The unexpected high prevalence of HBV subgenotype D4 in patients with chronic hepatitis B in Galicia, a northwestern Spanish region, reflects strong links with Latin America.

BACKGROUND: Hepatitis B virus (HBV) comprises 9 genotypes and multiple subgenotypes that depict differences in geographic distribution, clinical outcome and response to antiviral therapy. However, the molecular epidemiology of HBV geno/subgenotypes is globally scarce. In Spain, HBV genotype D seems to be more prevalent in the northwestern regions compared to the rest of the country for unclear reasons. METHODS: HBV genotyping was performed using geno2pheno on a S gene fragment amplified from plasma collected from all chronic hepatitis B individuals attended at one reference hospital in Santiago de Compostela, the Galicia's capital town. Phylogenetic and phylogeographic analyses using a fragment of 345 bp were performed in all viremic specimens. To avoid misleading allocation as consequence of short fragment analysis, several bioinformatic controls were used. RESULTS: A total of 320 individuals with persistent serum HBsAg+ and detectable HBV-DNA were seen between 2000 and 2016 (male 68.4%; median age, 52 years-old; native Spaniards 83.8%). HBV genotype distribution was as follows: A 15.3%; B 1.6%; C 2.5%; D 71.6%; E 3.1%; F 2.2%; G 3.1%; and H 0.6%. HBV genotype D was mostly represented by D4 and D2 subgenotypes (33.4% and 15% of total, respectively). Compared to chronic hepatitis B patients with genotypes B, C, E and G, HBV-D4 carriers tended to be older (54.2% had >50 years-old) and HBeAg-negative (85%). Moreover, 43% were female, 4.7% had cirrhosis, 10.2% hepatitis C and 6.4% HIV coinfection. Phylogenetic analyses could be performed on 82 HBV-D4 specimens; and 79 were confirmed as HBV-D4 using PhyML. Phylogeography using FasTree suggested at least two distinct introductions of HBV-D4 in Galicia, one from the Caribbean and South America, and another from India. CONCLUSIONS: HBV subgenotype D4 is the most prevalent HBV variant in chronic hepatitis B patients living in the northwest of Spain, representing 33.4% (107/320) of all chronic hepatitis B infections. This rate of HBV-D4 is among the highest reported worldwide. Epidemiological and phylogenetic analyses suggest a strong association with historical migrant exchanges with Latin America, and especially with the Caribbean basin.

Decline and changing profile of hepatitis delta among injection drug users in Spain.

BACKGROUND: Roughly 15 million people worldwide have hepatitis delta, the most severe form of chronic viral hepatitis that often leads to cirrhosis and liver cancer. Injection drug users (IDUs) are the largest HDV reservoir. Their resurgence in North America and Europe may represent a new opportunity for HDV to spread more widely. METHODS: We examined all consecutive active IDUs seen for the first time and enrolled in detoxification programmes at two clinics in Spain during two periods (1993-1996 and 2011-2014, respectively). Serum markers of HIV, HBV and HDV infection were tested. RESULTS: A total of 209 IDUs were examined in the first period. Mean age was 27-years-old. All had markers of past or current HBV infection. The rate of HIV-antibody (Ab), hepatitis B surface antigen (HBsAg) and HDV-Ab was as follows: 122 (58.4%), 73 (34.9%) and 62 (29.7%), respectively. Serum HDV-Ab was recognized in 53.4% of HBsAg+ and 16.9% of HBsAg- patients (P<0.001). Positivity for HDV-Ab was associated with HIV regardless HBsAg status. In the second period we tested 47 active IDUs. Anti-HDV was found in only two (4.2%), both immigrants from HDV endemic countries and with HBsAg+. CONCLUSIONS: Acute HBV-HDV coinfections and self-limited HDV infections were frequent in the 1990s among IDUs in Spain, especially in HIV+ individuals. In contrast, circulation of HDV has dramatically declined among active IDUs in Spain and is currently very rare, being concentrated in foreign immigrants. It may reflect the benefit of universal HBV vaccination as well as the success of needle exchange programmes in Spain.

Prevalencia y distribución del genotipo D del virus de la hepatitis B en Galicia (noroeste de España): influencia de la edad, el sexo y la procedencia / Prevalence and distribution of hepatitis B virus genotype D in Galicia (northwest of Spain): influence of age, sex and origin

Introducción. El virus de la hepatitis B (VHB) se clasifica filogenéticamente en genotipos y subgenotipos utilizados para estudios epidemiológicos. El objetivo es conocer la distribución de subgenotipos D del VHB en nuestro entorno. Pacientes y métodos. En 401 pacientes con antígeno de superficie del VHB positivo, ADN-VHB positivo, se amplificó y secuenció un fragmento del gen que luego se analizó mediante la aplicación on-line geno2pheno (hbv) del Instituto Max- Planck. Resultados. Se encontraron 259 (64,6%) pacientes con genotipo D: 53 no subgenotipables, 9 (4%) D1, 61 (30%) D2, 15 (7%) D3 y 121 (59%) D4. Los pacientes con VHB de subgenotipo D1 eran, de media, 23 años más jóvenes (p=0,0001) y con mayor proporción de mujeres (p<0,05). Conclusiones. El subgenotipo D4 del VHB es el mayoritario en nuestro entorno. Los pacientes con subgenotipo D1 procedían del extranjero, eran más jóvenes que los demás subgenotipos y con mayor proporción de mujeres. Estos resultados demuestran el interés de realizar estudios a nivel de subgenotipo de VHB (AU)

Introduction. Phylogenetically, hepatitis B virus (HBV) is classified into genotypes and subgenotypes used for epidemiological studies. The aim of this study is to know the distribution of HBV subgenotypes D in our environment. Patients and methods. From 401 patients HBV surface antigen positive, HBV DNA-positive, partial HBV-DNA S gene was amplified, sequenced and analysed using geno2pheno (hbv) (Max-Planck Institute) on line application. Results. We found 259 (64.6%) patients with HBV genotype D: 53 not subgenotypable, 9 (4%) D1, 61 (30%) D2, 15 (7%) D3 and 121 (59%) D4. Patients with D1 subgenotype were, on average, 23 years younger (p = 0.0001), with a higher proportion of women (p < 0.05). Conclusions. HBV subgenotype D4 was the most prevalent in our area. Patients with D1 subgenotype came from abroad were younger than the other subgenotypes and mostly women. These results show the interest of conducting studies at HBV subgenotype level (AU)