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

Hepatocellular carcinoma in chronic HBV-HCV co-infection is correlated to fibrosis and disease duration

Hepatocellular carcinoma (HCC) is a development of severe liver disease frequently due to HBV and/or HCV infection. The aim of this retrospective study was to evaluate the development of HCC in patients with HBV-HCV chronic infection compared with patients with single HBV or HCV infection and the viral and host factors correlated to HCC in co-infected patients. We studied 268 patients with histology proven chronic hepatitis: 56 had HBV-HCV co-infection (HBV-HCV group), 46 had HBV infection (HBV group) and 166 had HCV infection (HCV group). Patients were followed up for at least 3 years. Viral and host factors were studied. HCC was more frequent in HBV-HCV group (14%) compared with HBV (2%, p = 0.006) and HCV monoinfected (4%, p = 0.006). The Mantel-Haenszel test used to investigate the relationship between HBV-HCV co-infection and development of HCC indicated an association between development of HCC and HBV-HCV co-infection (p < 0.001). In the HBV-HCV group, patients with HCC were significantly older (p = 0.000), had longer disease duration (p = 0.001), higher blood glucose levels (p = 0.001), lower levels of steatosis (p = 0.02), higher levels of fibrosis (p = 0.000), higher HCV RNA (p = 0.01) than those without HCC. ALT, lipid profile, PNPLA3 variant distribution and HBV viral load did not differ among co-infected patients with or without HCC. In conclusion HCC was more frequent in our patients with HBV-HCV co-infection, than in those with HBV or HCV mono-infection; possible associated risk factors for HCC development seem a long duration of disease, high levels of fibrosis and carbohydrate intolerance

Epidemiological and etiological variations in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer and a leading cause of cancer-related deaths worldwide. The major risk factors for HCC development are chronic liver disease and cirrhosis due to hepatitis B virus (HBV) and/or hepatitis C virus (HCV), alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), steatohepatitis, intake of aflatoxin-contaminated food, diabetes, and obesity

Hepatitis c virus markers in infection by hepatitis c virus:In the era of directly acting antivirals

About 130-170 million people are infected with the hepatitis C virus (HCV) worldwide and more than 350000 people die each year of HCV-related liver diseases. The combination of pegylated interferon (Peg-IFN) and ribavirin (RBV) was recommended as the treatment of choice for chronic hepatitis C for nearly a decade. In 2011 the directly acting antivirals (DAA) HCV NS3/4A protease inhibitors, telaprevir and boceprevir, were approved to treat HCV-genotype-1 infection, each in triple combination with Peg-IFN and RBV. These treatments allowed higher rates of SVR than the double Peg-IFN + RBV, but the low tolerability and high pill burden of these triple regimes were responsible for reduced adherence and early treatment discontinuation. The second and third wave DAAs introduced in 2013-2014 enhanced the efficacy and tolerability of anti-HCV treatment. Consequently, the traditional indicators for disease management and predictors of treatment response should be revised in light of these new therapeutic options. This review article will focus on the use of the markers of HCV infection and replication, of laboratory and instrumental data to define the stage of the disease and of predictors, if any, of response to therapy in the DAA era. The article is addressed particularly to physicians who have patients with hepatitis C in care in their everyday clinical practice

SARS-CoV-2 infection: a hurricane that does not ignore chronic hepatitis

Background The COVID-19 pandemic significantly compromised screening, laboratory controls, clinical surveillance and treatment of chronic hepatitis patients and worsened their outcome, as evidenced by its significant correlation with advanced cirrhosis, liver decompensation and mortality. Results This pandemic significantly impaired also the sector of liver transplantation, whose wards, operating rooms, outpatients' facilities, and healthcare personnel have been dedicated to patients with COVID-19. In addition, screening and treatment for HBV infection have been delayed or suspended in in most countries, with an increased risk of viral reactivation. Similar delay or suspension have also occurred for universal hepatitis B vaccination programs in many countries. Likewise, COVID-19 pandemic has made unreachable the goal of elimination of HCV infection as a worldwide public-health issue predicted for 2030 by the WHO. Conclusion This review article demonstrates how COVID-19 pandemic is causing serious damage to the sector of liver disease, which has quickly lost the beneficial effects of years of study, research, and clinical and technological application, as well as considerable financial investments

Beta-lactam monotherapy or combination therapy for bloodstream infections or pneumonia due to Pseudomonas aeruginosa: a meta-analysis

Objectives: To compare the clinical and microbiological outcomes of patients treated with beta-lactam monotherapy or combination therapy for Pseudomonas aeruginosa infections. Data sources: MEDLINE, Google Scholar and the Cochrane Library.Study eligibility criteria and interventions: Experimental and observational studies published as full papers up to December 2020 that compared the efficacy of beta-lactams used as monotherapy or in combination with other active agents as empirical or targeted therapy for bloodstream infections or hospital-acquired pneumonia/ventilator-associated pneumonia due to P. aeruginosa were included in this meta-analysis. The outcomes evaluated were in-hospital mortality rate, 14 -day-or 30-day-mortality rate, microbiological cure rate and clinical cure rate.Results: Of 8363 citations screened, six randomized controlled trials, six prospective cohort studies and 21 retrospective cohort studies were included in the analysis, accounting for a total of 3861 subjects. Considering the 14 studies evaluating empirical therapy, no significant difference in mortality rate was observed between the two groups [relative risk (RR) 1.06, 95% confidence interval (CI) 0.86-1.30; P = 0.6]. Similar findings were obtained among the 18 studies analysing targeted therapy (RR 1.04, 95% CI 0.83- 1.31; P = 0.708); however, grouping the studies by design, higher mortality was observed among patients receiving monotherapy in five prospective studies (RR 1.37, 95% CI 1.06-1.79; P = 0.018). Finally, no differ-ence was observed between groups in terms of microbiological cure and clinical cure.Conclusions: This meta-analysis demonstrated no difference in mortality rate, clinical cure rate and mi-crobiological cure rate in patients treated with beta-lactam monotherapy or combination therapy for P. aeruginosa infections.(c) 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved

Hepatitis B virus infection in immigrant populations

Hepatitis B virus (HBV) is the most common cause of hepatitis worldwide, with nearly 350 million people chronically infected and 600000 deaths per year due to acute liver failure occurring during acute hepatitis or, more frequently, in HBV-related liver cirrhosis or hepatocellular carcinoma. Ongoing immigration from countries with a high HBV endemicity to those with a low HBV endemicity warrants particular attention to prevent the spread of HBV infection to the native population. This review article analyzes the epidemiology and virological and clinical characteristics of HBV infection in immigrant populations and in their host countries, and suggests prophylactic measures to prevent the spread of this infection. Among the immigrants from different geographical areas, those from South East Asia and sub-Saharan Africa show the highest prevalences of hepatitis B surface antigen (HBsAg) carriers, in accordance with the high endemicity of the countries of origin. The molecular characteristics of HBV infection in immigrants reflect those of the geographical areas of origin: HBV genotype A and D predominate in immigrants from Eastern Europe, B and C in those from Asia and genotype E in those from Africa. The literature data on the clinical course and treatment of HBsAgpositive immigrants are scanty. The management of HBV infection in immigrant populations is difficult and requires expert personnel and dedicated structures for their assistance. The social services, voluntary operators and cultural mediators are essential to achieve optimized psychological and clinical intervention

Epidemiology and management of hepatitis C virus infections in immigrant populations

Abstract Background At present, there is a continuous flow of immigrants from the south of the world to north-western countries. Often immigrants originate from areas of high-prevalence of viral hepatitis and pose a challenge to the healthcare systems of the host nations. Aims of this study is to evaluate the prevalence and virological and clinical characteristics of hepatitis C virus (HCV) infection in immigrants and the strategies to identify and take care of the immigrants infected with HCV. Main body We conducted an electronic literature search in several biomedical databases, including PubMed, Google Scholar, Scopus, Web of Science, using different combinations of key words: “HCV infection; chronic hepatitis C, immigrants; low-income countries”. We included studies written in English indicating the epidemiological data of HCV infection in the immigrant population, studies that assessed the clinical presentation, clinical management and treatment with directly acting antiviral agent in immigrants, HCV infection is unevenly distributed in different countries, with worldwide prevalence in the general population ranging from 0.5 to 6.5%. In Western countries and Australia this rate ranges from 0.5 to 1.5%, and reaches 2.3% in countries of south-east Asia and eastern Mediterranean regions, 3.2% in China, 0.9% in India, 2.2% in Indonesia and 6.5% in Pakistan; in sub-Saharan Africa the prevalence of HCV infection varies from 4 to 9%. Immigrants and refugees from intermediate/high HCV endemic countries to less- or non-endemic areas are more likely to have an increased risk of HCV infection due to HCV exposure in their countries of origin. Because of the high HCV endemicity in immigrant populations and of the high efficacy of directly acting antiviral agent therapy, a campaign could be undertaken to eradicate the infection in this setting. Conclusions The healthcare authorities should support screening programs for immigrants, performed with the help of cultural mediators and including educational aspects to break down the barriers limiting access to treatments, which obtain the HCV clearance in 95% of cases and frequently prevent the development of liver cirrhosis and hepatocellular carcinoma

Role of occult hepatitis B virus infection in chronic hepatitis C

The development of sensitive assays to detect small amounts of hepatitis B virus (HBV) DNA has favored the identification of occult hepatitis B infection (OBI), a virological condition characterized by a low level of HBV replication with detectable levels of HBV DNA in liver tissue but an absence of detectable surface antigen of HBV (HBsAg) in serum. The gold standard to diagnose OBI is the detection of HBV DNA in the hepatocytes by highly sensitive and specific techniques, a diagnostic procedure requiring liver tissue to be tested and the use of non-standardized non-commercially available techniques. Consequently, in everyday clinical practice, the detection of anti-hepatitis B core antibody (anti-HBc) in serum of HBsAg-negative subjects is used as a surrogate marker to identify patients with OBI. In patients with chronic hepatitis C (CHC), OBI has been identified in nearly one-third of these cases. Considerable data suggest that OBI favors the increase of liver damage and the development of hepatocellular carcinoma (HCC) in patients with CHC. The data from other studies, however, indicate no influence of OBI on the natural history of CHC, particularly regarding the risk of developing HCC

Liver fibrosis in human immunodeficiency virus/hepatitis C virus coinfection: Diagnostic methods and clinical impact

Several non-invasive surrogate methods have recently challenged the main role of liver biopsy in assessing liver fibrosis in hepatitis C virus (HCV)-monoinfected and human immunodeficiency virus (HIV)/HCV-coinfected patients, applied to avoid the well-known side effects of liver puncture. Serological tests involve the determination of biochemical markers of synthesis or degradation of fibrosis, tests not readily available in clinical practice, or combinations of routine tests used in chronic hepatitis and HIV/HCV coinfection. Several radiologic techniques have also been proposed, some of which commonly used in clinical practice. The studies performed to compare the prognostic value of non-invasive surrogate methods with that of the degree of liver fibrosis assessed on liver tissue have not as yet provided conclusive results. Each surrogate technique has shown some limitations, including the risk of over- or under-estimating the extent of liver fibrosis. The current knowledge on liver fibrosis in HIV/HCV-coinfected patients will be summarized in this review article, which is addressed in particular to physicians involved in this setting in their clinical practice