Incidence of non-Hodgkin's lymphoma among individuals with chronic hepatitis B virus infection

Although hepatitis C virus (HCV) infection has been shown to be associated with development of non-Hodgkin's lymphoma (NHL), few studies have investigated the association between chronic HBV infection and NHL. The purpose of this study was to compare the incidence of NHL between patients with and without chronic hepatitis B virus (HBV) infection. Using automated laboratory result and clinical data from two United States health systems, we identified individuals with chronic HBV infection from January 1, 1995 through December 31, 2001. Using each health system's population-based tumor registry, we identified all cases of NHL diagnosed through December 31, 2002. We excluded any individual with a history of NHL or human immunodeficiency virus (HIV). We fit Cox proportional hazards models to calculate hazard ratios comparing the incidence of NHL between chronic HBV-infected patients (N = 3,888) and patients without HBV (N = 205,203) drawn from the source populations. We identified 8 NHL cases in the chronic HBV infection cohort and 111 cases in the comparison cohort. Patients with chronic HBV infection were 2.8 times more likely to develop NHL than matched comparison patients (adjusted hazard ratio = 2.80, 95% confidence interval = 1.16-6.75), after controlling for age, race, sex, income, Charlson comorbidity index, study site, and HCV infection. CONCLUSION: chronic HBV-infected patients were nearly 3 times more likely to develop NHL than comparison patients.     

Cumulative incidence and risk factors for the development of hepatocellular carcinoma in patients with chronic hepatitis B who achieved sustained disappearance of viremia by nucleos(t)ide analog treatment

Aim

Nucleos(t)ide analog (NA) therapy has been reported to reduce the risk of hepatocellular carcinoma (HCC). However, some patients who achieve hepatitis B virus (HBV)‐DNA disappearance from serum by NA develop HCC. In this study, we investigated the cumulative incidence and risk factors for HCC in patients with chronic hepatitis B (CHB) who achieved sustained disappearance of viremia by NA treatment.

Methods

A total of 133 CHB patients (median age, 51 years; 79 men [59%]; 28 with cirrhosis [21%]) who received NA therapy and achieved HBV‐DNA disappearance from serum were analyzed retrospectively. We evaluated the cumulative incidence of HCC and risk factors associated with HCC based on data collected at the time of HBV‐DNA disappearance.

Results

Thirteen patients developed HCC during the follow‐up period. The 1‐, 3‐, and 5‐year cumulative incidence of HCC was 0.0%, 7.8%, and 11.1%, respectively. In multivariate analysis, advanced age (hazard ratio [HR], 4.601; 95% confidence interval [CI], 1.220–17.351; P = 0.024), liver cirrhosis (HR, 5.563; 95% CI, 1.438–21.519; P = 0.013), and higher HBV core‐related antigen (HBcrAg) levels (HR, 13.532; 95% CI, 1.683–108.815; P = 0.014) at the time of HBV‐DNA disappearance were significantly associated with the development of HCC.

Conclusion

Our findings indicate the importance of continuous HCC surveillance especially in patients with advanced age, cirrhosis, and/or higher serum levels of HBcrAg, even if they achieve HBV‐DNA disappearance.     

Basal core-promoter mutant of hepatitis B virus and progression of liver disease in hepatitis B e antigen-negative chronic hepatitis B.

BACKGROUND/AIMS: The long-term outcomes in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B are distinct from those in HBeAg-positive chronic hepatitis. However, the molecular virological factors that contribute to the progression of liver disease in this special clinical setting remain largely unknown. We thus investigated the association of hepatitis B virus (HBV) genotypes as well as precore/basal core-promoter mutations with the clinical and virological characteristics of patients with HBeAg-negative chronic hepatitis B in Taiwan. METHODS: HBV genotypes and sequences of precore and basal core-promoter regions of the HBV genome were determined in 174 HBeAg-negative chronic HBV infection patients including 62 inactive carriers and 112 with different stages of liver disease. RESULTS: HBV carriers with older age (> 50 years) (odds ratio, 9.09; 95% confidence interval (CI), 3.22-25, P < 0.001) and basal core-promoter mutant of HBV (odds ratio, 4.12; 95% CI, 1.41-12.03, P = 0.01) were associated with the development of liver cirrhosis and hepatocellular carcinoma (HCC). The gender-related risk factors associated with the development of liver cirrhosis and HCC were further analyzed, and basal core-promoter mutant was only associated with the development of liver cirrhosis and HCC in male carriers (odds ratio, 4.35; 95% CI, 1.30-14.52, P = 0.02). CONCLUSIONS: The risk of development of liver cirrhosis and HCC is significantly increased in patients with advanced age as well as with basal core-promoter mutant of HBV. In addition, basal core-promoter mutant might contribute to the gender difference of the progression of liver disease in HBeAg-negative chronic hepatitis B in Taiwan.     

