Surface Antigen Carriers Research Articles

Management of Patients with Hepatitis B Virus Infection Who Receive Immunosuppressive Treatment or Chemotherapy

Reactivation of hepatitis B virus (HBV) has been well documented as a complication in HBV surface antigen (HBsAg) carriers who receive cytotoxic or immunosuppressive therapy. With the recent introduction of newer agents with a high level of immunosuppressive effect, this unfavorable event often occurs in patients with HBsAg-negative and/or occult HBV infection. The first step in HBV reactivation management is the identification of the patients at risk of viral reactivation by testing for HBV serology prior to commencing immunosuppressive treatment or chemotherapy. Multiple publications have consistently indicated the benefit of prophylactic or preemptive antiviral therapy in this setting, and justified such approach before the start of cytotoxic therapy. Unresolved issues concerning such prophylactic approach remain in the situations of HBsAg-negative/anti-HBc-positive or negative status, which presumably consists of a large number of occult HBV infection cases. This topic review will summarize clinical issues related to HBV reactivation, focusing clinical manifestations, risk factors associated with HBV reactivation, and a growing body of evidence supporting preventive antiviral therapy in high-risk patients. (Korean J Med 2012;82:149-158)

Preventing Cancer with Vaccines: Progress in the Global Control of Cancer

The cancer control community is largely unaware of great advances in the control of major human cancers with vaccines, including the dramatic control of hepatocellular (liver) cancer with hepatitis B virus (HBV) vaccine, now used routinely in more than 90% of countries. The biotechnology revolution has given us a new generation of highly effective vaccines against major global killers, global funding for immunization is orders of magnitude higher than ever before, and the vaccine delivery infrastructure has improved very significantly even in the poorest countries. Liver cancer is the greatest cause of cancer deaths in men of sub-Saharan Africa and much of Asia. Even in highly endemic countries such as China, the prevalence of HB surface antigen carriers has fallen from 10% to 1%-2% in immunized cohorts of children, and liver cancer has already fallen dramatically in Taiwanese children. The Global Alliance for Vaccines and Immunization (now called the GAVI Alliance) has greatly expedited this success by providing HBV vaccine free for five years in most of the world's 72 poorest countries. HBV vaccination can serve as a model for the global control of human papillomavirus (HPV)-related cervical and other cancers with HPV vaccines. Cervical cancer is the greatest cause of cancer death in women in many developing countries; HPV vaccines are highly effective in preventing HPV infection and precancerous lesions in women, and the quadrivalent vaccine also prevents genital warts in men and women and precancerous anal lesions in men. HPV is causing a growing proportion of oropharyngeal cancers, and HPV-related noncervical cancers (penile, anal, and oropharyngeal) may exceed the incidence of cervical cancer within a decade in industrial countries, where cervical screening is effective, causing reevaluation of male HPV immunization. In developing countries, few women are screened for cervical precancerous lesions, making immunization even more important. Currently, 26 primarily industrial countries routinely immunize girls with HPV vaccine, and GAVI will begin to accept applications in 2012 to fund vaccine in developing countries that can deliver the vaccine and if GAVI can negotiate an acceptable price (one manufacturer has already offered a price of $5 per dose).

Prevalence of and Risk Factors for Hepatitis B Viremia After Spontaneous Hepatitis B Surface Antigen Seroclearance in Hepatitis B Carriers

In 118 previous hepatitis B surface antigen (HBsAg) carriers, low-level hepatitis B (HBV) viremia persisted at a rate of 15%-20% for >10 years after HBsAg seroclearance. The frequency of HBV viremia was significantly (P = .002) lower in patients with anti-HBsAg seroconversion (6 of 69 [8.7%]) than in those without seroconversion (15 of 49 [30.6%]).

