Hepatitis B crónica / Chronic B hepatitis

Chronic hepatitis B is a major public health problem, causing 30% of cirrhosis worldwide and up to 50% of hepatocellular carcinoma. In high prevalence regions, virus transmission is mainly vertical, which is associated with a risk of chronic disease in 90% of cases. The development of chronic hepatitis in adults is less than 5%, but it could reach up to 30% in patients with immunosuppression. In the evaluation of subjects with HBV infection is recommended to investigate risk factors for progression to cirrhosis and hepatocellular carcinoma, test for sexually transmitted infections and control liver comorbidities that will affect patient's prognosis, such as chronic alcohol consumption, nonalcoholic fatty liver disease and coinfection with hepatitis C and HIV. Management of patients with chronic hepatitis B includes testing and prevention for contacts, control of comorbidities, and specific treatment with antivirals when indicated. Treatment with nucleotide/nucleoside analogues is considered of choice as they are safe, achieves adequate control of viral replication and reduces the risk of liver complications. The goal of the WHO is to achieve a significant decrease in the prevalence of hepatitis B by 2030 through preventive measures in regions with a high prevalence of the disease.

La infección por el virus de la hepatitis B (VHB) es un importante problema de salud pública, estimándose que causa 30% de los casos de cirrosis a nivel mundial y hasta 50% de los hepatocarcinomas. En las regiones de alta prevalencia, la transmisión del virus es principalmente vertical, la que se asocia a un riesgo de cronificación de hasta 90%. Por el contrario, el desarrollo de hepatitis crónica en adultos es menor de 5% y en inmunosupresión puede alcanzar hasta 30%. En la evaluación de sujetos con infección por VHB es necesaria pesquisar factores de riesgo de progresión a cirrosis y hepatocarcinoma, detectar otras infecciones de transmisión sexual y controlar comorbilidades hepáticas que afectarán el pronóstico del paciente, como el consumo crónico de alcohol, el hígado graso no alcohólico o la coinfección con hepatitis C y VIH. El manejo de los pacientes con hepatitis B crónica requiere preocuparse del testeo y medidas de prevención para los contactos, control de comorbilidades y tratamiento específico con antivirales cuando existe indicación. El tratamiento con análogos de nucleótidos/nucleósidos se considera de elección al ser seguro, lograr un adecuado control de la replicación viral y disminuir riesgo de complicaciones hepáticas. El objetivo de la OMS es lograr una disminución significativa de la prevalencia de la hepatitis B el año 2030 a través de medidas preventivas en regiones de alta prevalencia de la enfermedad.

A Study of the Association between Diabetes Mellitus and Chronic Hepatitis B Virus Infection / Un Estudio de la Asociación entre la Diabetes Mellitus y la Infección Crónica por el Virus de la Hepatitis B

ABSTRACT Background: Hepatitis B virus (HBV) infection and diabetes mellitus are major health problems associated with significant morbidity and mortality. The published literature suggests an association of diabetes mellitus with liver disease. However, the role of HBV infection in diabetes aetiology is still controversial. The present study was conducted to explore the veracity of this enigmatic association among Pakistani subjects. Methodology: The blood samples and clinical information were collected from chronic HBV-positive patients Group 1 (n = 120), and their age and gender were matched with those of the healthy control subjects Group 2 (n = 120). Hepatitis B virus-positive patients were also subdivided into two groups; (Group 1a and Group 1b) with and without liver cirrhosis for evaluation of the prevalence of diabetes. Results: The study revealed that there were statistically significant differences in the biochemical parameters in the HBV-positive and control groups. There was no correlation between diabetes and HBV with the prevalence of diabetes mellitus being similar in subjects with and without HBsAg (11.7% in the positive group and 10% in the controls). Since there were a relatively large number (32.5%) of HBV-positive patients with liver cirrhosis, a comparison of biochemical parameters was also carried out to evaluate the extent of the liver damage and its association with diabetes. During the comparison of HBV patients with and without cirrhosis for the prevalence of diabetes, no aetiologic association was found with diabetes. Conclusion: Study revealed that there was no correlation between HBV infection and diaabetes despite the significantly different biochemical parameters in the HBV-infected group and control subjects.

