Epidemiology of Viral Hepatitis B and C Infections in Ibb City,Yemen

Background

The global epidemic of hepatitis B and hepatitis C is a serious publichealth problem. Chronic hepatitis B and hepatitis C are among the leading causes of preventable death worldwide. World Health Organization (WHO) estimates that up to two billion people in the world have been infected with HBV; about 350 million people live with chronic HBV infection, and about 600,000 people die from HBV- related liver disease or HCC each year. The endemicity of infection is considered high in Yemen. Data for prevalence of HBsAg and HCV antibodies in Ibb city in Yemen is rare and inadequate.

Objectives

The study was undertaken to study the epidemiology and prevalence of viral hepatitis (HBV) and (HCV) in Ibb city, Yemen.

Patients and Methods

554 pre-designed questionnaires and sera samples were collected in July 2010. Sera were tested for HBsAg and HCV antibodies by ELISA quantitative technique. Each individual’s data were collected in a pre-designed questionnaire.

Results

The prevalence of HBV in Ibb city was 1.81 %, whereas, the prevalence of HCV was 1.99 %.

Conclusions

This study revealed low level risk of hepatitis B virus and hepatitis C virus infections. Inadequate information on the prevalence and risk determinants of viral hepatitis among the different population groups in Yemen are responsible about morbidity and mortality of HBV and HCV in Ibb city, Yemen.     

An overview of hepatitis B prevalence,prevention, and management in the Pacific Islands and Territories

There are over 500–750 000 deaths per year because of hepatitis B virus (HBV)‐related cirrhosis and liver cancer worldwide and the World Health Organization Western Pacific Region has some of the highest endemic levels of HBV in the world, particularly within China, South East Asia and Pacific Island Countries and Territories (PICT). The PICT have unique ethnic diversity and a very high prevalence of smoking and metabolic syndrome, both important risk factors for liver fibrosis and liver cancer. However, in contrast to many Asian countries, there is little published data on HBV prevalence and related liver disease burden in PICT. In this review, the available published literature and World Health Organization data for HBV prevalence and related liver disease and liver cancer burden in PICT is outlined, and unmet needs for improving HBV prevention and control in the region are highlighted.     

Genetic basis of hepatitis virus-associated hepatocellular carcinoma: linkage between infection,inflammation, and tumorigenesis

Hepatitis virus infection is a leading cause of chronic liver disease, including cirrhosis and hepatocellular carcinoma (HCC). Although anti-viral therapies against hepatitis B virus (HBV) and hepatitis C virus (HCV) have dramatically progressed during the past decade, the estimated number of people chronically infected with HBV and/or HCV is ~370 million, and hepatitis virus-associated hepatocarcinogenesis is a serious health concern worldwide. Understanding the mechanism of virus-associated carcinogenesis is crucial toward both treatment and prevention, and the recently developed whole genome/exome sequencing analysis using next-generation sequencing technologies has contributed to unveiling the landscape of genetic and epigenetic aberrations in not only tumor tissues but also the background liver tissues underlying chronic liver damage caused by hepatitis virus infection. Several major mechanisms underlie the genetic and epigenetic aberrations in the hepatitis virus-infected liver, such as the generation of reactive oxidative stress, ectopic expression of DNA mutator enzymes, and dysfunction of the DNA repair system. In addition, direct oncogenic effects of hepatitis virus, represented by the integration of HBV-DNA, are observed in infected hepatocytes. Elucidating the whole picture of genetic and epigenetic alterations, as well as the mechanisms of tumorigenesis, will facilitate the development of efficient treatment and prevention strategies for hepatitis virus-associated HCC.