Hepatocellular Carcinoma and Other Liver Disease Among Greenlanders Chronically Infected with Hepatitis B Virus: A Population-Based Study

In Greenland, the prevalence of hepatitis B surface antigen carriers, reflecting chronic hepatitis B virus (HBV) infection, is 5%-10%. However, the incidence of cirrhosis and hepatocellular carcinoma in this population has been reported to be low. We investigated this discrepancy in a large population-based cohort study. In total, 8879 Greenlanders (16% of the population) were recruited for population-based surveys performed from May 5 to July 7, 1987, and from November 1 to November 21, 1998, with follow-up until March 31, 2010. HBV status was based on serological testing, supplemented by data from all available HBV registries in Greenland to determine changes in HBV status over time. Information on morbidity and mortality was obtained from the Patient Discharge Registry, the Cancer Registry, and the Central Registration System. Sex, age, ethnicity, and period-adjusted incidence rate ratios (IRRs) were estimated using Poisson regression. World standardized rates were derived from these and World Health Organization data. The 650 chronically HBV-infected persons had higher rates of hepatocellular carcinoma (adjusted IRR = 8.70; 95% CI = 2.06 to 36.7), liver disease (adjusted IRR = 5.73, 95% CI = 3.52 to 9.34), and all-cause mortality (adjusted IRR = 1.47; 95% CI = 1.21 to 1.79) than the 5160 HBV-negative persons. However, the world standardized incidence rates of hepatocellular carcinoma (38.5 cancers per 100 000 person-years) and cirrhosis (24 cases per 100 000 person-years) among chronically HBV-infected persons were low compared with results from population-based studies from countries with low, intermediate, and high rates of endemic HBV infection. The relatively low incidence of hepatocellular carcinoma and other HBV-related morbidity among chronic HBV-infected persons in Greenland suggest a more benign course of HBV among the Greenlandic Inuit than in populations in other parts of the world.

Article Commentary: Reactivated Hepatitis B Due to Medical Interventions: The Clinical Spectrum Expands

Reactivated hepatitis B is a potentially serious disorder that can result in liver failure and death. It has been described with a wide variety of immunosuppressive interventions, such as cancer chemotherapy, anti-rejection drugs and the use of tumour necrosis factor-α inhibitors and monoclonal antibody to B-cell antigen. It now appears reasonable to consider transarterial chemoembolization (TAC) for hepatocellular carcinoma as an additional medical intervention associated with hepatitis B reactivation. Pre-emptive antiviral treatment of hepatitis B surface antigen (HBsAg) carriers can prevent serious complications arising from immunosuppressive-induced viral reactivation. Specific recommendations for antiviral prophylaxis in HBsAg carriers undergoing TAC should be added to international management guidelines.

Treatment of Chronic Delta Hepatitis

Abstract This article does not have abstract.

Fighting against viral hepatitis: Lessons from Taiwan

Viral hepatitis and its sequelae are important health problems worldwide, including Taiwan. For the last 40 years, Taiwan's scientists and health care providers have worked hard to control these sequelae, and the results have been excellent. The author, Ding-Shinn Chen, had a key role in planning and establishing the control program in Taiwan, and participated in the endeavors from the very beginning. In this perspective, he describes how he became interested in research as a medical student, his encounters with hepatitis B and C, how he and his colleagues started early detection of hepatocellular carcinoma (HCC), how he helped Taiwan's government create and implement the Viral Hepatitis Control Program, and how the effectiveness of the program in the decrease of hepatitis B carriage and HCC was monitored. He also discusses how he pioneered the use of interferon-α plus ribavirin to treat chronic hepatitis C. Hepatitis B viral load as a risk factor for HCC and cirrhosis in hepatitis B surface antigen carriers is reviewed briefly, as is the prevention of sequelae by antiviral therapies. Finally, Dr. Chen discusses unresolved issues that must be addressed and predicts the changes of the patterns of liver disease in Taiwan beyond the mid-21st century, which is in part affected by the fight against viral hepatitis that was initiated in the early 1980s. Dr. Chen's perspective illustrates Taiwan's fight against viral hepatitis over the last 40 years. This experience can be shared by other countries in which the disease is equally prevalent.

Correlation between maternal hepatitis B surface antigen carrier status with social, medical and family factors in an endemic area: have we overlooked something?