Impact of previous hepatitis B infection on the clinical outcomes from chronic hepatitis C? A population‐level analysis

Chronic coinfection with hepatitis C virus (HCV) and hepatitis B virus (HBV) is associated with adverse liver outcomes. The clinical impact of previous HBV infection on liver disease in HCV infection is unknown. We aimed at determining any association of previous HBV infection with liver outcomes using antibodies to the hepatitis B core antigen (HBcAb) positivity as a marker of exposure. The Scottish Hepatitis C Clinical Database containing data for all patients attending HCV clinics in participating health boards was linked to the HBV diagnostic registry and mortality data from Information Services Division, Scotland. Survival analyses with competing risks were constructed for time from the first appointment to decompensated cirrhosis, hepatocellular carcinoma (HCC) and liver‐related mortality. Records of 8513 chronic HCV patients were included in the analyses (87 HBcAb positive and HBV surface antigen [HBsAg] positive, 1577 HBcAb positive and HBsAg negative, and 6849 HBcAb negative). Multivariate cause‐specific proportional hazards models showed previous HBV infection (HBcAb positive and HBsAg negative) significantly increased the risks of decompensated cirrhosis (hazard ratio [HR]: 1.29, 95% CI: 1.01‐1.65) and HCC (HR: 1.64, 95% CI: 1.09‐2.49), but not liver‐related death (HR: 1.02, 95% CI: 0.80‐1.30). This is the largest study to date showing an association between previous HBV infection and certain adverse liver outcomes in HCV infection. Our analyses add significantly to evidence which suggests that HBV infection adversely affects liver health despite apparent clearance. This has important implications for HBV vaccination policy and indications for prioritization of HCV therapy.     

Hepatitis B viral load predicts survival of HCC patients undergoing systemic chemotherapy

HCC is a common cause of morbidity and mortality. For patients who are not candidates for curative surgery, systemic chemotherapy is one of the standard treatments. In parts of China and the Far East, over 80% of HCC patients have chronic HBV infection. In this study, we aimed to assess the relationship between pre-chemotherapy HBV viral load and the survival of HCC patients. HBV infection status was determined prior to chemotherapy in 188 patients, 170 of whom had evidence of HBV chronic infection/exposure (160 hepatitis B surface antigen [HBsAg]-positive, 10 HBsAg-negative/hepatitis B core antibody-positive). Of these, 125 had pretreatment HBV DNA levels determined via real-time PCR. Virological data were analyzed using conventional clinical variables to identify factors that influenced survival. Multivariate analysis revealed that high total bilirubin (P = 0.0016; hazard ratio = 1.040 per 1 muM increase; 95% CI 1.015-1.065), HCV infection (P = 0.0095; hazard ratio = 6.955; 95% CI 1.606-30.129), and high HBV DNA level (P = 0.0217; hazard ratio = 1.650; 95% CI 1.076-2.531) affected survival significantly. Exploratory analysis revealed that high levels of pretreatment HBV DNA had a significantly higher incidence of severe hepatitis during chemotherapy. CONCLUSION: For HCC patients with HBV chronic infection/exposure, a high viral load prior to treatment is an adverse factor for survival and may be associated with a higher incidence of severe hepatitis during chemotherapy. Future strategies to improve the prognosis of HCC patients undergoing chemotherapy should consider supportive therapy that incorporates antiviral therapies to reduce HBV viral load.     

