Transcriptome Classification Reveals Molecular Subgroups in Patients with Hepatitis B Virus.

Hepatitis B virus (HBV) specifically infects hepatocytes, which can cause progressive liver fibrosis and a significantly increased risk of liver cancer. Multiple studies indicated host genetic, virological, and immunological factors could affect the HBV infection. However, the underlying mechanism involved in HBV infection remained unclear. Based on the analysis of gene expression data of 124 HBV patients (GEO accession: GSE84044), molecular subgroups of patients infected with hepatitis B virus were identified in this study, including C1, C2, and C3 groups. The age, fiber, degree of chemical and inflammation, and gene expression difference were also compared among the three sampling groups. Furthermore, the liver index was calculated using 93 liver-specific genes. The liver-specific gene expression in different molecular subgroups of HBV patients was thoroughly analyzed and then was compared with fibrosis and inflammation levels. Results showed that the C2 group was the youngest and the C3 group had the highest degree of fibrosis and inflammation. Enrichment analysis showed that metabolism-related pathways were mainly expressed in the C1 and C2 groups, and inflammation-related pathways and proteoglycans in cancer were highly expressed in the C1 and C3 groups. The liver index was higher in the C2 group than in the C1 and C3 groups, and it was the lowest in the C3 group. Macrophage M1/M2 and neutrophils were significantly different in the three groups. M1 was mainly abundant in the C3 group, and M2 and neutrophils were mainly abundant in the C2 group. This study provides novel information to understand the mechanisms of HBV infection in chronic hepatitis B (CHB) patients.

Use of hepatitis B virus core-related antigen to evaluate natural history of chronic hepatitis B.

BACKGROUND AND AIM: Hepatitis B core-related antigen (HBcrAg) has been shown to correlate with various viral markers in chronic hepatitis B, but its role in defining natural history is not well studied. We aimed to investigate the use of HBcrAg to define different phases of chronic hepatitis B. METHODS: Stored residual serum samples from longitudinal cohorts of chronic hepatitis B patients in Hong Kong and Japan were studied. Viral markers were measured in three serial serum samples for each patient. Patients were divided into six groups for analysis: hepatitis B e antigen (HBeAg)-positive chronic infection (EPI), HBeAg-positive chronic hepatitis (EPH), HBeAg seroconversion (ES), HBeAg-negative chronic hepatitis (ENH), HBeAg-negative chronic infection (ENI), and HBsAg seroclearance (SS). RESULTS: In total, 166 patients followed up for 100 (76-113) months were included. HBcrAg was correlated with hepatitis B virus DNA and HBsAg levels in both HBeAg-positive and HBeAg-negative patients. HBcrAg cut-off of ≥ 6.0 log U/mL could best differentiate HBeAg-positive from HBeAg-negative patients (area under receiver operating characteristic curve of 0.99, P < 0.001). HBcrAg could not differentiate patients in EPI and EPH phases, but HBcrAg declined dramatically at HBeAg seroconversion. In HBeAg-negative patients, HBcrAg ≥ 4.0 log U/mL could best differentiate ENH from ENI (area under receiver operating characteristic curve of 0.81; P < 0.001), with high specificity (81.6%) but only moderate sensitivity (65.7%) at baseline. Undetectable HBcrAg was found in 17%, 63%, and 89% patients in ENH, ENI, and SS groups at the last visit, respectively. CONCLUSIONS: HBcrAg provides useful information to stage the natural history of chronic hepatitis B, particularly identifying HBeAg-positive patients and HBeAg-negative patients with active disease.

HBV Genotype-Specific Levels of Hepatitis B Surface Antigen Improve HBV Phenotype Definition.

Controversies exist regarding the classification of the different clinical phases of chronic hepatitis B (CHB) because hepatitis B virus (HBV) DNA and alanine aminotransferase levels fluctuate over time.1,2 To improve the distinction of clinical phases and the associated spectrum of clinical outcome,3,4 hepatitis B surface antigen (HBsAg) levels may be of help.5-7 We hypothesize that HBV genotype specific HBsAg levels are needed for the identification of different clinical HBV disease phases.7.

