Prognostic impact of hepatitis B virus infection in patients with primary cervical cancer.

BACKGROUND: Hepatitis B virus (HBV) infection has been associated with an increased risk of a few malignancies. However, the prognostic impact of HBV infection remains unclear in cervical cancer. OBJECTIVE: To explore the association between HBV infection and survival outcomes of patients with primary cervical cancer, using overall survival (OS) and disease-free survival (DFS) as primary endpoints. METHODS: This analysis was performed retrospectively with newly diagnosed cervical cancer patients admitted to the Department of Gynecologic Oncology at the Sun Yat-sen Memorial Hospital of Sun Yat-sen University from June 2013 to October 2019, who were enrolled and followed up. The Kaplan-Meier method and Cox proportional hazard analysis were used to examine the performance of HBV infection in predicting OS and DFS. RESULTS: Patients were followed up for a median of 37.17 months (95% CI, 34.69-39.65). Among the 695 patients, 87 (12.5%) were serologically positive for hepatitis B surface antigen (HBsAg), and 276 (39.7%) had a prior history of HBV infection. There was no significant difference between HBsAg-positive group and HBsAg-negative patients concerning OS or DFS. Multivariate analysis showed prior HBV infection was an independent favorable prognosticator for OS (HR, 0.335; 95% CI, 0.153-0.0.734; p = 0.006) and DFS (HR, 0.398; 95% CI, 0.208-0.691; p = 0.002). CONCLUSION: We provide the first clinical evidence that suggests prior HBV infection as an independent favorable prognostic factor for patients with primary cervical cancer.

Overweight with HBV infection limited the efficacy of TACE in hepatocellular carcinoma by inhibiting the upregulated HMGB1.

BACKGROUND: Transarterial chemoembolization (TACE) is an effective treatment for patients with hepatocellular carcinoma (HCC). However, the impact of hepatitis B viral (HBV) infection and body mass index (BMI) on TACE is controversial. The present study aimed to compare the influence of HBV and high BMI on TACE outcomes in advanced HCC. METHODS: Based on HBV infection history and BMI, patients were assigned to different subgroups. Blood samples were collected and analyzed by an enzyme-linked immunosorbent assay (ELISA) kit. The primary endpoint was progression-free survival (PFS) and the overall survival (OS) in the population. RESULTS: Compared to overweight combined HBV patients who received TACE, people with normal weight or no viral infection had significantly better OS and PFS. Sex, age, portal vein tumor thrombus, BCLC, ECOG, and tumor diameter are the main risk factors affecting PFS and OS. Except for the postoperative fever, no significant difference was detected in adverse reactions. Irrespective of TACE, the average expression of HMGB1 in hepatitis or obesity patients was higher than that in normal individuals and did not show upregulation after TACE. Patients without overweight or HBV infection had a low expression of serum HMGB1 that was substantially upregulated after TACE. CONCLUSIONS: In this study, overweight combined HBV infection patients had shorter PFS and OS than other HCC patients. Thus, HBV and BMI maybe two factors affecting the efficacy of TACE via upregulated HMGB1.

Adoption of Euvax-B vaccine in Nineveh

Hepatitis B infection is one of the most important health problems around the world. The high mortality rate of the hepatitis B encouraged research that led to the finding of an effective vaccine against it. The aim of the present study was to find out the use of the Euvax-B vaccine in sectors of Nineveh province. According to the results obtained in this study, in the next five years, the vaccination coverage for the second and third doses needs to improve(AU)

La infección por hepatitis B es uno de los más importantes problemas de salud del mundo. La alta tasa de mortalidad de la hepatitis B impulsó las investigaciones que llevaron a encontrar una vacuna eficaz contra la misma. El objetivo del presente estudio fue conocer el uso de la vacuna Euvax-B en sectores de la provincia de Nínive. De acuerdo con los resultados obtenidos, en los próximos cinco años, se debe incrementar la cobertura de inmunización de la segunda y tercera dosis de la vacuna(AU)

Everolimus Related Fulminant Hepatitis in Pancreatic Neuroendocrine Tumor With Liver Metastases: A Case Report and Literature Review.