Risk of all‐type cancer,hepatocellular carcinoma,non‐Hodgkin lymphoma and pancreatic cancer in patients infected with hepatitis B virus

The increased risk of hepatocellular carcinoma (HCC) among patients infected with hepatitis B virus (HBV) is well established; however, long‐term risk estimates are needed. Recently, it has been suggested that HBV is associated with non‐Hodgkin lymphoma (NHL) and pancreatic cancer (PC). The aim of this Danish nationwide cohort study was to evaluate the association between HBV infection and all‐type cancer, HCC, NHL and PC. A cohort of patients infected with HBV (n = 4345) and an age‐ and sex‐matched population‐based comparison cohort of individuals (n = 26 070) without a positive test for HBV were linked to The Danish Cancer Registry to compare the risk of all‐type cancer, HCC, NHL and PC among the two groups. The median observation period was 8.0 years. Overall, the incidence rate ratio (IRR) for all‐type cancer among HBV‐infected patients was 1.1 (95% confidence intervals (CI) 0.9–1.3). The IRR of HCC was 17.4 (CI 5.5–54.5), whereas the IRR of PC and NHL was 0.9 (CI 0.3–2.5) and 1.2 (CI 0.4–3.6), respectively. HBV‐infected patients had a 10‐year risk of 0.24% (Cl 0.12–0.44) for HCC, whereas the comparison cohort had a 10‐year risk of 0.03% (Cl 0.02–0.07) for HCC. The risk of all‐type cancer, NHL and PC was not higher in the HBV‐infected cohort compared to non‐HBV infected. We found a 17‐fold higher risk of HCC for HBV‐infected individuals.     

Trends in incidence of hepatocellular carcinoma after diagnosis of hepatitis B or C infection: a population-based cohort study, 1992-2007

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the major risk factors for hepatocellular carcinoma (HCC). We examined trends in the incidence of HCC among a population-based cohort of people infected with HBV or HCV. HBV and HCV cases notified to the New South Wales Health Department between 1992 and 2007 were linked to the Central Cancer Registry, Registry of Births, Deaths and Marriages, and National HIV/AIDS Registries. Crude HCC incidence rates were estimated using person-time methodology. Age-standardized incidence rates were calculated using the 2001 Australian population. Trends in incidence were examined using join point regression models. Between 1992 and 2007, 1201 people had a linked HCC record: 556 of those with HBV; 592 with HCV; 45 with HBV/HCV co-infection; and 8 with HIV co-infection. The overall age-standardized HCC incidence rates declined non-significantly from 148.0 (95% confidence intervals (CI) 63.7, 287.4) per 100,000 population in 1995 to 101.2 (95% CI 67.3, 144.6) in 2007 among the HBV monoinfected group and significantly from 151.8 (95% CI 62.4, 299.8) per 100,000 population to 75.3 (95% CI 50.8, 105.5) among the HCV monoinfected group. However, incidence rates in the HCV monoinfected group progressively increased from the period 1992-1997 to 2004-2007 when adjusted for age, sex, and birth cohort, and the total number of cases per annum continued to increase. Despite declines in the age-adjusted incidence rates of HCC over time, the absolute number of cases increased likely due to the ageing cohort and an increasing prevalence of both hepatitis B and C in Australia.     

Association of HLA-DRB1*13 and TNF-alpha gene polymorphisms with clearance of chronic hepatitis B infection and risk of hepatocellular carcinoma in Thai population

