Outcome Of Chronic Hepatitis B Virus Infection Research Articles

Persistent Effect of IFNAR-1 Genetic Polymorphism on the Long-Term Pathogenesis of Chronic HBV Infection

Genetic polymorphism of IFNAR-1 plays a large role in determining the clearance or chronicity after hepatitis B virus (HBV) exposure. However, it is not clear whether type I interferon receptor-1 (IFNAR-1) variations continuously exert their effects to influence the final outcomes following HBV chronicity, including acute-on-chronic hepatitis B liver failure (ACLF-HBV), chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Here we report that these four potential outcomes of chronic HBV infection are strongly associated with IFNAR-1 polymorphisms through a hospital-based case-control study of 663 cases. ACLF-HBV and HCC were each compared with CHB+LC. In comparison with the G/G genotype, the C/G and C/C genotypes at both single-nucleotide polymorphism (SNP) sites (rs1012335 and rs2257167) showed significant susceptibility to ACLF-HBV (the highest odds ratio [OR] reached 2.374; 95% CI = 1.488, 3.788; p < 0.001 for the C/G genotype at rs2257167), as well as HCC (OR = 2.475; 95% CI = 1.435, 4.426; p < 0.001 for the C/C genotype at rs1012335). The C allele at both loci was a susceptibility allele for ACLF-HBV and HCC, with the highest ORs reaching 1.653 (95% CI = 1.233, 2.216; p < 0.01 at rs1012335) in the ACLF-HBV group, and 1.659 (95% CI = 1.274, 2.159; p < 0.01 at rs1012335) in the HCC group. A strongly linked disequilibrium was also found within these two alleles (p < 0.001). Our research indicates that genetic polymorphisms of IFNAR-1 not only contribute to the determination of clearance or chronicity in the early stages of HBV exposure, but they also persistently influence pathogenesis over the long-term process of chronic HBV infection.

On‐treatment monitoring of chronic hepatitis B virus infection: An Asian–Pacific perspective

Chronic infection with hepatitis B virus (HBV) is a major global health problem and an important cause of morbidity and mortality from sequelae of liver cirrhosis and hepatocellular carcinoma. In the past decades, better understanding of the natural history and immunopathogenesis of chronic HBV infection and of the development of many powerful antiviral agents has allowed us to improve therapeutic efficacy. Among these agents, nucleos(t)ide analogs are important and potent viral suppressors. However, when administered alone, they are not able to permanently eradicate HBV, and long-term maintenance therapy is required for therapeutic efficacy. Additionally, prolonged treatment is frequently associated with the emergence of drug-resistant HBV mutants. Before an 'ideal' drug(s), or drug combination, with optimal antiviral efficacy and negligible rates of drug resistance becomes available, the on-treatment monitoring approach using serum HBV DNA level as a predictor for therapeutic efficacy and drug resistance is useful. However, most countries in the Asia-Pacific region have low income economies, insufficient medical care systems, and low awareness of the disease among the general population and government officers. The easy approach of the road-map concept using an affordable drug to treat chronic HBV infection is more important in this region. There is already evidence that the long-term outcomes of chronic HBV infection can be improved under well-managed antiviral therapy. Profound and long-lasting suppression of HBV replication, either maintained on-therapy or sustained after stopping therapy, has been identified as the key determinant for achieving the goals of therapy, for reducing liver damage, and for preventing development of cirrhosis and/ or hepatocellular carcinoma.

