A holistic evaluation of patients with chronic Hepatitis D virus (HDV) infection enrolled in the Italian PITER-B and delta cohort.

BACKGROUND AND AIMS: We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility. METHODS: This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model. RESULTS: Of 5492 HBsAg-positive enrolled patients, 4152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age ≤ 40 years vs. 2.1%; P < 0.001), more often females (males 43.0% vs. 68.6%; P < 0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care. CONCLUSIONS: CHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN.

Reduction of the Risk of Hepatocellular Carcinoma over Time Using Direct-Acting Antivirals: A Propensity Score Analysis of a Real-Life Cohort (PITER HCV).

The treatment of hepatitis C virus (HCV) with direct-acting antivirals (DAA) leads to high sustained virological response (SVR) rates, but hepatocellular carcinoma (HCC) risk persists in people with advanced liver disease even after SVR. We weighted the HCC risk in people with cirrhosis achieving HCV eradication through DAA treatment and compared it with untreated participants in the multicenter prospective Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. Propensity matching with inverse probability weighting was used to compare DAA-treated and untreated HCV-infected participants with liver cirrhosis. Kaplan-Meier analysis and competing risk regression analysis were performed. Within the first 36 months, 30 de novo HCC cases occurred in the untreated group (n = 307), with a weighted incidence rate of 0.34% (95%CI: 0.23-0.52%), compared to 63 cases among SVR patients (n = 1111), with an incidence rate of 0.20% (95%CI: 0.16-0.26%). The 12-, 24-, and 36-month HCC weighted cumulative incidence rates were 6.7%, 8.4%, and 10.0% in untreated cases and 2.3%, 4.5%, and 7.0% in the SVR group. Considering death or liver transplantation as competing events, the untreated group showed a 64% higher risk of HCC incidence compared to SVR patients (SubHR 1.64, 95%CI: 1.02-2.62). Other variables independently associated with the HCC occurrence were male sex, increasing age, current alcohol use, HCV genotype 3, platelet count ≤ 120,000/µL, and albumin ≤ 3.5 g/dL. In real-life practice, the high efficacy of DAA in achieving SVR is translated into high effectiveness in reducing the HCC incidence risk.

Predicting de-novo portal vein thrombosis after HCV eradication: A long-term competing risk analysis in the ongoing PITER cohort.

BACKGROUND & AIMS: Sustained virological response (SVR) by direct-acting antivirals (DAAs) may reverse the hypercoagulable state of HCV cirrhosis and the portal vein thrombosis (PVT) risk. We evaluated the incidence and predictive factors of de novo, non-tumoral PVT in patients with cirrhosis after HCV eradication. METHODS: Patients with HCV-related cirrhosis, consecutively enrolled in the multi-center ongoing PITER cohort, who achieved the SVR using DAAs, were prospectively evaluated. Kaplan-Meier and competing risk regression analyses were performed. RESULTS: During a median time of 38.3 months (IQR: 25.1-48.7 months) after the end of treatment (EOT), among 1609 SVR patients, 32 (2.0%) developed de novo PVT. A platelet count ≤120,000/µL, albumin levels ≤3.5 mg/dL, bilirubin >1.1 mg/dL, a previous liver decompensation, ALBI, Baveno, FIB-4, and RESIST scores were significantly different (p < 0.001), among patients who developed PVT versus those who did not. Considering death and liver transplantation as competing risk events, esophageal varices (subHR: 10.40; CI 95% 4.33-24.99) and pre-treatment ALBI grade ≥2 (subHR: 4.32; CI 95% 1.36-13.74) were independent predictors of PVT. After HCV eradication, a significant variation in PLT count, albumin, and bilirubin (p < 0.001) versus pre-treatment values was observed in patients who did not develop PVT, whereas no significant differences were observed in those who developed PVT (p > 0.05). After the EOT, esophageal varices and ALBI grade ≥2, remained associated with de novo PVT (subHR: 9.32; CI 95% 3.16-27.53 and subHR: 5.50; CI 95% 1.67-18.13, respectively). CONCLUSIONS: In patients with HCV-related cirrhosis, a more advanced liver disease and significant portal hypertension are independently associated with the de novo PVT risk after SVR.

Profiling the risk of hepatocellular carcinoma after long-term HCV eradication in patients with liver cirrhosis in the PITER cohort.

