Analysis of clinical characteristics and risk factors of hepatic fibrosis in children with chronic hepatitis B combined with metabolic-related fatty liver disease / 中华肝脏病杂志

Objective: To compare the clinical and pathological features of children with chronic viral hepatitis B combined with metabolic-associated fatty liver disease (CHB-MAFLD) and chronic viral hepatitis B alone (CHB alone), and to further explore the effect of MAFLD on the progression of hepatic fibrosis in CHB. Methods: 701 initially treated CHB children confirmed by liver biopsy admitted to the Fifth Medical Center of the PLA General Hospital from January 2010 to December 2021 were collected continuously. They were divided into CHB-MAFLD and CHB-alone groups according to whether they were combined with MAFLD. A retrospective case-control study was conducted. CHB-MAFLD was used as the case group, and 1:2 propensity score matching was performed with the CHB alone group according to age and gender, including 56 cases in the CHB-MAFLD group and 112 cases in the CHB alone group. The body mass index (BMI), metabolic complications, laboratory indicators, and pathological characteristics of liver tissue were compared between the two groups. The related factors affecting liver disease progression in CHB were analyzed by a binary logistic regression model. The measurement data between groups were compared using the t-test and rank sum test. The χ (2) test was used for the comparison of categorical data between groups. Results: Alanine aminotransferase (ALT, P = 0.032) and aspartate aminotransferase (AST, P = 0.003) levels were lower in the CHB-MAFLD group than those in the CHB alone group, while BMI (P < 0.001), triglyceride (TG, P < 0.001), total cholesterol (P = 0.016) and the incidence of metabolic syndrome (P < 0.001) were higher in the CHB alone group. There were no statistically significant differences in HBsAg quantification or HBV DNA load between the two groups (P > 0.05). Histologically, the proportion of significant liver fibrosis (S2-S4) was higher in the CHB-MAFLD group than that in the CHB alone group (67.9% vs. 49.1%, χ (2) = 5.311, P = 0.021). Multivariate regression results showed that BMI (OR = 1.258, 95% CI: 1.145 ~ 1.381, P = 0.001) and TG (OR = 12.334, 95% CI: 3.973 ~ 38.286, P < 0.001) were the risk factors for hepatic steatosis occurrence in children with CHB. MAFLD (OR = 4.104, 95% CI: 1.703 ~ 9.889, P = 0.002), liver inflammation (OR = 3.557, 95% CI: 1.553 ~ 8.144, P = 0.003), and γ-glutamyl transferase (OR = 1.019, 95% CI: 1.001 to 1.038, P = 0.038) were independent risk factors for significant hepatic fibrosis in children with CH. Conclusion: MAFLD occurrence is related to metabolic factors in children with CHB. Additionally, the combination of MAFLD may promote liver fibrosis progression in CHB patients.

Validation of the Brazilian version of the hepatitis B quality of life evaluation instrument - HBQOL, and its application to patients with chronic hepatitis B in Cascavel - PR

Abstract The objective of this study is to validate the specific questionnaire for Hepatitis B HBQOL (Hepatitis B Quality of Life Instrument, version 1.0) for the Brazilian version, in addition to testing its applicability in patients with hepatitis B under treatment and comparing the quality of life between patients using first-line drugs (tenofovir and entecavir). For the validation, the back-translation technique was used in a sample of 47 patients. Factor analysis was performed between the items in each domain of the questionnaire and the internal consistency was calculated using Cronbach's α coefficient. In assessing the applicability of the validated questionnaire, interviews were carried out with 124 patients. Sociodemographic and treatment data were collected to characterize the sample and perform correlation analyzes. The results demonstrate that the Brazilian version of the questionnaire was successfully validated. In the analysis carried out among the 124 patients, the domains psychological well-being and stigma obtained the highest scores in quality of life and the lowest level of education conferred better results in these two domains. The comparison between tenofovir and entecavir showed no significant difference in patients' quality of life. The use of this validated instrument can make therapeutic decisions more rational