Hepatitis B virus (HBV) infection is endemic in many countries, but the risk factors for HBV carriage in the obstetric population are unclear. A survey on 1,580 women attending the antenatal clinic in an endemic region was conducted in order to examine the prevalence of and factors associated with maternal HBV carriage, including socio-demographic, medical, and previous obstetrical and family history, by means of a questionnaire. The prevalence of maternal HBV carriage was 9.1%, and 4.8% of women with a history of hepatitis B vaccination were found to be HBV carriers. Factors associated with maternal HBV carriage were residency status (adjusted odds ratio [aOR] 3.65 for immigrants; aOR 7.62 for non-residents), positive family history (aOR 3.72 for infected mother; aOR 5.36 for other family members), no previous vaccination (aOR 4.39) and having previous HBsAg testing (aOR 2.26). The findings suggest that there was probably an overlooked role of horizontal transmission within the family setting in addition to perinatal transmission in determining the likelihood of HBV infection in our obstetric population. Reconfirmation of hepatitis B status might be necessary among individuals with a history of vaccination to ensure the effectiveness of their immunoprotection.

Hepatocellular carcinoma: the point of view of the hepatitis B virus

Hepatitis B virus (HBV) infection is the main risk factor for hepatocellular carcinoma (HCC) development, as suggested by many epidemiological and molecular studies (1–13) and as dramatically confirmed by data from Taiwan where the universal childhood vaccination program against HBV determined a striking reduction of new infections in infancy and a parallel decrease of liver cancer incidence in childhood (14). Despite the availability of a very efficacious vaccine, however, HBV infection is still a major health problem worldwide, with an estimate of 400 million chronic carriers of the HBV surface antigen (HBsAg), many of whom suffer from progressive forms of liver disease and show a high propensity to develop HCC. Furthermore, when other risk factors for HCC development—such as hepatitis C virus (HCV) infection, Aflatoxin B1 exposure, alcohol abuse and metabolic factors as obesity and diabetes—coexist with HBV infection, a considerable increase of the relative risk for cancer development occurs, probably due to a synergic pro-oncogenic effect of the different factors (13,15–19). Consequently, the World Health Organization includes HBV in ‘group 1’ human carcinogens classifying it among the most important oncogenic agents after tobacco smoking. HCC development underlies complex and multifactorial pathogenetic mechanisms. Much evidence indicates that HBV exerts its prooncogenic properties playing a role in many of these mechanisms. Moreover, this virus seems to maintain its pro-oncogenic role also in cases with persistence of viral genomes in the liver of individuals who are negative for circulating HBsAg (namely, ‘occult’ HBV infection) (20). Here, we review the different aspects of HBV involvement in heapatocarcinogenesis.

Could Complement C4 be an Alternative to Biopsy for Chronic Hepatitis B Histopathologic Findings?