     

Cause of death in individuals with chronic HBV and/or HCV infection, a nationwide community-based register study

Summary.  Studies on chronic viral hepatitis and mortality have often been made on selected populations or in high-endemic countries. The aim of this study was to investigate the causes of death and the mortality rates in the nationwide cohorts of people chronically infected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) in Sweden, a low-endemic country. All notifications on chronic HBV infection and HCV infection 1990–2003 were linked to the Cause of Death Register. A total of 9517 people with chronic HBV infection, 34 235 people with HCV infection and 1601 with chronic HBV–HCV co-infection were included, and the mean observation times were 6.4, 6.3 and 7.9 years, respectively. The mortality in the cohorts was compared with age- and gender-specific mortality in the general population and standardized mortality ratios (SMR) were calculated. All-cause mortality was significantly increased, SMR 2.3 (HBV), 5.8 (HCV) and 8.5 (HBV–HCV), with a great excess liver-related mortality in all cohorts, SMR 21.7, 35.5 and 46.2, respectively. In HCV and HBV–HCV infected there was an increased mortality due to drug-related psychiatric diagnoses (SMR: 20.7 and 27.6) and external causes (SMR: 12.4 and 11.4), predominantly at younger age. To conclude, this study demonstrated an increased all-cause mortality, with a great excess mortality from liver disease, in all cohorts. In people with HCV infection the highest excess mortality in younger ages was from drug-related and external reasons.     

Hepatitis B virus infection and hepatocellular carcinoma in sub-Saharan Africa: Implications for elimination of viral hepatitis by 2030?

Elimination of viral hepatitis in sub-Saharan Africa by 2030 is an ambitious feat. However, as stated by the World Health Organization, there are unprecedented opportunities to act and make significant contributions to the elimination target. With 60 million people chronically infected with hepatitis B virus (HBV) of whom 38800 are at risk of developing highly fatal hepatocellular carcinoma (HCC) every year, sub-Saharan Africa faces one of the greatest battles towards elimination of viral hepatitis. There is a need to examine progress in controlling the disproportionate burden of HBV-associated HCC in sub-Saharan Africa within the context of this elimination target. By scaling-up coverage of hepatitis B birth dose and early childhood vaccination, we can significantly reduce new cases of HCC by as much as 50% within the next three to five decades. Given the substantial reservoir of chronic HBV carriers however, projections show that HCC incidence and mortality rates in sub-Saharan Africa will double by 2040. This warrants urgent public health attention. The trends in the burden of HCC over the next two decades, will be determined to a large extent by progress in achieving early diagnosis and appropriate linkage to care for high-risk chronic HBV infected persons.     

The state of hepatitis B and C in Europe: report from the hepatitis B and C summit conference*

Worldwide, the hepatitis B virus (HBV) and the hepatitis C virus (HCV) cause, respectively, 600,000 and 350,000 deaths each year. Viral hepatitis is the leading cause of cirrhosis and liver cancer, which in turn ranks as the third cause of cancer death worldwide. Within the WHO European region, approximately 14 million people are chronically infected with HBV, and nine million people are chronically infected with HCV. Lack of reliable epidemiological data on HBV and HCV is one of the biggest hurdles to advancing policy. Risk groups such as migrants and injecting drug users (IDU) tend to be under-represented in existing prevalence studies; thus, targeted surveillance is urgently needed to correctly estimate the burden of HBV and HCV. The most effective means of prevention against HBV is vaccination, and most European Union (EU) countries have universal vaccination programmes. For both HBV and HCV, screening of individuals who present a high risk of contracting the virus is critical given the asymptomatic, and thereby silent, nature of disease. Screening of migrants and IDUs has been shown to be effective and potentially cost-effective. There have been significant advances in the treatment of HCV and HBV in recent years, but health care professionals remain poorly aware of treatment options. Greater professional training is needed on the management of hepatitis including the treatment of liver cancer to encourage adherence to guidelines and offer patients the best possible outcomes. Viral hepatitis knows no borders. EU Member States, guided by the EU, need to work in a concerted manner to implement lasting, effective policies and programmes and make tackling viral hepatitis a public health priority.     