RESUMEN Antecedentes: La infección por el virus de la hepatitis B (VHB) y la diabetes mellitus son problemas de salud importantes asociados con morbilidad y mortalidad significativas. La literatura publicada sugiere una asociación de la diabetes mellitus con las enfermedades hepáticas. Sin embargo, el papel de la infección por VHB en la etiología de diabetes sigue siendo contro-versial. El presente estudio fue conducido con el propósito de explorar la veracidad de esta enigmática asociación entre sujetos paquistaníes. Metodología: Se recogieron muestras de sangre e información clínica de pacientes crónicos VHB positivos Grupo 1 (n = 120), y su edad y género fueron comparados con los de los sujetos sanos del control Grupo 2 (n = 120). Los pacientes positivos al virus de la hepatitis B también se subdividieron en dos grupos, a saber, (Grupo 1a y Grupo 1b) con y sin cirrosis hepática en relación con la prevalencia de la diabetes. Resultados: El estudio reveló que hubo diferencias significativas en estos dos grupos en los parámetros bioquímicos entre el grupo de control y el grupo VHB positivo. En estos dos grupos no hubo correlación entre la diabetes y el VHB. Puesto que hubo un número relativamente grande (32.5%) de pacientes VHB positivos con cirrosis hepática, se realizó también una comparación de los parámetros bioquímicos a fin de comprender el grado del daño hepático y su asociación con la diabetes. Durante la comparación de los pacientes con VHB con y sin cirrosis en relación con la prevalencia de diabetes, no se halló asociación etiológica con la diabetes. Conclusión: Este estudio reveló que no hubo correlación entre la infección por VHB y la diabetes, a pesar de los parámetros bioquímicos significativamente diferentes entre el grupo infectado por el VHB y los sujetos del control.

Serum regucalcin is a useful indicator of liver injury severity in patients with hepatitis B virus-related liver diseases

Regucalcin is a soluble protein that is principally expressed in hepatocytes. Studies of regucalcin have mainly been conducted in animals due to a lack of commercially available kits. We aimed to develop an enzyme-linked immunosorbent assay (ELISA) to quantify serum regucalcin in patients with hepatitis B virus (HBV)-related disease. High-titer monoclonal antibodies and a polyclonal antibody to regucalcin were produced, a double-antibody sandwich ELISA method was established, and serum regucalcin was determined in 47 chronic hepatitis B (CHB) patients, 91 HBV-related acute-on-chronic liver failure (HBV-ACLF) patients, and 33 healthy controls. The ELISA demonstrated an appropriate linear range, and high levels of reproducibility, sensitivity, specificity, accuracy, and stability. The median serum regucalcin concentrations in HBV-ACLF and CHB patients were 5.46 and 3.76 ng/mL, respectively (P<0.01), which were much higher than in healthy controls (1.72 ng/mL, both P<0.01). For the differentiation of CHB patients and healthy controls, the area under curve (AUC) was 0.86 with a cut-off of 2.42 ng/mL, 85.7% sensitivity, and 78.8% specificity. In contrast, the AUC of alanine aminotransferase (ALT) was lower (AUC=0.80, P=0.01). To differentiate ACLF from CHB, the AUC was 0.72 with a cut-off of 4.26 ng/mL, 77.0% sensitivity, and 61.2% specificity while the AUC of ALT was 0.41 (P=0.07). Thus, we have developed an ELISA that is suitable for measuring serum regucalcin and have shown that serum regucalcin increased with the severity of liver injury due to HBV-related diseases, such that it appears to be more useful than ALT as a marker of liver injury.

