A high prevalence of hepatitis B virus strains sharing a single S gene variant in Pakistan.

Pre-S Deletion and Complex Mutations of Hepatitis B Virus Related to Advanced Liver Disease in HBeAg-Negative Patients

Infection with hepatitis B virus (HBV) is a major global public health problem, with an estimated prevalence of 350 million chronic carriers worldwide, and 1.5 million in the United States. The majority of HBV-infected individuals are concentrated in Asia and subSaharan Africa, but the incidence is rising is Western countries as a result of changing migration patterns. Chronic HBV infection can lead to liver cirrhosis, hepatic decompensation, and premature death. As many as 25% of HBV-infected patients will develop hepatocellular carcinoma (HCC), which is the fourth most common solid tumor worldwide. As much as a 50% reduction in the incidence of HBV transmission has been achieved in certain countries through widespread vaccination programs. Reduction in the morbidity and mortality of HBV-related HCC has been achieved as a result of intensive screening programs and through antiviral treatment with agents such as lamivudine and interferon. Because the majority of HCC cases worldwide are HBV-associated, HCC is truly a preventable malignancy. Given the considerable number of patients who are at risk for developing chronic HBV infection and its deadly sequelae, the costs associated with screening and treatment are similarly enormous. The challenge, therefore, is to select those patients most likely to benefit from HBV treatment and HCC screening to maximize the benefit-cost ratio of such programs. Any opportunity to optimize selection of patients for HBV treatment and HCC screening, and thereby reduce the incidence of HCC, should result in a significant public health benefit. HBV has been classified into eight genotypes, designated by capital letters A through H. HBV genotypes have distinct geographic distributions, with genotypes B and C being the most prevalent in Asia. Several studies have demonstrated that genotype C is associated with a higher prevalence of hepatitis B e antigen (HBeAg), more active hepatitis, and more advanced liver disease than genotype B. In a cross-sectional study of 270 Taiwanese HBV carriers with various forms of liver disease, genotype C was more prevalent in patients with cirrhosis and in those with HCC older than 50 years compared with age-matched asymptomatic carriers. Furthermore, HBV genotype C has been shown to be an independent risk factor for development of HCC. In a study of 426 Chinese patients infected with HBV, 25 patients developed HCC during a median follow-up of 121 weeks. Cirrhosis and HBV genotype C infection were independently associated with HCC development. In a study of 4,841 Taiwanese male hepatitis B s antigen (HBsAg) carriers, there were 154 cases of HCC diagnosed during a 14-year follow-up period. HBV DNA levels and HBV genotypes were determined for all patients with HCC and 316 control subjects. Results indicated that the risk of HCC increased with increasing HBV viral load. Moreover, genotype C was associated with an increased risk of HCC compared with other HBV genotypes (adjusted odds ratio [OR] 5.11; 95% CI, 3.20 to 8.18). In that study, the association of HBV genotype C and HBV viral load with HCC risk appeared to be additive. The adjusted OR of HCC for those carrying genotype C and with viral load in the highest quintile was 26.49 (95% CI, 10.41 to 67.42) compared with those carrying other HBV genotypes and lower viral loads. These and other recent studies have been paramount in our understanding of the factors that influence clinical outcome in HBV infection. However, it appears that HBV genotype is only one of the elements associated with hepatocarcinogenesis. Mutations in the basic core promoter (BCP) and precore regions carry an increased risk of HCC. In a cross-sectional, retrospective study of 160 chronic HBV carriers and 200 patients with HCC, advanced age, male sex, the precore A1896 mutation, the BCP T1762/A1764 mutation, and a high HBV load were significantly associated with development of HCC. There has also been recent interest in studying the relationship among HBV genotypes, subgenotypes, and mutations encountered in HBV carriers. Whether these have additive or synergistic effects on the risk of HCC development remains unclear. It has been reported that patients with genotype B have a higher chance of harboring precore mutations when compared with patients with genotype C. In the same study, core promoter mutations, T1653 mutations, HBV DNA levels of at least 4 log10 copies/mL, and cirrhosis were shown on to be independent risk factors for HCC. HBV genotype C has been classified into four subgenotypes: HBV/C1-C4. The designation of the two most widely disseminated subgenotypes is controversial. HBV/C1 (or Cs) is commonly found in Southeast Asia. HBV/C2 (or Ce) is found in East Asia including Japan and China. There are limited data on the clinical implications and JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 26 NUMBER 2 JANUARY 1

Most cases of hepatocellular carcinoma (HCC) are associated with cirrhosis related to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Changes in the time trends of HCC and most variations in its age-, sex-, and race-specific rates among different regions are likely to be related to differences in hepatitis viruses that are most prevalent in a population, the timing of their spread, and the ages of the individuals the viruses infect. Environmental, host genetic, and viral factors can affect the risk of HCC in individuals with HBV or HCV infection. This review summarizes the risk factors for HCC among HBV- or HCV-infected individuals, based on findings from epidemiologic studies and meta-analyses, as well as determinants of patient outcome and the HCC disease burden, globally and in the United States.