BACKGROUND AND AIMS: Severe liver disease markers assessed before HCV eradication are acknowledged to usually improve after the SVR. We prospectively evaluated, in the PITER cohort, the long-term HCC risk profile based on predictors monitored after HCV eradication by direct-acting antivirals in patients with cirrhosis. METHODS: HCC occurrence was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the post-treatment variables associated with de-novo HCC; their predictive power was presented in a nomogram. RESULTS: After the end of therapy (median follow-up:28.47 months), among 2064 SVR patients, 119 (5.8%) developed de-novo HCC. The HCC incidence was 1.90%, 4.21%, 6.47% at 12-, 24- and 36-months from end-of-therapy, respectively (incidence rate 2.45/100 person-years). Age, genotype 3, diabetes, platelets (PLT)≤120,000/µl and albumin ≤3.5g/dl levels were identified as pre-treatment HCC independent predictors. Adjusting for age, the post-treatment PLT≤120,000/µl (AdjHR 1.92; 95%CI:1.06-3.45) and albumin≤3.5g/dl (AdjHR 4.38; 95%CI 2.48-7.75) values were independently associated with HCC occurrence. Two different risk profiles were identified by combining long-term post-therapy evaluation of PLT ≤ vs. >120,000/µl and albumin ≤ vs. >3.5g/dl showing a significant different HCC incidence rate of 1.35 vs. 3.77/100 p-y, respectively. CONCLUSIONS: The nomogram score based on age, PLT and albumin levels after SVR showed an accurate prediction capability and may support the customizing management for early HCC detection.

Salivary proteomic analysis in asymptomatic and symptomatic SARS-CoV-2 infection: Innate immunity, taste perception and FABP5 proteins make the difference.

BACKGROUND AND AIM: SARS-CoV-2 infection spawns from an asymptomatic condition to a fatal disease. Age, comorbidities, and several blood biomarkers are associated with infection outcome. We searched for biomarkers by untargeted and targeted proteomic analysis of saliva, a source of viral particles and host proteins. METHODS: Saliva samples from 19 asymptomatic and 16 symptomatic SARS-CoV-2 infected subjects, and 20 controls were analyzed by LC-MS/MS for untargeted peptidomic (flow through of 10 kDa filter) and proteomic (trypsin digestion of filter retained proteins) profiling. RESULTS: Peptides from 53 salivary proteins were identified. ADF was detected only in controls, while IL1RA only in infected subjects. PRPs, DSC2, FABP5, his-1, IL1RA, PRH1, STATH, SMR3B, ANXA1, MUC7, ACTN4, IGKV1-33 and TGM3 were significantly different between asymptomatic and symptomatic subjects. Retained proteins were 117, being 11 highly different between asymptomatic and symptomatic (fold change ≥2 or ≤-2). After validation by LC-MS/MS-SRM (selected reaction monitoring analysis), the most significant discriminant proteins at PCA were IL1RA, CYSTB, S100A8, S100A9, CA6, and FABP5. CONCLUSIONS: The differentially abundant proteins involved in innate immunity (S100 proteins), taste (CA6 and cystatins), and viral binding to the host (FABP5), appear to be of interest for use as potential biomarkers and drugs targets.

Advanced liver disease outcomes after hepatitis C eradication by human immunodeficiency virus infection in PITER cohort.

BACKGROUND: Liver disease progression after Hepatitis C Virus (HCV) eradication following direct-acting antiviral (DAA) treatment in the real-life setting according to Human Immunodeficiency Virus (HIV) coinfection was evaluated. METHODS: Patients consecutively enrolled in PITER between April 2014 and June 2019 and with at least 12-weeks follow-up following treatment were analysed. Cox regression analysis were used to evaluate HIV coinfection and factors independently associated with liver disease outcomes following viral eradication in DAA treated patients with pre-treatment liver cirrhosis. RESULTS: 93 HIV/HCV coinfected and 1109 HCV monoinfected patients were evaluated during a median follow-up of 26.7 (range 6-44.6) and 24.6 (range 6.8-47.3) months, respectively. No difference in the cumulative HCC incidence and hepatic decompensation was observed between coinfected and monoinfected patients. Age (Hazard Ratio [HR] = 1.08; 95% CI 1.04-1.13), male sex (HR = 2.76; 95% CI 1.28-5.96), lower albumin levels (HR = 3.94; 95% CI 1.81-8.58), genotype 3 (HR = 5.05; 95% CI 1.75-14.57) and serum anti-HBc positivity (HR = 1.99, 95% CI 1.01-3.95) were independently associated with HCC incidence. Older age (HR = 1.03; 95% CI 1.00-1.07), male sex (HR = 2.13; 95% CI 1.06-4.26) and lower albumin levels (HR = 3.75; 95% CI 1.89-7.46) were independently associated with the appearance of a decompensating event after viral eradication. CONCLUSION: Different demographic, clinical and genotype distribution between HIV coinfected vs those monoinfected, was observed in a representative cohort of HCV infected patients in Italy. Once liver cirrhosis is established the disease progression is decreased, but still persists regardless of viral eradication in both coinfected and monoinfected patients. In patients with cirrhosis, HIV coinfection was not associated with a higher probability of liver complications, after viral eradication.