Association of serum levels of C-reactive protein with CRP-717 T/C polymorphism and viremia in HCV and HBV carriers

Abstract INTRODUCTION: The present study investigated the association of the rs2794521 polymorphism in the CRP gene in individuals with chronic hepatitis B and C, correlating it with markers of hepatic inflammation, fibrosis scores, viral load, and plasma protein levels. METHODS: The study analyzed 185 blood samples obtained from patients with hepatitis B (n=74) and hepatitis C (n=111) and 300 samples from healthy donors. Genotyping was performed by real-time polymerase chain reaction, and protein levels were quantified using the automated immunoturbidimetric method. RESULTS: The TT genotype was the most frequent in all studied groups and was associated with higher plasma levels of the protein but not with the progression of liver disease. Low levels of C-reactive protein were associated with increased viremia and scores indicative of severe fibrosis and cirrhosis. CONCLUSIONS: The present results demonstrated a close relationship between the ability of the virus to replicate and cause liver damage and low serum concentrations of C-reactive protein. Future research may determine if these results can be interpreted as a possible form of escape for the virus by decreasing its action as an opsonin and decreasing phagocytosis, which are functions of C-reactive protein in the immune response.

Búsqueda de infección por Hepatitis B en familiares de portadores crónicos de la provincia de Huanta, Ayacucho -Perú / Search of Hepatitis-B infection in relatives of chronic carriers in the province of Huanta, Ayacucho, Peru

RESUMEN Un plan de eliminación del virus de hepatitis B (HBV) es factible porque la inmunización ha tenido buen impacto, tal como ha sucedido en la provincia de Huanta en Perú. El objetivo de nuestro estudio fue determinar la frecuencia de la infección por HBV en familiares de portadores del antígeno de superficie del virus de la hepatitis B (HBsAg). Este estudio transversal incluyó a 39 familiares de portadores crónicos, identificados en el Hospital de Apoyo de Huanta. Se recolectaron datos sociodemográficos y muestras de sangre. La frecuencia total de infección por HBV fue de 10,3 % y la mayoría correspondía a infección crónica (7,7 %). Una tercera parte tenía antecedentes de infección por HBV. Los miembros de la familia con infección por HBV fueron mayormente adultos alcohólicos y no vacunados. En conclusión, encontramos una alta frecuencia de HBV en familiares de portadores de HBsAg, esta estrategia ayudaría a identificar portadores crónicos que pueden ser tratados y contribuir a un plan de eliminación de HBV.

ABSTRACTS A plan of elimination of the virus of B hepatitis (HBV) is feasible because the immunization has had good impact, as it has been documented in the province of Huanta in Peru. The objective of our study was to determine the frequency of the infection by HBV in relatives of carriers of the surface antigen of the virus of hepatitis B (HBsAg). This cross-sectional study included 39 relatives of chronic carriers, identified at Hospital de Apoyo de Huanta. Sociodemographic data and blood samples were collected. The total frequency of infection by HBV was 10.3%, and the majority corresponded to chronic infection (7.7%). One third had a history of infection by HBV. The family members with HBV infection were mainly adult alcoholics who had not been vaccinated. In conclusion, we found a high frequency of HBV in relatives of carriers of HBsAg. This strategy would help identify chronic carriers that can be treated and to contribute to a plan for the elimination of HBV.

Lamivudine, Entecavir, or Tenofovir Treatment of Hepatitis B Infection: Effects on Calcium, Phosphate, FGF23 and Indicators of Bone Metabolism