Hepatitis B leads to chronic liver disease, cirrhosis, and hepatocellular cancer. Viral markers and other laboratory tests used in diagnosis and follow-up of chronic hepatitis B (CHB) do not correlate well with disease activity and liver histopathology. For this reason, alternative tests that indicate disease activity are needed. We aimed to investigate the utility of serum complement levels for follow-up in patients with CHB with normal and high transaminase levels. One hundred forty-three patients that were evaluated between 2009 and 2010 were included in the study. Hepatitis B early antigen negative CHB cases with high transaminase levels were evaluated as the first group, and cases with normal transaminase level (inactive hepatitis B surface antigen carrier) as the second group, patients with cirrhosis were included as a third group. Age, sex, hepatitis B surface antigen, anti-HBcAg IgM, hepatitis B early antigen, anti-δ, anti-HCV, anti-HIV, serum hepatitis B virus (HBV) DNA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltranspeptidase (GGT), complement C3, and C4 levels of both groups were compared. The relationship between Knodell histologic activity index (HAI) score and fibrosis in liver biopsy specimens and serum complement levels of cases with high transaminase levels were investigated. There were 49 patients with CHB with high transaminase levels; (Female/Male: 22/27). Mean age was 42.3±15.7 y, ALT=104.41±101.74, AST=69.7±65.2, GGT=35.37±20.4, C3 level=104.2±28.8, C4=16.11±4.17, and HBV DNA >2000 IU/mL (>105 copies/mL) in all cases. Remaining 27 patients had cirrhosis. There were 67 patients with CHB with normal transaminase levels (Female/Male: 32/35). Mean age was 39.56±12.9 y, ALT=22.7±5.5, AST=22±5.18, GGT=48.8±60.4, C3=117.85±22.15, and C4=21.44±5.46. Serum complement C4 level in 4 of the CHB cases with normal transaminase levels was low. Serum C3 (P=0.024) and C4 (P=0.001) levels in patients with CHB with high transaminase level were significantly lower. Low serum complement levels were negatively correlated with Knodell-HAI scores in patients with high transaminase levels (r=-0.84; P<0.001). There was no correlation between HAI and HBV DNA, AST, ALT, and GGT. There was no significant correlation between complement C3 and C4 levels and ALT, AST, HBV DNA, and GGT in any of the groups. Child score in patients with cirrhosis negatively correlated with both C3 (P=0.001) and C4 levels (P=0.001). Complement levels in patients with cirrhosis and CHB with high transaminase levels did not significantly differ. Serum complement C4 levels (in contrast to virologic markers and transaminases) significantly correlate with liver biopsy findings and may be a useful indicator of disease activity and/or damage in patients with CHB with high transaminase levels.

Predictive power of hepatitis B 1762T/1764A mutations in plasma for hepatocellular carcinoma risk in Qidong, China

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality with nearly 700,000 deaths occurring annually. Hepatitis B virus (HBV) is a major contributor to HCC and acquired mutations in the HBV genome may accelerate its pathogenesis. In this study, a matched case-control investigation of 345 men who died of HCC and 625 controls were nested within a cohort of male hepatitis B surface antigen (HBsAg) carriers from Qidong, China. Matched preserving odds ratios (ORs) were used as a measure of association and 95% confidence intervals (CIs) as a measure of precision. Real-time polymerase chain reaction allowed for a quantitative comparison of the levels of the HBV 1762(T)/1764(A) mutation in cases and controls. A total of 278 (81%) of the cases were positive for the HBV 1762(T)/1764(A) mutation compared with 250 (40%) of the controls. The matched preserving OR of 6.72 (95% CI: 4.66 to 9.68) strongly indicated that cases were significantly more probably than controls to have the mutation. Plasma levels of DNA harboring the HBV mutation were on average 15-fold higher in cases compared with controls (P < 0.001). Most strikingly, the level of the mutation in the 20 controls who later developed and died of HCC were on average 274-fold higher than controls who did not develop HCC. Thus, within this cohort of HBsAg carriers at high risk of developing HCC, individuals positive for the HBV 1762(T)/1764(A) mutation at enrollment were substantially more probably to subsequently develop HCC, with a higher concentration of the mutation in plasma enhancing predisposition for cancer development.

Prevalence of reactivation of hepatitis B virus replication in rheumatoid arthritis patients

Reactivation of hepatitis B involves the reappearance of active necroinflammatory liver disease after an inactive hepatitis B surface antigen (HBsAg) carrier state or resolved hepatitis B, occurring during or after immunosuppression therapy or chemotherapy. We prospectively investigated the reactivation rate for hepatitis B virus (HBV) DNA replication in cases of rheumatoid arthritis (RA) with resolved hepatitis B. HBV markers were evaluated in 428 RA patients. Patients with positive findings of HBsAg or HBV DNA at enrolment were excluded. The study population comprised 422 RA patients, with resolved hepatitis B diagnosed in 135 patients based on HBsAg-negative and antihepatitis B core antibody/antihepatitis B surface antibody-positive results. HBV DNA was measured every 3 months in this group, and if HBV DNA became positive after enrolment, measurement was repeated every month. HBV DNA became positive (≥3.64 log copies/mL) in 7 of 135 patients for 12 months. Use of biologic agents was significantly more frequent in patients who developed reactivation of HBV DNA replication (85.7%) than in patients who did not (36.0%, p = 0.008). Hazard ratios for use of biologic agents and etanercept were 10.9 (p = 0.008) and 6.9 (p = 0.001), respectively. RA patients with resolved hepatitis B need careful monitoring when receiving biologic agents, regardless of HBV DNA levels.

