Poor immune response to coronavirus disease vaccines in decompensated cirrhosis patients and liver transplant recipients

Background and aimsRecent studies have reported poor humoral immune response to mRNA vaccines in patients with chronic liver disease (CLD). However, the immunogenicity of ChAdOx1 (vector-based) and BBV152 (inactivated virus) vaccines in patients with CLD and liver transplant recipients (LTRs) is unknown. Therefore, we aimed to assess the immunogenicity of ChAdOx1 and BBV152 vaccines in patients with CLD (including cirrhosis patients) and LTRs.MethodsIn this single-center prospective study, consecutive completely vaccinated (ChAdOx1 or BBV152) non-cirrhosis CLD patients, those with cirrhosis, and LTRs were compared with matched healthy controls for anti-spike antibody and cellular response.ResultsSixty healthy individuals, 50 NCCLD patients, 63 compensated and 50 decompensated cirrhosis, and 17 LTRs were included. The proportion of non-responders was similar among the healthy control (8 %), non-cirrhosis CLD (16 %), and compensated cirrhosis groups (17.5 %;p = 0.3). However, a higher proportion of patients with decompensated cirrhosis (34 %) and LTRs (59 %) were non-responders than the healthy controls (p = 0.001). Cluster of differentiation (CD) 4-effector cells were lower in patients with non-cirrhosis CLD and compensated cirrhosis. CD4-naïve, CD4-effector, B, and B-memory cells were lower in the decompensated cirrhosis group. Although the central memory cells were higher in the decompensated cirrhosis group, they could not differentiate into effector cells. CD4- and CD8-naïve cells were higher in the marrow in the LTRs, while the CD4-effector memory cells and CD4- and CD8-effector cells were lower in the LTRs. Furthermore, B cells were more deficient in the LTRs, suggesting poor antibody response.ConclusionPatients with decompensated cirrhosis and LTRs demonstrated suboptimal humoral and cellular immune responses against recombinant and inactivated COVID-19 vaccines.     

Refining the Baveno VI elastography criteria for the definition of compensated advanced chronic liver disease

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Relationship between insulin resistance and serum alanine aminotransferase as a surrogate of NAFLD (nonalcoholic fatty liver disease) in obese Korean children

There has been increasing number of obese children who accompany obesity-related comorbidities. It has been known that nonalcoholic fatty liver disease (NAFLD) as one of obesity-related comorbidities is related with insulin resistance. So, we investigated the relation between insulin resistance and NAFLD, using serum alanine aminotransferase (ALT) as a surrogate of NAFLD among obese children in Korea. The study subjects were 909 obese children aged 9–12 years (boys 613, girls 296). Body mass index (BMI), waist circumference (WC), blood pressure, fasting blood glucose, fasting insulin, lipid profile were measured. ALT, liver enzyme was used as a surrogate of NAFLD and homeostasis model assessment of insulin resistance (HOMA-IR) was used as the index of insulin resistance. The prevalence of elevated serum ALT (≥40 mg/dl) was 33.4% in boys, and 19.6% in girls respectively. In boys, ALT was correlated with BMI, waist circumference, total cholesterol, triglyceride, HDL-cholesterol, systolic and diastolic blood pressure, HOMA-IR, fasting serum insulin. Odds ratio for HOMA-IR against the elevated ALT (≥40 mg/dl) was 1.061 (95% confidence interval, 1.020–1.103, P = 0.003). In girls, ALT was correlated with BMI, waist circumference, total cholesterol, triglyceride, glucose, systolic and diastolic blood pressure, HOMA-IR, fasting serum insulin. Odds ratio for HOMA-IR against the elevated ALT (≥40 mg/dl) was 1.042 (95% confidence interval, 0.998–1.088, P = 0.063). Among obese Korean children, insulin resistance and ALT, lipid profile, BMI, WC, blood pressure showed significant correlation. Especially, in boys, higher ALT is founded to be independently associated with insulin resistance.     