CD24 polymorphisms affect risk and progression of chronic hepatitis B virus infection

T-cell immunity to hepatitis B virus (HBV) is involved in both viral clearance and the pathogenesis of cirrhosis and hepatocellular carcinoma following chronic HBV infection. It is therefore of great interest to analyze whether genetic polymorphism of genes involved in the immune response may determine the outcomes of chronic HBV infection. Here we report that CD24 polymorphisms affect the risk and progression of chronic HBV infection. Thus the CD24 P170(T) allele, which is expressed at a higher level, is associated with an increased risk of chronic HBV infection. Among the chronic HBV patients this allele shows recessive association with more rapid progression to liver cirrhosis and hepatocellular carcinoma in comparison to the P170(C) allele. In contrast, a dinucleotide deletion at position 1527-1528 (P1527(del)), which reduces CD24 expression, is associated with a significantly reduced risk of chronic HBV infection. To confirm the role for CD24 in liver carcinogenesis, we compared the size of liver tumor developed in CD24(-/-) and CD24(+/-) HBV transgenic mice. Our data demonstrate that targeted mutation of CD24 drastically reduced the sizes of spontaneous liver cancer in the HBV transgenic mice. These data demonstrate that genetic variation of CD24 may be an important determinant for the outcome of chronic HBV infection.

Special populations with hepatitis B virus infection

Treatment of patients with chronic hepatitis B virus (HBV) infection who have advanced disease or comorbidities can be challenging, and recommendations may differ from standard guidelines. Among the special populations that merit specific consideration are patients with compensated or decompensated cirrhosis, organ transplantation, acute hepatitis B, pregnancy, coinfection with hepatitis C and/or D virus, chronic renal failure, and children. Major advances have been made in management of many of these special populations because of recent increasing availability of oral nucleosides, which are generally well tolerated and highly effective despite presence of other morbidities or viral infections. Also important have been changes in the management of hepatitis B during the peri-liver transplantation period that allows for prevention of reinfection in the majority of cases. However, much remains to be done to determine which patients should be treated and which should be monitored on no specific therapy. Outcomes of chronic HBV infection in persons with coinfection and in children have varied from different areas of the world, but it is not clear whether these differences are due to host and racial differences or to viral genotypic differences. Further studies are particularly needed in assessing the safety and efficacy of therapy in pregnant women, in children, and in patients with hepatitis D and C virus coinfection.

The natural history of chronic hepatitis B virus infection

Chronic hepatitis B virus (HBV) infection has a complicated course. Three phases are identified: an immune tolerant phase with high HBV DNA and normal alanine aminotransferase (ALT) levels associated with minimal liver disease; an immune active phase with high HBV DNA and elevated ALT levels with active liver inflammation; and an inactive phase with HBV DNA levels < 2000 IU/mL and normal ALT levels with minimal inflammation and fibrosis on liver biopsy. Affected persons can move progressively from one phase to the next and may revert backward. The primary adverse outcomes of chronic HBV infection are hepatocellular carcinoma (HCC) and cirrhosis. Published natural history studies were reviewed and ranked by the strength of evidence regarding the study design. Factors with the highest evidence of risk for development of HCC or cirrhosis from population-based prospective cohort studies include male sex, family history of HCC, HBV DNA level above 2000 IU/mL in persons above age 40, HBV genotypes C and F, and basal core promoter mutation. Those with the next highest level of evidence include aflatoxin exposure, and heavy alcohol and tobacco use. Improved methods to identify persons at highest risk of developing HCC or cirrhosis are needed to allow intervention earlier with antiviral therapy in appropriate patients. Future studies should include prospective follow-up of established population-based cohorts as well as new cohorts recruited from multiple centers stratified by HBV genotypes/subgenotypes and clinical phase to determine the incidence of the various HBV phases, HCC, and cirrhosis. Also, nested case-control studies assessing immunological and host genetic factors among persons with active and inactive disease phases, HCC, and cirrhosis could be conducted using these types of cohorts.