LIVER BIOPSY: IMPORTANCE OF SPECIMEN SIZE IN THE DIAGNOSIS AND STAGING OF CHRONIC VIRAL HEPATITIS

Liver biopsy is the gold standard method for the grading and staging of chronic viral hepatitis, but optimal biopsy specimen size remains controversial. The aim of this study was to evaluate the quality of liver specimen (number of portal tracts) and to evaluate the impact of the number of portal tracts in the staging of chronic hepatitis. Material and Methods: 468 liver biopsies from consecutive patients with hepatitis C virus and hepatitis B virus infection from 2009 to 2010 were evaluated. Results: The length of fragment was less than 10 mm in 43 cases (9.3%), between 10 and 14 mm in 114 (24.3%), and ≥ 15 mm in 311 (64.4%); of these, in 39 (8.3%) cases were ≥ 20 mm. The mean representation of portal tracts was 17.6 ± 2.1 (5-40); in specimens ≥ 15 mm the mean portal tract was 13.5 ± 4.7 and in cases ≤ 15 mm was 11.4 ± 5.0 (p = 0.002). Cases with less than 11 portal tracts were associated with F3, and cases with 11 or more portal tracts with F2 (p = 0.001). Conclusion: this study demonstrated the good quality of liver biopsy and a relationship between the macroscopic size of the fragment and the number of portal tracts.

Characteristics of an outpatient chronic hepatitis B virus infection cohort / Caracterização de uma coorte ambulatorial de pacientes com infecção por vírus da hepatite B crônica

ABSTRACT Objective: To characterize a chronic hepatitis B cohort based on initial and follow-up clinical evaluations. Methods: A retrospective and descriptive analysis of clinical and laboratory data from chronic HBsAg adult carriers, without HIV, unexposed to treatment, with at least two outpatient visits, between February 2006 and November 2012. Fisher´s exact test, χ², Wilcoxon, Spearman, multiple comparisons and Kappa tests were applied, the level of significance adopted was 5%, with a 95% confidence interval. Results: 175 patients with mean age of 42.95±12.53 years were included: 93 (53.1%) were men, 152 (86.9%) were negative for hepatitis B e-antigen (HBeAg), 3 (1.7%) had hepatitis C coinfection, 15 (8.6%) had cirrhosis, and 2 (1.1%) had hepatocellular carcinoma. Genotype A predominated. Sixty-six patients (37.7%) had active hepatitis, 6 (3.4%) presented immune tolerance, and 38 (21.7%) were inactive carriers. Exacerbations and/or viral breakthrough were detected in 16 patients (9.1%). In 32 patients (18.3%), hepatitis B virus DNA remained persistently elevated and alanine aminotransferase levels were normal, whereas in 17 (9.7%), there was low hepatitis B virus DNA and alterated alanine aminotransferase. If only initial alanine aminotransferase and hepatitis B virus DNA values were considered, 15 cases of active hepatitis would not have been detected. Advanced fibrosis was more common in HBeAg-positive patients, and it was significantly associated with transaminases, hepatitis B virus DNA, and age. Conclusion: Many patients had active hepatitis, but almost 25%, who were HBeAg non-reactive, were only identified because of combined analyses of the hepatitis B virus DNA and transaminases levels, sometimes associated with histological data, after clinical follow-up. .

