Lorenzo Onorato

Hepatitis B virus and hepatitis C virus infection in healthcare workers.

Approximately 3 million healthcare workers per year receive an injury with an occupational instrument, with around 2000000 exposures to hepatitis B virus (HBV) and 1000000 to hepatitis C virus (HCV). Although an effective HBV vaccine has been available since the early eighties, and despite the worldwide application of universal vaccination programs started in the early nineties, HBV still remains a prominent agent of morbidity and mortality. There is no vaccine to limit the diffusion of HCV infection, which progresses to chronicity in the majority of cases and is a major cause of morbidity and mortality worldwide due to a chronic liver disease. Healthcare workers are frequently exposed by a mucosal-cutaneous or percutaneous route to accidental contact with human blood and other potentially infectious biological materials while carrying out their occupational duties. Mucosal-cutaneous exposure occurs when the biological material of a potentially infected patient accidentally comes in contact with the mucous membranes of the eyes or mouth or with the skin of a healthcare worker. Percutaneous exposure occurs when an operator accidentally injures himself with a sharp contaminated object, like a needle, blade or other sharp medical instrument. About 75% of the total occupational exposure is percutaneous and 25% mucosal-cutaneous, the risk of infecting a healthcare worker being higher in percutaneous than in mucosal-cutaneous exposure. All healthcare workers should be considered for HBV vaccination and should meticulously apply the universal prophylactic measures to prevent exposure to HBV and HCV.

Occult HBV infection in HCC and cirrhotic tissue of HBsAg-negative patients: a virological and clinical study

Aim To evaluate the virological and clinical characteristics of occult HBV infection (OBI) in 68 consecutive HBsAg-negative patients with biopsy-proven cirrhosis and HCC. Methods HBV DNA was sought and sequenced in plasma, HCC tissue and non-HCC liver tissue by PCRs using primers for HBV core, surface and x regions. OBI was identified by the presence of HBV DNA in at least two different PCRs. Results OBI was detected in HCC tissue of 13 (20%) patients and in non-HCC liver tissue of 3 of these 13. OBI was detected in HCC tissue of 54.5% of 11 anti-HBs- negative/anti-HBc-positive patients, in 29.4% of 17 anti-HBs/anti-HBc-positive and in 5% of 40 anti-HBs/anti-HBc-negative (p < 0.0005). The 13 patients with OBI in HCC tissue more frequently than the 55 without showed Child-B or -C cirrhosis (53.9% vs. 5.5%, p < 0.0001) and BCLC-B or -C stages (46.1% vs. 1.8%, p < 0.0001). The pre-S1, pre-S2 and S region sequences in HCC tissue showed amino acid (AA) substitutions (F19L, P24L, S59F, T131I, Q129H) and deletions (in positions 4,8, 17 and 86) in the S region, AA substitutions (T40S, P124K, L54P, G76A, N222T and I273L) in pre-S1 region and AA substitutions in pre-S2 region (P41H and P66L). In the 3 patients showing OBI also in non-HCC liver tissue the S, pre-S1 and pre-S2 sequencing displayed patterns of mutations different. Conclusions The study showed a significant correlation between OBI and the severity of liver damage, several patterns of mutations in the S, pre-S1 and pre-S2 regions in HCC tissue, some at their first description.

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.

Hepatitis B virus infection in undocumented immigrants and refugees in Southern Italy: demographic, virological, and clinical features

BackgroundThe data on hepatitis b virus (HBV) infection in immigrants population are scanty. The porpoise of this study was to define the demographic, virological, and clinical characteristics of subjects infected with HBV chronic infection in a cohort of immigrants living in Naples, Italy.MethodsA screening for HBV infection was offered to 1,331 immigrants, of whom 1,212 (91%) (831 undocumented immigrants and 381 refugees) accepted and were screened for hepatitis B surface antigen (HBsAg) and anti-hepatitis B core antibody (HBc). Those found to be HBsAg positive were further investigated at third-level infectious disease units.ResultsOf the 1,212 immigrants screened, 116 (9.6%) were HBsAg positive, 490 (40.4%) were HBsAg negative/anti-HBc positive, and 606 (50%) were seronegative for both. Moreover, 21 (1.7%) were anti-human immunodeficiency virus positive and 45 (3.7%) were anti-hepatitis C virus positive. The logistic regression analysis showed that male sex (OR: 1.79; 95%CI: 1.28–2.51), Sub-Saharan African origin (OR: 6.18; 95%CI: 3.37–11.36), low level of schooling (OR: 0.96; 95%CI: 0.94–0.99), and minor parenteral risks for acquiring HBV infection (acupuncture, tattoo, piercing, or tribal practices, OR: 1.54; 95%CI: 1.1–2.16) were independently associated with ongoing or past HBV infection. Of the 116 HBsAg-positive immigrants, 90 (77.6%) completed their diagnostic itinerary at a third-level infectious disease unit: 29 (32.2%) were asymptomatic non-viremic HBsAg carriers, 43 (47.8%) were asymptomatic viremic carriers, 14 (15.6%) had chronic hepatitis, and four (4.4%) had liver cirrhosis, with superimposed hepatocellular carcinoma in two.ConclusionsThe data illustrate the demographic, clinical and virological characteristics of HBV infection in immigrants in Italy and indicate the need for Italian healthcare authorities to enhance their support for providing screening, HBV vaccination, treatment, and educational programs for this populations.

