A prominent role of Hepatitis D Virus in liver cancers documented in Central Africa

Abstract Background Hepatocellular Carcinoma (HCC) is one of the commonest cancers in Central Africa, a region with the unusual peculiarity to be hyperendemic for infections with Hepatitis B, C and D viruses. However, data estimating the respective proportions of HCC cases attributable to these viruses are still limited in this area. The current study was undertaken to determine the role of these viruses in HCC compared to non-HCC Cameroonian patients. Methods A case–control study was conducted in the Gastroenterology Unit of Central Hospital of Yaounde in collaboration with Centre Pasteur of Cameroon. Blood samples of all HCC cases (n = 88) and matched control individuals without known liver disease (n = 85) were tested for serological markers of Hepatitis B, C and D viral infections using commercially available enzyme immune-assay kits. Hepatitis B and C viral loads were quantified for positive patients by real-time PCR using commercial kits. Results The mean age was 46.0 ± 18 and 42.1 ± 16 years old for HCC-patients and controls, respectively for a 2.3 Male/Female sex ratio. The prevalence of hepatitis B surface antigen, antibody to HCV and antibody to HDV were significantly higher in HCC patients (65.90, 20.26 and 26 % respectively) than in control patients (9.23, 4.62 and 1 %) (P < 2.5 10−5). The risk factors analysis showed that both HBV and HCV infections were strongly associated with HCC development in Cameroon with crude odds ratios of 15.98 (95 % CI 6.19-41.25) and 7.33 (95 % CI 2.09-25.77), respectively. Furthermore, the risk of developing HCC increased even more significantly in case of HBV and HDV co-infections with the odd ratio of 29.3 (95 % CI, 4.1-1231). HBV-DNA level was significantly higher in HBsAg-positive HCC-patients than in HBsAg-positive controls with (6.3 Log IU/mL and 5.7 Log IU/mL) respectively (P < 0.05). Conclusion HBV and HCV infections are the mains factors of HCC development in Cameroon. Our results show that patients co-infected with HDV are at very high risk to develop HCC. An active surveillance program of patients and, foremost, an easier access to antivirals and primary prevention measures are crucial steps to reduce the incidence of HCC in this country. Due to the lack of truly efficient antiviral therapy, the fate of HDV-infected patients remains, however, particularly worrying

The role of hepatitis C virus genotypes and core mutations in hepatocellular carcinoma in Cameroon

International audienceBackground: Hepatitis C virus (HCV) infection is known to be an important risk factor for hepatocellular carcinoma (HCC) in Cameroon. However, the effect of HCV-related factors on HCC development still remains unknown in the Central Africa. In this study, we investigated the role of HCV genotypes and core mutations in HCC development in Cameroonian patients.Methods: A case-control study was conducted using patients with HCV-related HCC and matched controls individuals with chronic HCV infection but without HCC. HCV genotypes and mutations were determined using a hemi-nested amplification and sequencing analysis focus on the core and NS5B HCV regions.Results: We identify HCV genotype 1, 2 and 4 in both groups. Interestingly, genotype 4 was significantly more prevalent in HCC patients (53.3%). Overall, distribution of genotypes was very different between cases and controls (P = 4.2 E-7). The risk factors analysis showed that infection with HCV-4 is strongly associated with HCC development with odd ratio, 95% confidence interval and p-values of 7.4 (95% CI: 2.08-26.6; P = .001). Furthermore, the risk of developing HCC increased even more significantly in case of infection with HCV subtype 4f with the odd ratio of 20.8 (95% CI, 4.1-66.8; P < .001). Mutations K10R, T72E, K74R and G77A were significantly more frequent in patients with HCC. Remarkably, HCV-4f isolates from HCC patients carried significantly more mutations when compared to controls with HCV-4f or others genotypes (P = .0001).Conclusions: Our results indicate that patients infected with HCV-4f or with selected variants affecting HCV core gene are at increased risk to develop HC

Hepatitis E virus infection as a promoting factor for hepatocellular carcinoma in Cameroon: Preliminary Observations

Objectives: To determine the seroprevalence of hepatitis E virus (HEV) infection in patients with chronic hepatitis and/or hepatocellular carcinoma (HCC) and to assess its potential consequences for disease progression. Methods: We conducted a prospective case-control study on patients with HCC hepatitis B or C related and non-HCC patients including patients with CLD and patients without clinical evidence of liver disease. Anti-HEV IgG and IgM were tested by ELISA using commercially available kits. Liver damage was assessed by alanine aminotransferase, aspartate aminotransferase, platelets and prothrombin measurements. Results: We observed a significant anti-HEV IgG carriage in HCC patients compared to non-HCC subjects with CLD (41.8% vs 12.6%; P = 9.1 E-6; OR = 4.8, 95%CI: 2.3-10.6). HCC patients with HEV infection display more profound alterations of circulating liver enzymes, platelets count and prothrombin time than HCC patients without sero-reactivity to HEV. Conclusion: Overall, this study indicates a high prevalence of HEV infection in Cameroonian patients with CLD and HCC. These data suggest either that patients with liver tumors are more susceptible to hepeviral infection or that, in a tropical context, HEV might promote the progression of liver diseases towards tumor. Keywords: Hepatocellular carcinoma, Hepatitis E, Seroprevalence, Anti-HEV IgG, Anti-HEV Ig

Broad Range of Hepatitis B Virus (HBV) Patterns, Dual Circulation of Quasi-Subgenotype A3 and HBV/E and Heterogeneous HBV Mutations in HIV-Positive Patients in Gabon.