RESUMO Objetivo: Caracterizar uma coorte de pacientes com hepatite B crônica, segundo parâmetros iniciais e evolutivos. Métodos: Análise retrospectiva e descritiva dos dados clínicos e laboratoriais de portadores crônicos adultos do HBsAg, sem HIV, virgens de tratamento, com ao menos duas consultas ambulatoriais entre fevereiro de 2006 a novembro de 2012. Empregaram-se os testes exato de Fisher, χ², Wilcoxon, Spearman, Kappa e comparações múltiplas, o nível de significância estatística adotado foi de 5% e intervalo de confiança de 95%. Resultados: Foram incluídos 175 pacientes com média de idade de 42,95±12,53 anos, 93 (53,1%) do sexo masculino, 152 (86,9%) não reagentes para o antígeno e (HBeAg), 3 (1,7%) coinfectados com hepatite C, 15 (8,6%) cirróticos e 2 (1,1%) com carcinoma hepatocelular. Predominou o genótipo A. Constataram-se hepatite ativa em 66 pacientes (37,7%), imunotolerância em 6 (3,4%), estado de portador inativo em 38 (21,7%), exacerbações e/ou escapes virais em 16 (9,1%). Em 32 (18,3%), havia DNA viral persistentemente elevado e alanina aminotransferase normal; em 17 (9,7%), carga viral constantemente baixa e alanina aminotransferase alterada. Se fossem considerados apenas transaminases e DNA viral iniciais, 15 casos de hepatite ativa não teriam sido evidenciados. Fibrose avançada foi mais prevalente em HBeAg reagentes e associou-se direta e significativamente ao DNA do vírus da hepatite, idade e transaminases. Conclusão: Grande parte dos pacientes apresentou hepatite ativa. Porém, aproximadamente um quarto (todos pertencentes ao grupo HBeAg não reagente) foram identificados somente em função da análise conjunta das mensurações sequenciais de DNA do vírus da hepatite e transaminases, por vezes aliada a dados histológicos, após seguimento. .

Whole-genome sequences of influenza A(H3N2) viruses isolated from Brazilian patients with mild illness during the 2014 season

The influenza A(H3N2) virus has circulated worldwide for almost five decades and is the dominant subtype in most seasonal influenza epidemics, as occurred in the 2014 season in South America. In this study we evaluate five whole genome sequences of influenza A(H3N2) viruses detected in patients with mild illness collected from January-March 2014. To sequence the genomes, a new generation sequencing (NGS) protocol was performed using the Ion Torrent PGM platform. In addition to analysing the common genes, haemagglutinin, neuraminidase and matrix, our work also comprised internal genes. This was the first report of a whole genome analysis with Brazilian influenza A(H3N2) samples. Considerable amino acid variability was encountered in all gene segments, demonstrating the importance of studying the internal genes. NGS of whole genomes in this study will facilitate deeper virus characterisation, contributing to the improvement of influenza strain surveillance in Brazil.

Hepatitis B virus genotypes in Southeast Brazil and its relationship with histological features

Data concerning the relationship between hepatitis B virus (HBV) genotypes and liver histology are scarce. The aim of this study was to compare HBV non-B and non-C genotypes according to demographic features, clinical status, HBV-DNA levels and liver histology in Rio de Janeiro. One hundred twenty one consecutive chronic HBV-infected patients were enrolled during two-year period and data were prospectively collected. Sera were tested for HBV genotyping using restriction fragment length polymorphism. Liver biopsy was obtained from patients with either increased alanine aminotransferase (ALT) or HBV-DNA levels. Genotype A was the most common, found in 82 (68%) patients, followed by F in 19 (15%), D in 17 (14%), B in one (1%) and C in two (2%). There was no association between HBV genotypes A, D and F and gender (p = 0.37), age (p = 0.78), race (p = 0.22), mode of infection (p = 0.94), HB "e" antigen status (p = 0.37) and HBV-DNA levels (p = 0.47). The ALT levels were lower in genotype D (75%) compared with A (47%) and F (55%) (p = 0.05). Liver biopsy showed lower inflammation [histological activity index (HAI) = 4] and fibrosis (F) (= 0) scores in genotype D than in genotypes A (HAI = 5, p < 0.001; F = 2, p = 0.008) or F (HAI = 5, p = 0.009; F = 2, p = 0.01). Genotype A was the most prevalent in chronic HBV-infected patients and genotype D patients presented with less intense liver disease.

