in the general population. The mechanism described in previous studies mainly focused on inflammation and stress, which not only exists in CLD, but also emerges in common chronic diseases, leaving the specific mechanism unknown. This review was to summarize the prevalence and risk factors of depression in CLD including chronic hepatitis B, chronic hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease, and to point out the possible underlying mechanism of this potential link. Clarifying the origins of this common comorbidity (depression and CLD) may provide more information to understand both diseases.