Considerable evidence suggests that host genetic factor play an important role in the pathogenesis and clinical outcome of chronic hepatitis B virus (HBV) infection in several ethic groups. Association study was performed included 150 chronic HBV patients, 100 resolved hepatitis B and 150 healthy individuals with similar ethic background. Interestingly, human leucocyte antigen (HLA)-DR13 show a strong association with the clearance of HBV [odds ratio (OR) = 0.04, 95% confidence interval (CI) = 0.00-0.26, corrected P-value (P(c)) = 0.0008] similar to reports from several ethic groups. TNF-alpha promoter polymorphisms (-863, -308 and -238) were also analysed. Only -863 C allele was found to be significantly decreased in chronic HBV patients compared with healthy control (P(c) = 0.03, OR = 0.54, 95% CI = 0.35-0.84 respectively). This -863C allele was not in linkage disequilibrium with HLA-DR13 suggesting that other genetic markers linked with -863C might influence clearance of chronic HBV infection in Thai. When stratified chronic HBV patients into patients without hepatocellular carcinoma (HCC) and with HCC, the -863 A allele was significantly increased in the HCC group compared to healthy control (P(c) = 0.003, OR = 2.61, 95% CI = 1.49-4.60). Haplotype analysis (-863/-308/-238) revealed that the homozygosity of the haplotype (CGG/CGG) was a protective marker for HCC (OR = 0.37, 95% CI = 0.17-0.79, P(c) = 0.02). One can propose that carriers of -863A genotype are associated with increased levels of TNF-alpha in the liver in response to HBV infection and induce hapatocyte damage that may finally lead to HCC development. Additional study is needed to validate these finding and to further explore the genetic pathogenesis of HBV infection.     

Outcome of hepatitis B and C virus‐associated hepatocellular carcinoma occurring after renal transplantation

Kidney transplant recipients (KTR) are subjected to immunosuppressive therapy that can enhance hepatitis B and C virus replication, leading to cirrhosis and hepatocellular carcinoma (HCC). The aim of this study was to assess the prevalence and outcome of HCC in KTR. Case‐control study. Patients with chronic HBV and/or HCV infection who underwent kidney transplantation between 1976 and 2011 and subsequently developed HCC were compared to a control group of patients with chronic HBV and/or HCV infection, matched for gender and age at HCC diagnosis, who did not receive kidney transplantation. Among 2944 KTR, 330 had hepatitis B and/or C. Fourteen developed HCC, a period prevalence of 4.2%. Age at HCC diagnosis was 52.6 ± 6.5 years (53.5 ± 5.7 in controls, P=.76). Time between transplantation and HCC diagnosis was 16.7 ± 2.7 years. Six HCCs were related to HBV, six to HCV and two to co‐infection with HBV and HCV. Immunosuppressive therapy was comparable in HBV, HCV and HBV+HCV patients. At diagnosis, 71% of patients met Milan criteria (65% in the control group, P=.4). Alpha‐fetoprotein levels, tumour characteristics and treatment modalities were comparable between both groups. Patient survival 2 years after HCC diagnosis was 28% in KTR, compared to 68% in controls (P=.024). Survival after HCC diagnosis is significantly worse in KTR compared to nontransplanted patients with HBV and/or HCV. Prevention is crucial and should be based on viral eradication/suppression before or after transplantation.     

Case–control study for the identification of virological factors associated with fulminant hepatitis B

Background:  Host and viral factors can promote the development of fulminant hepatitis B (FHB), but there have been no case–control studies for figuring out virological parameters that can distinguish FHB.
Methods:  In a case–control study, virological factors associated with the development of FHB were sought in 50 patients with FH developed by transient hepatitis B virus (HBV) infection (FH-T) and 50 with acute self-limited hepatitis B (AHB) who were matched for sex and age. In addition, 12 patients with FH developed by acute exacerbation (AE) of asymptomatic HBV carrier (ASC) (FH-C) were also compared with 12 patients without FH by AE of chronic hepatitis B (AE-C).
Results:  Higher HBV DNA levels, subgenotype B1/Bj, A1762T/G1764A, G1896A, G1899A and A2339G mutation were significantly more frequent ( P  < 0.05), while hepatitis B e-antigen was less frequent in the FH-T patients than AHB. In multivariate analysis, G1896A mutation (odds ratio [OR], 13.53; 95% confidence interval [CI], 2.75–66.64), serum HBV DNA more than 5.23 log copies/mL (OR, 5.14; 95% CI, 1.10–24.15) and total bilirubin more than 10.35 mg/mL (OR, 7.81; 95% CI, 1.77–34.51) were independently associated with a fulminant outcome by transient HBV infection. On the other hand, in comparison with the patients between FH-C and AE-C groups, there was no significant difference of virological factors associated with the development of FHB.
Conclusion:  A number of virological factors have been defined that may distinguish FH-T from AHB in a case–control study. The pathogenic mechanism of FHB between transient HBV infection and AE of ASC would be different.     