Molecular characteristics and stages of chronic hepatitis B virus infection

Hepatitis B virus (HBV) is a common viral pathogen that causes a substantial health burden worldwide. Remarkable progress has been made in our understanding of the natural stages of chronic HBV infection. A dynamic balance between viral replication and host immune response is pivotal to the pathogenesis of liver disease. Knowledge of the HBV genome organization and replication cycle can unravel HBV genotypes and molecular variants, which contribute to the heterogeneity in outcome of chronic HBV infection. Most HBV infections are spontaneously resolved in immunocompetent adults, whereas they become chronic in most neonates and infants at a great risk of developing complications such as cirrhosis and hepatocellular carcinoma (HCC). Those with chronic HBV infection may present in one of the four phases of infection: immune tolerance, immune clearance [hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB)], inactive carrier state, and reactivation (HBeAg-negative CHB). Understanding the dynamic nature of chronic HBV infection is crucial in the management of HBV carriers. Long-term monitoring and optimal timing of antiviral therapy for chronic HBV infection help to prevent progression of HBV-related liver disease to its later stage, particularly in patients with higher risk markers of HCC, such as serum DNA concentration, HBeAg status, serum aminotransferase, HBV genotypes, and pre-core or core mutants.

The influence of hepatitis B virus genotype and subgenotype on the natural history of chronic hepatitis B

Chronic infection with hepatitis B virus (HBV) is associated with a high lifetime risk of developing hepatocellular carcinoma (HCC) and cirrhosis of the liver. To review the studies published to date regarding the association of HBV genotypes and subgenotypes in the development of adverse sequelae from HBV. Review of the literature for articles describing studies of HBV genotype/subgenotypes and development of HCC, cirrhosis, and liver-related death. Eight genotypes of HBV (A through H), which differ from each other in viral genome sequence by more than 8%, and multiple subgenotypes, which differ from each other by 4-8% have been identified. Recently, studies investigating the association between the risks of developing HCC and cirrhosis by specific HBV genotypes and subgenotypes have reported marked differences in outcome. Certain HBV genotypes and subgenotypes, including genotype C, B2-5, and F1, appear to be associated with a higher risk of developing HCC, and others, including genotypes B1, B6, and A2, appear to be associated with a lower risk of complications of HBV. Our understanding of the role of HBV genotypes and subgenotypes on the outcome of HBV infection is limited, as few population-based prospective studies have been performed and most studies compare only the outcome in areas where two genotypes predominate whereas others have not examined subgenotypes. Studies to date suggest that HBV genotypes/subgenotypes have important influences on the outcome of chronic HBV infection, but more population-based prospective studies examining multiple genotypes are needed.

Clinical analysis of HBV-infected patients with genotype C

AIM: To investigate the distribution of hepatitis B virus (HBV) genotypes in Yan’an region of China, and to examine the relationship between the clinical types of the patients infected with HBV genotype C and the clinical virological and biochemical outcome of chronic HBV infection. METHODS: One hundred and twenty-two chronic HBV-infected patients with HBV DNA positive and a disease history of more than 12 months were randomly selected from Yan’an region, and the genotypes were detected in 121 patients, consisting of 58 chronic asymptomatic HBV carriers (ASC), 46 chronic hepatitis B (CHB) patients and 17 liver cirrhosis (LC) patients. Real time fluorescence quantitative polymerase chain reaction (FQ-PCR) and time-resolved fluoroim munoassay (TRFIA) were used to measure their HBV DNA contents and HBV marker quantity, respectively. Micro-PCR and hybridizationELISA were used to detect HBV genotypes. RESULTS: Of the 121 serum samples with detected genotypes, 116 were of genotype C (95.87%, 95%CI: 92.32%-99.42%). In the genotype C group, the HBV DNA level and HBeAg quantity were markedly higher in the ASC group than in the CHB group or the LC group (t = 3.94, 4.75, P = 0.000, 0.000; t = 4.82, 3.94, P = 0.000, 0.001). However, HBeAb quantity and ALT level were markedly lower in the ASC group than in the CHB or the LC group (t = 3.71, 12.09, P = 0.000, 0.000; t = 12.44, 7.81, P = 0.000, 0.000). No significant differences in HBV DNA level, HBeAg quantity or ALT level were observed between the CHB group and the LC group (P = 0.38, 0.58, 0.047); significant difference in age was observed among the ASC, CHB and LC groups (t = 5.07, 9.72, 4.99, P = 0.000, 0.000, 0.000) and the mean age in ASC group was the lowest ; the male percentage was significantly higher in ASC group than in CHB or in the LC group (χ