Epidemiología, evolución y respuesta a tratamiento con diferentes esquemas de la hepatitis B crónica en pacientes pediátricos / Epidemiology, evolution and response to different treatment options of pediatric patients with chronic hepatitis B

La hepatitis B crónica constituye un problema de salud pública a nivel mundial y la población pediátrica no se encuentra excluida de este problema. El objetivo fue evaluar la epidemiología de esta patología en pacientes pediátricos en Venezuela y la respuesta de estos pacientes a las diferentes opciones terapéuticas que disponemos. Se realizó estudio multicéntrico y retrospectivo. Se incluyeron todos los pacientes pediátricos con infección crónica por virus B que consultan a diferentes consultas de Gastroenterología Pediátrica en el país. De 15537 pacientes pediátricos que acudieron a consultas de Gastroenterología pediátricas de diferentes centros hospitalarios encontramos 148 pacientes con hepatitis B crónica dado por persistencia Ags VHB positivo por más de 6 meses que representan el 1% de los pacientes evaluados. De los 148 pacientes 111 (75%) pertenecen al sexo masculino y 37 (25%) al sexo femenino, en edades comprendidas desde 1 año hasta 18 años con promedio de 11,25 años y un tiempo de seguimiento comprendido de entre 3 meses y 14 años con un promedio de 4,45 años. Se evaluaron las formas de transmisión para la adquisición de la infección crónica por VHB entre las que tenemos 65 pacientes (44%) habían tenido patologías oncológicas, 3 (2%) patologías hematológicas, antecedentes intervenciones quirúrgicas 3 (2%), transmisión vertical 11 (7%), transmisión horizontal 4 (3%), insuficiencia renal crónica 2 (1,3%), cardiópatas 1 (0,7%) y se desconoce la causa en 59 (40%). De los 148 pacientes 72 (49%) son portadores activos dado por Ags VHB positivo, Age VHB positivo y ADN VHB positivo. De los 72 pacientes portadores activos 44 (61%) tenían aminotranferasas normales y 28 (39%) tenían aminotranferasas elevadas, 34 (47%) tenían carga viral para VHB mayor de 20000 UI/ ml y 38 (53%) carga viral entre 2000 a 20000 UI/ml. De los 72 pacientes portadores activos se les realizó biopsia hepática a 55 pacientes de los cuales 52 tenían hallazgos de infección...

Chronic hepatitis B represents a major public health problem world wide and pediatric population is not excluded from this reality. We aimed to assess the epidemiology of this disease in pediatric patients in Venezuela and the response of these patients to different treatment options available. A retrospective and multicenter study was conducted. We included all pediatric patients with chronic infection by virus B who were evaluated in different Pediatric Gastroenterology Units all over the the country. Out of 15537 pediatric patients attending Pediatric Gastroenterology Units in different hospitals, 148 resulted with the diagnosis of chronic hepatitis B given by a positive and persistent Ags HBV for more than 6 months. This represented 1% of all patients evaluated. Of all 148 patients, 111 (75%) were male and 37 (25%) female, aged from 1 year up to 18 years (average 11,25 years). The follow-up period ranged from 3 months to 14 years (average 4.45 years). Most frecuent transmission of HBV infection was related to onchological pathologies in 65 patients (44%), hematologic diseases in 3 (2%), surgery 3 (2%), vertical transmission 11 (7%), horizontal transmission 4 (3%), chronic renal insufficiency 2 (1.3%), cardiopathy 1 (0.7%) and unknown cause in 59 (40%). 72 patients (49%) were considered active carriers with positives Ags HBV, Age HBV and HBV DNA. Out of these 72 patients, 44 (61%) had normal aminotranferases and 28 (39%) had high levels of aminotransferases, 34 (47%) had viral load over 20000 UI/ml and 38 (53%) viral load between 2000 and 20000 UI/ml. 55 patients underwent liver biopsy: 52 had findings of chronic HBV infection, 17 (31%) had fibrosis, 1 featured cirrhosis and 3 (2% of the total number of patients) had no liver injury by HBV. This was considered the group of inmunotolerants. 52 patients were treated. 1 patient received Lamivudine with a positive response, 12 patients received monotherapy with Pegylated Interferon (7 patients responded)...

Relation of hepatitis B core antigen expression with histological activity, serum HBeAg, and HBV DNA levels.