Lamivudine resistance mutations in patients infected with hepatitis B virus genotype D

To determine the distribution of viral genotypes for primary or acquired lamivudine resistance. A total of 283 patients with chronic hepatitis B virus (HBV) infection (245 patients with chronic hepatitis B and 38 inactive hepatitis B surface antigen carriers) were included in the study. The HBV genotype was determined by using quantitative real-time polymerase chain reaction and sequence analysis, and tyrosine-methionine-aspartate-aspartate (YMDD) motif mutations were determined using the reverse transcriptase hybridization method. Lamivudine resistance was determined in a total of 25 (10.7%) chronic hepatitis B patients. Eight subjects (4%) had primary resistance to lamivudine, and 17 (53.1%) had secondary resistance to lamivudine. Genotype D, which was isolated from 267 of the patients with chronic HBV infection, was the dominant genotype in Turkey. Identification of YMDD motif mutations should have a positive impact on the selection of proper antiviral medication for patients, even for those who are nucleoside naïve.

Abstract P5-15-01: Lamivudine Prophylaxis during Adjuvant Chemotherapy in Breast Cancer Patients with Hepatitis B Surface Antigen

Abstract Background: Reactivation of hepatitis B virus (HBV) in inactive hepatitis B surface antigen (HBsAg) carriers receiving cytotoxic chemotherapy is a well known complications resulting in hepatic dysfunction. Lamivudine has been reported to have a role in controlling HBV reactivation during chemotherapy. Our study aimed to report the role of lamivudine prophylaxis in breast cancer patients undergoing adjuvant chemotherapy. Methods: We retrospectively reviewed medical records of 3530 patients with stage 1-3 breast cancer who received neoadjuvant and/or adjuvant chemotherapy from January 2000 to December 2009. One hundred seventy-one HBsAg positive patients with normal baseline liver function were identified. Patients who received lamivudine before the first day of chemotherapy were regarded as lamivudine prophylaxis group and the others as non-prophylaxis group. Hepatotoxicity was assessed according to Common Terminology Criteria for Adverse Events (CTCAE, version 3.0). HBV reactivation was defined as an increase in HBV DNA levels of 10-folds or more when compared with baseline level or absolute increase of HBV DNA level that exceeded 200x 106 IU/ml or positive sero-conversion of HBV DNA. The efficacy of lamivudine prophylaxis was evaluated with grade of hepatotoxicity and HBV DNA levels during and after adjuvant chemotherapy. Results: Of 171 patients, 70 patients received lamivudine prophylaxis and 101 patients did not. Median age of control group and study group were 45 years (range, 29-72) and 46(range, 29-67) (p=0.892). Median follow up duration was 48.5 months. Sixty-seven of 101 patients in non-prophylaxis group and 68 of 70 patients in prophylaxis group received anthracycline containing chemotherapy (p=&amp;lt;0.0001). Two (2.9%) patients in prophylaxis group and 13 (12.9%) patients in non-prophylaxis group experienced grade 2 or higher hepatotoxicities (p=0.027). HBV reactivation tend to occur more frequently in non-prophylaxis group compared with prophylaxis group (6.9% vs. 1.4%, p=0.143). One patient in non-prophylaxis group died of fulminant hepatitis after HBV reactivation. Interruption rate of adjuvant chemotherapy was higher in non-prophylaxis group compared with prophylaxis group (9.9% vs.1.4%, p=0.028). Among patients treated with anthracycline containing chemotherapy, the frequency of grade ≥2 hepatotoxicities (2.9% vs. 13.4%, p=0.026) was significantly higher in non-prophylaxis group; HBV reactivation (1.5% vs. 7.5%, p=0.115) tend to be higher in non-prophylaxis group. In patients receiving non-anthracycline containing chemotherapy, lamivudine prophylaxis did not make difference in hepatotoxicities or HBV reactivation. Conclusion: Fewer hepatotoxicities occurred in lamivudine prophylaxis group with less frequent interruption of scheduled chemotherapy. Lamivudine showed tendency to reduce HBV reactivation in breast cancer patients receiving cytotoxic chemotherapy. Lamivudine prophylaxis should be considered in HBsAg positive breast cancer patients who are candidates of neoadjuvant and/or adjuvant chemotherapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-15-01.