Association between anti-HBc positivity and hepatocellular carcinoma in HBsAg-negative subjects with chronic liver disease: A meta-analysis

AbstractA meta-analysis was performed to ascertain to what extent hepatitis B surface antigen (HBsAg)-negative/anti-hepatitis B core (anti-HBc)-positive subjects with chronic liver disease are at a higher risk of developing hepatocellular carcinoma (HCC) than the anti-HBc-negative.All studies included had to fulfill the following characteristics and inclusion criteria: they investigated the relationship between HBsAg-negative/anti-HBc-positive serology and the occurrence of HCC, whether a case–control or cohort study, they provided relative risk (RR) or odds ratios (ORs) and 95% confidence intervals (CIs), were available as a full text written in English, and were published and indexed up to April 2015.Twenty-six original studies met the inclusion criteria, allowing a meta-analysis on 44,553 patients. The risk of HCC among the 9986 anti-HBc-positive subjects was 67% higher than in the 34,567 anti-HBc-negative (95% CI = 1.44–1.95, P < 0.0001). The results were similar when groups of patients with a different stage of liver disease (patients with chronic liver disease, patients with cirrhosis), with different ethnicity (Asian and non-Asian) and etiology (HCV and non-HCV) were considered. The risk of HCC was significantly higher in the 651 anti-HBs/anti-HBc-positive patients (RR = 1.36; 95% CI = 1.17–1.58, P = 0.03) and in the 595 anti-HBs-negative/anti-HBc-positive subjects (RR = 2.15; 95% CI = 1.58–2.92, P < 0.0001) than in the 1242 anti-HBs/anti-HBc negative. However, the RR from 8 studies indicated that the risk of HCC was 35% lower among the anti-HBs/anti-HBc-positive subjects compared to the anti-HBs-negative/anti-HBc-positive (RR = 0.65; 95% CI = 0.52–0.8, P < 0.0001).This meta-analysis shows that in HBsAg-negative subjects with chronic liver disease, anti-HBc positivity is strongly associated with the presence of HCC, an association observed in all subgroups according to the stage of the disease, etiology, and ethnicity.

Role of genetic polymorphisms in hepatitis C virus chronic infection

AIM To analyze the host genetics factors influencing the clinical course and the response to antiviral treatment in patients with chronic hepatitis C (CHC). METHODS We conducted an electronic search on the PubMed and MEDLINE (2000-2014) databases and Cochrane library (2000-2014). A total of 73 articles were retrieved and their data were extensively evaluated and discussed by the authors and then analyzed in this review article. RESULTS Several studies associated polymorphisms in the interleukin 28B gene on chromosome 19 (19q13.13) with a spontaneous viral clearance in acute hepatitis C and with the response to pegylated interferon (Peg-IFN)-based treatment in chronic hepatitis C patients. Other investigations demonstrated that inosine triphosphate pyrophosphatase genetic variants protect hepatitis C virus-genotype-1 CHC patients from ribavirin-induced anemia, and other studies that a polymorphism in the patatin-like phospholipase domain-containing protein 3 was associated with hepatic steatosis in CHC patients. Although not conclusive, some investigations suggested that the vitamin D-associated polymorphisms play an important role in the achievement of sustained virologic response in CHC patients treated with Peg-IFN-based antiviral therapy. Several other polymorphisms have been investigated to ascertain their possible impact on the natural history and on the response to treatment in patients with CHC, but the data are preliminary and warrant confirmation. CONCLUSION Several genetic polymorphisms seem to influence the clinical course and the response to antiviral treatment in patients with CHC, suggesting individualized follow up and treatment strategies.

Clinical Findings of HCV Chronic Infection in Undocumented Immigrants and Low-Income Refugees in Three Areas of Southern Italy

