Cardiovascular disease risk in liver transplant recipients transplanted due to chronic viral hepatitis

Background: Cardiovascular disease (CVD) is a major cause of morbidity and mortality after liver transplantation, mostly in patients transplanted for nonalcoholic steatohepatitis, obesity and diabetes. Few data exist on cardiovascular diseases among patients transplanted for viral hepatitis. Objective: Our aim is to clarify the cardiovascular risk and subclinical vascular damage among liver transplant recipients for chronic viral hepatitis (i.e. hepatits C virus, hepatis B virus and hepatitis D virus infection). Methods: Adult patients (age ≥ 18 years) with orthotopic liver transplants (OLT) due to viral hepatitis who signed informed consent, and were admitted for a routine follow-up between June 2019 and September 2020 at the Infectious Disease outpatient clinic of the University of Campania Luigi Vanvitelli, Naples, Italy, were prospectively enrolled. An estimation of cardiovascular risk was assessed using three main risk charts, echocolor-Doppler of epiaortic vessels was performed to assess subclinical Intima-Media changes. Results: A total of 161 patients were evaluated; of these 15 were excluded because not affected by viral hepatitis. 146 patients were considered. 83 patients (56.8%) were considered at high cardiovascular risk according to Framingham, 54 patients (36.9%) to American Heart Association Arteriosclerotic Cardiovascular Disease (ASCVD) score and 19 (13.0%) to Heart Score. Only 8 patients (5.4%) showed a normal carotid ultrasound, while 52 patients (35.6%) had a carotid artery Intima-Media Thickness (IMT) and 86 (58.9%) an atherosclerotic plaque. Conclusions: Liver transplant recipients for virus-related associated liver disease are, in light of the high percentage of carotid lesions, at high risk of CVD. Risk charts compared to subclinical carotid lesions which represent damage already established and a real localization of the disease, seem to underestimate the cardiovascular risk. A chronic inflammatory status, could play a key role. It's important to raise the awareness of cardiovascular risk in liver transplant patients to prevent cardiovascular diseases and improve the timing of early diagnosis of premature vascular lesions

HDV can constrain HBV genetic evolution in hbsag: Implications for the identification of innovative pharmacological targets

Chronic HBV + HDV infection is associated with greater risk of liver fibrosis, earlier hepatic decompensation, and liver cirrhosis hepatocellular carcinoma compared to HBV mono-infection. However, to-date no direct anti-HDV drugs are available in clinical practice. Here, we identified conserved and variable regions in HBsAg and HDAg domains in HBV + HDV infection, a critical finding for the design of innovative therapeutic agents. The extent of amino-acid variability was measured by Shannon-Entropy (Sn) in HBsAg genotype-D sequences from 31 HBV + HDV infected and 62 HBV mono-infected patients (comparable for demographics and virological-parameters), and in 47 HDAg genotype-1 sequences. Positions with Sn = 0 were defined as conserved. The percentage of conserved HBsAg-positions was significantly higher in HBV + HDV infection than HBV mono-infection (p = 0.001). Results were confirmed after stratification for HBeAg-status and patients’ age. A Sn = 0 at specific positions in the C-terminus HBsAg were correlated with higher HDV-RNA, suggesting that conservation of these positions can preserve HDV-fitness. Conversely, HDAg was characterized by a lower percentage of conserved-residues than HBsAg (p < 0.001), indicating higher functional plasticity. Furthermore, specific HDAg-mutations were significantly correlated with higher HDV-RNA, suggesting a role in conferring HDV replicative-advantage. Among HDAg-domains, only the virus-assembly signal exhibited a high genetic conservation (75% of conserved-residues). In conclusion, HDV can constrain HBsAg genetic evolution to preserve its fitness. The identification of conserved regions in HDAg poses the basis for designing innovative targets against HDV-infection

Salvage therapy with tenofovir followed by adefovir maintenance in a cirrhotic patient with a lamivudine resistant HBV flare

A 36 year old man with chronic hepatitis B and cirrhosis was admitted in our Department for the onset of jaundice, ascites and ALT flare (x 35 u.n.v.) while under lamivudine treatment. Serum HBV-DNA was 1.48 x 10(6) IU/ml and lamivudine (LAM) resistance mutations were present. Tenofovir (TDF) 300 mg/day was added to LAM after its off-label use was authorised. HBV-DNA decreased in a biphasic manner and became undetectable by day 45. A parallel improvement in ALT and bilirubin values was detected. Tenofovir was substituted with adefovir dipivoxil 10 mg/day. Ten months after this switch HBV-DNA remained undetectable. Tenofovir is an effective salvage therapy for critically ill patients with LAM-resistant HBV flares and can be switched to adefovir after HBV-DNA becomes undetectable. Local cost and reimbursement policies are important determinants in antiviral therapy

[Prevalence and risk factors for bacteriuria in patients with cirrhosis]