Modulation of Serum Interleukin-18 Concentrations and Hepatitis B Virus DNA Levels During Interferon Therapy in Patients with Hepatitis B e-Antigen-Positive Chronic Hepatitis B

The aim of this study was (1) to determine plasma values of interleukin-18 (IL-18) in patients with different clinical manifestations of hepatitis B (HB) and (2) to analyze the correlation between presence of circulatory levels of IL-18 and levels of HB virus (HBV) DNA during interferon-alpha (IFN-α)-induced HBe seroconversion in patients with chronic HB (CHB). The IL-18 levels in serum did not significantly differ between healthy control subjects (99 ± 25 pg/mL), HB-immune patients (85 ± 33), and asymptomatic carriers of HB surface antigen (144 ± 44 pg/mL). In contrast, anti-HBe (HBV DNA <10⁴ copies/mL, 555 ± 248, P < 0.05), anti-HBe (HBV DNA >10⁴ copies/mL, 280 ± 85, P < 0.05), and HBe-antigen-reactive (373 ± 108, P < 0.0001) patients with symptomatic CHB had significantly elevated levels in circulation compared with healthy control subjects (99 ± 25 pg/mL). An inverse correlation was found between serum HBV DNA copies and IL-18 levels during therapy (r = -0.54, P < 0.001). We consistently observed an IFN-α-induced suppression of viral replication, which was followed by the alanine aminotransferase (ALT) flare. There was a significant increase in IL-18 production after the ALT flare, where the peak of IL-18 preceded or coincided with the time of HBe seroconversion in patients who cleared the virus. These results suggest that IL-18 is involved in the pathogenesis of CHB and that IFN-α therapy can augment the production of IL-18 in patients with CHB.

Association Between the Various Mutations in Viral Core Promoter Region to Different Stages of Hepatitis B, Ranging of Asymptomatic Carrier State to Hepatocellular Carcinoma

The objective of this study was to determine the association of 19 mutations with frequencies ≥ 10% in the core promoter region of hepatitis B virus (HBV) with chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma (HCC). Eight hundred forty-six asymptomatic hepatitis B surface antigen carriers (ASCs), 235 CHB patients, 188 cirrhosis patients, and 190 HCC patients with intact data of HBV genotyping, DNA sequencing, and serological parameters were studied. Nucleotides with the highest frequencies in HBV genotypes B and C from all ASCs were treated as wild-type nucleotides. Mutations at nt.1674, nt.1719, nt.1762, nt.1764, nt.1846, nt.1896, and nt.1913 in genotype C were significantly associated with CHB, cirrhosis, and HCC, as compared with ASCs. C1673T, A1726C, A1727T, C1730G, C1766T, T1768A, C1773T, and C1799G in genotype C were significantly associated with cirrhosis compared with the CHB patients, whereas these mutations were inversely associated with HCC compared with the cirrhosis patients. Multivariate regression analyses showed that age, male, abnormal alanine aminotransferase (ALT), T1768A, A1762T/G1764A, and A1846T were independently associated with cirrhosis compared with ASCs and the patients with CHB. Age, abnormal ALT, HBV DNA (≥10(4) copies/ml), genotype C, C1653T, T1674C/G, T1753V, and A1762T/G1764A were independently associated with HCC compared with those without HCC. Haplotypic carriages with two or more HBV mutations were significantly associated with HCC. T1674C/G, C1653T, and T1753V were specific for HCC. A1762T/G1764A had a moderate sensitivity and specificity for HCC. C1673T, A1726C, A1727T, C1730G, C1766T, T1768A, C1773T, and C1799G in genotype C are specific for cirrhosis. A1846T and T1674C/G are novel factors independently associated with cirrhosis and HCC, respectively.

