ABSTRACT
BACKGROUND: Identification of outcome predictors is one of the unmet needs in chronic HDV infection. Until recently, no reliable quantitative assays for HDV RNA were available. AIMS: To evaluate the impact of baseline viremia on natural history of HDV infection in a cohort of patients whose serum samples were stored at their first visit 15 years ago. METHODS: Quantitative HBsAg, HBeAg, HBeAb, HBV DNA, HDV RNA, genotypes, and liver disease severity were assessed at baseline. Patients who were no longer on active follow-up were recalled and re-evaluated in August 2022. RESULTS: The majority of patients were male (64.9%); the median age was 50.1 years; and all patients were Italian, with only three born in Romania. All were HBeAg negative with HBV genotype D infection. Patients were subdivided three groups: 23 were in active follow-up (Group 1), 21 were recalled due to no longer being in follow-up (Group 2), and 11 died (Group 3). Liver cirrhosis was diagnosed in 28 subjects at the first visit; 39.3% of diagnosed patients were in Group 3, 32.1% were in Group 1 and 28.6% were in Group 2 (p = 0.001). Baseline HBV DNA IU/mL Log10 were 1.6 (1.0-5.9) in Group 1, 1.3 (1.0-4.5) in Group 2, and 4.1 (1.5-4.5) in Group 3; median baseline HDV RNA Log10 levels were 4.1 (0.7-6.7) in Group 1, 3.2 (0.7-6.2) in Group 2, and 5.2 (0.7-6.7) in Group 3, resulting significantly higher rates among patients in Group 3 compared to the other groups (p = 0.038). Eighteen patients in Group 2, as compared to 7 in Group 1, had undetectable HDV RNA at the follow-up evaluation (p = 0.001). CONCLUSIONS: HDV chronic infection is a heterogeneous disease. It may not only progress but also improve over time in patients, who eventually become HDV RNA-undetectable. HDV RNA levels may help identify the subgroup of patients with less progressive liver disease.
Subject(s)
Hepatitis D , Hepatitis , Humans , Male , Female , Middle Aged , Follow-Up Studies , Hepatitis B e Antigens , Hepatitis B virus/genetics , DNA, Viral , RNA, Viral/genetics , Hepatitis D/epidemiologyABSTRACT
BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) may progress to severe liver fibrosis and cirrhosis. A limited number of studies with a long follow up assessed fibrosis progression and related predictors in untreated patients with a histological diagnosis of NAFLD. This study aims to investigate rate and predictors of NAFLD progression. METHODS: For 9 (2-16.7) years, we followed up a cohort of patients histologically diagnosed. Disease progression was defined by a composite endpoint as evidence of cirrhosis in patients without cirrhosis at baseline, evidence of de novo occurrence of cirrhosis complications, histologically established worsening of stage 1 of fibrosis or increase of 20% in liver stiffness by transient elastography in patients rejecting a second liver biopsy. RESULTS: A total of 91 patients were enrolled. Of them, 31 had NAFL and 60 NASH. A second liver biopsy was performed in 22 NASH patients and in 4 NAFL. Disease progression was observed in 38.5% NASH and in 12.0% NAFL (p = 0.034). Patients with portal inflammation had a higher risk of progression (66.7% vs 26%, p = 0.021). High triglycerides levels, advanced fibrosis at baseline and the duration of follow-up predict disease progression (p = 0.021; OR = 6.93, 95% CI 1.33-36.08, p = 0.43; OR 8.37; 95% CI 1.07-65.58 and p = 0.034; OR = 0.88; 95% CI 0.78-0.99, respectively). CONCLUSIONS: Our results reinforce the evidence that, in the absence of pharmacologic treatment, NASH progresses in about 40% of patients. Liver biopsy is the only mean to discriminate NAFL from NASH. The prognostic role of portal inflammation needs to be explored in larger series.
ABSTRACT
Background: LC has been associated with hyporesponsiveness to several vaccines. Nonetheless, no data on complete serological and B- and T-cell immune response are currently available. Aims: To assess, in comparison with healthy controls of the same age and gender, both humoral and cellular immunoresponses of patients with LC after two or three doses of the mRNA Pfizer-BioNTech vaccine against SARS-CoV-2 and to investigate clinical features associated with non-response. Material and methods: 179 patients with LC of CTP class A in 93.3% and viral etiology in 70.1% of cases were longitudinally evaluated starting from the day before the first dose to 4 weeks after the booster dose. Their antibody responses were compared to those of healthcare workers without co-morbidities. In a subgroup of 40 patients, B- and T-cell responses were also compared to controls. Results: At d31, d90 and d180 after BNT162b2 vaccine, no detectable SARS-CoV-2 IgG response was observed in 5.9%, 3.9% and 7.2% of LC patients as compared to 0 controls (p < 0.03). A delay in B-cell and lack of prompt T-cell response compared to healthcare workers was also registered. A significant correlation between antibody titers and cellular response was observed. A MELD score > 8 was the only independent predictor of poor d31 response (p = 0.028). Conclusions: Our results suggest that cirrhotic patients have a slower and in <10% suboptimal immune response to SARS-CoV-2 vaccination. Rates of breakthrough infections were comparable between cirrhotics and controls. The booster dose was critical in inducing both humoral and cellular responses comparable to controls.
ABSTRACT
BACKGROUND AND AIMS: The WHO has solicited all countries to eliminate HCV by 2030. The Italian government started routine screening for HCV infection in January 2021, initially targeting subjects born between 1969 and 1989. With the aim of achieving micro-elimination, we designed a hospital-wide project focusing on inpatients born from 1935 to 1985 and conducted it in our institution. METHOD: All inpatients aged 35 to 85, admitted from 10 February 2020 to 9 February 2021 for many different diseases and conditions underwent HCV antibody (HCVAb) testing by third-generation ELISA. When positive, reflex HCV RNA testing and genotyping were performed. Clinical history, fibrosis diagnosis, laboratory data and concomitant medications were available for all. RESULTS: The HCV screening rate of inpatients was 100%. In total, 11,748 participants were enrolled, of whom 53.50% were male. The HCVAb positivity rate was 3.03%. The HCVAb rate increased with age and was higher for patients born between 1935 and 1944 (4.81%). The rate of HCV RNA positivity was 0.97%. The vast majority (80.70%) of HCV RNA-positive participants were 55 or older; in about 40% of cases, HCV RNA-positive patients were unaware of their infection. Although 16 patients died after HCV chronic infection diagnosis (two due COVID-19) or HCV treatment prescription (one due to COVID-19), 74.56% of patient HCV diagnoses were linked to HCV treatment, despite their co-morbidities. All patients older than 65 who died had an active HCV infection. CONCLUSION: The present study revealed a rate of active HCV infections among inpatients lower than what has been reported in the past in the general population; this appears to be a result of the widespread use of pangenotypic direct-acting antiviral agents (DAAs). The overall rate of active infection was lower than the rate observed in the 1935-1954 cohort. The high rate of inpatients unaware of HCV infections and the high number of deaths among subjects with an active HCV infection born from 1935 to 1954, suggest that, at least in southern Italy, targeted screening of this birth cohort may be required to reduce the number of undiagnosed cases and hidden infections.