Prevalence of Hepatitis B Virus Genotype D in Precore Mutants Among Chronic Liver Disease Patients from New Delhi, India

Hepatitis B is one of the most important causes of chronic viral hepatitis world wide. Mutations in the precore region of the hepatitis B virus (HBV) genome are frequently found in hepatitis B envelope antigen-negative cases. Data from India on the HBV genotype-associated distribution of precore mutations are limited. Our objective in this study was to genotype and detect the precore mutant with a point mutation from G to A at nucleotide 1896 using ligase chain reaction (LCR) and direct sequencing. A total of 115 cases of chronic liver disease were screened. The cases were evaluated on the basis of history, clinical examination, liver function profile, and serological test for HBV infection, which includes HBsAg, anti HBcIgG, HBeAg using commercially available ELISA kits. The cases, which were HBeAg+, HBeAg-, and HBV DNA+, were subjected to LCR and confirmed by direct sequencing. Of 115 chronic liver disease cases, 50 (43.5%) cases were HBV DNA positive. All cases were subjected to LCR; 11 (22%) cases confirmed the presence of precore mutants, while the remaining 39 (78%) were classified as the wild form of the virus. HBV genotyping by direct sequencing revealed that genotype D was predominant in both wild and mutant forms of the virus. We conclude that the HBV genotype distribution was not significantly different between precore mutants and the wild form of the virus (P>0.05). North Indian patients with genotype D were more likely to have persistent HBV infection with precore mutants. HBV genotypes correlate with the clinical outcome of chronic HBV infection.

Correlation of interleukin‐10 gene haplotype with hepatocellular carcinoma in Taiwan

Polymorphisms in cytokine genes can influence immune responses, inflammation and tissue injury, and may affect the outcome of hepatitis B virus (HBV) infection. We analyzed single nucleotide polymorphisms (SNP) in the interleukin (IL)-10 gene among 344 HBV carriers and 208 patients with hepatocellular carcinoma (HCC). Genotypes and haplotypes were tested for association with HCC. IL-10/-592 C/C genotype was associated with a higher risk for HCC compared with IL-10/-592 A/C and A/A genotypes [odds ratio (OR): 2.1, 95% confidence interval (CI): 1.2-3.6]. IL-10/1927 A/A genotype was also associated with a higher risk for HCC compared with IL-10/1927 A/C and C/C genotypes (OR: 1.5, 95% CI: 1.0-2.2). Haplotype analysis revealed that the homozygosity of the C-A haplotype (defined by SNPs at positions -592 and 1927) of IL-10 gene conveys the highest risk for HCC among HBV carriers compared with the homozygosity for the A-C haplotype (OR: 2.6, 95% CI: 1.3-4.9). The results demonstrate that IL-10 gene polymorphism can affect the outcome of chronic HBV infection. Further studies are necessary to clarify how variation in the IL-10 gene affects IL-10 function and risk of HCC.

Natural History of Chronic Hepatitis B Virus Infection: What We Knew in 1981 and What We Know in 2005