Serum HBV RNA quantification: useful for monitoring natural history of chronic hepatitis B infection.

BACKGROUND: As an alternative biomarker of intrahepatic covalently closed circular DNA (cccDNA) transcriptional activity, hepatitis B virus (HBV) RNA may evolve during long-lasting virus-host interactions during chronic hepatitis B viral infection. The distribution pattern of serum HBV RNA levels in the natural course of chronic HBV infection remains unclear. The aim of this study was to evaluate the levels of HBV RNA during the natural course of CHB and the role in distinguishing the natural history of HBV infection. METHODS: A total of 291 treatment-naïve chronic HBV carriers were enrolled. Based on the clinical, biochemical, serological, and histological data as well as HBV DNA levels, patients were classified into the following four categories: the immune-tolerant phase (IT,n = 35), HBeAg-positive immune-active phase (EPIA,n = 121), inactive chronic hepatitis B(ICH,n = 77) and HBeAg-negative immune reactive hepatitis (ENH,n = 58) [corrected]. The parameters and distribution patterns of serum HBV RNA were evaluated in relation to viral replication status, immune phase, disease category and Child-Pugh class. The relationships between serum HBV RNA and other serum hepatitis B viral markers were also analyzed. RESULTS: Serum HBV RNA levels were significantly lower in the HBeAg-negative patients compared to those in the HBeAg-positive patients, with the lowest levels seen in inactive carriers. In HBeAg-negative patients, serum HBV RNA levels increased if there is reactivation to active hepatitis and showed obvious superiority for the combination of serum HBV DNA (cutoff>3.39 Log copies/mL) and HBsAg (cutoff>2.74 Log IU/mL) in discriminating between 'HBeAg-negative immune reactive' phase and inactive chronic hepatitis B phases of HBeAg-negative chronic HBV infection. Serum HBV RNA levels were positively correlated with serum HBV DNA and HBsAg levels in all chronic HBV-infected patients. A stratified analysis revealed that a correlation between serum HBV RNA and HBV DNA or HBsAg was present in HBeAg-positive patients; however, in HBeAg-negative patients, serum HBV RNA was positively correlated with HBV DNA only. CONCLUSION: During the natural course of chronic HBV infection, serum HBV RNA levels vary. Serum HBV RNA can act as a biomarker to predict the natural history of disease in chronic hepatitis B patients. In treatment-naïve HBeAg-negative chronic HBV-infected individuals, serum HBV RNA shows superiority in differentiating the 'HBeAg-negative reactive' phase.

Determination of hepatitis B phenotype using biochemical and serological markers.

The aim of this study was to assess the validity of categorization of chronic hepatitis B viral infection into stages or phases based upon measures of disease activity and viral load, assuming these phenotypes will be useful for prognostication and determining the need for antiviral therapy. We assessed the phenotype of hepatitis B of 1,390 adult participants enrolled in the Hepatitis B Research Network Cohort Study, using a computer algorithm. Only 4% were immune tolerant, while 35% had chronic hepatitis B (18% e antigen positive and 17% e antigen negative) while 23% were inactive carriers. Strikingly, 38% of participants did not fit clearly into any one of these groups and were considered indeterminant. The largest subset of indeterminants had elevated serum aminotransferases with low levels of HBV DNA (less than 10,000 iu/mL). Subsequent determination of hepatitis B phenotype on the next available laboratory tests showed that 64% remained indeterminant. These findings call into question the validity of conventional staging of hepatitis B, in large part because of the substantial proportion of patients who do not fit readily into one of the usual stages or phases. Further studies are needed of the indeterminant category of chronic hepatitis B viral infection, including assessments of whether patients in this group are perhaps in transition to another phase or if they are a distinct phenotype with a need to assess liver disease severity and need for antiviral therapy. (ClinicalTrials.gov identifier NCT01263587).

Nationwide longitudinal analysis of acute liver failure in taiwan.