Background: Everolimus, an immunosuppressant, is approved for the treatment of advanced renal cell carcinoma, metastatic hormone receptor-positive breast cancer, and pancreatic neuroendocrine tumors (P-NETs) but has been reported to be related to hepatitis B reactivation. Here, we present the first case of fatal fulminant hepatitis B reactivation in a man with P-NET accompanied by multiple liver metastases who received everolimus and octreotide long-acting repeatable (LAR). Case Presentation: A 45-year-old male had a history of chronic hepatitis B infection. He was found to have a complicated liver cyst incidentally, and then he underwent biopsy, which disclosed a grade 2 neuroendocrine tumor (NET). Subsequent MRI of the abdomen and PET revealed a solid mass at the pancreatic tail with numerous liver tumors favoring metastases and peripancreatic lymph node metastases. Transarterial chemoembolization (TACE) of the right lobe of the liver was performed, and he started to take 5 mg everolimus twice a day and 20 mg octreotide LAR every month 8 days after the 1st TACE. No hepatitis B virus (HBV) prophylaxis treatment was administered. He then underwent laparoscopic distal pancreatectomy and splenectomy three and half months after the initial treatment of everolimus. He continued everolimus 5 mg twice a day and octreotide 20 mg every month after the operation. Three months later, hepatic failure occurred due to acute hepatitis B flare-up-related fulminant hepatic failure since other possible causes of hepatic failure were excluded. Five days after hepatic failure presented, hepatic failure was apparent, and pulseless ventricular tachycardia occurred. The patient expired after failed resuscitation. Conclusion: A literature review of everolimus-related hepatitis B reactivation was conducted. In P-NET patients with chronic hepatitis B who will undergo everolimus treatment, HBV prophylaxis should be considered since fatal hepatitis B reactivation might occur under rare conditions.

Serum lactate level predicts 6-months mortality in patients with hepatitis B virus-related decompensated cirrhosis: a retrospective study.

The prediction of prognosis is an important part of management in hepatitis B virus (HBV)-related decompensated cirrhosis patients with high long-term mortality. Lactate is a known predictor of outcome in critically ill patients. The aim of this study was to assess the prognostic value of lactate in HBV-related decompensated cirrhosis patients. We performed a single-centre, observational, retrospective study of 405 HBV-related decompensated cirrhosis patients. Individuals were evaluated within 24 h after admission and the primary outcome was evaluated at 6-months. Multivariable analyses were used to determine whether lactate was independently associated with the prognosis of HBV-related decompensated cirrhosis patients. The area under the ROC (AUROC) was calculated to assess the predictive accuracy compared with existing scores. Serum lactate level was significantly higher in non-surviving patients than in surviving patients. Multivariable analyses demonstrated that lactate was an independent risk factor of 6-months mortality (odds ratio: 2.076, P < 0.001). Receiver operating characteristic (ROC) curves were drawn to evaluate the discriminative ability of lactate for 6-months mortality (AUROC: 0.716, P < 0.001). Based on our patient cohort, the new scores (Model For End-Stage Liver Disease (MELD) + lactate score, Child-Pugh + lactate score) had good accuracy for predicting 6-months mortality (AUROC = 0.769, P < 0.001; AUROC = 0.766, P < 0.001). Additionally, the performance of the new scores was superior to those of existing scores (all P < 0.001). Serum lactate at admission may be useful for predicting 6-months mortality in HBV-related decompensated cirrhosis patients, and the predictive value of the MELD score and Child-Pugh score was improved by adjusting lactate. Serum lactate should be part of the rapid diagnosis and initiation of therapy to improve clinical outcome.

Estimates of Cancer Mortality Attributable to Carcinogenic Infections in Italy.