乙型及丙型肝炎患者发生肝细胞癌的风险预测：REVEAL-HBV/HCV研究的回顾

乙型肝炎病毒（HBV）及丙型肝炎病毒（HCV）的慢性感染是肝细胞癌（HCC）的主要致病原因。全球约有3亿5千万人为HBV的慢性感染者;HCV慢性感染者则有2亿人。全球每年约有50万人死于乙型肝炎引起的HCC,另有25万人死于丙型肝炎引起的HCC。乙型肝炎慢性感染者,其血中HBV DNA及ALT持续处于高水平是HCC最重要的预测因子。其他的危险因子还包括HBV C基因型、HBV基础核心促进子A1762T/G1764A双突变、男性、老年、肝癌家族史、酗酒习惯、以及与HCV或人类免疫不全病毒的合并感染等。根据REVEAL-HBV研究的资料,我们发展出简单易用的列线图,可利用非侵入性的临床特征准确地预测慢性乙型肝炎患者发生HCC的风险。丙型肝炎慢性感染患者发生HCC最重要的预测因子包括高血中HCV RNA水平、高ALT水平、HCV基因型以及老年等。REVEAL-HCV研究案例中,与HCV RNA水平低于检测范围且低ALT水平者相比,HCV RNA可测得、高ALT水平且感染第一型病毒的案例具有最高的HCC发生风险,其多变项调整后的风险比值（95%CI）为21.87（5.09～93.95）,这些发现对于慢性丙型肝炎的临床处置具有重要的意义。     

Hepatitis B-related hepatocellular carcinoma: epidemiological characteristics and disease burden

Summary. Worldwide, 350 million people are chronically infected with hepatitis B virus (HBV) who are at greater risk of hepatocellular carcinoma (HCC) compared with uninfected people. The relative risks of HCC among people infected with HBV ranges from 5 to 49 in case–control studies and from 7 to 98 in cohort studies. More than 50% of HCC cases worldwide and 70–80% of HCC cases in highly HBV endemic regions are attributable to HBV. Incidence of HCC (per 100 000 person/year) among people with chronic HBV infection ranges from 400 to 800 in male and from 120 to 180 in female. Factors associated with increased risk of HCC include demographic characteristics (male sex and older age), lifestyles (heavy alcohol consumption and smoking), viral factors (genotype C, D F, high level of HBV DNA, core/precore mutation) and clinical factors (cirrhosis, elevated alpha‐fetoprotein (AFP) and alanine aminotransferase (ALT)). HBV‐related HCC has extremely poor prognosis with median survival less than 16 months. Survival rates of HBV‐related HCC ranged from 36% to 67% after 1 year and from 15% to 26% after 5 year of diagnosis. Older age, liver function impairment, vascular invasion, tumour aggressiveness and elevated AFP are associated with HCC survival. Global burden of HBV‐related liver disease is still a major challenge for public health in the 21st century. While decreases in incidence of HBV infection have been observed in birth cohorts following the introduction of universal infant HBV vaccination programme, HBV‐related HCC incidence in is projected to increase for at least two decades because of the high prevalence of chronic HBV infection and prolonged latency to HCC development. To reduce HBV‐related HCC continued expansion of universal infant HBV vaccination is required along with antiviral therapy targeted to those individuals at highest risk of HCC. Broad public health strategies should include routine testing to identify chronic HBV infection, improved health infrastructures including human resource to provide diagnosis and treatment assessment.     

Significance of viral status on occurrence of hepatitis B-related hepatocellular carcinoma

Hepatitis B virus (HBV) infection remains a challenging global health problem, with more than 350 million people chronically infected and at risk of developing hepatocellular carcinoma (HCC). Interactions that occur among host, environmental, and viral factors determine the natural course and predict the prognosis of patients with chronic HBV infection. In the past decades, several important viral factors of predictive of HCC have been identified, such as high hepatitis B surface antigen level, seropositivity of hepatitis B e antigen, high viral load, viral genotype, and specific viral sequence mutations. Identification of certain viral risk factors for HCC development and stratification of patient risk are very important to perform future surveillance programs. In this article, we thus reviewed the risk of viral factors involved in hepatocarcinogenesis.     