ABSTRACT Background. Patients with chronic hepatitis B virus (HBV) are often treated with nucleoside/nucleotide antiviral agents and metabolic bone toxicity is a possible concern. Objective. To determine the relationships between fibroblast growth factor 23 (FGF23), a phosphaturic hormone, bone mineral density (BMD), and bone biochemical abnormalities in these patients. Material and methods. This is a cross-sectional observational study comparing HBV-infected subjects treated for at least one year with tenofovir (TDF), lamuvidine (LVD), entacavir (ETV), or not treated (CON). Patients with abnormalities in either calcium (Ca), phosphate (PO4), intact parathyroid hormone (iPTH) or FGF23 were further evaluated with BMD by DXA. Results. No difference in liver enzymes or renal function seen among groups, but hypophosphatemia was seen in all groups with the highest incidence with TDF treatment (14%). FGF 23 levels were found to be elevated in 11.1% of TDF patients, 2.77% amongst controls. No elevations were found in the LVD or ETV groups. Among a subset of subjects (FGF23, PO4, and/or Ca abnormalities) who underwent further evaluation, 67% had insufficient 25-OH vitamin D, and 30% had elevated 24 h urinary Ca or PO4 excretion. No patients with FGF23 abnormalities had urine abnormalities. 40% had low DXA Z-score (<-2) at spine or hip but there was no difference between control and antiviral treatment groups and the mean FRAX score was 2.33% for major osteoporotic fractures and 0.29% for hip fracture. Conclusion. Abnormalities in bone metabolism, particularly involving vitamin D insufficiency, in HBV-treated subjects were observed with a small increased likelihood in TDF treated patients.

Serum microRNA-30c levels are correlated with disease progression in Xinjiang Uygur patients with chronic hepatitis B

We aimed to investigate the potential role and mechanism of microRNA-30c (miR-30c) in the pathological development of chronic hepatitis B (CHB). The serum levels of miR-30c in hepatitis B virus (HBV) carrier Xinjiang Uygur patients with inactive, low-replicative, high-replicative and HBe antigen-positive CHB were investigated. HepG2 cells were co-transfected with pHBV1.3 and miR-30c mimic or inhibitor or scramble RNA. The effects of miR-30c dysregulation on HBV replication and gene expression, cell proliferation and cell cycle were then investigated. miR-30c was down-regulated in Xinjiang Uygur patients with CHB compared to healthy controls and its expression level discriminated HBV carrier patients with inactive, low-replicative, high-replicative and HBe antigen-positive risk for disease progression. Overexpression of miR-30c significantly inhibited HBV replication and the expressions of HBV pgRNA, capsid-associated virus DNA and Hbx in hepatoma cells. Moreover, overexpression of miR-30c significantly inhibited cell proliferation and delayed G1/S phase transition in hepatoma cells. Opposite effects were obtained after suppression of miR-30c. Our results indicate that miR-30c was down-regulated in Xinjiang Uygur patients with CHB, and miR-30c levels could serve as a marker for risk stratification of HBV infection. Down-regulation of miR-30c may result in the progression of CHB via promoting HBV replication and cell proliferation.

An in-house real-time polymerase chain reaction: standardisation and comparison with the Cobas Amplicor HBV monitor and Cobas AmpliPrep/Cobas TaqMan HBV tests for the quantification of hepatitis B virus DNA

This study aimed to standardise an in-house real-time polymerase chain reaction (rtPCR) to allow quantification of hepatitis B virus (HBV) DNA in serum or plasma samples, and to compare this method with two commercial assays, the Cobas Amplicor HBV monitor and the Cobas AmpliPrep/Cobas TaqMan HBV test. Samples from 397 patients from the state of São Paulo were analysed by all three methods. Fifty-two samples were from patients who were human immunodeficiency virus and hepatitis C virus positive, but HBV negative. Genotypes were characterised, and the viral load was measure in each sample. The in-house rtPCR showed an excellent success rate compared with commercial tests; inter-assay and intra-assay coefficients correlated with commercial tests (r = 0.96 and r = 0.913, p < 0.001) and the in-house test showed no genotype-dependent differences in detection and quantification rates. The in-house assay tested in this study could be used for screening and quantifying HBV DNA in order to monitor patients during therapy.

