APOBEC3C S188I Polymorphism Enhances Context-Specific Editing of Hepatitis B Virus Genome.

Single-nucleotide polymorphism in APOBEC3C (resulting in a serine to isoleucine in position 188) is present in approximately 10% of African populations and greatly enhances restriction against human immunodeficiency virus-1 and simian immunodeficiency virus by improving dimerization and DNA processivity of the enzyme. In this study, we demonstrated in culture and in infected patients that hepatitis B virus (HBV) could be edited by APOBEC3CS188I. Using next-generation sequencing, we demonstrated that APOBEC3CS188I led to enhanced editing activity in 5'TpCpA→5'TpTpA context. This constitutes a new hallmark of this enzyme, which could be used to determine its impact on HBV or nuclear DNA.

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

BACKGROUND: 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 HCC.

Enrichment in selected genotypes, basal core and precore mutations of hepatitis B virus in patients with hepatocellular carcinoma in Cameroon.

Worldwide, the development of hepatocellular carcinoma (HCC) is known to be influenced by several hepatitis B viral factors. However, the effect of hepatitis B virus (HBV) genotypes and a landscape of nucleotide changes affecting the precore (PC) and basal core promoter (BCP) during infection leading to HCC remain largely unknown in the Central Africa region. Thus, we performed a case-control study on patients with HBV-related HCC and matched controls without HCC but with chronic HBV infection. Genotypes and mutation spectrums were evaluated using a hemi-nested amplification and sequencing analysis focused on the BCP and PC regions. We identified the co-circulation of HBV quasi-subgenotype A3 (QS-A3) and genotype E in both groups. Interestingly, HBV-QS-A3 was significantly more prevalent in patients with HCC (80.0%) than in controls (31.9%, P = 4.5 E-7, OR = 11.5, 95% CI: 3.8-38.5). HBV mutation spectra and nucleotide changes were significantly more polymorphic in patients with HCC. Remarkably, HCC patients infected with HBV-QS-A3 were significantly more mutated compared to patients infected with genotype E (P < 0.0001). In addition, G:C>T:A transversions, generally associated with aflatoxin B1 exposure in tropical regions, were significantly more prevalent in HCC patients infected either with HBV-QS-A3 or HBV genotype E (P = 2.2 E-05) when compared to controls. In conclusion, our results indicate that patients infected with HBV-QS-A3 are at increased risk to develop HCC. In addition, viral genomes isolated for patients with tumour are more heavily altered than those found in controls. Preferential targeting of these patients for antiviral treatment is of paramount importance to reduce future HCC incidence in Cameroon.

Screening, diagnosis and care cascade for viral hepatitis B and C in Yaoundé, Cameroon: a qualitative study of patients and health providers coping with uncertainty and unbearable costs.

OBJECTIVES: To document patients' and healthcare professionals' (HCP) experiences with hepatitis B virus (HBV) and hepatitis C virus (HCV) diagnosis and care, as well as consequences of these infections on patients' life trajectories in Cameroon, an endemic country in sub-Saharan Africa. DESIGN: Qualitative sociological study combining in-depth interviews and observations of medical consultations. Interviews and observations transcripts were thematically analysed according to the following themes: circumstances and perceptions surrounding hepatitis screening, counselling and disclosure, information provided by HCP on hepatitis prevention and treatment, experience of access to care and treatment, social/economic trajectories after diagnosis. SETTING: HIV and gastroenterology/medical services in two reference public hospitals in Yaoundé (Cameroon). PARTICIPANTS: 12 patients affected by HBV and/or HCV (co-infected or not with HIV), 14 HCP, 14 state and international stakeholders. FINDINGS: Many patients are screened for HBV and HCV at a time of great emotional and economic vulnerability. The information and counselling delivered after diagnosis is limited and patients report feeling alone, distressed and unprepared to cope with their infection. After screening positive, patients struggle with out-of-pocket expenditures related to the large number of tests prescribed by physicians to assess disease stage and to decide whether treatment is needed. These costs are so exorbitant that many decide against clinical and biological follow-up. For those who do pay, the consequences on their social and economic life trajectories are catastrophic. CONCLUSION: Large out-of-pocket expenditures related to biological follow-up and treatment pose a real challenge to receiving appropriate care. Free or reasonably priced access to hepatitis B and C treatments can only be effective and efficient at reducing the hepatitis disease burden if the screening algorithm and the whole pretherapeutic assessment package are simplified, standardised and subsidised by comprehensive national policies orientated towards universal healthcare.