Acute liver failure (ALF) is uncommon but fatal. Current management is based mostly on clinical experience. We aimed to investigate the incidence, etiology, outcomes, and prognostic factors of ALF in Taiwan. Patients with the admission diagnosis of ALF between January 2005 and September 2007 were identified from the Longitudinal Health Insurance Database of Taiwan. ALF was further confirmed by disease severity based on laboratory orders, prescriptions, and duration of hospital stay, and acute onset without prior liver disease. Prognostic factors were identified using Cox regression analysis. During the study period, 218 eligible cases were identified from 28,078 potential eligible ALF patients. The incidence was 80.2 per million person-years in average and increased with age. The mean age was 57.9 ±â€Š17.1 years and median survival was 171 days. The most common etiologies were viral (45.4%, mainly hepatitis B virus) and followed by alcohol/toxin (33.0%). Independent prognostic factors included alcohol consumption (hazard ratio, HR, 1.67 [1.01-2.77]), malignancy (HR 2.90 [1.92-4.37]), frequency of checkups per week for total bilirubin (HR 1.57 [1.40-1.76]), sepsis (HR 1.85 [1.20-2.85]), and the use of hemodialysis/hemofiltration (HR 2.12 [1.15-3.9]) and proton pump inhibitor (HR 0.94 [0.90-0.98]). Among the 130 patients who survived ≥90 days, 66 (50.8%) were complicated by liver cirrhosis. Eight (3.7%) were referred for liver transplantation evaluation, but only 1 received transplantation and survived. ALF in Taiwan is mainly due to viral infection. Patients with malignancy and alcohol exposure have worst prognosis. The use of proton pump inhibitor is associated with improved survival. Half of the ALF survivors have liver cirrhosis.

Staging chronic hepatitis B into seven categories, defining inactive carriers and assessing treatment impact using a fibrosis biomarker (FibroTest®) and elastography (FibroScan®).

BACKGROUND & AIMS: The first aim was to extend the validation of FibroTest® (FT) and transient elastography (TE) as markers of occurrence of cirrhosis without complications (F4.1), oesophageal varices (F4.2), and severe complications (F4.3) in patients with chronic hepatitis B (CHB). The second aim was to validate a previous definition of an inactive carrier based on normal FT and ActiTest® (normal-FT-AT). The third aim was to assess the long-term dynamics of fibrosis in patients with sustained virological response. METHODS: The 10-year updated individual data of 1434 patients were pooled from two prospective cohorts. RESULTS: Of the 1312 patients without a history of complications, varices had occurred after 10 years in 14 patients (F4.2, incidence of 1.7%, 95% CI [0.6-2.8]), and severe complications in 25 (F4.3 3.7% [1.8-5.7]), including hepatocellular carcinoma (HCC) in 21 (3.7% [1.5-5.8]). Using Cox-multivariate analysis adjusted for treatment, viral load, HBeAg status and ALT, FT, and TE were predictive of liver complications (n=37; AUROC=0.83 [0.71-0.90]; p<0.0001) and (n=8/844; AUROC=0.82 [0.72-0.89]; p<0.0001) respectively. Normal FT-AT better identified patients with lower fibrosis progression than the ALT-based standard: 3/163 (1.8%) vs. 16/181 (8.8%; p=0.004) in the Paris cohort, and 5/195 (2.6%) vs. 15/228 (6.6%; p=0.05) in the Bordeaux cohort. Of the 582 responders, 23 had complications (incidence 6.2% [3.2-9.1]) including 19 HCC (5.8% [2.6-9.0]) and 10 with varices (2.6% [0.8-4.4]). Of the 138 responders with advanced fibrosis, only 31% (15-47%) had fibrosis regression. CONCLUSIONS: FibroTest® and TE identified three categories of cirrhosis with increasing morbidity. Normal FibroTest® and ActiTest® were better able to identify inactive hepatitis B carriers than the standard definition. Despite virological response, the overall incidence of cirrhosis increased, with a remaining 5.8% risk of HCC.

