HBV Group Research Articles

Non-Invasive Assessment of Liver Fibrosis Through Echosens Fibro Meter Virus

Background: Non-invasive methods for liver fibrosis assessment have replaced liver particularly for monitoring viral infections such as HBV and HCV. No studies have validated this test in NAFLD patient with high-risk factors. Methods: This study was done in patients presenting with chronic viral hepatitis B, chronic viral hepatitis C and NAFLD patient with high-risk factors whenever the necessity of liver biopsy was apparent in deciding the appropriate treatment plan. Echosens FibroMeter Virus test was done to determine the stage of fibrosis and the necroinflammatory status in this cohort of patients in a tertiary care hospital, Metro MAS in Jaipur, from September 2013 to April 2015. Results: Analysis of data from 57 patients, 24 (42%) of whom had chronic HBV infection and 7 (12%) chronic HCV infection, and 26 NAFLD patients with high risk factors (46%) was done. The median age was 50.1 12.0 (range 19–78). The mean body mass index (BMI) was 26.6 2.6 in the HBV group, 23.7 2.2 in the HCV group and 33.2 1.2 in the NAFLD group. The distribution of FibroMeter results was: F0–F1: 9 (12.2%), F1: 2 (3.3%), F1–F2: 23 (41.4%), F2: 9 (14.8%), F2–F3: 6 (11%), F3: 3 (5.0%), F3–F4: 7 (12.3%). The distribution of the necroinflammatory activity was: A0–A1: 9 (15.6%), A1–A2: 27 (47.1%), A2–A3: 21 (37.3%). No statistically significant differences were seen in this study between patients with chronic viral hepatitis and NAFLD regarding mean fibrosis scores (P = 0.468) or mean necroinflammatory activity scores (P = 0.72). Conclusion: FibroMeter Virus results should be interpreted in clinical context and potential confounding factors should be identified on a case-bycase basis. FibroMeter was also reproducible in NAFLD cohort of patients. Direct comparative study of this test with liver biopsy will further validate the sensitivity and specificity of FibroMeter test.

NGF and P75NTR gene expression is associated with the hepatic fibrosis stage due to viral and non-viral causes.

This study evaluated the relative mRNA expression levels of nerve growth factor (NGF) and the p75 neurothrophin receptor (p75NTR) in different histological stages of human liver disease. Fifty-one liver biopsy specimens obtained from patients with hepatitis B virus (n = 6), hepatitis C virus (n = 28), and non-viral hepatitis – (n = 9) and standard histological liver (n = 8) as controls (CT) were subjected to qPCR and histopathological exams. Our data revealed a significant difference in the NGF expression levels between the three patient groups and the Control group. p75NTR expression levels in the HCV and NVH groups were higher than those observed in the HBV and Control groups. In cases of liver cirrhosis, higher p75NTR mRNA expression was observed, whereas NGF was expressed at higher levels in patients with hepatic fibrosis. NGF expression was lower in the F1 liver fibrosis stage, and p75NTR receptor expression continuously and proportionately increased compared to the increase in the degree of fibrosis and was significantly higher in livers in fibrosis stages 3 and 4. The hepatic levels of NGF and p75NTR were decreased and increased, respectively, relative to the stage of inflammatory activity. A positive correlation between p75NTR and NGF gene expression was observed in livers with mild to moderate fibrosis, though not in cases of severe fibrosis and cirrhosis.ConclusionOur results demonstrate that the course of chronic liver disease can be regulated by NGF and p75NTR, which function by decreasing or inhibiting hepatocyte regeneration and proliferation.

Hepatocellular carcinoma in chronic HBV-HCV co-infection is correlated to fibrosis and disease duration

Hepatocellular carcinoma (HCC) is a development of severe liver disease frequently due to HBV and/or HCV infection. The aim of this retrospective study was to evaluate the development of HCC in patients with HBV-HCV chronic infection compared with patients with single HBV or HCV infection and the viral and host factors correlated to HCC in co-infected patients. We studied 268 patients with histology proven chronic hepatitis: 56 had HBV-HCV co-infection (HBV-HCV group), 46 had HBV infection (HBV group) and 166 had HCV infection (HCV group). Patients were followed up for at least 3 years. Viral and host factors were studied. HCC was more frequent in HBV-HCV group (14%) compared with HBV (2%, p = 0.006) and HCV monoinfected (4%, p = 0.006). The Mantel-Haenszel test used to investigate the relationship between HBV-HCV co-infection and development of HCC indicated an association between development of HCC and HBV-HCV co-infection (p < 0.001). In the HBV-HCV group, patients with HCC were significantly older (p = 0.000), had longer disease duration (p = 0.001), higher blood glucose levels (p = 0.001), lower levels of steatosis (p = 0.02), higher levels of fibrosis (p = 0.000), higher HCV RNA (p = 0.01) than those without HCC. ALT, lipid profile, PNPLA3 variant distribution and HBV viral load did not differ among co-infected patients with or without HCC. In conclusion HCC was more frequent in our patients with HBV-HCV co-infection, than in those with HBV or HCV mono-infection; possible associated risk factors for HCC development seem a long duration of disease, high levels of fibrosis and carbohydrate intolerance.

