Immunogenicity, Immune Dynamics, and Subsequent Response to the Booster Dose of Heterologous versus Homologous Prime-Boost Regimens with Adenoviral Vector and mRNA SARS-CoV-2 Vaccine among Liver Transplant Recipients: A Prospective Study

BACKGROUND: Heterologous prime-boost vaccination potentially augments the immune response against SARS-CoV-2 in liver transplant (LT) recipients. We investigated immunogenicity induced by different primary prime-boost vaccination protocols and the subsequent response to the booster vaccine among LT recipients. METHODS: LT recipients, who received primary immunisation with ChAdOx1/ChAdOx1 or ChAdOx1/BNT162b2, were administered the third dose of mRNA-1273 three months following the primary vaccination. Blood samples were collected before and after primary vaccination and post-booster. The levels of receptor binding domain antibody (anti-RBD) and neutralising antibody (sVNT) and spike-specific T-cell responses were assessed. RESULTS: Among the 89 LT recipients, patients receiving ChAdOx1/BNT162b2 had significantly higher anti-RBD titres, sVNT, and cellular response after primary vaccination than those receiving ChAdOx1/ChAdOx1 (p 90% of LT patients, with only 12.3% positive against the Omicron variant. CONCLUSIONS: ChAdOx1/BNT162b2 evoked a significantly higher immunological response than ChAdOx1/ChAdOx1 in LT recipients. The booster strategy substantially induced robust immunity against wild type in most patients but was less effective against the Omicron strain

The impact of stigma on quality of life and liver disease burden among patients with nonalcoholic fatty liver disease

Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL. Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p <0.0001). In multivariate analyses, experience with stigmatization or discrimination due to NAFLD was the strongest independent predictor of lower HRQL scores (beta from -5% to -8% of score range size, p <0.02). Experience with stigmatization due to obesity was associated with lower Activity, Emotional Health, Fatigue, and Worry domain scores, and being uncomfortable with the term “fatty liver disease” with lower Emotional Health scores (all p <0.05). In addition to stigma, the greatest disease burden as assessed by LDB was related to patients’ self-blame for their liver disease. Conclusions: Stigmatization of patients with NAFLD, whether it is caused by obesity or NAFLD, is strongly and independently associated with a substantial impairment of their HRQL. Self-blame is an important part of disease burden among patients with NAFLD. Impact and implications: Patients with nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), may experience impaired health-related quality of life and stigmatization. Using a specifically designed survey, we found that stigmatization of patients with NAFLD, whether it is caused by obesity or the liver disease per se, is strongly and independently associated with a substantial impairment of their quality of life. Physicians treating patients with NAFLD should be aware of the profound implications of stigma, the high prevalence of self-blame in the context of this disease burden, and that providers’ perception may not adequately reflect patients’ perspective and experience with the disease

Prevalence of hepatitis D virus infection among patients with chronic hepatitis B infection in a tertiary care centre in Thailand

Abstract Knowledge about the epidemiology of hepatitis D virus (HDV) is essential for effective screening and management. Our study aimed to update the prevalence of HDV infection among patients with hepatitis B virus (HBV) infection at hepatology clinics in Thailand. We enrolled HBV-infected patients from hepatology clinics at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between June 2022 and November 2023. Demographic, biochemical characteristics, and liver-related complications (LRC), including cirrhosis and hepatocellular carcinoma, were reviewed. The competitive enzyme and chemiluminescence immunoassays were used to detect anti-HDV antibodies. Real-time polymerase chain reaction (RT-PCR) was used to test for HDV RNA in anti-HDV-positive patients. The HDV genotype was identified in detectable HDV RNA samples. Of the 702 enrolled patients, four (0.6%) had positive and equivocal for both anti-HDV tests. Two (50.0%) of the four patients tested positive for HDV RNA and genotype 1 was identified; one had multiple risk factors. Anti-HDV seroprevalence was not significantly different between patients with and without LRC. In conclusion, HDV co-infection is less common in Thailand than globally. Additionally, our study identified genotype 1, the predominant HDV genotype worldwide, and observed co-infection even without LRC

The association between vitamin D receptor polymorphism and phases of chronic hepatitis B infection in HBV carriers in Thailand

Vitamin D receptor (VDR) polymorphism partly regulates the immune system and is associated with hepatic flare in chronic Hepatitis B virus infection (HBV). Our study identified the association between two distinct phases, VDR polymorphisms and HBV inactive carrier (IC) and chronic hepatitis (CH). Chronic HBV patients were enrolled from February to August 2020. An HBV viral load (VL) < 2,000 IU/ml twice for 6 months apart, with no prior history of HBV treatment, defined the IC phase. Six common polymorphisms in the VDR gene, including CdX-2, GATA, FokI, Bsml, ApaI, and TaqI, were studied using real-time PCR. The different outcomes in allele, genotype, and haplotype frequencies in between groups and linkage disequilibrium (LD) mapping were analyzed. Among 324 enrolled patients, there were 163 patients in IC and 161 patients in CH phases. The mean vitamin D levels were not statistically different between groups. The proportion of allele frequencies of CdX-2 in IC and CH was 53.7% and 62.7% for G allele, and 46.3% and 37.3% for A allele (p 0.019). The proportion of GG genotype of CdX-2 was less frequently found in patients with IC compared to that in patients with CH (27% vs 41%, p 0.028). By multivariate analysis, CdX-2 G/A genotypes were independently associated with IC, with adjusted odd ratio (OR) 1.83 (1.10–3.04), p 0.019. The LD mapping of single nucleotide polymorphisms (SNP) revealed high LD scores in Bsml/ApaI/TaqI (BAT) haplotype in both groups while, CdX-2/GATA and GATA/FokI demonstrated high LD score only in CH group. CdX-2 G/A genotypes were independently associated with IC status in Thai patients with chronic HBV infection. The difference in LD of the CdX-2/GATA and GATA/FokI haplotypes in between groups may represent a non-random selection resulting in the variation of immune control

Allele and genotype frequencies of six VDR SNPs including <i>CdX-2</i>, <i>GATA</i>, <i>Fok</i>I, <i>Bsm</i>l, <i>Apa</i>I and <i>Taq</i>I in patients with HBeAg positive (N 62) and negative (N 254).

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Haplotype frequencies of VDR SNPs in HBV inactive carrier and chronic hepatitis phases.

Haplotype frequencies of VDR SNPs in HBV inactive carrier and chronic hepatitis phases.</p

Baseline characteristics of patients with HBV inactive carrier (IC) and chronic hepatitis (CH) phases.

Baseline characteristics of patients with HBV inactive carrier (IC) and chronic hepatitis (CH) phases.</p

Allele and genotype frequencies of six VDR SNPs, including <i>CdX-2</i>, <i>GATA</i>, <i>Fok</i>I, <i>Bsm</i>l, <i>Apa</i>I, and <i>Taq</i>I in healthy controls.

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Univariate and multivariate regression analysis of factors associated with HBV inactive carrier (IC) phase.

Univariate and multivariate regression analysis of factors associated with HBV inactive carrier (IC) phase.</p

Genomic organization and linkage disequilibrium (LD) mapping of six SNPs of vitamin D receptor (<i>VDR</i>) gene.

Patients with HBV inactive carrier (IC), chronic hepatitis (CH) phases and the general population.</p