Preventing Infection-Associated Cancer: From Bench to Hillside

The direct cytopathic effects of the hepatitis B virus (HBV) on subsequent liver damage are not fully understood in HBV-infected patients. However, associations between the prevalence of various HBV genotypes and the extent of liver damage have been reported from different parts of the world. The purpose of this study was to determine the distribution of HBV genotypes in patients with chronic HBV infection in Bangladesh, a country of 160 million people, of which approximately 3–6 million are chronically infected HBV patients. In addition, whole and partial genome sequencing of HBV was performed to evaluate the relationship between HBV mutations and genotypes. We found that 42% of the patients with low HBV DNA and normal levels of alanine aminotransferase (ALT) had HBV genotype D. In contrast, the HBV genotype C was dominant among patients with high HBV DNA levels (>2000 IU/ml) and elevated ALT and in patients with liver cirrhosis (LC) and hepatocellular carcinomas (HCC). Whole and partial genome sequences of HBV revealed that most patients with LC and HCC had HBV genotype C with mutations at the T1762/A1764 positions. It seems that Bangladesh represents a borderline country, situated within East Asia, which mainly consists of individuals with HBV genotypes B and C, whereas in the western parts of Asia, HBV genotypes A and D are prevalent. Bangladesh is, therefore, an excellent model for the comparison of the pathophysiology of three major HBV genotypes in a single population. The findings of this study suggest a possible association between HBV viral factors and the extent of liver damage in chronic HBV-infected patients.

Hepatitis B virus genotypes in the United States: results of a nationwide study

High HBV Viral Loads in HIV-Infected Pregnant Women at a Tertiary Hospital, South Africa

Aim: Hepatitis B virus (HBV) is not uncommon among animal and non-animal handlers. The brutality of HBV infection and the outcome of treatment is linked with exact HBV genotypes. No study on the circulation of HBV genotypes has been reported among animal and non-animal handlers in Nigeria. This study was intended to evaluate the genotypic distribution among animal and non-animal handlers in Osun State, Nigeria. Study Design: Cross-sectional study. Place and Duration of Study: Ladoke Akintola University of Technology (LAUTECH), Nigeria, between June 2015 and July 2019. Methods: Blood samples were obtained from HBsAg positive individuals and screened for HBV-DNA from cohorts of animal and non-animal handlers. HBV-DNA was extracted, amplified and genotyped using a multiplex PCR technique with primers specific for six genotypes of HBV (Genotype A, B, C, D, E and F). Results: Results showed that a total of 11 (6.1%) of the 180 animal and non-animal handlers evaluated were positive to HBsAg and 4.4% were positive for HBV-DNA by a semi-nested PCR using HBV specific primer pairs. The molecular analysis of the sera of 11 HBsAg positive animal and non-animal handlers showed that 72.7% of them had a true HBV infection. Results further show that genotype E (75.0%) was predominant over genotype A (12.5%) and mix genotypes (D and E) with 12.5% prevalence. Other genotypes were not detected. Of the 8 positive HBV-DNA samples, 7 (87.5%) were males and one (12.5%) was a female. All animal and non-animal handlers with true HBV infection were found to harbour HBV genotype E predominantly. Conclusion: The molecular analysis of HBV-DNA and genotypes circulating among animal and non-animal handlers shows that the majority of the subjects with true HBV infection were found to predominantly harbour HBV genotype E in Osun state, Nigeria. The study further highlights the predominance HBV genotype E in Nigeria.

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Lamivudine Plus Low-Dose Hepatitis B Immunoglobulin to Prevent Recurrent Hepatitis B Following Liver Transplantation

Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality and healthcare expenditure in patients with chronic liver disease. There are no consensus guidelines on diagnosis and management of HCC in India. The Indian National Association for Study of the Liver (INASL) set up a Task-Force on HCC in 2011, with a mandate to develop consensus guidelines for diagnosis and management of HCC, relevant to disease patterns and clinical practices in India. The Task-Force first identified various contentious issues on various aspects of HCC and these issues were allotted to individual members of the Task-Force who reviewed them in detail. The Task-Force used the Oxford Center for Evidence Based Medicine-Levels of Evidence of 2009 for developing an evidence-based approach. A 2-day round table discussion was held on 9th and 10th February, 2013 at Puri, Odisha, to discuss, debate, and finalize the consensus statements. The members of the Task-Force reviewed and discussed the existing literature at this meeting and formulated the INASL consensus statements for each of the issues. We present here the INASL consensus guidelines (The Puri Recommendations) on prevention, diagnosis and management of HCC in India.