Several infectious agents are ascertained causes of cancer, but the burden of cancer mortality attributable to carcinogenic infections in Italy is still unknown. To tackle this issue, we calculated the rate and regional distribution of cancer deaths due to infections sustained by seven pathogens ranked as group 1 carcinogenic agents in humans by the International Agency for Research on Cancer. Population attributable fractions related to these agents were applied to annual statistics of cancer deaths coded according to the 10th International Classification of Diseases. The estimated burden of cancer mortality attributable to carcinogenic infections in Italy during the period 2011-2015 was 8.7% of all cancer deaths registered yearly, on average. Approximately 60% of deaths occurred in men, and almost the whole burden was due to four infectious agents (Helicobacter pylori, hepatitis C virus, high-risk human papillomavirus, and hepatitis B virus). The analysis of regional distribution showed a higher number of infection-related cancer deaths in the northern regions, where the estimates reached 30 (Liguria) and 28 (Friuli Venezia Giulia) deaths per 100,000 inhabitants in 2015. Since one-twelfth of cancer deaths were attributable to these modifiable risk factors, the implementation of appropriate prevention and treatment interventions may help to reduce the impact of these infections on cancer mortality.

Mortality trend due to Hepatitis B and C in the city of São Paulo, 2002-2016.

OBJECTIVE: To describe mortality due to hepatitis B and C as underlying cause in the municipality of São Paulo, verifying the trend of these rates, and to assess the association of these diseases with others, from 2002 to 2016. METHODS: This is a time series study on mortality due to hepatitis B and C according to sex, with data from the Sistema de Informação de Mortalidade (SIM - Mortality Information Sistem). Prais Winsten regression was used in rate trend analysis. RESULTS: The findings of this study showed a trend of decline of mortality from hepatitis B and C in recent years, particularly among males. These infections were important associated causes of liver cell carcinoma and HIV. The proportion of deaths under 70 years of age stands out. CONCLUSIONS: The study provides a baseline for research on mortality trend and the impact of interventions, given the history of expanded detection and supply of treatments, including the most recent antivirals in Brazil, since 2015.

Depressive symptoms and risk of liver-related mortality in individuals with hepatitis B virus infection: a cohort study.

The impact of depression on the risk of liver-related mortality in individuals with hepatitis B virus (HBV) infection remains unclear. We examined the association between depression, HBV infection, and liver-related mortality. A total of 342,998 Korean adults who underwent health examinations were followed for up to 7.8 years. Depressive symptoms were defined as a Center for Epidemiologic Studies-Depression score ≥ 16. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). During 1,836,508 person-years of follow-up, 74 liver-related deaths and 54 liver cancer deaths were identified (liver-related mortality rate of 4.0 per 105 person-years and liver cancer mortality rate of 2.9 per 105 person-years). Subjects with depressive symptoms had an increased risk of liver-related mortality with a corresponding multivariable aHR of 2.00 (95% CI 1.10-3.63) compared to those without depressive symptoms. This association was more evident in HBsAg-positive participants with a corresponding multivariable aHR of 4.22 (95% CI 1.81-9.88) than HBsAg-negative participants (P for interaction by HBsAg positivity = 0.036). A similar pattern was observed in relation to liver cancer mortality. In this large cohort, depressive symptoms were associated with an increased risk of liver-related mortality, with a stronger association in HBsAg-positive individuals.

Mortality from liver diseases attributable to hepatitis B and C in the EU/EEA - descriptive analysis and estimation of 2015 baseline.

Background: WHO has set target to reduce mortality attributable to hepatitis B (HBV) and hepatitis C (HCV) by 65% by 2030, with 2015 as baseline. We aimed to describe the European Union/European Economic Area (EU/EEA) baseline mortality from liver diseases, as defined by WHO Core-10 indicator through ICD-10 codes, and estimate mortality attributable to HBV and HCV.Methods: Age-standardised mortality rates per 100,000 for hepatocellular carcinoma (HCC, ICD-10 C22.0), chronic liver disease (CLD, ICD-10 K72-K75) and chronic viral hepatitis B and C (CHB/CHC, ICD-10 B18.1-B18.3) were calculated by gender, age-group and country using 2015 Eurostat data. Because aetiology fraction (AF) estimates were lacking for HCC and CLD as defined by C10, number of deaths in EU/EEA countries in 2015 from liver cancer (ICD-10 C22) and 'cirrhosis and other chronic liver diseases' (ICD-10 B18-B18.9, I85-I85.9, I98.2, K70-K70.3, K71.7, K74-K74.9, K75.2, K75.4-K76.2, K76.4-K76.9 and K77.8) were adjusted by corresponding AF estimates from Global Burden of Disease publications.Results: In 2015, there were wide variations across countries in mortality rates from HCC, CLD and CHB/CHC. A 2015 mortality baseline of 63,927 deaths attributable to HBV and HCV is proposed, that includes 55% of liver cancer and 45% of 'cirrhosis and other chronic liver diseases' deaths.Conclusions: The HBV and HCV attributable mortality in the EU/EEA is high. Greater efforts are needed to identify HBV and HCV infections at an early stage and link cases to care to reduce mortality from liver diseases. Country-specific AF estimates are needed to accurately estimate HBV, HCV associated mortality.