Potential Serum Markers for Monitoring the Progression of Hepatitis B Virus-Associated Chronic Hepatic Lesions to Liver Cirrhosis

BACKGROUND/AIMS: To screen for serum protein/peptide biomarkers of hepatitis B virus (HBV)-associated chronic hepatic lesions in an attempt to profile the progression of HBV-associated chronic hepatic lesions using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) techniques. METHODS: Using SELDI-TOF MS, serum protein/peptide profiles on the CM10 ProteinChip arrays were obtained from a training group including 26 HBV-associated hepatocellular carcinoma patients with liver cirrhosis (LC), 30 HBV-associated LC patients, 85 patients at different stages of liver fibrosis, and 30 asymptomatic HBV carriers. The most valuable SELDI peak for predicting the progression to LC in HBV-infected patients was identified. RESULTS: A SELDI peak of M/Z 5805 with value for predicting LC in HBV-infected patients was found and was identified as a peptide of the C-terminal fraction of the fibrinogen alpha-chain precursor, isoform 1. CONCLUSIONS: The peptide of the C-terminal fraction of the fibrinogen alpha-chain precursor, isoform 1 with M/Z 5805, may be a serological biomarker for progression to LC in HBV-infected patients.

Long-term efficacy of tenofovir disoproxil fumarate therapy after multiple nucleos(t)ide analogue failure in chronic hepatitis B patients

BACKGROUND/AIMS: The efficacy of tenofovir disoproxil fumarate (TDF) for the treatment of chronic hepatitis B (CHB) patients following prior treatment failure with multiple nucleos(t)ide analogues (NAs) is not well defined, especially in Asian populations. In this study we investigated the efficacy and safety of TDF rescue therapy in CHB patients after multiple NA treatment failure. METHODS: The study retrospectively analyzed 52 CHB patients who experienced failure with two or more NAs and who were switched to regimens containing TDF. The efficacy and safety assessments included hepatitis B virus (HBV) DNA undetectability, hepatitis B envelop antigen (HBeAg) seroclearance, alanine transaminase (ALT) normalization and changes in serum creatinine and phosphorus levels. RESULTS: The mean HBV DNA level at baseline was 5.4 +/- 1.76 log10 IU/mL. At a median duration of 34.5 months of TDF treatment, the cumulative probabilities of achieving complete virological response (CVR) were 25.0%, 51.8%, 74.2%, and 96.7% at 6, 12, 24, and 48 months, respectively. HBeAg seroclearance occurred in seven of 48 patients (14.6%). ALT levels were normalized in 27 of 31 patients (87.1%) with elevated ALT at baseline. Lower levels of HBV DNA at baseline were significantly associated with increased CVR rates (p < 0.001). However, CVR rates did not differ between TDF monotherapy or combination therapy with other NAs, and were not affected by mutations associated with resistance to NAs. No significant adverse events were observed. CONCLUSIONS: TDF is an efficient and safe rescue therapy for CHB patients after treatment failure with multiple NAs.

Epidemiological, serological and molecular aspects of hepatitis B and C in children and teenagers of municipal daycare facilities schools and schools in the city of Santos / Aspectos epidemiológicos, sorológicos e moleculares das hepatites B e C em crianças e adolescentes de creches e escolas municipais na cidade de Santos

Objective: To estimate the prevalence of the serological markers anti-HBc, HBsAg and anti-HBs of hepatitis B and anti-HCV of hepatitis C among children and teenagers enrolled at daycare facilities, kindergartens and municipal elementary education network in the city of Santos, São Paulo, Brazil. Methods: A cross-sectional study was carried out from June 28 to December 14, 2007, in which 4,680 finger-prick blood samples were collected from children and teenagers. A survey questionnaire was applied to their family members. The sample was dimensioned using the software Epi Info version 6 with expected frequency of 1%, acceptable error of 0.5% and confidence interval of 95%. The serological tests were performed using the ELISA technique. The molecular analysis was performed using the technique of polymerase chain reaction in House. Results: Age of the studied population ranged from 7 months to 18 years and 1 month. The general prevalence of anti-HBc reagent was 0.1%, HBsAg was 0.02% and anti-HCV was 0.02%. Conclusions: In children, the general prevalence of serological markers for hepatitis B and C in the city of Santos was low when compared with literature data. .