Current features of infective endocarditis in persons on hemodialysis: a prevalence study with case control design from the prospective multicenter SEI cohort.

PURPOSE: Persons on hemodialysis (HD) are at high risk of infective endocarditis (IE). In non-comparative retrospective studies, a higher rate of mortality was reported in IE on HD. We assessed risk factors, clinical characteristics, and outcomes of IE in HD. METHODS: This was a prevalence study with a case control methodology on a set of data from the prospectively followed cohort of the Studio Endocarditi Italiano (SEI), conducted between 2004 and 2011. Included were 42 consecutive cases of IE HD subjects and 126 controls not on HD, matched for age, sex, type of IE, and heart side involved. Clinical, echocardiographic, microbiological features, and disease complications and therapeutic modalities were assessed. RESULTS: HD patients were more often diabetics (42.9 vs 18.2 % in no-HD; p = 0.007) and immune-suppressed (16.7 vs 3.2 %; p = 0.02), and had a higher rate of predisposing cardiac conditions (45 vs 25 %; p = 0.031). A higher prevalence of health care-related acquisition and a shorter diagnostic delay was observed in IE on HD, that was more likely to be caused by staphylococci and less by streptococci (p < 0.002). Cardiac surgery was performed in 38 % of HD patients and 36.5 % of no-HD patients (p = 0.856). Complications were similar and in-hospital mortality did not differ significantly (26.2 % in HD vs 15.9 % in no-HD; p = 0.168). CONCLUSIONS: IE in persons on HD is characterized by distinctive clinical features, including a higher prevalence of some important comorbidities. Inconsistent with prior studies, we could not confirm a higher rate of complications and mortality in HD patients with IE.

Predicting the occurrence of embolic events: an analysis of 1456 episodes of infective endocarditis from the Italian Study on Endocarditis (SEI).

BACKGROUND: Embolic events are a major cause of morbidity and mortality in patients with infective endocarditis. We analyzed the database of the prospective cohort study SEI in order to identify factors associated with the occurrence of embolic events and to develop a scoring system for the assessment of the risk of embolism. METHODS: We retrospectively analyzed 1456 episodes of infective endocarditis from the multicenter study SEI. Predictors of embolism were identified. Risk factors identified at multivariate analysis as predictive of embolism in left-sided endocarditis, were used for the development of a risk score: 1 point was assigned to each risk factor (total risk score range: minimum 0 points; maximum 2 points). Three categories were defined by the score: low (0 points), intermediate (1 point), or high risk (2 points); the probability of embolic events per risk category was calculated for each day on treatment (day 0 through day 30). RESULTS: There were 499 episodes of infective endocarditis (34%) that were complicated by ≥ 1 embolic event. Most embolic events occurred early in the clinical course (first week of therapy: 15.5 episodes per 1000 patient days; second week: 3.7 episodes per 1000 patient days). In the total cohort, the factors associated with the occurrence of embolism at multivariate analysis were prosthetic valve localization (odds ratio, 1.84), right-sided endocarditis (odds ratio, 3.93), Staphylococcus aureus etiology (odds ratio, 2.23) and vegetation size ≥ 13 mm (odds ratio, 1.86). In left-sided endocarditis, Staphylococcus aureus etiology (odds ratio, 2.1) and vegetation size ≥ 13 mm (odds ratio, 2.1) were independently associated with embolic events; the 30-day cumulative incidence of embolism varied with risk score category (low risk, 12%; intermediate risk, 25%; high risk, 38%; p < 0.001). CONCLUSIONS: Staphylococcus aureus etiology and vegetation size are associated with an increased risk of embolism. In left-sided endocarditis, a simple scoring system, which combines etiology and vegetation size with time on antimicrobials, might contribute to a better assessment of the risk of embolism, and to a more individualized analysis of indications and contraindications for early surgery.