Clinical Patterns and Outcome of Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease.

Background: Nonalcoholic fatty liver disease (NAFLD) may develop into liver cirrhosis and hepatocellular carcinoma (HCC). The aim of this study was to compare the clinical patterns and survival outcomes of NAFLD-related HCC patients and those of alcoholic liver disease (ALD)-related or hepatitis B virus (HBV)-related HCC patients. Methods: A total of 622 HCC patients with associated NAFLD (n = 56), ALD (n = 173), or HBV infection (n = 393) were enrolled. The clinical characteristics and survival were analyzed according to the underlying liver diseases. Results: NAFLD-related HCC patients were more commonly older women and had more metabolic risk factors but were less likely to have cirrhosis and ascites, compared to ALD-related or HBV-related HCC patients. NAFLD-related HCC more often had an infiltrative pattern (P=0.047), a larger tumor (P=0.001), more macrovascular invasion (P=0.022), and exceeded the Milan criteria (P=0.001), but was less frequently diagnosed during tumor surveillance (P=0.025). Survival analysis did not show any difference among NAFLD-related, ALD-related, and HBV-related HCC patients. Furthermore, propensity score matching analysis did not reveal a significant difference in the median survival between the different groups (NAFLD vs. ALD, 14.0 months [95% confidence interval (CI), 2.0-26.0] vs. 13.0 months [95% CI, 0-26.3]; P=0.667, NAFLD vs. HBV, 14.0 months [95% CI, 2.0-26.0] vs. 12.0 months [95% CI, 4.3-17.8]; P=0.573). Conclusions: NAFLD-related HCCs were more often detected at an advanced stage with infiltrative patterns, although they showed no significant difference in survival compared to ALD-related or HBV-related HCCs. A future prospective research should be focused on identifying NAFLD patients who require strict surveillance in order to early detect and timely treat HCC.

Identification of a Novel Eight-lncRNA Prognostic Signature for HBV-HCC and Analysis of Their Functions Based on Coexpression and ceRNA Networks.

Studies have demonstrated the prognosis potential of long noncoding RNAs (lncRNAs) for hepatocellular carcinoma (HCC), but specific lncRNAs for hepatitis B virus- (HBV-) related HCC have rarely been reported. This study was aimed at identifying a lncRNA prognostic signature for HBV-HCC and exploring their underlying functions. The sequencing dataset was collected from The Cancer Genome Atlas database as the training set, while the microarray dataset was obtained from the European Bioinformatics Institute database (E-TABM-36) as the validation set. Univariate and multivariate Cox regression analyses identified that eight lncRNAs (TSPEAR-AS1, LINC00511, LINC01136, MKLN1-AS, LINC00506, KRTAP5-AS1, ZNF252P-AS1, and THUMPD3-AS1) were significantly associated with overall survival (OS). These eight lncRNAs were used to construct a risk score model. The Kaplan-Meier survival curve results showed that this risk score can significantly differentiate the OS between the high-risk group and the low-risk group. Receiver operating characteristic curve analysis demonstrated that this risk score exhibited good prediction effectiveness (area under the curve (AUC) = 0.990 for the training set; AUC = 0.903 for the validation set). Furthermore, this lncRNA risk score was identified as an independent prognostic factor in the multivariate analysis after adjusting other clinical characteristics. The crucial coexpression (LINC00511-CABYR, THUMPD3-AS1-TRIP13, LINC01136-SFN, LINC00506-ANLN, and KRTAP5-AS1/TSPEAR-AS1/MKLN1-AS/ZNF252P-AS1-MC1R) or competing endogenous RNA (THUMPD3-AS1-hsa-miR-450a-TRIP13) interaction axes were identified to reveal the possible functions of lncRNAs. These genes were enriched into cell cycle-related biological processes or pathways. In conclusion, our study identified a novel eight-lncRNA prognosis signature for HBV-HCC patients and these lncRNAs may be potential therapeutic targets.