Objetivo: Estimar a prevalência de marcadores sorológicos anti-HBc, AgHBs e anti-HBs da hepatites B e anti-HCV da hepatite C em crianças e adolescentes matriculados em creches e escolas de ensino infantil e fundamental da rede municipal na cidade de Santos, São Paulo. Métodos: Estudo transversal realizado no período de 28 de junho a 14 de dezembro de 2007, no qual foram coletadas 4.680 amostras de sangue colhidas através de punção capilar. Foi aplicado um questionário nos familiares das crianças e adolescentes. Para o cálculo da amostra, foi utilizado o programa Epi Info versão 6 com frequência esperada de 1%, erro aceitável de 0,5% e nível de confiança de 95%. Os exames sorológicos foram realizados utilizando a técnica de ELISA. O estudo molecular foi realizado pela técnica de reação em cadeia de polimerase in House. Resultados: A idade da população estudada variou de 7 meses a 18 anos e 1 mês. A prevalência geral do anti-HBc reagente foi de 0,1%, do AgHBs foi de 0,02% e do anti-HCV foi de 0,02%. Conclusão: A prevalência geral em crianças dos marcadores sorológicos para hepatites B e C na cidade de Santos foi baixa, quando comparada com os dados de literatura. .

Clinical and laboratory characteristics associated with dyslipidemia and liver steatosis in chronic HBV carriers

Introduction Chronic hepatitis B virus (HBV) infection and liver steatosis (LS) are the most common causes of chronic liver disease, and their coexistence is frequently observed in clinical practice. Although metabolic syndrome is the main cause of LS, it has not been associated with HBV infection. The aims of this study were to describe the lipid profile and prevalence of LS among HBV carriers and to identify the characteristics associated with LS in this group. Methods This retrospective cross-sectional study included hepatitis B surface antigen (HBsAg)-positive patients evaluated during 2011 and 2012. Results Of the 83 patients included, the mean age was 46.4±12.5 years, 53% were men, and 9.1% were hepatitis B e antigen (HBeAg) -positive. These patients exhibited the following lipid profile: total cholesterol = 175.4±38.8mg/dL, low-density lipoprotein (LDL) = 113.0±32.7mg/dL, and triglycerides = 91.1±45.2mg/dL. Their fasting glucose was 95.3±14.5g/dL, and fasting insulin was 6.1±5.9µIU/mL. Liver steatosis was observed on abdominal ultrasound in 11.3% of individuals. Factors associated with the presence of LS included higher levels of total cholesterol, prothrombin activity, fasting insulin, and body mass index (BMI) as well as lower levels of aspartate aminotransferase (AST). Conclusions These findings suggest that LS in patients with chronic HBV appears to be a consequence of metabolic alterations and insulin action rather than of viral factors. .

Is HBsAg Loss an Ideal End-point of Oral Antiviral Therapy in Chronic Hepatitis B Patients? / 대한소화기학회지

No abstract available.