Screening for Chronic Hepatitis B in Patients Undergoing Chemotherapy for Lymphoma or Colon Cancer

Purpose: Approximately 350 to 400 million people are hepatitis B surface antigen (HBsAg) carriers. HBsAg carriers who receive cytotoxic or immunosuppressive therapy are at significant risk of hepatitis B (HBV) reactivation. Spontaneous reactivation may occur in up to 22% of HBV-infected patients with previously negative HBeAg status. Cytotoxic therapy has been shown in prospective studies to confer a threefold greater risk of viral reactivation. Patients undergoing chemotherapy are often not screened for HBV infection, and prophylactic antiviral therapy is markedly underused. The use of steroids with chemotherapy for patients with hematologic malignancies poses the greatest risk of reactivation, up to 67%. For solid tumors such as breast cancer, a slightly lower risk of 40% exists. There does not appear to be extensive data reporting the reactivation risk of HBV for chemotherapy in colon cancer. Methods: This was a retrospective chart review of patients at Scott & White Healthcare Hospital who have undergone chemotherapy for lymphoma or colon cancer. For each patient, liver function tests (LFTs) were trended for the duration of the chemotherapy. We reviewed the charts to determine if patients were screened for HBV prior to chemotherapy induction. If patients were HbsAg-positive, we further reviewed the chart for initiation of chemoprophylaxis. HBV screening rate and 95% Confidence Interval (CI) were estimated for entire cohort, both normal and abnormal LFT groups. HBV screening rates between the 2 groups were compared using Chi-square test. SAS version 9.2 (SAS Institute INC, Cary, NC) was used for statistical analysis. Results: Approximately 800 lymphoma and 500 colon cancer cases were found and preliminary analysis was performed on 242 patients. See table 1 for descriptive statistics. Two patients were excluded as they did not have any LFTs. Of the 240 patients, 110 had normal LFTs and 130 abnormal LFTs. See table 2 for comparison of HBV screening results between the normal and abnormal LFT groups. Screening rates between the two groups were significantly different (p-value=0.0244). A total of 17 patients received HBV screening (screening rate 7.02% with 95% CI of (4.15-11.01%). One of the excluded patients received screening.Table 1Table 2Conclusion: As our preliminary analysis has shown, screening rates in our study were low. Despite guidelines, chemoprophylaxis of HbsAg carriers is low prior to cancer chemotherapy. Our data analysis is ongoing and will be complete at the time of publication.

Exploring risk factors of hepatitis B virus-associated hepatocellular carcinoma: prospective verse retrospective studies