Changing indications for liver transplant: slow decline of hepatitis viruses in Italy.

Background: The indications to LT are changing rapidly in Europe and the U.S. mainly due to the extensive use of direct-acting antiviral agents (DAA) against HCV. Italy was an endemic area for viral hepatitis.Methods: The study reviewed liver transplant registry of a leading Italian centre from the year 2014 (the year before the extensive use of DAA in Italy) to December 2018, with the scope of recording trends in indications. The indications were categorised as: HCV; HBV ± HDV; alcohol-dependent liver disease (ALD); NASH; mescellaneous. Transplants for decompensation or hepatocellular carcinoma were analysed separately. The data were analysed using standard statistical methods.Results: During the study period 463 LTs were accomplished. For the scope of the present study second transplants and transplant in patients <18 years were eliminated; in all, 397 patients were analysed. Overall, HCV infection was the main aetiological factor leading to transplant (139/397, 35%) followed by alcohol use (20.9%), HBV ± HDV (15.8%) and NASH (12.8%). In the decompensation group HCV decreased from 41.9% in 2014 to 14.3% in 2018 while alcohol increased (p < .001); in the HCC group, HCV decreased from 52.6% to 34% and alcohol and NASH increased; the number and proportion of HBV infections remained stable over time, with a 56% prevalence of HDV among decompensated patients.Conclusion: LT landscape is rapidly evolving; hepatitis virus infections still maintain a remarkable proportion among the indications for LT in an area that reached in the past high endemic levels for hepatitis C and B.

Temporal Trends in the Epidemiology of HIV in Turkey.

OBJECTIVE: The aim of this study was to analyze the temporal trends of HIV epidemiology in Turkey from 2011 to 2016. METHODS: Thirty-four teams from 28 centers at 17 different cities participated in this retrospective study. Participating centers were asked to complete a structured form containing questions about epidemiologic, demographic and clinical characteristics of patients presented with new HIV diagnosis between 2011 and 2016. Demographic data from all centers (complete or partial) were included in the analyses. For the cascade of care analysis, 15 centers that provided full data from 2011 to 2016 were included. Overall and annual distributions of the data were calculated as percentages and the Chi square test was used to determine temporal changes. RESULTS: A total of 2,953 patients between 2011 and 2016 were included. Overall male to female ratio was 5:1 with a significant increase in the number of male cases from 2011 to 2016 (p<0.001). The highest prevalence was among those aged 25-34 years followed by the 35-44 age bracket. The most common reason for HIV testing was illness (35%). While the frequency of sex among men who have sex with men increased from 16% to 30.6% (p<0.001) over the study period, heterosexual intercourse (53%) was found to be the most common transmission route. Overall, 29% of the cases presented with a CD4 count of >500 cells/mm3 while 46.7% presented with a CD4 T cell count of <350 cells/mm3. Among newly diagnosed cases, 79% were retained in care, and all such cases initiated ART with 73% achieving viral suppression after six months of antiretroviral therapy. CONCLUSION: The epidemiologic profile of HIV infected individuals is changing rapidly in Turkey with an increasing trend in the number of newly diagnosed people disclosing themselves as MSM. New diagnoses were mostly at a young age. The late diagnosis was found to be a challenging issue. Despite the unavailability of data for the first 90, Turkey is close to the last two steps of 90-90-90 targets.

Hepatitis B virus among hematopoietic stem cell transplant recipients: Antiviral impact in seroconversion, engraftment, and mortality in a Latin American center.

