Abstract
Hepatitis B virus (HBV) genotype E almost exclusively occurs in African people, and its presence is more commonly associated with the development of chronic HBV (CHB) infection. Moreover, an epidemiological link has been found between the distribution of HBV genotype E infection and African countries with high incidences of hepatocellular carcinoma. As part of a programme for the health assessment of migrants, we evaluated 358 young African subjects for HBV infection; 58.1% (208/358) were positive for an HBV marker, and 54 (25.5%) had CHB. Eighty-one percent of the CHB subjects were infected with HBV genotype E, with a median serum HBV-DNA of 3.2 (IQR: 2.7–3.6) logIU/ml. All patients had high serum HBsAg titres (10,899 [range 5,359–20,272] IU/ml), and no correlation was found between HBsAg titres and HBV-DNA plasma levels. RT sequence analysis showed the presence of a number of immune escape mutations: strains from all of the patients had a serine at HBsAg position 140; 3 also had T116N, Y100C, and P142L+S143L substitutions; and 1 had a G112R substitution. Six (18%) patients had stop-codons at position 216. In 5 of the 9 (26.5%) CHB patients, ultrasound liver biopsy, quantification of total intrahepatic HBV-DNA and cccDNA, and RT/HBsAg sequencing were performed. The median (IQR) total intrahepatic HBV-DNA was 766 (753–1139) copies/1000 cells, and the median (IQR) cccDNA was 17 (10–27) copies/1000 cells. Correlations were observed for both total intrahepatic HBV-DNA and cccDNA with serum HBV-DNA, while no correlation was found for the HBsAg titres. A difference of 2.5/1,000 nucleotides was found in the HBsAg sequences obtained from plasma and from liver tissue, with 3 cases of possible viral anatomical compartmentalization. In conclusion, a high rate of CHB infection due to the E genotype was demonstrated in a group of immigrants from Western Africa. An analysis of the viral strains obtained showed the virological characteristics of immune escape, which may be the cause of viral replication persistence. Moreover, a fair percentage of stop codon mutations were found. The lack of correlation between HBsAg titres and plasma or intrahepatic HBV-DNA found in these subjects suggests a pathway of virus production that is not linked to HBsAg secretion. Studies with a larger number of patients with CHB due to the E genotype are advisable to corroborate these observations.
Highlights
At least 2 billion people have been infected with hepatitis B virus (HBV) worldwide, and approximately 360 million patients have a chronic HBV infection (CHB), which appears to cause 50% to 60% of the hepatocellular carcinoma (HCC) cases [1] worldwide
HBV genetic analysis conducted in the CHB subjects revealed that most of the migrants (>80%) were infected with the HBV E genotype, and Reverse Transcriptase (RT) sequencing analysis of the viral strains obtained showed a high prevalence of mutations correlated with immune escape phenomena (Echevarria et al, JMV 2006)
Our results revealed a prevalence (>15%) of CHB higher than that reported by Coppola, who described an Hepatitis B S antigen (HBsAg) prevalence ranging from 7% to 14% among African migrants in southern Italy
Summary
Africa is considered a region with high endemicity as it has an estimated Hepatitis B S antigen (HBsAg) seroprevalence of 6–20%, which is higher in rural than in urban areas. HBsAg seroprevalence can first be detected in African children 1–3 years old, and it increases with age, growing to 12–16% in 6 to 15-year-old African adolescents [2]. HBV genotypes A, D and E are the most frequent genotypes found in Africa. Genotype A is found predominantly in Southern, Eastern and Central Africa, while genotype D is most common in Northern Africa. HBV genotype E, first described in 1992, predominates in Western Africa and has not been detected outside of Africa [2]. It has been hypothesized that HBV genotype E was introduced into the African population only within the past 200 years, probably through cross-species transmission [3]
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