Hepatocellular carcinoma in African Blacks: Recent progress in etiology and pathogenesis

Occult hepatitis B virus (HBV) infection was shown to be present in 75% of Black Africans with hepatocellular carcinoma (HCC) in whom the tumor was hitherto not thought to be caused by chronic HBV infection. The association between chronic HBV infection and the development of the tumor is thus even closer than was originally thought. HBV viral load was found to be significantly higher in patients with HCC than in Black African controls. As in other populations, HBV e antigen-positive patients with hepatocellular carcinoma had significantly higher viral loads than patients negative for this antigen. The significance of this finding is discussed. The risk for HCC development with genotype A of HBV, the predominant genotype in African isolates, has not been investigated. Genotype A was shown to be 4.5 times more likely than other genotypes to cause HCC in Black Africans, and tumours occurred at a significantly younger age. Increasing numbers of patients with human immunodeficiency virus (HIV) and HBV co-infection are being reported to develop HCC. A preliminary case/control comparison supports the belief that HIV co-infection enhances the hepatocarcinogenic potential of HBV. A study from The Gambia provides the first evidence that dietary exposure to aflatoxin B(1) may cause cirrhosis and that this may play a contributory role in the pathogenesis of aflatoxin-induced HCC. An animal model has provided experimental support for the clinical evidence that dietary iron overload in the African is directly hepatocarcinogenic, in addition to causing the tumor indirectly through the development of cirrhosis.     

Correlates of chronic hepatitis B virus infection in the general adult population of China: Systematic review and meta-analysis

Chronic infection with hepatitis B virus (HBV) is a significant public health issue in China. Understanding factors associated with chronic HBV is important to enable targeted screening and education and to improve early diagnosis and prevention of disease progression. This systematic review and meta-analysis aimed to identify and describe correlates of chronic HBV among Chinese adults. Searches were conducted in MEDLINE, EMBASE and grey literature up to 25 June 2020. Eligible papers included observational studies in adults of the general population in China that reported factors associated with chronic HBV, measured by Hepatitis B surface antigen (HBsAg). Meta-analysis was performed using fixed-effect models of HBsAg prevalence among factors, and of adjusted odds ratios (ORs) for chronic HBV associated with each factor. Overall 39 articles were included, covering 22 factors, including a range of sociodemographic, behavioural and medical factors. In meta-analysis of eligible studies, a range of factors were significantly associated with higher HBsAg prevalence, including middle age, male sex, being married, rural residence, lower education, smoking, having a HBsAg positive household contact, family history of HBV, history of surgery or blood transfusion. The adjusted ORs varied, from 1.11 (95% CI 1.05–1.18) for smoking to 5.13 (95% CI 4.99–5.26) for having a HBsAg positive household contact. In Chinese adults, a range of factors are associated with chronic HBV infection, which may help inform targeted screening in the general population.     

Factors associated with isolated anti‐hepatitis B core antibody in HIV‐positive patients: impact of compromised immunity

Summary. In regions that are hyperendemic for chronic hepatitis B virus (HBV) infection, prevalence of and risk factors associated with isolated anti‐hepatitis B core antibody (anti‐HBc) in HIV‐positive patients are less well described. HIV‐positive patients who were tested for hepatitis B surface antigen (HBsAg), anti‐hepatitis B surface antibody (anti‐HBs) and anti‐HBc at designated hospitals for HIV care in Taiwan were included for analysis. HBV DNA was detected by real‐time polymerase chain reaction in patients with and without isolated anti‐HBc. Of 2351 HIV‐positive patients, 450 (19.1%) were HBsAg positive, 411 (17.5%) were anti‐HBc positive alone and 963 (41.0%) for both anti‐HBs and anti‐HBc. Compared with patients who were positive for both anti‐HBs and anti‐HBc, patients with isolated anti‐HBc were older, less likely to have anti‐hepatitis C virus antibody (anti‐HCV), had lower CD4 lymphocyte counts and higher plasma HIV RNA loads. Older age (adjusted odds ratio, 1.029; 95% confidence interval, 1.015–1.043) and CD4 <100 cells/μL (adjusted odds ratio, 1.524; 95% confidence interval, 1.025–2.265) were independently associated with isolated anti‐HBc by logistic regression, while presence of anti‐HCV and injecting drug use were not. HBV DNA was detectable in 8.3% of 277 patients with isolated anti‐HBc and 14.3% of 56 patients with both anti‐HBs and anti‐HBc (P = 0.160). In a country hyperendemic for HBV infection, HIV‐positive patients at older age and with CD4 <100 cells/μL were more likely to have isolated anti‐HBc, suggesting that compromised immunity plays a role in the presence of this marker.     