Caracterización de los pacientes con infección crónica por virus de la hepatitis B sin indicación de tratamiento / Characterization of patients with chronic hepatitis B virus infection without indication for treatment

La infección crónica por el virus de la hepatitis B (VHB) es un proceso dinámico que resulta de la interacción entre la replicación del VHB y la respuesta inmune del huésped. De acuerdo con los documentos de consenso de la EASL y la AEEH, no está indicado el tratamiento en la fase de tolerancia inmune y en la de portador inactivo. Sin embargo, en las 2 fases hay situaciones, que podríamos denominar «zona gris» de la infección crónica por el VHB, en las que no es fácil la clasificación correcta de los pacientes y en las que es posible plantear el inicio del tratamiento. En la fase de tolerancia inmune puede estar indicado el tratamiento en profesionales sanitarios cuyas responsabilidades requieren su participación en procedimientos invasivos, así como en mujeres embarazadas HBeAg positivo y ALT normal con valores altos de ADN-VHB, en las que está indicado el tratamiento antiviral oral durante el último trimestre del embarazo para reducir el riesgo de la transmisión vertical del VHB de la madre al hijo. En la fase de portador inactivo, en los pacientes HBeAg negativo con ALT persistentemente normal y ADN-VHB ≥ 2.000 UI/ml, la intensidad de la lesión hepática determinará la indicación de tratamiento. En estos pacientes, si ya existe una cirrosis establecida, está indicado el tratamiento si el ADN-VHB es detectable, independietemente del valor de la ALT

Chronic infection by the hepatitis B virus (HBV) is a dynamic process that results from the interaction between HBV replication and the host’s immune response. In accordance with the consensus document of the European Association for the Study of the Liver, treatment is not indicated for the immune tolerant and inactive carrier phases. However, there are situations in the 2 phases (which we could call gray areas of chronic HBV infection) in which the correct categorization of patients is not easy and in which the start of treatment can be proposed. In the immune tolerant phase, treatment could be indicated for health professionals whose responsibilities require their participation in invasive procedures. Treatment could also be indicated for pregnant women who are HBeAg-positive, ALT normal and have high HBV DNA values and for whom oral antiviral treatment is indicated during the last trimester of pregnancy to reduce the risk of vertical HBV transmission from mother to child. For patients in the inactive carrier phase who are HBeAg-negative with persistent normal ALT levels and HBV DNA ≥2000 IU/mL, the intensity of the hepatic lesion will determine the indication for treatment. If these patients already have established cirrhosis then treatment is indicated if the HBV DNA is detectable, regardless of the ALT level

Seguimiento bioquímico, serológico y virológico en pacientes con infección crónica por el virus de la hepatitis B no tratados: portador inactivo, hepatitis crónica HBeAg negativo e inmunotolerante / Biochemical, serological and virologic follow-up in patients with chronic untreated hepatitis B virus infection: inactive carrier, chronic HBeAg-negative and immunetolerant hepatitis

En los pacientes con infección crónica por VHB no tratados es necesario un seguimiento bioquímico, serológico y virológico mientras persista la infección. En los pacientes portadores inactivos el seguimiento sirve para detectar reactivación o pérdida del HBsAg. Tras la pérdida del HBsAg no se recomienda seguimiento salvo que el paciente requiera un tratamiento inmunosupresor. En los pacientes con hepatitis crónica HBeAg negativo con ALT normal y carga viral entre 2.000 y 20.000 UI/ml se precisa un seguimiento para valorar la progresión de la enfermedad. En los pacientes inmunotolerantes el seguimiento sirve para valorar seroconversión espontánea del HBeAg

Biochemical, serological and virologic follow-up is necessary for patients with chronic untreated HBV infection while the infection persists. For patients who are inactive carriers, follow-up helps detect reactivation or loss of HBsAg. After the loss of HBsAg, follow-up is not recommended unless the patient requires immunosuppressive therapy. For patients with chronic HBeAg-negative hepatitis with normal ALT levels and a viral load between 2000 and 20,000 IU/mL, follow-up is required to assess the progression of the disease. For patients who are immune-tolerant, follow-up helps assess the spontaneous seroconversion of HBeAg

Serum HBsAg quantification in treatment-naïve Indian patients with chronic hepatitis B.