Correlation between hepatitis B surface antigen titers and HBV DNA levels

To assess the correlation between serum HBsAg titers and hepatitis B virus [HBV] DNA levels in patients with hepatitis B envelop antigen-negative [HBeAg -ve] HBV genotype-D [HBV/D] infection. A total of 106 treatment- na‹ve, HBeAg -ve HBV/D patients were included; 78 in the inactive carrier [IC] state and 28 in the active hepatitis [AH] stage. HBV DNA load and HBsAg titers were tested using TaqMan real-time polymerase chain reaction [PCR] and automated chemiluminescent microparticle immunoassay, respectively. The median [range] log10 HbsAg titer was significantly lower in the IC group compared with AH group, 3.09 [-1 to -4.4] versus 3.68 [-0.77 to 5.09] IU/mL, respectively; P < 0.001. The suggested cutoff value of HBsAg titer to differentiate between the two groups was 3.79 log10 IU/mL. In addition, there was a significant positive correlation between HBsAg and HBV DNA levels in the whole cohort, AH, and IC groups [r = 0.6, P < 0.0001; r = 0.591, P = 0.001; and r = 0.243, P = 0.032, respectively]. Serum HBsAg titers may correlate with HBV DNA in treatment-na‹ve HBeAg -ve HBV/D patients, and supports the use of HBsAg levels in clinical practice as a predictor of serum HBV DNA levels.

Relevamiento de la carga viral en áreas geográficas de Argentina con alta prevalencia del virus de hepatitis B / [Viral load survey from geographical areas within Argentina with high hepatitis B virus prevalence].

Several studies have demonstrated that viral load is a key factor to determine the development of HBV infection and to assess treatment options for the disease. There is a lack of studies analyzing viral load levels in chronic hepatitis B patients in Argentina and the epidemiologic information is limited. The aim of this study was to determine viral load levels and its distribution in patients diagnosed with chronic hepatitis B from geographical areas with high prevalence for HBV in Argentina. Fifty-one per cent of the study population had HBV DNA levels > or = 10(4) copies/ml and a median viral load of 11,910 copies/ml. The viral load was significantly higher in HBeAg seropositive patients compared with those seronegative for HBeAg (P < 0.05). Salta and Entre Ríos provinces showed low viral loads, while Chaco, Misiones and Formosa provinces had a median viral load ranging between 10(4) and 10(5) copies/ ml. This is the first study providing detailed information on viral load in chronic hepatitis B patients from Argentina. Availability of viral load levels in chronic hepatitis B enables evaluation of implementation of actions to analyze follow-up and/or treatment options for preventing disease complications, improving health care and diminishing the potential burden on the health care system.

Role of hyaluronic acid and laminin as serum markers for predicting significant fibrosis in patients with chronic hepatitis B

OBJECTIVES: The aim of this study was to evaluate the diagnostic performance of serum HA and LN as serum markers for predicting significant fibrosis in CHB patients. METHODS: Serum HA and LN levels of 87 patients with chronic hepatitis B and 19 blood donors were assayed by RIA. Liver fibrosis stages were determined according to the Metavir scoring-system. The diagnostic performances of all indexes were evaluated by the receiver operating characteristic (ROC) curves. RESULTS: Serum HA and LN concentrations increased significantly with the stage of hepatic fibrosis, which showed positive correlation with the stages of liver fibrosis (HA: r = 0.875, p < 0.001; LN: r = 0.610, p < 0.001). There were significant differences of serum HA and LN levels between F2-4 group in comparison with those in F0-F1 group (p < 0.001) and controls (p < 0.001), respectively. From ROC curves, 185.3 ng/mL as the optimal cut-off value of serum HA for diagnosis of significant fibrosis, giving its sensitivity, specificity, PPV, NPV, LR+, LR- and AC of 84.2 percent, 83.3 percent, 90.6 percent, 73.5 percent, 5.04, 0.19 and 83.9, respectively. While 132.7 ng/mL was the optimal cut-off value of serum LN, the sensitivity, specificity, PPV, NPV, LR+, LR- and AC were 71.9 percent, 80.0 percent, 87.2 percent, 60.0 percent, 3.59 percent, 0.35 percent and 74.7, respectively. Combinations of HA and LN by serial tests showed a perfect specificity and PPV of 100 percent, at the same time sensitivity declined to 63.2 percent and LR+ increased to 18.9, while parallel tests revealed a good sensitivity of 94.7 percent, NPV to 86.4 percent, and LR- declined to 0.08. CONCLUSIONS: Serum HA and LN concentrations showed positive correlation with the stages of liver fibrosis. Detection of serum HA and LN in predicting significant fibrosis showed good diagnostic performance, which would be further optimized by combination of the two indices. HA and LN would be clinically useful serum markers for predicting significant fibrosis in patients with chronic hepatitis B, when liver biopsy is contraindicated.