Risk of liver cirrhosis and hepatocellular carcinoma in subjects with hepatitis B and delta virus infection: A study from Kure, Japan

To investigate the effect of hepatitis delta virus (HDV) superinfection on the long-term outcome of Japanese subjects with chronic hepatitis B virus (HBV) infection, we examined the presence of antibodies to hepatitis delta antigen (anti-HD) in serial serum samples collected from 1127 subjects with chronic HBV infection. The subjects were followed for at least 36 months (mean: 121.3 months) between 1973 and 1991. Among 69 cases where anti-HD was detected, eight (12%) developed liver cirrhosis (LC) and six (9%) developed hepatocellular carcinoma (HCC). However, among 1058 cases without anti-HD, there were 43 patients (4%) who developed LC and 29 (3%) who developed HCC. The prevalence of LC and HCC was significantly higher among the cases with anti-HD than those without anti-HD. The proportion of LC and HCC per 1000 person years was 10.46 and 7.84, respectively among cases with anti-HD, and 4.05 and 2.73 among those without anti-HD, respectively. The overall relative risk of LC and HCC was 2.58 and 2.87, respectively; 95% confidence interval (CI): LC, 1.14–5.13; HCC, 1.03–6.23. These results indicate that in the Kure district in Japan, where HDV infection of persons infected with HBV is about 6%, such superinfection increases the risk of LC and HCC.     

Hepatitis B infection is associated with an increased incidence of thrombocytopenia in healthy adults without cirrhosis

The association between HBV infection and incident thrombocytopenia among subjects without cirrhosis or splenomegaly is unknown. Therefore, we sought to elucidate the association between HBV infection and the development of thrombocytopenia in a large cohort of apparently healthy men and women. A cohort study was performed in 122 200 participants without liver cirrhosis or splenomegaly who underwent comprehensive health examinations and were followed until December 2014. HBV infection was defined by the presence of hepatitis B surface antigen (HBsAg) at baseline. Thrombocytopenia was defined as a platelet count <150 000/μL. Cox proportional hazard models were used to estimate adjusted hazard ratios with 95% confidence intervals (CIs) for incident thrombocytopenia. HBsAg was positive in 4857 of 122 200 subjects (4.0%) at baseline. During 883 983 person‐years of follow‐up, 2037 incident cases of thrombocytopenia were identified (incident rate 2.3 per 1000 person‐years). HBsAg–positive subjects had a higher incidence of thrombocytopenia than did healthy controls (11.2 vs 1.9 per 1000 person‐years, respectively). The multivariate‐adjusted hazard ratio (95% CI) for incident thrombocytopenia comparing HBsAg‐positive to HBsAg‐negative subjects was 5.71 (5.10‐6.38). Strong associations between HBsAg positivity and thrombocytopenia were consistently observed across prespecified subgroups. In this large cohort study of an apparently healthy population, HBsAg positivity was strongly and independently associated with incident thrombocytopenia, indicating that mechanisms of thrombocytopenia other than portal hypertension may exist in healthy HBV carriers.     