BACKGROUND AND AIMS: There is paucity of Indian data regarding serum HBsAg levels (qHBsAg) in treatment-naïve chronic hepatitis B (CHB). This study was done to determine correlation of qHBsAg with hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA levels and its ability to independently categorize subgroups of CHB. METHODS: We studied 131 treatment-naive CHB patients and initially classified them based on HBeAg status. The HBeAg-positive group was further classified into immune tolerance (IT) and immune clearance (IC) phases based on serum alanine aminotransferase. HBeAg-negative patients were classified into low replicators (LR) and HBeAg-negative chronic hepatitis (ENH) based on DNA levels. HBsAg quantification was performed using the Architect chemiluminescence system. RESULTS: HBeAg-positive patients had higher DNA (7.89 vs. 2.69 log10 IU/mL) and higher qHBsAg (4.60 vs. 3.85 log10 IU/mL) compared to the HBeAg-negative group. Good correlation between qHBsAg and DNA was seen in HBeAg-positive (ρ = 0.6, p < 0.001) but not in HBeAg-negative CHB (ρ = 0.2). A qHBsAg level greater than 4.39 log10 IU/mL predicted HBeAg-positive state with 81 % sensitivity and 85 % specificity. However, among HBeAg-negative CHB, qHBsAg failed to discriminate between LR and ENH. CONCLUSIONS: A single point estimation of qHBsAg in treatment-naïve patients could predict replicative HBeAg-positive CHB, but was not helpful in defining replicative status in the HBeAg-negative CHB.

[Correlation study on Chinese medical syndrome types of chronic hepatitis B patients and HLA-DR13 gene, BCP mutation, and T-lymphocyte subsets].

OBJECTIVE: To explore the correlation between the HLA-DR13, basic core promoter (BCP), changes of T lymphocyte subset and clinical Chinese medical syndromes of chronic hepatitis B (CHB). METHODS: Totally 102 CHB patients were syndrome typed as Gan depression Pi deficiency syndrome (GDPDS), Pi-Shen yang deficiency syndrome (PSYDS), Gan-gallbladder dampness heat syndrome (GGDHS), Gan-Shen yin deficiency syndrome (GSYDS), and static blood blocking collaterals syndrome (SBBCS). Besides, 30 healthy subjects were recruited as the normal control group. The blood HBV-DNA level and HLA-DR13 gene were detected with real time fluorescent PCR. The expression of CD4+ and CD8+ in T lymphocytes was detected using flow cytometry. The mutation of serum A1762T/G1764A was detected using PCR sequencing. Hepatitis Be antigen (HBeAg) was detected with ELISA, and correlation between various Chinese medical syndrome types and objective indicators were analyzed. RESULTS: There was no statistical difference in HBV-DNA quantitative results among various syndrome types (P > 0.05). HBeAg positive rate was higher in GDPDS than in other syndrome types (P < 0.05). It was sequenced as GDPDS > GSYDS > SBBCS > GGDHS > PSYDS. Compared with the normal control group, percentages of CD3+ and CD3+ CD4+ were lower in PSYDS (P < 0.05). The ratio of CD3+ CD4+/CD3+ CD8 was lower in GGDHS and PSYDS than in the normal control group (P < 0.05). There was no statistical difference in the CD3+ CD8+ percentage among various syndrome types (P > 0.05). The quantitation of HLA-DR13 gene was lower in GDPDS and GSYDS than in the normal control group (P < 0.05). The positive rate of BCP mutation was higher in GSYDS than in other syndrome types (P < 0.05). CONCLUSION: Co-detection results of HLA-DR13 and BCP could be used as reference indices of Chinese medical syndrome typing of CHB.