Remarkable progress has been made in our understanding of the natural history of chronic hepatitis B virus (HBV) infection in the past 25 years. Availability of sensitive HBV DNA assays and application of sophisticated immunological techniques led to the recognition that HBV replication persists throughout the course of chronic HBV infection, and host immune response plays a pivotal role in HBV-related liver disease. Knowledge of the HBV genome organization and replication cycle led to the unraveling of HBV genotypes and molecular variants, which contribute to the heterogeneity in outcome of chronic HBV infection. The natural course of chronic HBV infection is now perceived as consisting of 4 phases: immune tolerance, immune clearance [hepatitis B e antigen (HBeAg)-positive chronic hepatitis], inactive carrier state, and reactivation (HBeAg-negative chronic hepatitis B). Understanding the dynamic nature of chronic HBV infection is crucial in the management of HBV carriers and underscores the need for long-term monitoring. Accumulating evidence indicates that antiviral therapy can prevent progression of HBV-related liver disease, particularly among patients with sustained response. Newer antiviral therapies with improved efficacy and decreased risk of resistance may lead to a complete revision of the chapter on the natural history of chronic HBV infection on the occasion of the golden jubilee of Hepatology.

Hepatitis B Virus Genotypes in Korea: An Endemic Area of Hepatitis B Virus Infection

Objectives: It has been reported that distribution of hepatitis B virus (HBV) genotypes shows geographic difference and are associated with clinical outcomes of HBV infection, including response to antiviral therapy and progression of chronic liver diseases. In this study, we analyzed the distribution of HBV genotypes according to the various clinical outcomes of chronic HBV infection in Korea, which is one of the most endemic areas of HBV infection. Methods: A total of 200 patients with chronic HBV infection were enrolled. Clinical diagnoses of the 200 patients with chronic liver diseases were as follows: hepatitis B e antigen (HBeAg)-positive healthy carrier (defined as HBeAg⁺, anti-HBe^–, HBV DNA⁺ by hybridization, normal transaminase; n = 40); inactive HBsAg carrier (n = 40); chronic hepatitis B (n = 40); liver cirrhosis (n = 40); hepatocellular carcinoma (n = 40). HBV genotypes were determined by nested polymerase chain reaction using genotype-specific primers. Results: All patients except 2 (inactive HBsAg carriers) were positive for nested PCR and they have genotype C regardless of clinical outcomes. Conclusions: HBV genotype was genotype C regardless of various clinical outcomes of chronic HBV infection in Korea. Considering that HBV genotypes have clinical relevance, distribution of HBV genotype in each area should be monitored when management for chronic HBV infection is planned.

The natural history of chronic hepatitis B virus infection.

Three stages of chronic hepatitis B virus (HBV) infection are recognized: the immune tolerant phase, the chronic hepatitis B phase, and the inactive hepatitis B carrier phase. Active liver disease is most often found in persons with elevated aminotransferase levels and HBV DNA levels >10(5) copies/mL. Possible risk factors for developing liver disease include older age, male gender, presence of hepatitis B e antigen (HBeAg), HBV genotype, mutations in the precore and core promoter regions of the viral genome, and coinfection with hepatitis D (delta) virus. All persons chronically infected with HBV should be followed every 6 to 12 months with aminotransferase levels. Those with elevated levels should be tested for HBeAg and its antibody (anti-HBe) as well as HBV DNA levels to determine if they are in need of further evaluation with a liver biopsy and are candidates for antiviral therapy. Future research will help clarify the outcome of chronic HBV infection.

Hepatitis B viral genotypes: Clinical relevance and molecular characteristics

Hepatitis B virus (HBV) infection is a global health problem and the clinical outcome of chronic HBV infection depends on the frequency and severity of hepatitis flares in the immune clearance phase. Currently, four subtypes and seven genotypes of HBV are identified and most have specific geographic distributions. The impact of HBV genotypes on the clinical outcome of chronic HBV infection has been partially clarified. In Taiwan, genotype C is associated with more severe liver disease and genotype B is associated with the development of hepatocellular carcinoma (HCC) in young non-cirrhotic patients. In contrast, genotype B has a relatively good prognosis in Japan and China and is rarely associated with the development of HCC. Similarly, genotype D is associated with more severe liver disease than genotype A in India and may predict occurrence of HCC in young patients. Although superinfection of HBV on top of hepatitis B carriers occurs in Taiwan, it is rarely associated with acute exacerbations. As to the response to antiviral treatment, genotypes C and D are associated with a lower response rate to interferon therapy compared with genotypes B and A. In addition, the subtype adw is reported to be associated with a higher risk of lamivudine resistance than ayw. In HBV subtype adw-infected HCC patients, genotype B responds better to embolization therapy and has a lower rate of HCC recurrence than genotype C. In summary, pathogenic and therapeutic differences do exist among HBV genotypes and determining the genotype in patients with chronic HBV infection would help gain further information for etiologic, clinical, virologic and anthropologic investigations. Further studies to clarify the molecular virological factors that contribute to these differences are awaited.