Subclinical and clinical atherosclerosis in non-alcoholic fatty liver disease is associated with the presence of hypertension

Background and aimsNon-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular (CV) risk. However, it is unclear whether NAFLD contributes independently to the development of CV disease. Our study aimed at assessing the differences in several indices of atherosclerosis, arterial stiffness and cardiac morphology among patients with isolated NAFLD, isolated hypertension (HT) or a combination of the two conditions.Methods and resultsA total of 169 participants (mean age = 50.4 ± 10.2 yrs; males = 73.6%) were divided according to the presence of NAFLD and HT into three groups: only NAFLD (55 patients), only HT (49 patients), and NAFLD + HT (65 patients). Exclusion criteria were a BMI≥35 kg/m² and a diagnosis of diabetes mellitus. Carotid ultrasonography was performed to measure markers of atherosclerosis and arterial stiffness. Cardiac remodeling was analyzed using echocardiography. The prevalence of subclinical and overt atherosclerosis was significantly higher in the NAFLD + HT patients as compared to the other two groups (atherosclerotic plaques: 43.1%, 10.9%, and 22.4% (p < 0.001) in NAFLD + HT, NAFLD, and HT groups, respectively). No differences were found among indices of arterial stiffening and cardiac remodeling across the three groups. In multivariate regression analysis, the coexistence of NAFLD and HT was an independent risk factor for overt atherosclerosis (OR = 4.88, CI 95% 1.14–20.93), while no association was found when either NAFLD or HT was considered alone.ConclusionOvert atherosclerosis was significantly present only in NAFLD + HT patients, but not in patients with isolated NAFLD. This implies that the impact of NAFLD on vascular structure and function could depend on the coexistence of other major CV risk factors, such as HT.     

Liver steatosis assessment: Correlations among pathology,radiology, clinical data and automated image analysis software

Quantitating hepatic steatosis is important in many liver diseases and liver transplantation. Since steatosis estimation by pathologists has inherent intra- and inter-observer variability, we compared and contrasted computerized techniques with magnetic resonance imaging measurements, pathologist visual scoring, and clinical parameters. Computerized methods applied to whole slide images included a commercial positive pixel count algorithm and a custom algorithm programmed at our institution. For all liver samples (n = 59), including pediatric, adult, frozen section, and permanent specimens, statistically significant correlations were observed between pathology, radiology, and each image analysis modality (r = 0.75–0.97, p < 0.0001), with the strongest correlations in the pediatric cohort. Statistically significant relationships were observed between each method and with body mass index (r = 0.37–0.56, p from <0.0001 to <0.05) and with albumin (r = 0.55–0.64, p < 0.05) but not with alanine aminotransferase or aspartate aminotransferase. Although pathologist assessments correlated (r = 0.64–0.86, 0.92–0.97, and 0.78–0.91 for microvesicular, macrovesicular, and overall steatosis, respectively), the absolute values of hepatic steatosis visual assessment were susceptible to intra- and inter-observer variability, particularly for microvesicular steatosis. Image analysis, pathologist assessments, radiology measurements, and several clinical parameters all showed correlations in this study, providing evidence for the utility of each method in different clinical and research settings.     

The conundrum of cryptogenic cirrhosis: Adverse outcomes without treatment options

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Effect of chronic alcohol consumption on the development and progression of non-alcoholic fatty liver disease (NAFLD)

A number of epidemiologic studies show a protective effect of light to moderate daily alcohol consumption on the development of non-alcoholic fatty liver disease (NAFLD). Although these small amounts of ethanol may prevent fatty liver, they may also be a risk factor for other diseases such as breast and colon cancer. Those individuals who have underlying hepatic steatosis or non-alcoholic steatohepatitis (NASH) should not use ethanol chronically since the data available at present do not support a beneficial effect of alcohol in this situation. Especially overweight and obese individuals may be more susceptible towards alcohol even at moderate doses. Animal experiments show a negative effect of ethanol on liver histology in either dietary or genetic NASH models. In addition, patients with NASH reveal a significant increased risk for hepatocellular cancer (HCC) even with social alcohol consumption. Thus, subjects with underlying NASH should abstain from alcohol at any amounts.