Chronic liver disease mortality attributable to hepatitis B and C in New Zealand

BACKGROUND: This research aimed to estimate the prevalence and population attributable risk percent (PAR%) of hepatitis B (HBV) and C (HCV) infection among chronic liver disease (CLD) deaths in New Zealand. The PAR% is the percentage of CLD cases attributable to either HBV or HCV. Within New Zealand, there are large differences in HBV prevalence by ethnic group, so prevalence and PAR% estimates were made separately for the three major ethnic groups. METHODS: The study sample was selected from CLD deaths between 1992 and 1997. Data were extracted from hospital records and coroners' reports. The prevalence and PAR% of HBV and HCV were estimated. RESULTS: Data were extracted for 303 of 359 decedents selected for inclusion. Hepatitis B virus and HCV test results were identified in 67 and 43%, respectively. Among those cases tested, the prevalence (and estimated PAR%) of HBV infection was 68% (PAR% 66%) for Pacific people, 54% (PAR% 52%) for Maori and 10% (PAR% 10%) for European New Zealanders. The prevalence (and estimated PAR%) of past or present HCV infection ranged between 8 and 15% (PAR% 8-14%) for the three major ethnic groups. CONCLUSIONS: The present study has demonstrated that HBV and HCV infections are important contributors to CLD mortality in New Zealand. With the introduction of universal hepatitis B vaccination in the late 1980s, we would expect the burden of CLD deaths attributable to HBV to decrease in the future. However, the burden of CLD deaths due to HCV is likely to increase.     

Epidemiology of Viral Hepatitis in Saudi Arabia: Are We Off the Hook?

Some 400 million people worldwide are currently infected with the hepatitis B virus (HBV), and the infection is common in the Middle East. Another 170 million people around the globe presently live with chronic hepatitis C virus (HCV) infection. Both HBV and HCV represent a worldwide epidemic. Despite significant decline in the prevalence of HBV and HCV infection in Saudi Arabia, these viral diseases cause significant morbidity and mortality, and impose a great burden on the country''s healthcare system. On the other hand, Saudi epidemiology studies have shown that the hepatitis A virus seroprevalence in the country has reduced considerably over the past two decades. The progress in mapping the epidemiological pattern of viral hepatitis in Saudi Arabia has not only aided our understanding of the disease, but has also exposed the small but relevant gaps in our identification of the intricate details concerning the disease''s clinical expression. In this review, we aim to document the timeline of viral hepatitis epidemiology in Saudi Arabia, while summarizing the relevant published literature on the subject.     

Autophagy and microRNA in hepatitis B virus-related hepatocellular carcinoma

Approximately 350 million people worldwide are chronically infected by hepatitis B virus (HBV). HBV causes severe liver diseases including cirrhosis and hepatocellular carcinoma (HCC). In about 25% of affected patients, HBV infection proceeds to HCC. Therefore, the mechanisms by which HBV affects the host cell to promote viral replication and its pathogenesis have been the subject of intensive research efforts. Emerging evidence indicates that both autophagy and microRNAs (miRNAs) are involved in HBV replication and HBV-related hepatocarcinogenesis. In this review, we summarize how HBV induces autophagy, the role of autophagy in HBV infection, and HBV-related tumorigenesis. We further discuss the emerging roles of miRNAs in HBV infection and how HBV affects miRNAs biogenesis. The accumulating knowledge pertaining to autophagy and miRNAs in HBV replication and its pathogenesis may lead to the development of novel strategies against HBV infection and HBV-related HCC tumorigenesis.     

