Gaia Caccamo

Occult HBV Infection

The long-lasting persistence of hepatitis B virus (HBV) genomes in the liver (with detectable or undetectable HBV DNA in the serum) of individuals testing negative for the HBV surface antigen (HBsAg) is termed occult HBV infection (OBI). Although in a minority of cases the lack of HBsAg detection is due to infection with variant viruses unrecognized by available assays (S-escape mutants), the typical OBI is related to replication-competent HBVs strongly suppressed in their replication activity. The causes of HBV suppression are not yet well clarified, although the host’s immune surveillance and epigenetic mechanisms are likely involved. OBI is a worldwide diffused entity, but the available data of prevalence in various categories of individuals are often contrasting because of the different sensitivity and specificity of the methods used for its detection in many studies. OBI may have an impact in several different clinical contexts. In fact, it can be transmitted (i.e., through blood transfusion and liver transplantation) causing classic forms of hepatitis B in newly infected individuals. The development of an immunosuppressive status (mainly by immunotherapy or chemotherapy) may induce OBI reactivation and development of acute and often severe hepatitis. Finally, evidence suggests that OBI can favor the progression of liver fibrosis, in particular in HCV-infected patients. The possible contribution of OBI to the establishment of cirrhosis also implies its possible indirect role in the development of hepatocellular carcinoma. On the other hand, OBI may maintain most of the direct transforming properties of the overt HBV infection, such as the capacity to integrate in the host’s genome and to synthesize pro-oncogenic proteins.

Hepatitis B virus and hepatitis C virus dual infection.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) share common mode of transmission and both are able to induce a chronic infection. Dual HBV/HCV chronic coinfection is a fairly frequent occurrence, especially in high endemic areas and among individuals at high risk of parenterally transmitted infections. The intracellular interplay between HBV and HCV has not yet been sufficiently clarified, also due to the lack of a proper in vitro cellular model. Longitudinal evaluation of serum HBV DNA and HCV RNA amounts has revealed that complex virological profiles may be present in coinfected patients. Dual HBV/HCV infection has been associated to a severe course of the liver disease and to a high risk of developing hepatocellular carcinoma. Despite the clinical importance, solid evidence and clear guidelines for treatment of this special population are still lacking. This review summarizes the available data on the virological and clinical features as well as the therapeutic options of the dual HBV/HCV infection, and highlights the aspects that need to be better clarified.

Analysis of occult hepatitis B virus infection in liver tissue of HIV patients with chronic hepatitis C.

Objective:Current data on the prevalence of occult hepatitis B virus (HBV) infection in HIV-positive individuals conflict. As occult HBV infection could have an impact on the outcome of liver disease in HIV-positive patients, we investigated a large number of HIV-positive/HBV-surface-antigen (HBsAg) negative subjects with hepatitis C virus (HCV) infection by using the ‘gold standard’ approach for occult HBV detection—analysis of liver DNA extracts. Methods:The presence or absence of HBV DNA was determined by PCR testing of four different viral genomic regions in DNA extracts of needle liver biopsy specimens of 101 HBsAg negative individuals with HIV/HCV co-infection. HBV genotyping was performed by sequencing analysis of the preS-S gene in occult HBV isolates from 18 cases. Results:Occult HBV infection was diagnosed in 42 of the 101 cases (41%). No clinically relevant difference was found between occult HBV-positive and -negative patients. HBV genotype D and A were detected, respectively, in 11 (61%) and 7 (39%) of 18 cases analysed. Conclusions:Occult HBV infection frequently occurs in HIV/HCV co-infected patients indicating the importance of performing prospective studies able to clarify its clinical impact in these patients. HBV genotype A is highly prevalent in HIV-infected subjects with occult HBV infection in a similar way to HBsAg/HIV-positive individuals.

High prevalence of non-organ-specific autoantibodies in hepatitis C virus-infected cirrhotic patients from southern Italy.

Non-organ-specific autoantibodies (NOSAs) are frequently found in patients with hepatitis C virus (HCV) chronic infection. Genetics is likely involved in the development of autoimmune reactivities, and differences in the prevalence of HCV-related autoantibodies among populations of various geographic areas should be expected. We evaluated the prevalence and the clinical impact of NOSAs in a series of HCV-infected patients from southern Italy. We studied 283 consecutive anti-HCV positive patients (162 men, 121 women, mean age 54.5 ± 13.5 years), 94 of whom were cirrhotics and 189 noncirrhotics. Serum from each patient and from 41 hepatitis B surface antigen (HBsAg)-positive/anti-HCV negative control subjects were tested (dilution 1:40) for autoantibodies by indirect immunofluorescence. Qualitative/quantitative HCV-RNA determinations were also performed. The prevalence of NOSAs was significantly higher in anti-HCV-positive subjects than in HBsAg-positive patients (P < 0.006). Autoantibodies were significantly associated with both cirrhosis (P < 0.0001) and older age (P < 0.05). No significant association between NOSAs and either female gender or virological parameters (HCV-RNA positivity, viral load, and genotype) was found. In conclusion, the autoantibody positivity in HCV-infected patients from southern Italy is significantly related to cirrhosis and older age, although its general prevalence is similar to that reported in populations from the north of the country.

