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BackgroundHepatocellular 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.ResultsIn Western countries, the number of NASH-related HCC cases is increasing, that of HBV- or HCV-related cases is declining due to the wide application of HBV universal vaccination and the introduction of effective therapies against HBV and HCV infections, and that of alcohol-related cases remaining substantially unchanged. Nevertheless, the burden of HCC is expected to increase worldwide in the next few decades, due to the population growth and aging expected in coming years. Overall, the abovementioned changes and future variations in lifestyle and in the impact of environmental factors in Western countries and a decreasing exposure to dietary aflatoxins and improved socio-economic conditions in developing countries will create new HCC epidemiology in the next few decades. ConclusionA substantial further reduction in cases of HCC requires a wider application of universal HBV vaccination and effective treatment of HBV- and HCV-related chronic hepatitis and cirrhosis, more effective campaigns to favor correct dietary habits and reduce alcohol consumption and the intensification of studies on HCC pathogenesis for future optimized prevention strategies.

Several investigations have been published on Hepatitis Delta Virus (HDV) infection in recent years, from which we have drawn the salient data to provide readers with useful information to improve their knowledge on the subject. HDV genotypes 5–8 have been recently imported to Western countries from central Africa, whose clinical relevance deserves further investigation. Ongoing HDV replication has been identified as an independent predictor of progression to cirrhosis and HCC for patients with HDV chronic hepatitis (HDV-CH). Long-term treatments of HDV-CH with standard or pegylated interferon alfa (peg-IFN-α) have all been unsatisfactory, leading to a sustained virological response (SVR) only in 20–30% of patients treated, faced with a poor tolerability and frequent serious adverse reactions; the addition of HBV nucleo(s)tide analogues to peg-IFN- α did not improve the rate of SVR. The improved knowledge of the HDV life cycle has allowed the development of direct acting agents towards key-points of the HDV life cycle, namely bulevirtide, lonafarnib and nucleic acid polymers. Preliminary data have shown that these drugs are more effective than interferon-based therapies, but adverse reactions are also common, which however seem toned down in combination therapy with other antivirals.

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.

To study in HBsAg chronic carriers the expression of liver hsa-miR-125a-5p and its correlation with liver HBV-DNA values and clinical presentation, 27 consecutive Caucasian, HBsAg/anti-HBe/HBV-DNA-positive patients who were naive to nucleos(t)ide analogues and interferon therapy and had no marker of HCV, HDV or HIV infection and no history of alcohol intake were enrolled. For each patient, liver HBV DNA and liver hsa-miR-125a-5p were quantified by real-time PCR in relation to β-globin DNA or RNU6B, respectively. Liver fibrosis and necroinflammation were graded by applying Ishak's scoring system. Liver hsa-miR-125a-5p was detected in all patients enrolled and a correlation between its concentration and liver HBV DNA was demonstrated (p<0.0001). Higher liver hsa-miR-125a-5p concentrations were observed in patients with HBV-DNA plasma level >10(3) IU/ml (p<0.02), in those with HAI >6 (p = 0.02) and those with fibrosis score >2 (p<0.02) than in patients with lower scores. Higher HBV-DNA liver concentrations were found in patients with abnormal AST (p = 0.005) and ALT serum levels (p = 0.05), in those with serum HBV DNA higher than 10E3 IU/mL (p = 0.001) and those with fibrosis score >2 (p = 0.02) than in patients with a lower load. By multivariate logistic regression analysis, liver hsa-miR-125a-5p was identified as an independent predictor of disease progression: O.R. = 4.21, C.I. 95% = 1.08-16.43, p<0.05, for HAI >6; O.R. = 3.12, C.I. 95% = 1.17-8.27, p<0.05, for fibrosis score >2. In conclusion, in HBsAg/anti-HBe-positive patients, the liver hsa-miR-125a-5p level correlated with liver and plasma HBV-DNA values and was associated to a more severe disease progression.