Integrated data on hepatitis B virus (HBV) patterns, HBV genotypes and mutations are lacking in human immunodeficiency virus type 1 (HIV-1) co-infected patients from Africa. This survey was conducted in 2010-2013 among 762 HIV-1-positive adults from Gabon who were predominantly treated with 3TC-based antiretroviral treatment. HBV patterns were identified using immunoassays detecting total antibody to hepatitis B core antigen (HBcAb), hepatitis B surface antigen (HBsAg), IgM HBcAb, hepatitis B e antigen (HBeAg), antibody to HBsAg (HBsAb) and an in-house real-time PCR test for HBV DNA quantification. Occult hepatitis B (OBI) was defined by the presence of isolated anti-HBc with detectable serum HBV DNA. HBV genotypes and HBV mutations were analyzed by PCR-direct sequencing method. Seventy-one (9.3%) patients tested positive for HBsAg, including one with acute hepatitis B (0.1%; 95% CI, 0.0%-0.2%), nine with HBeAg-positive chronic hepatitis B (CHB) (1.2%; 95% CI, 0.6%-2.2%), 16 with HBeAg-negative CHB (2.1%; 95% CI, 1.2%-3.3%) and 45 inactive HBV carriers (5.9%; 95% CI, 4.4%-7.8%). Sixty-one (8.0%; 95% CI, 6.2%-10.1%) patients showed OBI. Treated patients showed similar HBV DNA levels to those obtained in untreated patients, regardless of HBV patterns. Around 15.0% of OBI patients showed high (>1,000 UI/mL) viremia. The mutation M204V/I conferring resistance to 3TC was more common in HBV/A (47.4%) than in HBV/E isolates (0%) (P = .04). Our findings encouraged clinicians to promote HBV vaccination in patients with no exposure to HBV and to switch 3TC to universal TDF in those with CHB

Prevalence rates of patients with detectable HBV DNA results, patients with overt (presence of circulating HBsAg) HBV infection (acute or chronic), and patients with OBI.

<p>Prevalence rates of patients with detectable HBV DNA results, patients with overt (presence of circulating HBsAg) HBV infection (acute or chronic), and patients with OBI.</p

Diagnostic Performance and Usability of the Genedrive® HCV ID Kit in Two Decentralized Settings in Cameroon and Georgia

Point-of-care diagnostics have the potential to increase diagnosis and linkage to care and help reach the WHO targets to eliminate hepatitis C virus (HCV) by 2030. Here, we evaluated the diagnostic accuracy of Genedrive HCV ID assay for the qualitative detection of HCV RNA in decentralized settings in two low- and middle-income countries using fresh plasma specimens from 426 participants. The Abbott RealTime HCV assay was used as the gold standard. Genedrive HCV ID assay was conducted by different users. Users also completed questionnaires to assess the usability of Genedrive. At detection thresholds of 12 IU/mL or 30 IU/mL, 1000 IU/mL, and 2362 IU/mL, the sensitivity was 96.2% (95% CI: 92.7–98.4), 100% (98.2–100), and 100% (98.2–100), respectively; the specificity was 99.5% (95% CI: 97.4–100), 99.5% (97.5–100), and 98.7% (96.1–100), respectively. All genotypes detected using the gold-standard assay were also detected with Genedrive. Users found Genedrive easy to use. Genedrive is a simple and accurate test to confirm chronic HCV infection in decentralized, real-life, resource-limited settings. This novel diagnostic tool could contribute to closing the current gap in HCV diagnosis

Droplet digital PCR detects high rate of TP53 R249S mutants in cell-free DNA of middle African patients with hepatocellular carcinoma

International audienceHepatocellular carcinoma (HCC) is still a major killing malignancy in sub-Saharan Africa. Lifelong intoxication with aflatoxin B1 is considered as one of the primary causes of this situation. The role of aflatoxin in HCC from a given population is commonly estimated through the prevalence of R249S mutation of TP53, a hallmark for previous exposure to the mycotoxin. However, the role of AFB1 is barely known in large part of Africa. We conducted a survey on circulating cell-free DNA from 149 patients with HCC and 213 control subjects with and without liver diseases from Cameroon and Central African Republic using droplet digital PCR technique. We observed a mutation prevalence of 24.8% (n = 37/149) in patients with tumor and 5.6% (n = 12/213) in controls (P = 2.2E-07). Patients with mutations usually displayed significantly increased circulating alpha-fetoprotein (AFP) values, high hepatitis B virus (HBV) DNA loads as well as worsened values of blood cells count. Interestingly, the fraction of droplets positive for R249S was significantly larger in patients with liver cancer (15.3 ± 3.7%) than in controls (0.5 ± 0.3%, P = 7.1E-04). Our survey indicates that AFB1 is instrumental for HCC development in Middle Africa and that droplet digital PCR might be used in the region both to diagnose HCC and to conduct public health surveys on populations at risk of chronic aflatoxin intoxication

Phylogenetic analysis of a 765 bp HBV-S gene region from different HBV isolates, with Woolly Monkey strain (AY226578) as the root.

<p>The phylogenetic tree was inferred by the Bayesian method in the GTR model, with gamma-distributed rates at sites, 8 million generations and effective sample sizes greater than 1200. BPP (Branching Posterior Probability) are shown along the main nodes. HBV sequences obtained during this study are represented in red.</p

Mutation distribution graphs for the polymerase region.

<p>Sequence alignments were submitted to Mutation Reporter Tool (<a href="http://hvdr.bioinf.wits.ac.za/mrt/" target="_blank">http://hvdr.bioinf.wits.ac.za/mrt/</a>) to produce graphs for genotype A. None mutation found in nine sequences from genotype E. Letters preceding each locus on the X-axis show the reference motifs. To facilitate comparison, conserved loci were not suppressed.</p