Background: Hepatitis B virus (HBV) is a potentially life-threatening liver infection which may progress to liver failure and cirrhosis. Intrahepatic expression patterns of viral antigens detected by immunohistochemistry may have prognostic implications in disease process. Aim: In this study, we aimed to investigate the relationship between the HBV core antigen (HBcAg) expression and histological activity index (HAI), fibrosis, serum hepatitis B e-antigen (HBeAg) status and HBV DNA levels in patients with chronic HBV infection. Materials and Methods: A total of 114 liver biopsies from patients with chronic HBV infection were included in the study. Immunohistochemical expression of HBcAg and its relation with HAI, fibrosis, serum alanine aminotransferase (ALT) levels, HBeAg status and HBV DNA levels were assessed. Results: The presence of nuclear expression of HBcAg did not show any correlations with ALT levels, HAI and fibrosis score. When the groups were categorized according to the HBeAg status, nuclear HBcAg expression was found to be high in HBeAg positive patients. However, HBcAg nuclear expression showed significant correlations with HBV DNA levels and fibrosis scores in HBeAg negative but not HBeAg positive patients. HBV DNA levels were also significantly associated with HAI and fibrosis scores in HBeAg negative patients. Conclusions: Significant differences found between HBeAg positive and negative patients suggest that HBeAg negative disease is different from HBeAg positive disease, and also point outs that in HBeAg negative disease, patients with nuclear HBcAg expression and increased levels of HBV DNA levels are at a higher risk of developing progressive liver disease.

Evaluation of adefovir & lamivudine in chronic hepatitis B: correlation with HBV viral kinetic, hepatic-necro inflammation & fibrosis.

Background & objectives: Chronic hepatitis B is an important cause of morbidity and mortality. We conducted a study comparing the efficacy of adefovir and lamivudine with respect to their impact on serum and hepatic viral DNA clearance, and improvement in hepatic necro-inflammatory score, in naive patients of chronic hepatitis B. Methods: This prospective randomized pilot study was conducted in Lok Nayak Hospital, New Delhi, involving 30 patients of chronic hepatitis B (both e antigen positive and negative); 15 were randomly selected to receive either adefovir or lamivudine for a period of 6 months. Quantification of serum and hepatic HBV DNA levels was done by real time PCR and liver biopsy was done at the beginning and end of 6 months. Results: Serum ALT was elevated to 2 or more times normalized in both the groups. In the adefovir group, two patients became HBeAg negative. In the lamivudine group, one patient became HBeAg negative. After therapy HBV DNA was negative in 26.7 per cent patients from adefovir group and 13.3 per cent patients from lamivudine group. Serum HBV DNA levels were correlated with the hepatic levels before therapy (r=0.843; P<0.001) and after therapy (r=0.713, P<0.001) showing strong correlation. There was a median reduction of 1.92 and 2.06 log copies per ml in serum HBV DNA load after adefovir and lamivudine therapy, respectively. The mean reduction in the histotogy activity index (HAI) score was 2 and 1.53, fibrosis score was 2.33 and 3.06 after adefovir and lamivudine therapy respectively. Interpretation & conclusions: Adefovir and lamivudine treatment caused biochemical and serological improvement when administered for about 6 months with significant reduction in HBV DNA, serum and hepatic viral load without completely clearing the virus from either serum or liver. It also helped in reduction of the necro-inflammatory and fibrosis score of patients with chronic hepatitis B. Our study also showed significant correlation between serum and hepatic HBV DNA levels both before and after therapy. There was not enough evidence to show therapeutic advantage of one drug over the other in any of the parameters measured.

Hepatitis crónica viral / Chronic viral hepatitis

Los Virus Hepatitis B (VHB) y Hepatitis C (VHC) en la actualidad son infecciones frecuentes en el hombre, afectando a una proporción significativa de la población mundial. Estos son causa frecuente de hepatitis aguda y crónica, cirrosis hepática, hepatocarcinoma y trasplante hepático. En 105 últimos años ha habido un gran progreso en el conocimiento de la epidemiología e historia natural de la infección con el VHB y VHC. Además, se han logrado grandes avances en su tratamiento y con numerosas drogas actualmente en evaluación.