Major risk factors for hepatocellular carcinoma (HCC) vary by region and population. Chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), heavy alcohol intake, aflatoxin exposure, haemochromatosis, nonalcoholic fatty liver disease, obesity, diabetes mellitus and tobacco smoking have been suggested to be risk factors of HCC. However, chronic infection with HBV remains the major cause of HCC in the world. More than 50% of HCC cases worldwide and 80% of HCC cases in most high-risk areas, such as the Asia‐Pacific region and Africa, are attributable to HBV infection. The relative risk of HCC among individuals infected with HBV ranges from 5 to 49 in case‐control studies and from 7 to 98 in cohort studies [1]. In HBV endemic regions, HBV infection is usually acquired perinatally or in childhood, whereas in HBV nonendemic areas, it is mostly transmitted during adolescence or adulthood. Newborns become chronic HBV carriers at a very high rate (about 90%), while immune-competent adults are generally described as developing chronic infection at a rate of 5‐10%. HBV subgenotype C2 is more prone to causing chronic infection than HBV subgenotype B2 following acute hepatitis B [2]. Up to 40% of patients with chronic HBV infection will develop the life-threatening complications of HCC or decompensated liver cirrhosis (LC). Chronic hepatitis B (CHB), LC and HCC are progressive liver diseases and consecutive stages of HBVassociated hepatocarcinogenesis, although CHB may precede the asymptomatic hepatitis B surface antigen (HBsAg) carrier (ASC) state and HCC does not have to pass through the CHB or LC stage. Hepatitis B e antigen (HBeAg) expression indicates active viral replication. HBeAg expression, high viral load and alanine aminotransferase (ALT) levels are associated with an increased risk of HCC. HBV subgenotypes B2 and C2 are endemic in most parts of Asia, while subgenotype B1 is endemic in Japan. Chronic infection with HBV C2 is frequently associated with an increased risk of LC and HCC in patients older than 50 years, whereas chronic infection with HBV B2 is associated with HCC or HCC recurrence in young, mostly non-cirrhotic, patients. In comparison with infection with HBV B2 or C2, infection with HBV B1 is associated with fulminant hepatitis B, a lower incidence of HCC and the development of HCC when older. Different HBV genotypes display their own distinct mutation pattern in the preS region and in the enhancer II (EnhII)/basic core promoter (BCP)/precore region of the HBV genome. Takahashi and colleagues identified HCC-associated HBV mutations through the comparative analysis of full-length HBV isolates (95% genotype C) from sera of 40 Japanese patients with HCC. They found that deletions and missense mutations in the preS2 region, A1762T and G1764A (often appearing simultaneously, termed A1762T/G1764A) and T1753C/A mutations in the BCP region and G1613A and C1653T mutations in the EnhII region were more frequent in HCC patients [3]. This pioneering work has aroused great interest in the field. Many studies pertaining to the association of HBV mutations with the risk of HCC have been published during the past decade. It has been found that the HBV preS deletion, A1762T/G1764A, T1753V, C1653T and T31C are each associated with a significantly increased risk of HCC [4]. Of the two major HBV

The Role of Interferon in Hepatitis B Therapy.

Despite the introduction of new nucleos(t)ide analogues in recent years, peginterferon is still recommended as a potential first-line treatment option by current practice guidelines for the management of chronic hepatitis B. Peginterferon offers the advantage of higher sustained off-treatment response rates compared to nucleos(t)ide analogues because of its immunomodulatory effects. Sustained transition to the inactive hepatitis B surface antigen (HBsAg) carrier state can be achieved in about 30% of hepatitis B e antigen (HBeAg)–positive patients and 20% of HBeAg-negative patients. Recent studies have focused on identification of pretreatment and on-treatment factors that allow the selection of patients who are likely to achieve a sustained response to peginterferon therapy in order to avoid the side-effects and costs associated with unnecessary treatment. Future studies need to address whether specific virologic benchmarks can guide individualized decisions concerning therapy continuation and whether peginterferon combined with new potent nucleos(t)ide analogues improves treatment outcomes.

Prevalence of reactivation of hepatitis B virus replication in rheumatoid arthritis patients

Reactivation of hepatitis B involves the reappearance of active necroinflammatory liver disease after an inactive hepatitis B surface antigen (HBsAg) carrier state or resolved hepatitis B, occurring during or after immunosuppression therapy or chemotherapy. We prospectively investigated the reactivation rate for hepatitis B virus (HBV) DNA replication in cases of rheumatoid arthritis (RA) with resolved hepatitis B. HBV markers were evaluated in 428 RA patients. Patients with positive findings of HBsAg or HBV DNA at enrolment were excluded. The study population comprised 422 RA patients, with resolved hepatitis B diagnosed in 135 patients based on HBsAg-negative and antihepatitis B core antibody/antihepatitis B surface antibody-positive results. HBV DNA was measured every 3months in this group, and if HBV DNA became positive after enrolment, measurement was repeated every month. HBV DNA became positive (≥3.64log copies/mL) in 7 of 135 patients for 12months. Use of biologic agents was significantly more frequent in patients who developed reactivation of HBV DNA replication (85.7%) than in patients who did not (36.0%, p=0.008). Hazard ratios for use of biologic agents and etanercept were 10.9 (p=0.008) and 6.9 (p=0.001), respectively. RA patients with resolved hepatitis B need careful monitoring when receiving biologic agents, regardless of HBV DNA levels.