BACKGROUND: Hepatitis B virus (HBV) infection is a worldwide concern with a broad distribution. In immunosuppressed populations, such as solid organ and hematopoietic stem cell transplant (HSCT) recipients, it can reactivate leading to acute hepatic failure. Different risk factors are known for higher rates of reactivation, and entecavir, tenofovir, and lamivudine are often used for prophylaxis and treatment. However, data regarding the impact of antiviral drugs in neutrophil and platelet engraftment are still unknown and concern the management of viral hepatitis post-HSCT. METHODS: We performed a single-center, retrospective, observational study reviewing medical records of patients referred for hematopoietic stem cell transplant from 2010 to 2017, which were also HBV infected, aiming to describe outcomes related to antiviral treatment and also the impact on platelet and neutrophil recovery after transplant. A secondary goal consisted of analyzing the impact of HBV infection in early and late mortality post-HSCT. The study included patients with positive blood bank screening for hepatitis B infection (HBsAg, Anti-HBc or HBV-NAT), confirmed later on by a laboratory routine serology. RESULTS: A total of 1132 hematopoietic stem cell recipients were assessed between 2010 and 2017. Eighty-six patients were confirmed to have HBV infection, of which six were HBsAg-positive, 20 were isolated anti-HBc-positive, and 60 had resolved infection (anti-HBc-positive and anti-HBs-positive). With regard to prophylaxis, 19 patients underwent HSCT on HBV antiviral therapy or prophylaxis: two were HBeAg-positive, three were HBeAg-negative and HBV-DNA was only detectable in three of them. Moreover, one patient had an occult HBV infection. Regarding therapy, 9 patients were on entecavir, 6 patients on lamivudine, two on tenofovir, and two of them on a combination of tenofovir + lamivudine due to HIV co-infection. Reverse seroconversion was not identified in any patients receiving antiviral therapy or prophylaxis, but it was detected in one patient with occult hepatitis B and another with resolved infection. No severe side effects led to therapy discontinuation in the treated group, which also did not have any significant delay in neutrophil or platelet engraftment when compared to patients without antiviral therapy. In addition, the only factors associated with increased mortality were transplant onset after 50 years, allogeneic transplant and myeloablative conditioning regimens. Interestingly, the presence of HBsAg or detectable HBV-DNA was not related to worse outcomes, neither the use of rituximab. In multivariate analysis, the use of antiviral therapy, the occurrence of graft-versus-host disease or CMV reactivation also was not linked to increased mortality. CONCLUSIONS: To sum up, HBV serology, ALT, and HBV-DNA monitoring are essential to detect hepatic flares earlier, even in populations with chronic inactive hepatitis, due to the possibility of later seroconversion. HBV infection was not related to increased 2-year mortality post-transplant. Antiviral prophylaxis did not cause any important clinical or laboratory side effects that could demand discontinuation, and its use was not associated with later neutrophil and platelet engraftments.

Toxicity and Survival of Hepatocellular Carcinoma Patients with Hepatitis B Infection Treated with Yttrium-90 Radioembolization: An Updated 15-Year Study.

PURPOSE: To evaluate the toxicity and survival of hepatocellular carcinoma (HCC) secondary to hepatitis B virus (HBV) infection treated with yttrium-90 transarterial radioembolization (TARE) over a 15-year period. MATERIALS AND METHODS: This study retrospectively analyzed 93 consecutive patients with HBV HCC-all derived from an original cohort of 1,000 patients-who were treated with TARE via standard radiation segmentectomy/lobectomy between December 2003 and December 2018. This group comprised 80 males and 13 females, with 79 having only HBV and 14 having additional liver comorbidities. Toxicity grades were determined by Common Terminology Criteria for Adverse Events, version 5.0. Overall survival (OS) was reported using intention-to-treat (ITT), censored, or competing risk. Univariate/multivariate analyses were used to evaluate predictors of OS. RESULTS: Posttreatment grade 3/4 toxicities included albumin (1.1%), bilirubin (4.3%), aspartate transaminase (6.5%), and alanine transaminase (3.2%). Median censored OS was 16.9 months (95% confidence interval [CI], 11.8-23.5): 17.5 months (95% CI, 11.5-86.9) for Child-Pugh (CP) A and 14.5 months (95% CI, 5.2-22.5) for CP B; not reached, 16.9 months (95% CI, 11.2-68.7), and 11.5 months (95% CI, 8.6-17.5) for Barcelona Clinic Liver Cancer (BCLC) A, B, and C, respectively. Multivariate analysis revealed albumin, alpha-fetoprotein, and portal vein thrombosis as independent predictors of ITT OS and albumin and tumor size as predictors when curative therapy was assigned as a competing risk. CONCLUSIONS: This retrospective study showed that TARE therapy resulted in minimal toxicity in patients with HBV-derived HCC. Patients with CP A or BCLC A disease had superior survival outcomes compared to patients with CP B and BCLC B/C disease. These findings suggest that TARE is a viable treatment option for certain patient groups with HCC tumors secondary to HBV infection.