Hepatitis B (HBV) and Hepatitis C (HCV) virus are common viral infections, affecting at a large worldwide population. These viruses are frequent cause of acute and chronic hepatitis, cirrhosis, hepatocellular carcinoma and liver transplantation. In the last few years, the knowledge of the epidemiology and natural history of HBV and HCV infections have markedly improved. Furthermore, considerable progress have been achieved in the efficacy of treatment and several new drugs are currently under evaluation.

[Chronic hepatitis B: a study of 15 cases]

The aim of this study is to describe clinical, biological, histological aspects and outcome of children with chronic hepatitis B [CHB], and to analysis treatment modalities. a retrospective study of 15 children with CHB was conducted between January 1992 and December 2003. All patients had HBs Ag> 6 months, fourteen had Hbe Ag. Initial histological examination was performed in eight cases. intrafamilial horizontal transmission was noted in five cases. Fifty three percent of patients presented symptoms: asthenia [57 percent], anorexia [1 case], loss of weight [1 case], digestive disturbance [3 cases], abdominal pain [5 cases]. Cytolysis was noted in eight patients [53, 3 per cent], they had positive Ag Hbe. Liver emzymes were increased in eight cases [53.3%], they had positive Hbe Ag, mean rate of AST was 95.6 UI/I [extremes: 56 -251], mean rate of ALT was 118,8 Ul/l [extremes: 50 - 204]. Four patients had chronic active hepatitis and four had chronic persistent hepatitis. Three patients received I'interferon a; seroclearance was noted in two patients without negativation of HBs Ag. Twelve patients didn't receive any antiviral therapy, liver emzymes were decreased in three patients, seroclearance of HBe Ag was noted in five cases and HBs Ag elimination was noted in only one patient. Chronic hepatitis B is often asymptomatic and transmitted horizontaly. Antiviral therapy must be indicated in children with viral replication and active chronic hepatitis. Large vaccination at birth reduces vertical transmission and prevalence particularly in endemic areas

[Hepatic steatosis in chronic hepatitis B: contributing factors and effect on fibrosis]

To determine factors that contribute to the steatosis's formation in chronic hepatitis B, to evaluate its influence on the development of hepatic fibrosis and to research aim eventual relation to virologic factors in a Tunisian cohort of patients. All patients with chronic hepatitis B confirmed by data of liver biopsy were included in this study, which was enrolled from 1990 to 2006. The studied parameters were: age, gender, body mass index, transaminases, cholesterol, triglycerides. glycaemia and DNA rate, status HBe antigen and the degree of activity and histological fibrosis was estimated according to the score of METAVIR. Fifteen patients [34.1%] among the 44 patients includes in this study had hepatic steatosis; that was mild in 10 patients [66.6%], moderate in 3 cases [20%] and severe in 2 patients [13.4]. The antigen HBe was negative in 27 patients [62.22%.] The mean age of the patients having a steatosis was of 32.33 years versus 27.75 years for those who had no it [p=0.185]. The transaminases rate was superior in patients with steatosis than those without, the difference was not significant. Univariate correlation between predictor variables was studied. Significant predictors to steatosis included body mass index [p=0.011] and cholesterol [p=0.037]. HBe Ag status was not associated with steatosis. Neither activity nor fibrosis was correlated with steatosis. In Tunisian patients, factors contributing to the formation of steatosis during the chronic hepatitis B were the body mass index and the rate of cholesterol. The steatosis did not seem to have an influence on the development of the hepatic fibrosis and seems to be independent on the viral effect

The Degrees of Hepatocyte Cytoplasmic Expression of Hepatitis B Core Antigen correlate with Histologic Activity of Liver Disease in the Young Patients with Chronic Hepatitis B Infection