Bacterial infections occur frequently in patients with cirrhosis and may worsen the disease outcome. We investigated the prevalence of bacteriuria in 500 consecutive patients with cirrhosis, in different Child-Pugh stages (41.4% A; 40.8% B; 17% C) and analysed the associated risk factors. Most of the cirrhosis cases were virus related; alcohol abuse was recorded in 6.2% of the patients. Bacteriuria was detected in 139 (27.8%) cases: 32.4% were more than 100,000 cfu/ml; 7.9% between 100,000 and 1.000,000 cfu/ml and the remaining cases more than 1000,000 cfu/ml. Escherichia coli was the most frequent isolated agent (84.5%); Proteus spp. strains were detected only in bacteriuria with more than 100,000 cfu/ml. At univariate analysis, female gender, age and presence of diabetes were significantly associated to bacteriuria, while Child-Pugh stage and the presence of hepatocellular carcinoma were not. In a multivariate model, only female gender and diabetes were significantly associated to bacteriuria. These results indicate that advanced cirrhosis was not a risk for bacteriuria, that was associated rather to gender and diabetes, which are common risk factors for bacteriuria in non-cirrhotic patients

Safety and Efficacy of Direct Antiviral Agents for Hepatitis C in Patients with Malignancies Other Than Liver Cancer: A Case Series

(1) Background: direct-acting antivirals (DAA) are the current standard of care for chronic hepatitis C. Oncologic patients remain among the most difficult-to-treat subgroups of hepatitis C virus (HCV)-infected patients due to their clinical frailty and complex therapeutic protocols received. (2) Methods: we retrospectively collected and analysed clinical data of 30 consecutive patients treated with DAA, between 2015 and 2022, for chronic HCV infection in the context of oncologic disease. (3) Results: most patients were females (63.3%), median age was 67 years, HCV genotype 1 was prevalent (60%), and median HCV RNA levels were 2.2 x 10(6) IU/mL. The most common malignancy was breast cancer (37%), and the chief oncologic drugs co-administered with DAAs were tamoxifen, platinum derivatives, cyclophosphamide, paclitaxel, rituximab and doxorubicin. Overall, 50% of patients had chronic hepatitis. A total of 76.7% underwent a sofosbuvir-based treatment. Sustained virological response 12 weeks after the end of therapy (SVR12) was reached in all patients. After SVR12, two patients died. DAA treatment was well tolerated; no patients had to stop DAA treatment or showed any adverse event or drug-drug interaction specifically attributable to DAAs. (4) Conclusions: DAA treatment should be promptly offered to oncologic patients with chronic hepatitis C in order to achieve aminotransferase normalization and viremia control, making antineoplastic therapy feasible and safe

[Prevalence and risk factors for bacteriuria in patients with cirrhosis]

Bacterial infections occur frequently in patients with cirrhosis and may worsen the disease outcome. We investigated the prevalence of bacteriuria in 500 consecutive patients with cirrhosis, in different Child-Pugh stages (41.4% A; 40.8% B; 17% C) and analysed the associated risk factors. Most of the cirrhosis cases were virus related; alcohol abuse was recorded in 6.2% of the patients. Bacteriuria was detected in 139 (27.8%) cases: 32.4% were more than 100,000 cfu/ml; 7.9% between 100,000 and 1.000,000 cfu/ml and the remaining cases more than 1000,000 cfu/ml. Escherichia coli was the most frequent isolated agent (84.5%); Proteus spp. strains were detected only in bacteriuria with more than 100,000 cfu/ml. At univariate analysis, female gender, age and presence of diabetes were significantly associated to bacteriuria, while Child-Pugh stage and the presence of hepatocellular carcinoma were not. In a multivariate model, only female gender and diabetes were significantly associated to bacteriuria. These results indicate that advanced cirrhosis was not a risk for bacteriuria, that was associated rather to gender and diabetes, which are common risk factors for bacteriuria in non-cirrhotic patients

Bacterial pneumonia in patients with liver cirrhosis, with or without HIV co-infection: a possible definition of antibiotic prophylaxis associated pneumonia (APAP)

Introducion: Bacterial infections frequently complicate liver cirrhosis. The aim of this study was to identify risk factors and clinical impact of bacterial pneumonia in patients with cirrhosis. Materials and methods: Bacterial infection prevalence study: consecutive patients with cirrhosis were enroled over a six-month period in 13 Italian centres. Pneumonia and other infections were diagnosed by standard methods. Pneumonia study: cirrhotic patients with pneumonia were enroled for an additional six-month period and HIV-positive patients were included. Results: Pneumonia was the fourth most frequent infection. In the two parts of the study, 79 cases of pneumonia were recorded and 441 patients with cirrhosis without infections served as controls. Seventy-eight patients had extra-pulmonary infections. There were no clinical differences between HIV-negative and -positive cases with pneumonia. Previous gastro-intestinal bleeding (p =.02) and long-term prophylactic antibiotic use (p &lt;.0001) were associated with pneumonia. Hospital stay was longer and renal failure more frequent than in patients without infections. Pneumonia was hospital acquired (HAP) in 6 cases, healthcare associated (HCAP) in 24 and community acquired (CAP) in 28. A new category of antibiotic prophylaxis associated pneumonia (APAP) was proposed for 21 cases. Cultures were positive in 21/79 patients (26.6%) with Gram-positive isolates in 57%. Unfavourable outcomes were recorded in 11.4% of the cases (3.6% of CAP, 33% of HAP, 12.5% of HCAP and 14.3% of APAP). Conclusions: Receiving antibiotic prophylaxis was associated with pneumonia and the study identified a new sub-group of patients, who require broad spectrum initial antibiotic therapy