[Chronic liver diseases--new therapy. Are biopsies necessary?]. / Chronische Lebererkrankungen--neue Therapie. Benötigen wir die Biopsie?

Chronic liver disease can often reliably be assessed only by examination of biopsy material. In this article the possible indications for liver biopsy in viral hepatitis B and C, autoimmune liver disease, steatohepatitis and hereditary metabolic diseases are described. A biopsy may be useful in cases with unclear clinical or serological situations or with questionable chronicity and comorbidities. The assessment of biopsy material should be based on guideline-based classification systems. The value of biopsy diagnosis benefits from a close interdisciplinary clinical pathological cooperation.

Use of the International Classification of Diseases, 9th revision, coding in identifying chronic hepatitis B virus infection in health system data: implications for national surveillance.

OBJECTIVE: With increasing use electronic health records (EHR) in the USA, we looked at the predictive values of the International Classification of Diseases, 9th revision (ICD-9) coding system for surveillance of chronic hepatitis B virus (HBV) infection. MATERIALS AND METHODS: The chronic HBV cohort from the Chronic Hepatitis Cohort Study was created based on electronic health records (EHR) of adult patients who accessed services from 2006 to 2008 from four healthcare systems in the USA. Using the gold standard of abstractor review to confirm HBV cases, we calculated the sensitivity, specificity, positive and negative predictive values using one qualifying ICD-9 code versus using two qualifying ICD-9 codes separated by 6 months or greater. RESULTS: Of 1 652 055 adult patients, 2202 (0.1%) were confirmed as having chronic HBV. Use of one ICD-9 code had a sensitivity of 83.9%, positive predictive value of 61.0%, and specificity and negative predictive values greater than 99%. Use of two hepatitis B-specific ICD-9 codes resulted in a sensitivity of 58.4% and a positive predictive value of 89.9%. DISCUSSION: Use of one or two hepatitis B ICD-9 codes can identify cases with chronic HBV infection with varying sensitivity and positive predictive values. CONCLUSIONS: As the USA increases the use of EHR, surveillance using ICD-9 codes may be reliable to determine the burden of chronic HBV infection and would be useful to improve reporting by state and local health departments.

[hFgl2 protein expression in peripheral blood mononuclear cells in different clinical types of liver disease].

OBJECTIVE: To detect hFgl2 expression in peripheral blood mononuclear cells in patients with chronic hepatitis B and liver cancer and explore its association with the severity of chronic hepatitis B. METHODS: The protein expression of hFgl2 in peripheral blood mononuclear cells was detected in 78 patients with chronic hepatitis B (including mild, moderate, or severe cases), chronic severe hepatitis, or liver cancer, with 20 healthy volunteers as controls. The data were analyzed in comparison with the patients' alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBiL and) levels. RESULTS: hFgl2 protein expression was significantly higher in patients with chronic severe hepatitis and liver cancer than in the healthy volunteers and patients with chronic hepatitis B. The patients with chronic severe hepatitis had significantly higher hFgl2 protein expression than patients with liver cancer. In severe cases of chronic hepatitis B, hFgl2 protein expression was positively correlated with ALT, AST and TBiL, but these correlations were not found in mild or moderate cases. CONCLUSIONS: Peripheral blood mononuclear cells express hFgl2 protein, whose expression level increases with the severity of chronic hepatitis B.

Performance of risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B) score in classifying treatment eligibility under 2012 Asian Pacific Association for the Study of the Liver (APASL) guideline for chronic hepatitis B patients.