BackgroundIntroduced in 2013–2014, the second- and third-wave directly acting antivirals (DAAs) have strongly enhanced the efficacy and tolerability of anti-HCV treatment, with a sustained virological response (SVR) in 90–95% of cases treated. The aim of this paper was to focus on the type and prevalence of viral strains with a reduced sensitivity to DAAs and on treatment choices for DAA-experienced patients.MethodsThe Medline was searched for “HCV infection”, “HCV treatment”, “Directly acting antivirals”,“HCV resistance”.ResultsMost patients who did not achieve an SVR have been found to be infected with HCV mutant strains with a reduced susceptibility to these drugs. These mutants occur frequently in the NS5A region, with a moderate frequency in the NS3/4A regions and rarely in the NS5B region. Treatment-induced mutants resistant to NS5A DAAs persist for years after treatment discontinuation, whereas those resistant to the NS3 DAAs have a shorter duration.ConclusionsPatients who have failed HCV treatment with DAA agents have several re-treatment options, but re-treatment selection may be intricate and resistance testing is recommended to optimize this choice. It is, therefore, important to bear in mind that the correct determination of HCV genotype and subtype and the identification of RASs are essential elements for choosing the optimal re-treatment. It is supposed that it is useful to give readers some other suggestions regarding therapeutic reprocessing.

IntroductionKidney transplant recipients and patients on the waiting list for kidney transplant who acquire SARS-CoV-2 infection are at serious risk of developing severe COVID-19, with an increased risk of mortality for the their immunosuppressive state; other risk factors for mortality have been identified in some comorbidities such as obesity, diabetes, asthma and chronic lung disease.Materials and MethodsThe COVID-19 pandemic has led to a sharp reduction in kidney transplants in most countries, mainly due to the concern of patients on the waiting list for their potential increased susceptibility to acquire SARS-CoV-2 infection in healthcare facilities and for the difficulties of transplant centers to ensure full activity as hospitals have had to focus most of their attention on COVID-19 patients. Indeed, while the infection curve continued its exponential rise, there was a vertical decline in kidney donation/transplant activity.ConclusionThis review article focuses on the damage induced by SARS-CoV-2 infection on kidney and on the adverse effect of this pandemic on the entire kidney transplant sector.

To compare the efficacy of pegylated-interferon (Peg-IFN) α-2a or α-2b and ribavirin given as dual therapy versus triple therapy (Peg-IFN and ribavirin plus boceprevir or telaprevir) in patients with HCV-1 chronic hepatitis naïve for anti-HCV therapy or relapsers to dual therapy in relation to the presence of constitutional, clinical and virological predictors of treatment response. Included in the meta-analysis were studies meeting these criteria: original data from randomized trials on the efficacy of dual versus triple therapy in therapy-naïve patients or relapsers; at least one primary outcome clearly defined: sustained virological response in patients with or without rapid virological response (RVR), with genotype 1a or 1b, low or high HCV load, IL28-B CC or non-CC genotype, mild or severe fibrosis; odds ratio estimates of relative risk (RR) and 95% confidence intervals; English language; and published up to the end of June 2013. Seven original studies met the inclusion criteria, allowing a meta-analysis on 3,652 patients. Triple therapy was more effective than dual, regardless of IL-28B genotype, HCV sub-genotype, liver fibrosis, and baseline HCV load. In 1,045 patients who achieved RVR, SVR was more frequently achieved with dual therapy (RR = 1.11; p = 0.002) than triple. The same results were achieved when only the therapy-naïve patients were considered. Triple therapy provides a significantly higher SVR rate than dual therapy, but dual therapy obtains a significantly higher SVR rate in patients with RVR. The data stress the clinical importance of a 4-week lead-in phase in direct-acting antiviral-based treatment.