Management of viral hepatitis B.

Hepatitis B virus (HBV) infection is a major global health concern and is the most common cause of chronic liver disease worldwide. The natural history and clinical outcomes of chronic HBV infection are determined by the viral replication cycle and the host immune responses. Treatment of chronic hepatitis B is directed at interrupting the natural history by suppressing HBV replication before development of any significant irreversible liver cell damage. Effective antiviral therapies should be followed by sustained suppression of HBV-DNA, normalization of transaminases levels and a stable stage of HBeAg seroconversion with persistence of circulating anti-HBeAg antibodies. Two major classes of antiviral therapeutic agents that have been approved for treatment of chronic hepatitis B are immunomodulating agents (i.e. interferon) and the nucleoside analogs (i.e. lamivudine). A 4-6 month course of interferon-alpha has resulted in improvement of survival in 20%-30% of patients with chronic hepatitis B who had elevated serum ALT levels without hepatic decompensation. Interferon-alpha therapy is associated with HBeAg seroconversion; normalization of ALT levels, reduced hepatic inflammation, and possibly reduced disease progression to cirrhosis and hepatocellular carcinoma. Interferon can also be used with caution in patients with early compensated cirrhosis. A 12-month course of lamivudine has been shown to be well tolerated and effective. Lamivudine can be used in decompensated cirrhosis and immunosuppressed patients and for prevention of recurrent HBV infection after liver transplantation. The response rates after 3 years of lamivudine therapy account for 40-65%. A major problem of antiviral treatment is the emergence of drug resistance conferred by mutations in the YMDD motif of HBV reverse transcriptase. The prevalence of YMDD mutations increases with longer durations of antiviral therapies and this has been detected in 20% of immunocompetent patients receiving lamivudine per year. Contentious issues remain when to stop the treatment if HBeAg seroconversion does not occur. Many new immunomodulatory therapies and antiviral agents are in various stages of clinical development and have shown some promise. Among newer HBV antivirals, adefovir dipivoxil, entecavir, emtricitabine, DAPD and clevudine appear to be at least as potent as lamivudine in suppressing HBV replication. In vitro studies have shown that YMDD mutations confer cross-resistance between lamivudine and emtricitabine. However, adefovir, dipivoxil, lobucavir, DAPD and possibly clevudine suppress replications of both YMDD mutants and wild types of HBV. Immunomodulatory approaches for treatment of chronic hepatitis B are conceptually attractive, but newer agents used to date (thymosin-alpha, interleukin-12, therapeutic vaccines) have not demonstrated sufficient efficacy for widespread use. Combinations of an immunomodulatory agent and nucleoside analog may improve the therapeutic efficacy and reduce the emergence of drug resistance. Nevertheless, combinations of interferon and lamivudine therapies do not confer such additional benefits. The next challenge for HBV treatment is to use antivirals in combination and/or in cyclical therapy to minimize the emergence of drug resistance and increase efficacy, particularly to achieve sustainable post-treatment suppression of HBV. Randomized prospective control trials of combined antiviral therapies given simultaneously or sequentially are needed to establish safe and effective combined regimens that can be recommended for future treatment strategies.

Natural history of chronic hepatitis B virus infection in adults with emphasis on the occurrence of cirrhosis and hepatocellular carcinoma.

