Basal core promoter and precore mutations among hepatitis B virus circulating in Brazil and its association with severe forms of hepatic diseases

Chachá, Silvana Gama Florêncio; Gomes‐Gouvêa, Michele Soares; Malta, Fernanda de Mello; Ferreira, S. E. S.; Villanova, Márcia G.; Souza, Fernanda Fernandes; Teixeira, Andreza Corrêa; Passos, Afonso Dinis da Costa; Pinho, João Renato Rebello; Martinelli, Ana de Lôurdes Candolo

doi:10.1590/0074-02760160540

Cited by 8 publications

(7 citation statements)

References 27 publications

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“…Review of the full-text articles led to the exclusion of 303, and the inclusion of 162 articles in the analysis ( Figure 1 , Figure 2 ). 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 ,…”

Section: Resultsunclassified

“…According to EASL 2012 criteria (eight studies), 830 (19•3%) of 4300 participants were eligible for treatment. This number was highest in the Americas (36% [95% CI [33][34][35][36][37][38][39]) and in Europe (32% [29][30][31][32][33][34][35]) and lowest in the African region (18% [16][17][18][19]). According to AASLD criteria (four studies), 246 (8%) of 3030 participants were eligible.…”

Section: Pollack Et Al (2014) 131mentioning

confidence: 99%

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Estimating the proportion of people with chronic hepatitis B virus infection eligible for hepatitis B antiviral treatment worldwide: a systematic review and meta-analysis

Tan

Bhadoria

Cui³

et al. 2021

The Lancet Gastroenterology & Hepatology

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Summary Background In 2016, of the estimated 257 million people living with chronic hepatitis B virus (HBV) infection worldwide, only a small proportion was diagnosed and treated. The insufficiency of information on the proportion of people infected with HBV who are eligible for treatment limits the interpretation of global treatment coverage. We aimed to estimate the proportion of people with chronic HBV infection who were eligible for antiviral treatment worldwide, based on the WHO 2015 guidelines. Methods In this systematic review and meta-analysis, we searched Medline, EMBASE, and the Cochrane databases from Jan 1, 2007, to Jan 31, 2018, for studies describing HBsAg-positive people in the population or health-care facilities. We extracted information from published studies using a standardised form to estimate the frequency of cirrhosis, abnormal alanine aminotransferase (ALT), HBV DNA exceeding 2000 IU/mL or 20 000 IU/mL, presence of HBeAg, and eligibility for treatment as per WHO and other guidelines as reported in the studies. We pooled proportions through meta-analysis with random effects. The study was registered with PROSPERO, CRD42020132345. Findings Of the 13 497 studies, 162 were eligible and included in our analysis. These studies included 145 789 participants. The pooled estimate of the proportion of cirrhosis was 9% (95% CI 8–10), ranging from 6% (4–8) in community settings to 10% (9–11) in clinic settings. Examining the proportion of participants who had characteristics used to determine eligibility in the WHO guidelines, 1750 (10·1%) of 17 394 had HBV DNA exceeding 20 000 IU/mL, and 20 425 (30·8%) of 66 235 had ALT above the upper limit of normal. 32 studies reported eligibility for treatment according to WHO or any other guidelines, with a pooled estimate of eligibility at 19% (95% CI 18–20), ranging from 12% (6–18) for studies in community settings to 25% (19–30) in clinic settings. Interpretation Many studies described people with HBV infection, but few reported information in a way that allowed assessment of eligibility for treatment. Although about one in ten of the 257 million people with HBV infection (26 million) might be in urgent need of treatment because of cirrhosis, a larger proportion (12–25%) is eligible for treatment in accordance with different guidelines. Future studies describing people with HBV infection should report on treatment eligibility, according to broadly agreed definitions. Funding WHO and US Centers for Disease Control and Prevention.

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Section: Resultsunclassified

Section: Pollack Et Al (2014) 131mentioning

confidence: 99%

Estimating the proportion of people with chronic hepatitis B virus infection eligible for hepatitis B antiviral treatment worldwide: a systematic review and meta-analysis

Tan

Bhadoria

Cui³

et al. 2021

The Lancet Gastroenterology & Hepatology

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“…These two mutations are located in the BCP, which overlaps with the X gene. The presence of these double mutations is thought to exacerbate the host's immune response, increase viral replication and modify the coding region of the X protein causing the progression of CLD (46). H94Y and I127L/T/N/S mutations have been associated to K130M/V131I in previous studies (47,48).…”

Section: Discussionmentioning

confidence: 99%

Association between host TNF‑α, TGF‑β1, p53 polymorphisms, HBV X gene mutation, HBV viral load and the progression of HBV‑associated chronic liver disease in Indonesian patients

et al. 2019

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In developing countries, including Indonesia, there is a high mortality rate associated with the progression of hepatitis B virus (HBV)-associated chronic liver disease (CLD). The pathogenesis of HBV infection is influenced by viral and host factors. To determine potential associations between these factors, host single nucleotide polymorphisms (SNPs) on TNF-α, TGF-β1 and p53, HBV X gene mutation and HBV viral load were investigated in patients with HBV-associated CLD in Surabaya, Indonesia. Sera were collected from 87 CLD patients with HBV infection. TNF-α, TGF-β1 and p53 SNPs were genotyped by PCR restriction fragment length polymorphism. The HBV X gene was sequenced and compared with reference strains to determine mutations and the viral load was measured using reverse transcription-quantitative PCR. In Indonesian patients, no association between TNF-α, TGF-β1 and p53 SNPs and CLD or X gene mutation were identified. A total of 23% (20/87) of samples had HBV X gene mutations, including ten substitution types, one deletion and one insertion. Multinomial regression analysis revealed that the K130M/V131I mutations were correlated with CLD progression (OR, 7.629; 95% CI, 1.578-36.884). Significant differences in viral load were found in HBV-infected patients who had X gene mutations, such as R87W/G, I127L/T/N/S and K130M/V131I mutations (P<0.05). The presence of K130M and V131I mutations may be predictive for the progression of HBV-associated CLD in Indonesia.