Human immunodeficiency virus-1 (HIV-1) is characterised by a vast genetic diversity classified into distinct phylogenetic strains and recombinant forms. We describe the HIV-1 molecular epidemiology and evolution of 129 consecutive HIV-1 positive migrants living in Milan (northern Italy). Polymerase gene sequences of 116 HIV-1 subtype-B positive patients were aligned with HIV-1 reference sequences (https://www.ncbi.nlm.nih.gov/) by using MAFFT alignment and edited by using Bioedit software. A maximum likelihood (ML) phylogenetic tree was performed by MEGA7 and was visualised by using FigTree v1.4.3. Of 129 migrants, 35 were born in Europe (28 in Eastern Europe), 70 in the Americas (67 in South America), 15 in Africa and nine in Asia; 76.4% were men who have sex with men (MSM). The serotype HIV-1-B prevailed (89.9%), followed by -C, -F1, -D and -A. Compared with 116 HIV-B patients, the 13 with HIV-non-B showed lower Nadir of CD4+ cell/mmc (𝑃 = 0.043), more frequently had sub Saharan origin (38.5 𝑣𝑠. 1.72%, 𝑃 = 0.0001) and less frequently were MSM (40 𝑣𝑠. 74.5%, 𝑃 = 0.02). The ML phylogenetic tree of the 116 HIV-1 subtype-B positive patients showed 13 statistically supported nodes (bootstrap > 70%). Most of the sequences included in these nodes have been isolated from male patients from the Americas and the most common risk factor was MSM. The low number of HIV-1 non-B subtype patients did not allow to perform this analysis. These results suggest a shift of HIV-1 prevention projects' focus and a continuous monitoring of HIV-1 molecular epidemiology among entry populations. Prevention efforts based on HIV molecular epidemiology may improve public health surveillance setting.

The aim of this study is to provide updates on the characteristics of chronic HBsAg carriers in Italy before the advent of new drugs eliminating or functionally inactivating the genome HBV reservoirs. HBV endemicity has greatly decreased in Italy over the past decades. A not negligible number of chronic HBsAg carriers are still alive in the country. Chronic HBsAg carriers consecutively referring to 9 units in Italy were prospectively enrolled for a 6-month period in 2019. Multiple logistic regression analysis was performed to identify independent predictors of treatment. A total of 894 cases was recruited (sex ratio 1.6; mean age 53.7 ± 13.5 years). The proportion of subjects born abroad was 19.0%; only 1% of cases reported current heavy alcohol intake (> 4 units/day). Chronic HBV infection, chronic HBV hepatitis, and subjects with liver cirrhosis and/or HCC represented 24.8%, 55%, and 19.3% of cases, respectively. After exclusion of the 222 subjects with chronic HBV infection, the proportion of subjects under therapy was as high as 89.3%. A more severe liver disease (OR 2.52; 95% CI = 1.25–5.14) resulted an independent predictor of the likelihood of treatment; male sex was marginally associated (OR 1.67; 95% CI = 1.02–2.76) to the chance of treatment. People born abroad had same chance than Italians native to be treated (OR 2.12; 95% CI = 0.9–4.97). The high proportion of subjects under treatment and the absence of gender and ethnic barrier against treatment sound good news. These updated figures may represent reference data for evaluating the potential impact of forthcoming new therapy against HBV-related disease.

Background The detection of baseline resistance mutations to new direct-acting antivirals (DAAs) in HCV chronically infected treatment-naïve patients could be important for their management and outcome prevision. In this study, we investigated the presence of mutations, which have been previously reported to be associated with resistance to DAAs in HCV polymerase (NS5B) and HCV protease (NS3) regions, in sera of treatment-naïve patients. Findings HCV RNA from 152 naïve patients (84 % Italian and 16 % immigrants from various countries) infected with different HCV genotypes (21,1a; 21, 1b; 2, 2a; 60, 2c; 22, 3a; 25, 4d and 1, 4k) was evaluated for sequence analysis. Amplification and sequencing of fragments in the NS5B (nt 8256–8640) and NS3 (nt 3420–3960) regions of HCV genome were carried out for 152 and 28 patients, respectively. The polymorphism C316N/H in NS5B region, associated with resistance to sofosbuvir, was detected in 9 of the 21 (43 %) analysed sequences from genotype 1b-infected patients. Naturally occurring mutations V36L, and M175L in the NS3 protease region were observed in 100 % of patients infected with subtype 2c and 4. Conclusion A relevant proportion of treatment naïve genotype 1b infected patients evaluated in this study harboured N316 polymorphism and might poorly respond to sofosbuvir treatment. As sofosbuvir has been approved for treatment of HCV chronic infection in USA and Europe including Italy, pre-treatment testing for N316 polymorphism on genotype 1b naïve patients should be considered for this drug.