Clinical implications of HBsAg quantification in patients with chronic hepatitis B

Quantification of serum hepatitis B surface antigen [HBsAg] helps the management of patients with chronic hepatitis B virus [HBV] infection. Median HBsAg levels differ significantly during the natural history of HBV infection, progressively declining from immune tolerance to inactive phase. The combination of an HBsAg <1000 lU/mL and HBV DNA <2000 lU/mL at a single time point accurately identifies true inactive carriers. During antiviral treatment, HBsAg levels decline more rapidly in patients under peg-interferon [Peg-IFN] than in those under nucleos[t]ide analogues [NUC], and in responders to peg-IFN compared to non responders suggesting that a response-guided therapy in both HBeAg-positive and -negative patients treated with Peg-IFN could improve to cost-effectiveness of this therapeutic approach. Given the low rates of HBsAg clearance on NUC therapy, new studies to test whether Peg-IFN and NUC combination fosters HBsAg decline in long-term responders to NUC, are being explored

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.

Simultaneous quantitation of serum HBV DNA and HBeAg can distinguish between slow and fast viral responses to antiviral therapy in patients with chronic hepatitis B / A quantificação simultânea do DNA VHB e do AgHBe séricos podem distinguir entre resposta viral lenta e rápida à terapêutica anti-viral em pacientes com hepatite crônica B

BACKGROUND: The quantitation of serum HBeAg is not commonly used to monitor viral response to therapy in chronic hepatitis B. METHODS: In this study, 21 patients receiving varying therapies were followed and their viral response monitored by concomitant viral load and HBeAg quantitation in order to study the meaning and the kinetics of both parameters. RESULTS: It was possible to distinguish between three different patterns of viral response. The first was characterized by a simultaneous decrease in serum HBV DNA and HBeAg. The second pattern was characterized by a decrease in serum HBeAg but persistent detection of HBV DNA. The third pattern was characterized by undetectable HBV DNA with persistent HBeAg positivity, which points to a non-response (Pattern III-B) except when HBeAg levels showed a slow but steady drop, characterizing a "slow responder" patient (Pattern III-A). CONCLUSIONS: The first pattern is compatible with a viral response. A long-term HBeAg seropositivity with a slow and persistent decrease (Pattern III-A) is also compatible with a viral response and calls for a prolongation of anti-viral treatment.

INTRODUÇÃO: A quantificação do AgHBe sérico não é habitualmente utilizada para monitorizar a resposta viral ao tratamento da hepatite crônica B. MÉTODOS: Neste estudo, 21 pacientes sob tratamento com diferentes terapias foram acompanhados e a resposta viral monitorizada pela quantificação concomitante da carga viral e do AgHBe a fim de investigar o significado e a cinética de ambos os parâmetros. RESULTADOS: Distinguiram-se três diferentes padrões de resposta viral. O primeiro caracterizou-se pela redução simultânea do HBV DNA e AgHBe séricos. O segundo padrão caracterizou-se por uma redução do AgHBe porém com detecção persistente do HBV DNA. O terceiro padrão caracterizou-se por HBV DNA indetectável com positividade persistente do AgHBe, sugerindo ausência de resposta (Padrão III-B), exceto quando os níveis de AgHBe mostraram uma queda lenta porém persistente, caracterizando um "respondedor lento" (Padrão III-A). CONCLUSÕES: O primeiro padrão é compatível com resposta viral. Uma seropositividade prolongada do AgHBe porém com uma redução lenta e persistente (Padrão III-A) é também compatível com resposta viral, sugerindo o prolongamento do tratamento anti-viral.