Subcellular localizaton of HBcAg have been found to be related to the activity of liver disease and HBV replication. The aim of this study was to determine whether the degree of expression of HBcAg in the hepatocyte nucleus and cytoplasm reflects the level of viral replication and histological activity in chronic HBV infection. A total of 102 patients with biopsy proven chronic hepatitis B were included. There was a highly significant correlation between the levels of HBV DNA in serum and the degree of expression of HBcAg in the nucleus for HBeAg-positive(p=0.000) and negative patients(p=0.04). There was a highly significant, correlation between the degrees of expression of HBcAg in hepatocyte cytoplasm and histologic activities (p<0.01) for HBeAg-positive patients. The degrees of expression of HBcAg in the hepatocyte cytoplasm correlated positively with the lobular activities (p<0.01), but not correlated with the portal activity and fibrosis for HBeAg-negative patients. In conclusion, in the young patients with chronic B viral hepatitis, the degree of expression of HBcAg in the hepatocyte nucleus may affect viral load, and the degree of expression of HBcAg in the hepatocyte cytoplasm may affect histologic activities of liver disease.

Secreción de interferon por los linfocitos T periféricos de los portadores crónicos del virus de hepatitis B / Interferon G secretion by the peripheral lymphocyts T of the chronic carries of the hepatitis B virus

Previamente demostramos que los linfocitos T periféricos de los portadores crónicos del VHB activados “in vitro” con fitohemaglutinina (PHA) o con anticuerpos monoclonales anti-CD3 secretan interleucina-2 (IL-2) y expresan receptores para IL-2, IL-6 y para el factor de necrosis tumoral. Investigamos la producción de interferón por células T altamente purificadas (98 por ciento CD3+) de 14 pacientes infectados crónicamente por el VHB. Los linfocitos T se activaron con PHA sola (0.5g/mL) y con PHA añadiendo 100 L de sobrenadantes de monocitos (SMo) obtenidos después de la activación de los monocitos autólogos y alogénicos con lipopolisacárido. Los linfocitos T estimulados con PHA de los pacientes infectados por el VHB secretaron interferón en forma similar a los controles (438+129 vs. 577+127 pg/mL). En presencia de PHA más SMo autólogos, los linfocitos T de los pacientes no sufrieron modificación en la secreción de interferon, siendo la misma significativamente menor a la demostrada por las células T de los controles cultivadas en iguales condiciones (589+124 vs. 922+121 pg/mL; p<0.05). Al adicionar SMo alogénicos (PHA + SMo de controles), los linfocitos T de los portadores crónicos del VHB incrementaron la producción de interferón a una concentración significativamente mayor a la obtenida en presencia de PHA sola (752+123 vs. 438+129 pg/mL; p<0.01). En conclusión, los linfocitos T periféricos de los portadores crónicos del VHB son capaces de secretar interferón y responden incrementando esta secreción cuando son expuestos a factores solubles de monocitos alogénicos lo que indica que esta población celular T preserva su habilidad funcional para mediar respuestas inmunes

Diagnosis and treatment of viral liver fibrosis

This review summarized the diagnostic value of fibrosis biomarkers and the efficacy of anti-viral treatments on fibrosis progression. Non-invasive biomarkers can facilitate the screening and management of chronic hepatitis C and B. Screening for significant fibrosis is mandatory as very effective anti-viral treatments are available, permitting to stop or to reduce the fibrosis progression. The reduction of fibrosis progression will decrease the mortality due to complications of cirrhosis. In patients with chronic hepatitis C, pegylated interferons combined with ribavirin are effective in reducing fibrosis progression. In patients with chronic hepatitis B, lamivudine, adefovir and pegylated interferon are also effective in reducing fibrosis progression. In patients with chronic hepatitis Delta, pegylated interferon is also effective in reducing fibrosis progression

Relevancy between Liver Injury, Serum HBV-DNA, and Intrahepatic HBcAg in Young Male Chronic HBV Carriers / 대한소화기학회지