Cryoglobuline et facteurs associés chez le patient porteur de l'anticorps du virus de l'hépatite C dans un pays à ressources limitées

Introduction: le virus de l'hépatite C (VHC) a plusieurs manifestations extra hépatiques parmi lesquelles la cryoglubulinémie. La cryoglobulinémie se définit par la présence anormale dans le sang d'une ou plusieurs protéines (cryoglobuline) pouvant précipiter au froid. Méthodes: nous avons mené une étude transversale et analytique dans le service du laboratoire de biologie et l'unité d'hépatologie de l'Hôpital Général de Douala (HGD) pendant une durée de 6 mois. Etaient inclus dans le travail tous les patients acceptant de participer et porteurs d'un anticorps anti VHC avec ou sans traitement. Les cryoglobulines étaient recherchés par la méthode de Biuret et la classification était réalisée par une immunoélectrophorèse de Brouet. Une analyse multivariée a été réalisée, des facteurs de confusion tels que l'âge, le sexe et la durée après dépistage du VHC ont été ajustés.Résultats: nous avons inclus 116 patients. L'âge moyen était de 58,47 ± 9,95 ans. Le sexe masculin représentait 50,86% des cas. L'arthralgie était présente dans 69,80% des cas. La cryoglubiline était présente chez 63,80% des cas. Apres ajustement, le sexe féminin (ORa =2,18; IC à 95% [0,97-4, 90]; p= 0,059), l'asthénie seule (ORa =2,45; IC à 95% [1,04-5,80]; p= 0,041), l'asthénie couplée à l'arthralgie (ORa =2,84; IC à 95% [1,13-7, 10]; p= 0,026) et la présence de l'ARN du VHC (ORa =2,84; IC à 95% [1,13-7, 10]; p= 0,028) étaient des facteurs indépendamment associés à la présence de cryoglobuline.Conclusion: la prévalence de la cryoglobubine est élevée chez les patients porteurs de l'Ac anti VHC à l'HGD. Elle est recherchée par les méthodes biologiques simples. La recherche de cryoglobuline chez les patients porteurs du VHC est essentielle dans un pays à ressource limité

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

Hepatocellular 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.

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.

Sudden cardiac death in low-resource settings: lessons from a resuscitated cardiac arrest.

We report on the case of an adult black African who was resuscitated from several cardiac arrests but suffered behavioural impairment, and discuss diagnostic pitfalls. The aetiology of coronary free lesion myocardial infarction with depressed left ventricular function was diagnosed when the patient travelled abroad. The low prevalence of recognised sudden cardiac arrest (SCA), as well as the lack of diagnostic and appropriate resuscitation facilities in parts of sub-Saharan Africa lead to the mismanagement of victims. Increased awareness of SCA and its causes is urgently needed.

Statut vaccinal contre le virus de l'hepatite virale B et portage de l'antigene HBs chez les etudiants en medecine et Pharmacie de l'Universite de Douala au Cameroun

Objectif Le but de notre etude etait de determiner la prevalence de l'Ag HBs chez les etudiants en medecine et pharmacie de l'universite de Douala -Cameroun. Methodes Il s'agit d'une etude transversale; descriptive et analytique qui a porte sur les etudiants de la faculte de medecine et des sciences pharmaceutiques de l'universite de Douala-Cameroun. Nous avons inclus tout etudiant regulierement inscrit et acceptant de participer a l'etude. Les prelevements etaient traites par un test rapide puis par ELISA (automatic diagnostic). Les variables qualitatives ont ete comparees par un test de Chi-2; du test de Fischer et de l'Odds ratio. Resultats Cinq cent etudiants ont ete preleves. L'age median etait de 22 ans avec des extremes allant de 16 a 31 ans. Le sex ratio etait de 1;36 en faveur du sexe feminin. L'antigene HBs etait positif chez 28 etudiants soit 5;6. 88 etudiants soit 17;6 etaient vaccines contre l'hepatite virale B. Les etudiants qui avaient recu une; deux et trois doses de vaccin representaient respectivement 5 (n=25); 7;6(n=38) et 17;6(n=88). Huit etudiants soit 4;45 avait fait un dosage de l'anticorps anti HBs pour verifier l'efficacite vaccinale. Conclusion :La prevalence de l'Ag Hbs est de 5;6 chez les etudiants en medecine et pharmacie a Douala