Prevention of hepatocellular carcinoma in the Asia–Pacific region: Consensus statements

Among approximately 650 000 people who die from hepatocellular carcinoma (HCC) each year, at least two‐thirds live in Asia. Efforts to improve early diagnosis and treatment have not yet impacted mortality. An Asia–Pacific Working Party convened in Hong Kong in June 2008 to consider ways to prevent HCC in this region. Separate reviews have summarized epidemiology of HCC, preventive approaches related to hepatitis B virus (HBV), hepatitis C virus (HCV) and non‐viral liver diseases, and the role of surveillance to detect HCC at a curative stage. We now present Consensus Statements from these deliberations and reviews. As chronic hepatitis B is the most common cause of HCC in Asia, effective hepatitis B vaccination programs are the most important strategy to reduce HCC incidence. Prevention of HCV by screening blood donors, universal precautions against blood contamination in health‐care settings and reducing HCV transmission from injection drug use are also vital. There is strong evidence that effective antiviral therapy to control HBV infection or eradicate HCV substantially reduces (but does not abolish) HCC risk. With hemochromatosis, family screening, early diagnosis and correcting iron overload to prevent liver fibrosis prevents HCC. There is currently insufficient evidence to give firm recommendations on alcohol, obesity/metabolic risk factors and other liver diseases. HCC surveillance for high‐risk groups is recommended in individual cases but cost‐effectiveness is not as high as infant hepatitis B vaccination and screening blood for HCV. Widespread application of HCC surveillance in Asia–Pacific countries depends on economic factors and health‐care priorities.     

Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma

Chronic infection with viral hepatitis affects half a billion individuals worldwide and can lead to cirrhosis, cancer, and liver failure. Liver cancer is the third leading cause of cancer-associated mortality, of which hepatocellular carcinoma (HCC)represents 90%of all primary liver cancers. Solid tumors like HCC are complex and have heterogeneous tumor genomic profiles contributing to complexity in diagnosis and management. Chronic infection with hepatitis B virus (HBV),hepatitis delta virus (HDV), and hepatitis C virus (HCV) are the greatest etiological risk factors for HCC. Due to the significant role of chronic viral infection in HCC development, it is important to investigate direct (viral associated) and indirect (immune-associated) mechanisms involved in the pathogenesis of HCC. Common mechanisms used by HBV, HCV, and HDV that drive hepatocarcinogenesis include persistent liver inflammation with an impaired antiviral immune response, immune and viral protein-mediated oxidative stress, and deregulation of cellular signaling pathways by viral proteins.DNA integration to promote genome instability is a feature of HBV infection, and metabolic reprogramming leading to steatosis is driven by HCV infection. The current review aims to provide a brief overview of HBV, HCV and HDV molecular biology, and highlight specific viral-associated oncogenic mechanisms and common molecular pathways deregulated in HCC, and current as well as emerging treatments for HCC.     

miRNAs as Potential Biomarkers for Viral Hepatitis B and C

Around 257 million people are living with hepatitis B virus (HBV) chronic infection and 71 million with hepatitis C virus (HCV) chronic infection. Both HBV and HCV infections can lead to liver complications such as cirrhosis and hepatocellular carcinoma (HCC). To take care of these chronically infected patients, one strategy is to diagnose the early stage of fibrosis in order to treat them as soon as possible to decrease the risk of HCC development. microRNAs (or miRNAs) are small non-coding RNAs which regulate many cellular processes in metazoans. Their expressions were frequently modulated by up- or down-regulation during fibrosis progression. In the serum of patients with HBV chronic infection (CHB), miR-122 and miR-185 expressions are increased, while miR-29, -143, -21 and miR-223 expressions are decreased during fibrosis progression. In the serum of patients with HCV chronic infection (CHC), miR-143 and miR-223 expressions are increased, while miR-122 expression is decreased during fibrosis progression. This review aims to summarize current knowledge of principal miRNAs modulation involved in fibrosis progression during chronic hepatitis B/C infections. Furthermore, we also discuss the potential use of miRNAs as non-invasive biomarkers to diagnose fibrosis with the intention of prioritizing patients with advanced fibrosis for treatment and surveillance.     