BACKGROUND: REACH-B [Risk Estimation for Hepatocellular Carcinoma (HCC) in Chronic Hepatitis B] scoring system was developed to predict the risk of HCC in noncirrhotic chronic hepatitis B (CHB) patients. AIM: To evaluate the discriminatory performance of REACH-B scoring system in classifying anti-viral treatment eligibility of CHB patients according to the 2012 Asian Pacific Association for the Study of the Liver (APASL) treatment guideline. METHODS: A total of 904 noncirrhotic CHB were enrolled. Patients' age, gender, liver biochemistry, HBeAg status and HBV DNA levels were recorded. RESULTS: The minimum REACH-B risk score for patients to be eligible for anti-viral treatment was 7 for HBeAg-positive and 6 for HBeAg-negative patients. Among them, increasing REACH-B score was not significantly associated with eligibility for treatment [adjusted odds ratio (OR): 1.210, 95% confidence interval (CI): 0.979-1.494, P = 0.078] in HBeAg-positive patients, as shown by logistic regression analysis after adjusting for gender. In HBeAg-negative patients, REACH-B score significantly predicted the treatment eligibility (adjusted OR: 1.783, 95% CI: 1.607-1.979, P < 0.001). Discriminatory ability of REACH-B score to classify eligibility was poor for HBeAg-positive patients ≥40 years [area under receiver operating characteristic (AUC): 0.664, 95% CI: 0.533-0.795], but good/excellent for HBeAg-positive patients <40 years (AUC: 0.903; 95% CI: 0.841-0.964), HBeAg-negative patients ≥45 years (AUC: 0.883; 95% CI: 0.848-0.917) and HBeAg-negative patients <45 years (AUC: 0.907; 95% CI: 0.874-0.940). CONCLUSION: The discriminatory performance of the REACH-B scoring system in classifying anti-viral treatment eligibility based on the 2012 APASL guideline was good/excellent, except for ≥40 years old HBeAg-positive patients.

Aflatoxin M1 in the urine of non-carriers and chronic carriers of hepatitis B virus in Maringa, Brazil

Exposure to aflatoxins (AFs) in the diet may favour the development of hepatocellular carcinoma (HCC) and the acute exacerbation of hepatitis in chronic hepatitis B virus (HBV) carriers. Measurement of biomarkers such as aflatoxin M1 (AFM1), a metabolite of aflatoxin B1 (AFB1), in urine allows for the assessment of populations exposed to aflatoxins. The aim of this study was to investigate the occurrence of aflatoxin M1 in the urine of HBV carrier and non-carrier patients. One group included 43 randomly selected HBV carriers treated at two hospitals in the city of Maringa, Brazil, from March to June 2008. Control group consisted of 29 healthy adult volunteers with anti-HBs positive and HBsAg negative test results. Detection of AFM1 was performed by fluorescence using high performance liquid chromatography (HPLC) and post-column derivation with the Kobra Cell®. Of the 72 samples analysed, 05/29 (17.2%) AFM1 positive samples were from HBV non-carriers, and 16/43 (37.2%) of samples were from chronic HBV carriers. This study showed AFM1 in the urine of the two surveyed population. However, there is evidence that the chronic HBV carriers have a higher risk of developing HCC due to additive interaction between AFs and HBV.

A exposição às aflatoxinas (AFs) na dieta é um fator de risco para o desenvolvimento do carcinoma hepatocelular (CHC) e a exacerbação da hepatite aguda em indivíduos portadores do vírus da hepatite B (VHB). O uso de biomarcadores, como a aflatoxina M1 (AFM1) na urina, produto de biotransformação da aflatoxina B1 (AFB1), permite avaliar se a população está exposta às AFs. O objetivo do presente estudo foi investigar ocorrência de AFM1 na urina de portadores e não portadores crônicos do VHB. Foi selecionado um grupo, de forma aleatória, representado por 43 portadores do VHB atendidos em dois hospitais da cidade de Maringá, Brasil, no período de Março a Junho/2008. O grupo controle foi composto por 29 voluntários adultos saudáveis anti-HBs positivo e HBsAg negativo. A determinação de AFM1 foi realizada por meio de detecção por fluorescência em sistema de cromatografia a líquido de alta eficiência com derivação pós-coluna utilizando Kobra Cell®. Das 72 amostras analisadas, 05/29 (17,2%) foram positivas para AFM1 em indivíduos não portadores do VHB, e 16/43 (37,2%) de pacientes portadores do VHB. Este estudo demonstrou a ocorrência de AFM1 na urina dos dois grupos estudados. Entretanto, há evidências de que os portadores do VHB possuam alto risco no desenvolvimento do CHC devido ao efeito aditivo pela interação entre aflatoxinas e VHB.