Costs of viral hepatitis B in the Republic of Korea, 2002-2015.

The Republic of Korea has a high prevalence of hepatitis B virus (HBV) infection, and the policies concerning costly antiviral medication have been revised recently. However, in the past 10 years, no related research on costs has been conducted. The objective of this study was to estimate the economic burden of viral hepatitis B and determine the trend of changes in its costs between 2002 and 2015. Claims data from the National Health Insurance Service were used. To identify viral hepatitis B cases, the ICD-10th code B16, B17.0, B18.0 and B18.1 were used based on a primary diagnosis. This study was conducted from a societal perspective regarding both direct and indirect costs. Annual costs were adjusted for inflation by calculations based on the 2015 costs. The number of patients with viral hepatitis B increased from 213 758 in 2002 to 342 672 in 2015. The total socio-economic costs increased from 127.1 million USD in 2002 to 459.1 million USD in 2015, mainly due to the increase in pharmaceutical costs, which accounted for the largest proportion of total costs since 2009-220.5 million USD in 2015, which was ~15 times higher than that in 2002. The healthcare costs for viral hepatitis B accounted for 0.13% of the national health expenditure in 2002, increasing to 0.31% in 2015. The economic burden of viral hepatitis B has increased in the Republic of Korea. It is therefore essential to reduce the healthcare costs of HBV infection by establishing an effective management policy.

Mortality trend due to Hepatitis B and C in the city of São Paulo, 2002-2016 / Tendência de mortalidade por hepatites B e C no município de São Paulo, 2002-2016

ABSTRACT OBJECTIVE: To describe mortality due to hepatitis B and C as underlying cause in the municipality of São Paulo, verifying the trend of these rates, and to assess the association of these diseases with others, from 2002 to 2016. METHODS: This is a time series study on mortality due to hepatitis B and C according to sex, with data from the Sistema de Informação de Mortalidade (SIM - Mortality Information Sistem). Prais Winsten regression was used in rate trend analysis. RESULTS: The findings of this study showed a trend of decline of mortality from hepatitis B and C in recent years, particularly among males. These infections were important associated causes of liver cell carcinoma and HIV. The proportion of deaths under 70 years of age stands out. CONCLUSIONS: The study provides a baseline for research on mortality trend and the impact of interventions, given the history of expanded detection and supply of treatments, including the most recent antivirals in Brazil, since 2015.

RESUMO OBJETIVO: Descrever a mortalidade por hepatites B e C como causa básica no município de São Paulo, verificando a tendência dessas taxas, e avaliar a associação dessas doenças a outras no período de 2002 a 2016. MÉTODOS: Trata-se de um estudo de série temporal sobre mortalidade por hepatites B e C segundo sexo, com dados do Sistema de Informação de Mortalidade. A regressão de Prais Winsten foi usada na análise de tendência das taxas. RESULTADOS: Os achados do presente estudo mostraram tendência de declínio da mortalidade por hepatites B e C nos últimos anos, particularmente entre pessoas do sexo masculino. Essas infecções foram causas associadas importantes ao carcinoma de células hepáticas e ao HIV. Destaca-se a proporção de óbitos com menos de 70 anos de idade. CONCLUSÕES: O estudo fornece uma linha de base para pesquisas de tendência de mortalidade e de impacto de intervenções, visto o histórico de ampliação da detecção e oferta de tratamentos, incluindo os mais recentes antivirais no Brasil, desde 2015.

PD-1+ TIGIT+ CD8+ T cells are associated with pathogenesis and progression of patients with hepatitis B virus-related hepatocellular carcinoma.

Hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) is usually considered an inflammation-related cancer associated with chronic inflammation triggered by exposure to HBV and tumor antigens. T-cell exhaustion is implicated in immunosuppression of chronic infections and tumors. Although immunotherapies that enhance immune responses by targeting programmed cell death-1(PD-1)/PD-L1 are being applied to malignancies, these treatments have shown limited response rates, suggesting that additional inhibitory receptors are also involved in T-cell exhaustion and tumor outcome. Here, we analyzed peripheral blood samples and found that coexpression of PD-1 and T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) was significantly upregulated on CD4+ and CD8+ T cells from patients with HBV-HCC compared with those from patients with chronic HBV or HBV-liver cirrhosis. Additionally, PD-1+ TIGIT+ CD8+ T-cell populations were elevated in patients with advanced stage and progressed HBV-HCC. Importantly, PD-1+ TIGIT+ CD8+ T-cell populations were negatively correlated with overall survival rate and progression-free survival rates. Moreover, we showed that PD-1+ TIGIT+ CD8+ T cells exhibit features of exhausted T cells, as manifested by excessive activation, high expression of other inhibitory receptors, high susceptibility to apoptosis, decreased capacity for cytokine secretion, and patterns of transcription factor expression consistent with exhaustion. In conclusion, PD-1+ TIGIT+ CD8+ T-cell populations are associated with accelerated disease progression and poor outcomes in HBV-HCC, which might not only have important clinical implications for prognosis but also provide a rationale for new targets in immunotherapy.

Incidence of hospitalization for infection among patients with hepatitis B or C virus infection without cirrhosis in Taiwan: A cohort study.

BACKGROUND: Infection is a major complication in liver cirrhosis and causes major morbidity and mortality. However, the incidence and mortality related to these conditions in patients infected with hepatitis C virus (HCV) are unclear, as is whether antiviral therapy could change their infection risk. METHODS AND FINDINGS: In this community-based cohort study, a total of 115,336 adults (mean age 52.2 years; 35.6% men) without cirrhosis participating in the New Taipei City Health Screening in 2005-2008 were classified as having noncirrhotic HCV (NC-HCV) (n = 2,839), noncirrhotic hepatitis B virus (NC-HBV) (n = 8,316), or no HBV or HCV infection (NBNC) (n = 104,181). Participants were followed to their first hospitalization for infection or death after data linkage with the Taiwan National Health Insurance Research Database (NHIRD) and Death Registry. A Cox proportional hazard regression model, adjusted for age, sex, body mass index (BMI), smoking, alcohol consumption, education level, diabetes, renal function, systemic steroids, and history of hospitalization, was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and individual sites of infection and infection-related mortality. The reference group was NBNC participants with normal to mildly elevated alanine aminotransferase (ALT) (<1.5 times upper normal limit [UNL]) levels. To further address the impact of antiviral treatment on infection risk, we conducted analyses of data from the nationwide NHIRD and compared the risks for hospitalization because of infections and infection-related deaths between patients with HCV who received antiviral therapy (n = 20,264) and those who remained untreated (n = 104,360). During a median 8.2-year follow-up, the incidence of hospitalization for infection was substantially higher in NC-HCV patients. Compared to the reference group, NC-HCV was associated with a significantly higher risk for hospitalization because of overall infections (adjusted HR: 1.22; 95% CI: 1.12-1.33), but we observed no increased risk for patients in the NC-HBV (adjusted HR: 0.94; 95% CI: 0.88-1.01) or NBNC group with moderate to markedly elevated ALT levels (adjusted HR: 1.03; 95% CI: 0.93-1.14). For specific sites of infection, the NC-HCV group had increased risks for septicemia and lower respiratory tract, reproductive, and urinary tract infections. We noted no increased risk for infection-related death among patients with NC-HCV. Patients with HCV who received antiviral therapy had significantly reduced infection-related hospitalization and death risks (adjusted HR: 0.79; 95% CI: 0.73-0.84 for infection-related hospitalization and adjusted HR: 0.08; 95% CI: 0.04-0.16 for infection-related deaths). Study limitations include the exclusion of patients with cirrhosis from the cohort, the possibility of unmeasured confounding, and the lack of information on direct-acting antiviral agents (DAAs). CONCLUSIONS: In this study, patients with NC-HCV were at increased risk for hospitalization for infection, while no increased risk was observed for NC-HBV-infected patients.