The role of oncogenic viruses in the pathogenesis of hepatocellular carcinoma

HBV and HCV have major roles in hepatocarcinogenesis. More than 500 million people are infected with hepatitis viruses and, therefore, HCC is highly prevalent, especially in those countries endemic for HBV and HCV. Viral and host factors contribute to the development of HCC. The main viral factors include the circulating load of HBV DNA or HCV RNA and specific genotypes. Various mechanisms are involved in the host-viral interactions that lead to HCC development, among which are genetic instability, self-sufficiency in growth signals, insensitivity to antigrowth signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasiveness. Prevention of HBV by vaccination, as well as antiviral therapy against HBV and for HCV seem able to inhibit the development of HCC.     

Epidemiology and natural history of hepatitis B

Hepatitis B virus (HBV) is a common viral pathogen that currently infects an estimated 4 million people worldwide, including 400 million who have chronic infection. Persons with chronic HBV infection are at a lifelong risk of developing hepatocellular carcinoma (HCC) or cirrhosis, or both. Many persons with HBV are unaware that they carry the infection, and, of those who are chronically infected, only a minority receives routine, scheduled follow-up to monitor their disease status. Persons from high-risk populations, especially immigrants from nations where hepatitis B is highly endemic, should be tested for HBV seromarkers and should be vaccinated if they are found to be negative. The natural history of chronic HBV is a dynamic one: patients can fluctuate between periods of active liver inflammation and periods of inactive disease. Disease progression is influenced by various factors, including viral genotype and specific mutations, demographic features, concurrent viral infections, and social and environmental factors. Recent data suggest that antiviral therapy can decrease the risk of liver decompensation and liver-related death and reduce the risk of HCC in selected individuals with active liver disease and severe fibrosis. Persons identified with chronic HBV infection need lifelong, regular monitoring for the development of active liver disease and HCC.     

Hepatocellular carcinoma in the Asia pacific region

Primary liver cancer, particularly hepatocellular carcinoma (HCC) remains a significant disease worldwide. It is among the top three causes of cancer death in the Asia Pacific region because of the high prevalence of its main etiological agents, chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. In this region, the incidence of HCC has been static over recent decades. Older age is a major risk factor; the incidence increasing sharply after age 40 years. There is a male predilection, with male to female ratio of 3:1, except in elderly Japanese with equal sex incidence or female predominance. In most Asia‐Pacific countries, chronic HBV infection accounts for 75–80% of cases; Japan, Singapore and Australia/New Zealand are exceptions because of higher prevalence of HCV infection. In spite of advances in surgery, liver transplantation and newer pharmaco/biological therapies, the survival rate has improved only slightly over recent decades, and this could be attributable to earlier diagnosis (‘lead‐time bias’). The majority of patients present with advanced diseases, hence reducing the chance of curative treatment. The importance of HCC may decrease in two to three decades when the prevalence of chronic HBV infection decreases as a result of the universal HBV vaccination programs implemented in late 1980s in most Asia‐Pacific countries, and because of reduced incidence of medical transmission of HCV. However, transmission of HCV by injection drug use, and rising prevalence of obesity and diabetes, both independent risk factors for HCC, may partly offset this decline.     

Epidemiology of hepatitis C virus infection

Globally, hepatitis C virus (HCV) has infected an estimated 130 million people, most of whom are chronically infected. HCV-infected people serve as a reservoir for transmission to others and are at risk for developing chronic liver disease, cirrhosis, and primary hepatocellular carcinoma (HCC). It has been estimated that HCV accounts for 27% of cirrhosis and 25% of HCC worldwide. HCV infection has likely been endemic in many populations for centuries. However, the wave of increased HCV-related morbidity and mortality that we are now facing is the result of an unprecedented increase in the spread of HCV during the 20th century. Two 20th century events appear to be responsible for this increase; the widespread availability of injectable therapies and the illicit use of injectable drugs.     

Epidemiology of viral hepatitis and hepatocellular carcinoma

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.