Hepatitis B core‐related antigen levels after HBeAg seroconversion is associated with the development of hepatocellular carcinoma

Hepatitis B core‐related antigen (HBcrAg) is a novel serological marker for hepatitis B virus infection. Its clinical significance after HBeAg seroconversion has not been defined. We aimed to determine the relationship between HBcrAg levels after spontaneous HBeAg seroconversion and hepatocellular carcinoma (HCC). A total of 207 chronic hepatitis B patients with documented time of HBeAg seroconversion were enrolled. HBcrAg and HBsAg were checked within 3 years (as baseline), at 5 and 10 years after HBeAg seroconversion. HBV DNA was measured at the baseline. Multivariate Cox regression model was used to investigate the predictors for HCC development. The median follow‐up time was 13.1 (11.8‐15.5) years. Fourteen patients developed HCC (15‐year cumulative incidence: 7%). The median level of HBcrAg at baseline was significantly higher in patients who developed HCC when compared with patients without HCC (5.68 vs 4.78 log U/ml, respectively; P = .003). Cox proportional hazards model indicated that age of HBeAg seroconversion older than 40 years (hazard ratio (HR): 4.60; P = .049), presence of baseline cirrhosis (HR: 6.23; P = .003) and a higher baseline HBcrAg (HR: 1.75; P = .032) were independently associated with HCC development. A cut‐off value of baseline HBcrAg level ≥5.21 log U/mL yielded an AUROC of 0.74 with a negative predictive value of 97.7%. High HBcrAg levels within 3 years after HBeAg seroconversion were independently associated with the development of HCC in chronic hepatitis B patients.     

Increased risk of hip fracture associated with dually treated HIV/hepatitis B virus coinfection

HIV and hepatitis B virus (HBV) infections are each associated with reduced bone mineral density, but it is unclear whether HIV/HBV coinfection is associated with an increased risk of fracture. We determined whether dually treated HIV/HBV patients had a higher incidence of hip fracture compared to treated HBV‐monoinfected, antiretroviral therapy (ART)‐treated HIV‐monoinfected and HIV/HBV‐uninfected patients. We conducted a cohort study among 4156 dually treated HIV/HBV‐coinfected, 2053 treated HBV‐monoinfected, 96 253 ART‐treated HIV‐monoinfected, and 746 794 randomly sampled uninfected persons within the US Medicaid populations of California, Florida, New York, Ohio and Pennsylvania (1999–2007). Coinfected patients were matched on propensity score to persons in each comparator cohort. Weighted survival models accounting for competing risks were used to estimate cumulative incidences and hazard ratios (HRs) with 95% confidence intervals (CIs) of incident hip fracture for dually treated coinfected patients compared to (i) HBV‐monoinfected receiving nucleos(t)ide analogue or interferon alfa therapy, (ii) HIV‐monoinfected on ART and (iii) uninfected persons. Dually treated coinfected patients had a higher cumulative incidence of hip fracture compared to ART‐treated HIV‐monoinfected (at 5 years: 1.70% vs 1.24%; adjusted HR, 1.37 [95% CI, 1.03–1.83]) and uninfected (at 5 years: 1.64% vs 1.22%; adjusted HR, 1.35 [95% CI, 1.03–1.84]) persons. The cumulative incidence of hip fracture was higher among coinfected than treated HBV‐monoinfected patients (at 5 years: 0.70% vs 0.27%), but this difference was not statistically significant in competing risk analysis (adjusted HR, 2.62 [95% CI, 0.92–7.51]). Among Medicaid enrollees, the risk of hip fracture was higher among dually treated HIV/HBV‐coinfected patients than ART‐treated HIV‐monoinfected and uninfected persons.     

Predictors and survival in hepatitis B-related hepatocellular carcinoma in New South Wales, Australia