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“…Hepatitis B virus (HBV), a member of the family Hepadnaviridae , is characterized by asymptomatic, acute, or chronic hepatitis, which might progress to fulminant hepatic failure, cirrhosis, or hepatocellular carcinoma [ 1 , 2 ]. Currently, about 250 million of the world population are infected with chronic hepatitis B, and 65 million of those infected are women of childbearing age.…”

Section: Introductionmentioning

confidence: 99%

“…The most common mutations are pre-core (pre-C) and basal core promoter (BCP) mutations in the HBV core gene [ 5 , 7 ]. These mutations affect the expression of HBV e antigen (HBeAg) protein and have a significant association with progressive liver diseases such as liver cirrhosis and hepatocellular carcinoma (HCC) [ 2 , 8 ]. In addition, some mutations in the S region have an important role in the occurrence of occult HBV infection with undetectable levels of HBsAg [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Prevalence, genotype distribution and mutations of hepatitis B virus and the associated risk factors among pregnant women residing in the northern shores of Persian Gulf, Iran

Taherkhani

Farshadpour²

2022

PLoS ONE

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Background Considering perinatal transmission and the high rate of chronic hepatitis B virus (HBV) infection in infants, diagnosis of HBV infection during pregnancy and timely interventions are of great importance. Therefore, this study was performed to investigate the prevalence and genotype distribution of HBV infection and the associated risk factors among pregnant women in the northern shores of the Persian Gulf, South of Iran. Methods Serum samples of 1425 pregnant women were tested for the presence of HBsAg and HBcAb by ELISA (HBsAg one—Version ULTRA and HBc Ab ELISA kits, DIA.PRO, Milan, Italy). The seropositive samples were tested for the presence of HBV DNA by nested PCR, targeting S, X, pre-core (pre-C), and basal core promoter (BCP) regions of the HBV genome. The amplified fragments were sequenced by Sanger dideoxy sequencing technology to evaluate the genotype distribution and mutations of HBV infection by using the MEGA 7 software. The HBV seropositive pregnant women were tested for HCV and HIV coinfections by ELISA (HCV Ab and HIV Ab/Ag ELISA kits, DIA.PRO, Milan, Italy). Results Of 1425 participants, 15 pregnant women (1.05%, 95% CI: 0.64%-1.73%) were positive for HBsAg, 41 women (2.88%, 95% CI: 2.10%-3.88%) were positive for HBcAb, and 5 women (0.35%, 95% CI: 0.15% –0.82%) had HBV viremia with genotype D, sub-genotype D3 and subtype ayw2. One of the viremic samples was positive for HBcAb but negative for HBsAg, which is indicative of an occult HBV infection. HBsAg seroprevalence was higher among pregnant women aged 20 to 29 years, women in the third trimester of pregnancy, residents of Khormuj city, Afghan immigrants, illiterate women, and pregnant women with a history of tattoo and HBV vaccination. The highest rate of HBcAb seroprevalence was observed in residents of Borazjan city, Turk ethnicity, the age group >39 years, and those women with more parities and a history of abortion. Nevertheless, HBV seroprevalence among pregnant women was not statistically associated with these variables. In contrast, HBcAb seropositivity was significantly associated with the history of tattoo (P = 0.018). According to mutations analyses, seven amino acid substitutions in the HBsAg, one point mutation in the pre-C region, and five points mutations in the BCP region were detected. Besides, the BCP mutations caused amino acid substitutions in the X protein. Of note, the conversion of Ala → Val at amino acid 168 (A168V) and Thr → Pro at amino acid 127 (T127P) were detected in HBsAg of the occult HBV strain. Conclusion These results indicate a relatively low prevalence of HBV infection among pregnant women in the South of Iran, while tattooing is a risk factor for exposure to HBV infection. Moreover, all of the HBV-positive pregnant women were asymptomatic and unaware of their infection. Therefore, routine screening for HBV markers during pregnancy, appropriate treatment of HBV-infected women, and HBV vaccination are recommended to decrease mother-to-child transmission of HBV.

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Basal core promoter and precore mutations among hepatitis B virus circulating in Brazil and its association with severe forms of hepatic diseases

Cited by 8 publications

References 27 publications

Estimating the proportion of people with chronic hepatitis B virus infection eligible for hepatitis B antiviral treatment worldwide: a systematic review and meta-analysis

Estimating the proportion of people with chronic hepatitis B virus infection eligible for hepatitis B antiviral treatment worldwide: a systematic review and meta-analysis

Association between host TNF‑α, TGF‑β1, p53 polymorphisms, HBV X gene mutation, HBV viral load and the progression of HBV‑associated chronic liver disease in Indonesian patients

Prevalence, genotype distribution and mutations of hepatitis B virus and the associated risk factors among pregnant women residing in the northern shores of Persian Gulf, Iran

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