Noninvasive assessment of liver fibrosis with acoustic radiation force impulse imaging: increased liver and splenic stiffness in patients with liver fibrosis and cirrhosis.

PURPOSE: To evaluate acoustic radiation force impulse imaging (ARFI) of the liver and spleen as a new method for the noninvasive assessment of liver fibrosis (LF). MATERIALS AND METHODS: Three groups of 58 examinees were studied: (A) 20 healthy volunteers; (B) 18 patients with chronic viral hepatitis (CVH) B or C having liver fibrosis stages F 1 - 4 (assessed by liver biopsy; Ishak classification); and (C) 20 patients with liver cirrhosis (LC). All participants were examined using the Siemens ACUSON S 2000 Ultrasound Virtual Touch Tissue Quantification system. Ten measurements were performed on both liver lobes and three measurements on the spleen, and the obtained mean values (shear wave velocities [SWV] expressed in m/s) were compared between the groups. In 20 patients the splenic artery pulsatility index (SAPI) was also measured and correlated to the liver and splenic ARFI and histological stage of LF. RESULTS: Hepatic ARFI measurements demonstrated a significant correlation to LB results (Spearman's ρ = 0.766; ρ < 0.001) and SWV cut-off values of 1.3 (AUC 0.96) and 1.86 (AUC 0.99) could reliably differentiate between healthy (A) and non-cirrhotic CVH (B), as well as between non-cirrhotic CVH (B) and LC (C). Splenic SWV cut-off value of 2.73 (AUC 0.82) could differentiate between the patients with LC and non-cirrhotic CVH. A significant correlation was also observed between the SAPI and liver ARFI results (ρ = 0.56; p = 0.013). CONCLUSION: The hepatic and splenic SWV measured by ARFI increase with the LF stage, and the hepatic SWV correlate well with SAPI. This new technology enables simultaneous morphological, Doppler and elastometric examinations and might improve the accuracy of noninvasive liver fibrosis assessment.

Hepatitis b: historia natural: manejo del niño portador asintomático / Hepatitis b: natural history: management of asymptomatic carrier child

La hepatitis B es aún un problema de salud pública a nivel mundial. Según datos del CDC el 42% de las hepatitis B crónicas del adulto han sido adquiridas durante la infancia. La historia natural de la infección crónica por el VHB se caracteriza por tres fases: inicial de tolerancia inmune al virus; de “clearence” inmune de variable duración, y de remisión. Durante la infancia y sobre todo la adolescencia más del 80% de los pacientes con VHB seroconvierten a antiHBe. La historia natural de la infección crónica actualmente puede ser modificada por la indicación del tratamiento apropiado el que, en un porcentaje de pacientes, evita la progresión de la enfermedad y sus secuelas.

Hepatitis b is still a public health problem worldwide. According to the CDC for 42% of adult chronic hepatitis B have been acquired during childhood. The natural history of chronic HBV infection is characterized by three phases: initial immune tolerance to the virus; “clearance” immune of variable duration, and referral. During childhood and adolescence, especially more tan 80% of patients seroconverted to HBV antiHBe. The natural history of chronic infection can now be modified by appropiate treatment indicating that, in a proportion of patients, prevents the progression of the disease and its sequelae.

[Current problems of hepatitis]. / Aktuelle Probleme der Hepatitis.

New findings have been made in recent years on the various forms of the hepatitis virus in terms of disease course, its etiopathogenetic link with comorbidities and the definition of new forms in Central Europe. Epstein-Barr virus (EBV)- and cytomegalovirus (CMV)-induced hepatitis may occur in the so-called sero-negative group of hepatitis and direct demonstration of the viral genome in paraffin liver tissues is required to confirm the diagnosis. Since diagnosis of autoimmune hepatitis in daily practice may be difficult, a scoring system with simplified criteria has recently been developed.