Hepatitis B Virus (HBV) infection is a global health concern. HBV genotypes differ in disease potential and geographical distribution. These genotypes impact the diagnostic and preventive strategies. Furthermore, limited data are available on Torque Teno Virus (TTV) co-infections with HBV. Hence, this study evaluated HBV infection prevalence, genotype distribution, and the presence of TTV among HBV-positive patients. During the study period, a total of 1820 serum samples were collected and tested for HBsAg using ELISA method. Of this, 43 (2.36%) were HBsAg positive. These HBsAg-positive samples were further subjected to conventional PCR followed by Sanger sequencing for HBV and TTV genotype detection. In this study, only HBV genotypes D (subgenotype D2) (97%) and A (subgenotype A1) (3%) were detected. 15% of HBV-infected patients were positive for TTV in which genotype 1A was detected in 66.67% of cases and 1B in 33.33% of cases. To the best of our knowledge, this study represents the first of its kind from Puducherry to document Torque Teno Virus (TTV) co-infection in HBV-positive cases from the non-renal transplant population. This study underscores the significance of HBV genotypes and TTV co-infection in HBV patients. Further studies and surveillance are needed to monitor circulating HBV genotypes and explore TTV's role in co-infection, particularly its pathogenesis and clinical implications.

The major hepatitis B virus (HBV) genotypes in Japan are B and C. HBV genotype D (HBV/D), however, is widespread in a small area of Western Japan, where the Gianotti-Crosti syndrome caused by HBV subtype ayw, which is suspected to be HBV/D, was endemic in the 1970s. The aim of the study was to elucidate its origin, time of transmission, and spread in this area. Genotyping of HBV-DNA was done in 363 patients with HBV infection. The year of birth was checked in patients with HBV/D. The full genome sequences of 20 HBV/D strains, 2 of which were obtained from a single carrier with a 19-year-interval, were analyzed. An evolutionary rate, the date of the most recent common ancestor, and the effective number of HBV/D infections were calculated. Fifty-two of 363 patients were infected with HBV/D, and 39 were born in 1970s. In a phylogenetic tree, the 20 HBV/D strains produced a definite cluster, and the evolutionary rate was calculated to be 5.4 x 10(-5) nucleotide substitutions/site/year. The root of the tree was estimated to be in approximately 1,900 and began to spread from the 1940s, leading to a rapid increase of infected patients in the 1970s. From these results, it is suspected that HBV/D was likely transmitted to the area investigated approximately 100 years ago and then spread widely in the 1970s. From the history of the area and the genetic analysis, HBV/D in this area was speculated to be of Russian origin.

The role of genotype mixture and subgenotypes remains controversial in determining the clinical outcome of chronic hepatitis B virus (HBV) infection. We aimed to determine their role on the development and the recurrence of hepatocellular carcinoma (HCC). HBV genotypes, serum viral load and hepatitis B e antigen (HBeAg) seroconversion were determined in 462 HCC patients, 234 chronic hepatitis patients and 425 asymptomatic carriers born in Eastern China. In the 462 HCC patients, 62 (13.4%), 337 (72.9%) and 49 (10.6%) had HBV subgenotype B2, C2 and genotype mixture, respectively. Genotype mixture in HCC patients and hepatitis patients was associated with higher viral load than HBV C2 (P = 0.012, P = 0.000) and more frequent than asymptomatic carriers (P = 0.005, P = 0.000). HBV C2 was more prevalent in HCC patients compared with controls. Proportion of HBV B2 in HCC patients decreased consecutively from <30 to 50-59 years group (P = 0.024). Age-related changes of HBeAg seroconversion were not consistent with serum viral load in HCC patients with HBV B2 and genotype mixture, quite in contrast to hepatitis patients. By multivariate regression analysis, age >or=40 years and serum viral load (>or=10 000 copies/ml) were independently associated with hepatocarcinogenesis, whereas age <or=50 years and HBV B2 were independently associated with HCC recurrence after surgical resection. In conclusion, HBV coinfections with two or three genotypes were associated with higher viral load and more severe course of the disease. HBV B2 infection was related to HCC recurrence. HBV C2 predominance in HCC patients was related to the high prevalence in Eastern China.

Occult HBV infection—both hidden and mysterious