BACKGROUND/AIMS: Although the viral load is correlated with HBcAg, liver injury was not correlated to viral load in HBeAg positive patient. We aimed to study the inter-relationship of clinical parameters such as the level of HBV-DNA, the level of aminotransferase, intrahepatic expression of HBcAg and severity of histological liver damage in the young male chronic HBV carriers according to HBeAg status. METHODS: The study group included 85 young male patients (mean age: 19.8) with biopsy-proven chronic hepatitis B (HBeAg-positive group: n=60, HBeAg-negative group: n=25). RESUTLS: Serum levels of HBV-DNA and the expression of intrahepatic HBcAg in the HBeAg-positive group were significantly higher than in the HBeAg-negative (p<0.001), but fibrosis score was lower (p<0.01). Serum levels of HBV-DNA positively correlated with lobular activity, portal/periportal activity, biochemical activities in the HBeAg-negative group but negatively correlated in the HBeAg-positive group. There were no significant differences in histological activity according to the pattern of expression of intrahepatic HBcAg in both groups. The lobular activity correlated positively with biochemical activity in both groups, and portal/periportal activity correlated with biochemical activity only in the HBeAg-positive group. CONCLUSIONS: There are close correlations among liver injury, intrahepatic expression of HBcAg, and detectable HBV-DNA in the young male chronic HBV carriers with HBeAg-negativity, but in the HBeAg-positive group, the correlations are diversified.

Relationship between Serum HBV DNA Levels and Liver Histology in Chronic Hepatitis B / 대한소화기학회지

BACKGROUND/AIMS: Serum HBV DNA levels are correlated with hepatic histologic activity in chronic HBV infection based on HBeAg. Liver injury may persist, even though HBV DNA are not detected by hybridization assay. This study was to investigate whether serum HBV DNA levels determined by more sensitive quantitative method are correlated with histologic activities in chronic HBV infections. METHODS: This study included 66 chronic HBV infected patients. HBV DNA level was quantified by Cobas Amplicor HBV Monitor(TM). RESULTS: Serum HBV DNA levels in HBeAg-positive patients were significantly higher than HBeAg-negative patients. In HBeAg-positive patients, serum HBV DNA levels showed a significant negative correlation with portal-periportal activity and fibrosis (r=-0.451, -0.446 respectively). AST levels were correlated with lobular, portal-periportal activity and fibrosis (r=0.432, 0.365, 0.301 respectively), whereas ALT levels were related to lobular activity (r=0.294). Elevated AST levels predicted lobular activity, portal-periportal activity, and fibrosis with moderate to severe degree (OR 1.733, 95% CI 1.083-2.775; OR 1.518, 95% 1.028-2.243, p=0.336; OR 17.897, 95% CI 1.517-211.208, p=0.022, respectively). CONCLUSIONS: In HBeAg-positive patients, serum HBV DNA level correlates inversely with histologic activity. On the other hands AST level correlates with histologic activity and the stage of moderate or severe degree.

Treatment of chronic hepatitis B in children with prednisolone withdrawal followed by recombinant interferon alpha

Steroid withdrawal followed by interferon therapy is an alternative approach for treating chronic hepatitis B virus infection when there has been no therapeutic response to interferon alone. The effectiveness of steroid withdrawal followed by interferon therapy and factors predictive of the response were evaluated in 35 children with biopsy-proven chronic hepatitis B. Patients had received a 1-month course of prednisolone, 1 mg/kg per day orally, followed by a 2-week rest, and then were treated with interferon alpha 3 MU three times per week for 4-6 months. The serum aminotransferase values normalized in 80%, and negative seroconversion rates of HBeAg and HBV-DNA were 69% and 66%. The good response rate was associated with a pretreatment HBV-DNA level lower than 100 pg/ml and a posttreatment ALT level more than 200 IU/L. Normalization of ALT values usually took 5 months, and the clearance of HBV-DNA and HBeAg took 7.8 and 6.7 months, respectively. These results suggest that steroid withdrawal followed by interferon therapy is useful in the treatment of chronic hepatitis B in children, and that a good response rate can be expected in children with lower pretreatment HBV-DNA levels (< 100 pg/ml).