INTRODUCTION AND AIM In recent decades, Italy has become a land of immigration from countries suffering a socio-economic crisis. The aim of this study was to perform an organized screening to identify and offer care to immigrants with HCV infection. MATERIAL AND METHODS The screening, performed from 2012 to 2015, involved 1,727 immigrants in the Campania and Apulia regions in southern Italy. RESULTS Screening was accepted by 1,727 (85%) out of 2,032 immigrants interviewed; 70 (4.1%) of the 1,727 were anti-HCV-positive, all unaware of their serological condition, 31 (44.3%) of whom were HCV-RNA-positive and 39 negative. The 31 HCV-RNA-positive immigrants were further investigated at a third-level clinic of infectious diseases. The HCV viral load was 2.6 x 107 ± 7.7 x107 IU/mL, and 35.5% showed HCV-genotype 1a or 1b, 23.8% genotype 2 and 22.6% genotype 3. Two immigrants had liver cirrhosis and, in accordance with the Italian Healthcare Authority guidelines, received an interferon-free regimen and achieved a sustained virological response (SVR); 18 had chronic hepatitis, 6 of whom with a high risk of progression and received interferonbased therapy, with SVR in 4, whereas 12 at low risk were put on a waiting list for future interferon-free treatment, once licensed. The remaining 11 HCV-RNA-positive immigrants were considered HCV inactive chronic carriers and were included in a long-term observational program. CONCLUSION The screening program can be considered successful since it was accepted by 85% of the subjects interviewed and identified 70 anti-HCV-positive immigrants, all unaware of their clinical and virological condition.INTRODUCTION AND AIM In recent decades, Italy has become a land of immigration from countries suffering a socio-economic crisis. The aim of this study was to perform an organized screening to identify and offer care to immigrants with HCV infection. MATERIAL AND METHODS The screening, performed from 2012 to 2015, involved 1,727 immigrants in the Campania and Apulia regions in southern Italy. RESULTS Screening was accepted by 1,727 (85%) out of 2,032 immigrants interviewed; 70 (4.1%) of the 1,727 were anti-HCV-positive, all unaware of their serological condition, 31 (44.3%) of whom were HCV-RNA-positive and 39 negative. The 31 HCV-RNA-positive immigrants were further investigated at a third-level clinic of infectious diseases. The HCV viral load was 2.6 × 107 ± 7.7 ×107 IU/mL, and 35.5% showed HCV-genotype 1a or 1b, 23.8% genotype 2 and 22.6% genotype 3. Two immigrants had liver cirrhosis and, in accordance with the Italian Healthcare Authority guidelines, received an interferon-free regimen and achieved a sustained virological response (SVR); 18 had chronic hepatitis, 6 of whom with a high risk of progression and received interferon-based therapy, with SVR in 4, whereas 12 at low risk were put on a waiting list for future interferon-free treatment, once licensed. The remaining 11 HCV-RNA-positive immigrants were considered HCV inactive chronic carriers and were included in a long-term observational program. CONCLUSION The screening program can be considered successful since it was accepted by 85% of the subjects interviewed and identified 70 anti-HCV-positive immigrants, all unaware of their clinical and virological condition.

Eighteen-month lamivudine prophylaxis on preventing occult hepatitis B virus infection reactivation in patients with haematological malignancies receiving immunosuppression therapy

This study evaluated the long‐term efficacy and safety of an 18‐month lamivudine prophylaxis in 68 HBsAg‐negative/anti–HBc‐positive patients with oncohaematological disease.

Micro-RNAs in hepatitis B virus-related chronic liver diseases and hepatocellular carcinoma

MicroRNAs (miRNAs) are small non-coding RNAs that modulate gene expression at the post-transcriptional level by affecting both the stability and translation of complementary mRNAs. Several studies have shown that miRNAs are important regulators in the conflicting efforts between the virus (to manipulate the host for its successful propagation) and the host (to inhibit the virus), culminating in either the elimination of the virus or its persistence. An increasing number of studies report a role of miRNAs in hepatitis B virus (HBV) replication and pathogenesis. In fact, HBV is able to modulate different host miRNAs, particularly through the transcriptional transactivator HBx protein and, conversely, different cellular miRNAs can regulate HBV gene expression and replication by a direct binding to HBV transcripts or indirectly targeting host factors. The present review will discuss the role of miRNAs in the pathogenesis of HBV-related diseases and their role as a biomarker in the management of patients with HBV-related disease and as therapeutic targets.

Low prevalence of HTLV1/2 infection in a population of immigrants living in southern Italy

Aims To assess the prevalence of HTLV-1 and HTLV-2 infections in a cohort of immigrants living in southern Italy. Findings We screened for antibody to HTLV-1/2 infection 1,498 consecutive immigrants born in endemic areas (sub-Saharan Africa or southern-Asia) by a commercial chemiluminescent microparticle immunoassay. If confirmed in a Western blot assay, which differentiates anti-HTLV-1 from anti-HTLV-2, the positive sera were tested for specific HTLV RNA by a home-made PCR. The immigrants investigated were more frequently males (89.05%), young (median age 26 years), with a low level of education (median schooling 6 years), born in sub-Saharan Africa (79.70%). They had been living in Italy for a median period of 5 months. Only one (0.07%) subject was anti-HTLV-1 -positive/HTLV-1 RNA-negative; he was an asymptomatic 27-year-old male from Nigeria with 6 years’ schooling who stated unsafe sexual habits and unsafe injection therapy. Conclusions The data suggest screening for HTLV1 and HTLV-2 infections all blood donors to Italy from endemic countries at least on their first donation; however, a cost-effectiveness study is needed to clarify this topic.