The natural course of perinatally acquired hepatitis B virus (HBV) infection has three phases. In the first 'immune tolerance phase', patients are HBeAg positive and have high serum levels of HBV DNA, but have no symptoms, normal ALT levels and minimal histological activity. The second 'immune clearance phase' usually occurs between 15 and 35 years of age, during which HBV replication declines, accompanied by increased serum ALT levels and inflammatory activity in the liver; HBeAg to anti-HBe seroconversion is then observed, frequently preceded by a flare of the ALT level. The average rate of spontaneous HBeAg seroconversion is 10% per year. In the third 'low-replicative phase', serum HBsAg persists, but HBeAg is no longer detectable and HBV DNA can only be detected by PCR assay. During this phase, patients are usually asymptomatic and liver disease is inactive; some patients, however, may progress to cirrhosis and hepatocellular carcinoma (HCC). The ultimate outcome of chronic HBV infection appears to depend on the duration and severity of liver injury during the immune clearance phase. About 2.1% of patients with chronic type B hepatitis develop cirrhosis each year. Patients who have a severe acute exacerbation complicated by subacute hepatic failure or who have recurrent episodes of acute exacerbations with bridging hepatic necrosis are more likely to develop cirrhosis. A significant proportion of those with HBsAg eventually develop HCC; they have a 100-fold increased risk of HCC relative to those without. The development of HCC, however, is closely related to the severity of the underlying liver disease. The annual incidence of HCC is only 0.1% in asymptomatic HBsAg individual, 1% in patients with chronic hepatitis B, but increases to 3-10% in patients with cirrhosis. Some anti-HBe-positive patients continue to have active liver disease and they should be tested for HBV DNA by hybridization assay to determine whether the disease results from replicative precore mutant HBV infection or other causes of liver disease, such as superinfection with HCV and HDV. A substantial number of apparently healthy HBV-infected individuals are first recognized when they present with episodes of acute hepatitis. About 30% of these cases could be attributed to other hepatotropic virus superinfection. Acute viral hepatitis in patients with concurrent HBV infection is associated with an increased risk of fulminant hepatic failure. Finally, HBsAg disappears from serum in about 1% of patients each year. HCV superinfection can enhance the termination of HBsAg positivity. HCV, however, replaces HBV as the dominant cause of chronic viral hepatitis. The outcome of HBV-infected persons with 'spontaneous' seroclearance of HBsAg is usually favourable, though progress to cirrhosis and HCC is still possible.

Clinical course and consequences of hepatitis B infection

Hepatitis B virus (HBV) is a small enveloped virus containing partially double-stranded DNA. The DNA and HBV-specific DNA polymerase are surrounded by the HBV core antigen (HBcAg), which in turn is surrounded by a lipoprotein envelope containing the HBV surface antigen (HBsAg). Serum of HBV-infected patients contains complete virus particles, as well as non-infectious spherical or filamentous HBsAg particles. Acute hepatitis is characterized by the appearance of serum HBV markers, including HBsAg and IgM anti-HBc, which then disappear during convalescence. Persistence of HBsAg for more than 6 months indicates a carrier state. Chronic hepatitis develops in 90% of newborns who become infected, compared with 29–40% of children infected and 5–10% of adults infected. The immune status of the infected person also influences the development of chronic hepatitis. Chronic HBV infection can be diagnosed by serology (identification of HBsAg and HBV DNA), biochemistry (elevated aminotransferase levels) and liver biopsy. The last is important to assess the severity of disease, its stage and prognosis, and to exclude other hepatic diseases. The outcome of chronic HBV infection varies between individuals, with estimated 5-year survivals of 97% for chronic persistent hepatitis, 86% for chronic active hepatitis, and 55% for chronic active hepatitis with cirrhosis. Treatment with interferon α is effective in up to 40% of cases, but in view of the very large number of infected people worldwide, vaccination to prevent spread of the disease is a more cost-effective option.