Background and Aim: Incidence and mortality of hepatocellular carcinoma (HCC) has increased markedly over the last three decades in Australia. An increasing proportion of HCC cases is related to chronic viral hepatitis including hepatitis B virus (HBV) infection. However, there is very limited data on HBV‐related HCC survival. Methods: Data on HBV‐related HCC cases was obtained from a community‐based linkage study. HCC cases notified to the New South Wales (NSW) Central Cancer Registry (CCR) during the period 1994–2002 were linked to HBV notifications from the NSW Health Department. Age, sex, country of birth, year of diagnosis, tumor stage were extracted from the CCR database. Survival analysis was conducted to determine median survival and identify predictors of survival. Results: Over the 9‐year study period, 278 HCC cases were linked to chronic HBV infection. The majority of cases were male (83.5%) and overseas‐born (93.6%); Asian‐born cases accounted for 72.1%. Median survival following HCC diagnosis was 15.0 months. HCC survival was poorer among older age groups (P < 0.0001), and among cases with regional spread (hazard ratio, 3.23; 95% confidence interval, 1.83–5.69; P < 0.0001) and distant metastases (hazard ratio, 3.85; 95% confidence interval, 2.44–6.08; P < 0.0001). Sex, region of birth and study period (1994–1997 vs 1998–2002) were not associated with HCC survival. Conclusion: The vast majority of HBV‐related HCC were overseas‐born, however, region of birth was unrelated to HCC survival. The continued extremely poor HCC survival, including lack of improvement in HCC survival in more recent years, suggests low uptake of HCC screening programs. Public health strategies including early diagnosis and appropriate referral for antiviral therapy assessment and increased HCC screening among high‐risk populations are required to reduce HCC incidence and improve HCC survival.     

Hepatitis B surface antigenaemia and alpha-foetoprotein detection from dried blood spots: applications to field-based studies and to clinical care in hepatitis B virus endemic areas

In many resource-limited regions with endemic hepatitis B virus (HBV), there is limited infrastructure to collect, process, transport, and store blood samples for identification of persons with chronic HBV infection or with hepatocellular carcinoma (HCC). We describe the application of a simple technique using commercially available kits for detection of HBV surface antigen (HBsAg) and alpha-foetoprotein (AFP) in dried blood spots (DBS) collected on filter paper. Study participants included subjects with and without chronic HBV infection and subjects with HCC or cirrhosis. Three to five blood drops were dried on filter paper. Dried blood (equivalent to 20 muL) was eluted and tested for HBsAg by Determine(TM) HBsAg and for AFP by counter-current immuno-electrophoresis and radio-immunoassay (RIA). The primary analysis focused on comparison of DBS results to serum testing results as the gold standard. The sensitivity of DBS for detecting chronic HBV infection was 96% (98-98) with specificity of 100% (CI 99-100). Sensitivity of DBS in detecting AFP compared with serum RIA was 73% (60-86) with specificity of 90% (81-98). Both HBsAg and AFP recovery were unaffected when DBS were left at room temperature (30-33 degrees C) and under humid conditions for up to 28 days prior to elution. We conclude that DBS can be reliably used as an economical and logical alternative for detection of HBsAg in chronically infected patients and for AFP-based diagnosis of HCC in clinical situations which preclude adequate collection and processing of blood samples. Both research-oriented field studies and routine clinical care may benefit from application of these techniques in resource-limited settings.     

Lower serum viral loads in young patients with hepatitis-B-virus-related hepatocellular carcinoma

Advanced age and high hepatitis B virus (HBV) DNA level are risk factors associated with the development of HBV-related hepatocellular carcinoma (HCC). However, little is known about the role of viral load in the carcinogenesis of HCC in young people. A total of 183 HBV-related HCC patients and 202 HBV carriers were therefore enrolled to compare serum viral loads in young (40 years of age) age groups. Other factors associated with the development of HCC were also analysed. The results showed that serum alanine aminotransferase (38.7 +/- 24.1 vs 58.4 +/- 65.4 IU/L, P = 0.006) and HBV DNA levels (log(10) titre: 4.20 +/- 1.33 vs 4.80 +/- 1.39, P = 0.053) were lower in young HCC patients than in old HCC patients. There was a positive correlation between age and serum HBV DNA level in HCC patients but a negative correlation in HBV carriers. Young HCC patients with HBV genotype B infection had higher viral loads than those with genotype C infection (log(10) titre: 4.79 +/- 1.34 vs 3.27 +/- 0.60, P = 0.001). By multivariate logistic regression analyses, high serum HBV DNA level was associated with the development of HCC in old patients [odds ratio (OR) 1.584, 95% confidence interval (CI) 1.075-2.333] rather than in young patients (OR 0.848, 95% CI 0.645-1.116). In conclusion, viral factors in association with the development of HBV-related HCC in young patients may be different from their old counterparts. The complicated interplay between host and virus could be responsible for the emergence and aggressive outcome of early-onset HCC.