Resistance test guided retreatment of HCV infected patients with a previous failure to a NS5A inhibitor-containing regimen: the Italian Vironet C real life experience

Previous article in issueNext article in issue Introduction: There is a limited documentation about the retreatment of patients failing a recommended NS5A-containing regimen in Italy. Materials & methods: Within the VIRONET-C network, 386 NS5A-failing patients infected with different HCV-genotypes (GT) (GT1a/1b/2a-c/3a-b-g-h/4a-d-n-o-v=93/124/19/112/38) were analyzed. Retreatment of 105 failures was investigated. HCV-resistance-test was performed by Sanger-sequencing. Results: Failures following seven different NS5A-containing regimens were studied: 3D/2D (paritaprevir/ombitasvir ± dasabuvir) ± ribavirin (N = 72/4), daclatasvir/ledipasvir/velpatasvir + sofosbuvir ± ribavirin (N = 105/13…

Virological profiles in patients with chronic hepatitis C and overt or occult HBV infection

Abstract OBJECTIVES: The virological profiles of hepatitis B and C viruses (HBV and HCV) and their interplay in cases of coinfection are undefined. A suppressed and occult HBV infection may occur in hepatitis B surface antigen (HBsAg) negative patients with chronic hepatitis C. The HCV core protein is able to inhibit HBV “in vitro,” and serines at positions 99 and 116 are essential for such inhibition. We aimed to assess the HBV and HCV virological profiles in cases of coinfection and to evaluate the relationship between HCV core gene variability and HBV activity. METHODS: Eighty-two anti-HCV positive patients were examined: 35 cases were HBsAg positive, 24 were HBsAg negative with “occult”…

Neoangiogenesis-related genes are hallmarks of fast-growing hepatocellular carcinomas and worst survival. Results from a prospective study

Objective The biological heterogeneity of hepatocellular carcinoma (HCC) makes prognosis difficult. We translate the results of a genome-wide high-throughput analysis into a tool that accurately predicts at presentation tumour growth and survival of patients with HCC.Design Ultrasound surveillance identified HCC in 78 (training set) and 54 (validation set) consecutive patients with cirrhosis. Patients underwent two CT scans 6 weeks apart (no treatment in-between) to determine tumour volumes (V-0 and V-1) and calculate HCC doubling time. Baseline-paired HCC and surrounding tissue biopsies for microarray study (Agilent Whole Human Genome Oligo Microarrays) were also obtained. Predictors of su…

Update of the statements on biology and clinical impact of occult hepatitis B virus infection

In October 2018 a large number of international experts with complementary expertise came together in Taormina to participate in a workshop on occult hepatitis B virus infection (OBI). The objectives of the workshop were to review the existing knowledge on OBI, to identify issues that require further investigation, to highlight both existing controversies and newly emerging perspectives, and ultimately to update the statements previously agreed in 2008. This paper represents the output from the workshop.

Variability of reverse transcriptase and overlapping S gene in hepatitis B virus isolates from untreated and lamivudine-resistant chronic hepatitis B patients

Background The high degree of diversity of the hepatitis B virus (HBV) quasispecies in chronically infected individuals raises the possibility that HBV genetic variants favouring resistance to nucleoside/nucleotide analogues (NAs) might pre-exist to treatment. The aim of this study was to investigate the genetic variability of the entire HBV reverse transcriptase (RT) domain and of the overlapping S gene in a large series of untreated hepatitis B surface antigen carriers and in lamivudine (3TC)-resistant patients. Methods Sequencing analysis of the entire HBV RT domain of isolates from 100 untreated (treatment- naive group) and 59 3TC-resistant (3TC-resistant group) consecutive patients wit…

Hepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection.

Background & Aims: Occult hepatitis B virus (HBV) infection is characterized by persistence of HBV DNA into the tissue of hepatitis B surface antigen-negative individuals. The clinical relevance of this peculiar infection is still under debate. In particular, the impact of occult HBV infection in cases of hepatocellular carcinoma (HCC) is uncertain. We investigated the prevalence and molecular status of occult HBV in patients with HCC. Methods: We tested tumor tissues from 107 patients with HCC and the corresponding nontumor liver tissue from 72 of these patients for HBV DNA. We also examined liver specimens from 192 patients with chronic hepatitis. All cases were hepatitis B surface antige…

Transcriptional regulation of miR-224 upregulated in human HCCs by NFκB inflammatory pathways