Virological profiles in hepatitis B virus inactive carriers: monthly evaluation in 1-year follow-up study

Abstract: Study subject: We longitudinally evaluated the virological behaviour and the hepatitis B virus (HBV) genomic variability in inactive HBV surface antigen (HBsAg) chronic carriers.

A combination of different diagnostic tools allows identification of inactive hepatitis B virus carriers at a single time point evaluation.

Serial evaluation of hepatitis B virus (HBV) DNA and aminotransferase values is required for identification of inactive HBV carriers (ICs). Recently, HBV surface antigen quantification (qHBsAg) and liver stiffness measurement (LSM) have been proposed as diagnostic tools in chronic HBV infection. The aim of this study was to evaluate the efficacy of HBV DNA quantification, qHBsAg and LSM in diagnosing ICs at a single time point.

Acute kidney injury in cirrhotic patients undergoing contrast-enhanced computed tomography

AbstractContrast medium administration is one of the leading causes of acute kidney injury (AKI) in different clinical settings. The aim of the study was to investigate occurrence and predisposing factors of AKI in cirrhotic patients undergoing contrast-enhanced computed tomography (CECT).Datasets of 1279 consecutively hospitalized cirrhotic patients were retrospectively analyzed. Two hundred forty-nine of 1279 patients (mean age 64 ± 11 years, 165 male) who had undergone CECT were selected on the basis of the availability of serum creatinine (sCr) values evaluated before and after CECT (CECT group). In analogy, 203/1279 cases (mean age 66 ± 10 years, 132 male) who had not undergone CECT and had been tested twice for sCr in 7 days were also included as controls (Control group). AKI network criteria were employed to assess contrast-induced AKI (CI-AKI) development. Apart from lack of narrowed double sCr measurements, additional exclusion criteria were active bacterial infections, nephrotoxic drugs intake, and estimated glomerular filtration rate <30 mL/min.AKI developed in 22/249 (8.8%) and in 6/203 (3%) of the CECT and the Control groups, respectively (P = 0.01). The multivariate logistic regression analysis showed that AKI was significantly associated with contrast medium administration (odds ratio [OR]: 3.242, 95% confidence interval [CI]: 1.255–8.375; P = 0.015), female sex (OR: 0.339, 95% CI: 0.139–0.827; P = 0.017), and sCr values (OR: 0.124, 95% CI: 0.016–0.975; P = 0.047). In the CECT group, presence of ascites (OR: 2.796, 95% CI: 1.109–7.052; P = 0.029), female sex (OR: 0.192, 95% CI: 0.073–0.510; P = 0.001), and hyperazotemia (OR: 1.018, 95% CI: 1.001–1.037; P = 0.043) correlated with CI-AKI development at multivariate analysis.CI-AKI is a quite frequent occurrence in cirrhotic patients with female sex, presence of ascites, and hyperazotemia being the predisposing factors.

Atrial fibrillation in patients with cirrhosis

Few information is available regarding atrial fibrillation in cirrhotic patients. The aim of this study was to investigate the occurrence and clinical impact of atrial fibrillation in these patients.

Hypergammaglobulinemia is a strong predictor of disease progression, hepatocellular carcinoma, and death in patients with compensated cirrhosis

The outcome of compensated cirrhosis may vary considerably and cannot be predicted by routinely performed tests at present. The aim of this study was to evaluate possible predictors of clinical evolution in patients with Child‐Pugh (C‐P) class A cirrhosis because of untreatable causes by analysing clinical/biochemical/instrumental parameters evaluated at the time of diagnosis and during the subsequent long‐lasting follow‐up.

Response to the high diagnostic characteristics of HBsAg level in differentiation of Hepatitis B clinical presentations: myth or truth?

Response to the high diagnostic characteristics of HBsAg level in differentiation of Hepatitis B clinical presentations: myth or truth? 4. Keshvari M, Alavian SM, Sharafi H. How can we make decision for patients with chronic hepatitis B according to hepatitis B virus (HBV) DNA level? Hepat Mon. 2014;14:e15285. 5. Martinot-Peignoux M, Moucari R, Leclere L, et al. 725 quantitative HBsAg: a new specific marker for the diagnosis of HBsAg inactive carriage. J Hepatol. 2010;52:S282. 6. Yakut M, Bektas M, Seven G, et al. 398 characterization of the inactive HBsAg carrier state with 3 year followup. J Hepatol. 2011; 54:S159. 7. Tan Z, Li M, Kuang X, et al. Clinical implications of hepatitis B surface antigen quantitation in the natural history of chronic hepatitis B virus infection. J Clin Virol. 2014;59:228–234.