Background & Aims: miR-224 is up-regulated in human HCCs as compared to both paired peri-tumoral cirrhotic tissues and cirrhotic livers without HCC. Here, we have cloned the miR-224 regulatory region and characterized its transcriptional regulation by the NFκB-dependent inflammatory pathways. Methods: Mature miRNA expression was evaluated by a 2 step stem-loop real-time RT-PCR. The recruitment of polymerase II and transcription factors on the pre-miR-224 promoter has been assessed by ChIPSeq and ChIP. Results: We found miR-224 levels strongly up-regulated in both peri-tumoral cirrhotic livers and HCC samples as compared to normal livers. In silico analysis of the putative miR-224 promoter r…

Occult hepatitis B virus infection

Many studies have shown that hepatitis B virus infection may also occur in hepatitis B surface antigen-negative patients. This occult infection has been identified both in patients with cryptogenic liver disease and in patients with hepatitis C virus-related chronic hepatitis, and much evidence suggests that it may be a risk factor of hepatocellular carcinoma development. However several aspects of this occult infection remain unclear such as its prevalence and the factor(s) involved in the lack of circulating hepatitis B surface antigen. Moreover, it is uncertain whether the occult hepatitis B virus infection may contribute to chronic liver damage, considering that it is usually associated…

Occult hepatitis B virus infection and hepatocellular carcinoma development in patients with chronic hepatitis C

Current epidemiology of HCV in Sicily: the RESIST-HCV model

Background: Real-world data to guide hepatitis C virus (HCV)- related public health initiatives and linkage to care of patients are lacking in our region. Aims: To describe the epidemiological features of a large cohort of patients with chronic HCV infection from Sicily included in a regional network aimed at DAA treatment (RESIST-HCV). Methods: Demographic and clinical data were recorded on a web-based platform before starting treatment with DAAs. Gender, year of birth, HCV genotype, co-infections, stages of liver disease and co-morbidities were analyzed. Chi-square with Yates correc- tion was appliedto assess the differences between cohorts. Results: Overall, 15,270 patients were register…

Frequent NS5A and multiclass resistance in almost all HCV genotypes at DAA failures: What are the chances for second-line regimens?

Treatment of chronic hepatitis B: update of the recommendations from the 2007 Italian Workshop

Abstract The Italian recommendations for the therapy of hepatitis B virus (HBV)-related disease were issued in 2008. Subsequently in 2008 the nucleotide analogue (NA) Tenofovir was approved for antiviral treatment. The introduction of this important new drug has called for the current guidelines update, which includes some additional revisions: (a) the indication for therapy is extended to mild liver fibrosis and the indication for treatment is graded as “possible”, “optional” or “mandatory” according to the fibrosis stage; (b) two different treatment strategies are described: first line definite duration treatment with interferon, long-term treatment of indefinite duration with NA; (c) the…

Hepatitis E virus infection as a cause of acute hepatitis in Southern Italy

Abstract Background Hepatitis E virus (HEV) is a major cause of acute hepatitis in developing countries, whereas it is not considered a major health problem in Western World. Aims To investigate the spread of HEV and its possible role in causing acute hepatitis in Southern Italy. Methods Four hundred and thirty patients observed from April to December 2009 were studied and grouped as follows: 55 individuals with acute hepatitis (AH), 33 of whom cryptogenic; 321 individuals with chronic liver diseases (CLD), (278 Italians and 43 immigrants); 54 individuals without liver disease (control-group). Serum samples from all cases were tested for IgG anti-HEV antibodies and those positive to this te…

Statements from the Taormina expert meeting on occult hepatitis B virus infection

Giovanni Raimondo*, Jean-Pierre Allain, Maurizia R. Brunetto, Marie-Annick Buendia, Ding-Shinn Chen, Massimo Colombo, Antonio Craxi, Francesco Donato, Carlo Ferrari, Giovanni B. Gaeta, Wolfram H. Gerlich, Massimo Levrero, Stephen Locarnini, Thomas Michalak, Mario U. Mondelli, Jean-Michel Pawlotsky, Teresa Pollicino, Daniele Prati, Massimo Puoti, Didier Samuel, Daniel Shouval, Antonina Smedile, Giovanni Squadrito, Christian Trepo, Erica Villa, Hans Will, Alessandro R. Zanetti, Fabien Zoulim

Occult hepatitis B virus in liver tissue of individuals without hepatic disease

Abstract BACKGROUND/AIMS: While many data are available concerning occult hepatitis B virus (HBV) infection in patients with hepatic disorders, there is little information about this cryptic infection in individuals without liver disease. The aim of this study was to investigate the prevalence of occult HBV in the general population by examining liver specimens from a large series of HBV-surface-antigen negative individuals with no clinical and biochemical evidence of liver disease. METHODS: The presence of HBV DNA was evaluated by testing, through polymerase chain reaction techniques, DNA extracts from 98 liver-disease-free individuals who underwent liver resection or needle biopsy during …