Assessment of the Frequency of Autoantibodies inChronicViral Hepatitis.

Objective:To examine the occurrence frequency of auto-antibodies and autoimmune diseases in patients with chronic hepatitis B or C.Methods:A total of 67 patients diagnosed with chronic hepatitis B and 77 patients diagnosed with chronic hepatitis C infection based on HBs Ag, Anti HCV, HBe Ag, Anti HBe Ag, HBV DNA, HCV RNA, liver ultrasound, and liver biopsy results as well as 48 healthy individuals were included in this study. ANA, anti dsDNA, anti LKM, Anti-SMA, AMA, C-ANCA, P-ANCA, anti-SSA, anti-SSB, anti-Scl-70, anti Jo-1, anti-U1snRNP, anti-centromere, anti-Jo-1, anti tpo, and anti tg were studied in all individuals in each study group.Results:ANA positivity was detected in 8 (12%), 15 (19%) and 2 (4%) individuals in HBV, HCV and control groups, respectively. The difference between the groups was significant (P=0.04). Similarly, anti Tg was positive in one subject in HBV group, in 6 subjects (7%) in HCV group, and in one subject among controls, the difference being significant (P=0.04). There were no significant differences between the study groups in the frequency of other auto-antibodies.Conclusion:Similar to studies involving patients who received interferon and/or antiviral agents, an increased frequency of auto-antibodies was also detected in our patient group consisting of interferon and anti-viral naive subjects. The increase in the frequency of auto-antibodies reached statistical significance among individuals with HCV infection. Thus, pre-treatment assessment of auto-antibodies in newly diagnosed cases of chronic hepatitis B or hepatitis C infection may provide beneficial information on the future occurrence of auto-immune responses in these patients.

Non-invasive assessment of liver fibrosis through FibroMeter in patients with chronic viral hepatitis B and C

Results We analyzed data from 87 patients, 68 (78.2%) of which had chronic HBV infection and 19 (21.8%), chronic HCV infection. The median age was 44.9 ± 15.0 (range 17-75). The mean body mass index (BMI) was 26.0 ± 3.6 in the HBV group and 26.7 ± 3.2 in the HCV group. Overall, 36 patients (41.4%) had normal BMI, another 36 (41.4%) had a BMI equivalent for overweight status, and 15 (17.2%) had grade I obesity. The distribution of FibroMeter results was: F0-F1: 8 (9.2%), F1: 2 (2.3%), F1-F2: 43 (49.4%), F2: 11 (12.6%), F2F3: 8 (9.2%), F3: 7 (8.0%), F3-F4: 8 (9.2%). The distribution of the necroinflammatory activity was: A0-A1: 16 (18.4%), A1-A2: 52 (59.8%), A2-A3: 19 (21.8%). We identified no statistically significant differences between patients with HBV and HCV regarding mean fibrosis scores (p = 0.476) or mean necroinflammatory activity scores (p = 0.681). Conclusion The patients included in this study had varied ages and characteristics. FibroMeter classified most of them as F1-F2 but descriptive data should be interpreted in clinical context and potential confounding factors should be identified on a case-by-case basis.

Distinctive personality patterns in patients with chronic viral hepatitis

Results We have evaluated 29 patients with chronic viral hepatitis (21 females and 8 males – 9 with HBV and 20 with HCV) and 28 subjects for the control group (18 females and 10 males). The mean age in patients with chronic hepatitis was 47.97 ± 13.63 vs. 31.36 ± 8.28 in the control group. Comparing the results between the control group and the two subgroups with HBV and HCV infection we obtained the following statistically significant differences: • The HBV group presented 31 scales with significant differences compared to controls, with elevated scores for: OBS (obsessiveness), DEP (depression), ANG (anger), TPA (type A personality) and TRT (negative treatment indicators) scales and subscales TRT1 (low motivation) and TRT2 (inability to disclose), etc. • The HCV group presented 7 scales with significant differences compared to controls, with elevated scores mostly for scales related to the somatic connection. We also identified statistically significant differences between the two chronic hepatitis subgroups (namely 27 scales related to OBS (obsessions), DEP1 (lack of drive), ANG2 (irritability), and CYN (cynicism).

Outcomes after curative hepatectomy in patients with non-B non-C hepatocellular carcinoma and hepatitis B virus hepatocellular carcinoma from non-cirrhotic liver.

There is controversy regarding liver function of non-B, non-C hepatocellular carcinoma (NBNC-HCC) patients, the biological behavior of their tumors, and the outcome after surgical treatment. The aims of the present study were to compare clinicopathologic data and long-term clinical outcomes between NBNC-HCC patients and hepatitis B virus HCC (HBV-HCC) patients from non-cirrhotic liver after curative hepatectomy. Data for HBV-HCC patients (n = 360) and NBNC-HCC patients (n = 103) were retrospectively reviewed. The median age of patients in the NBNC group was significantly higher than that of the HBV group (63 years vs. 53 years, P < 0.001). Tumor size in the NBNC group was greater than that in the HBV group (5.1 cm vs. 3.8 cm, P < 0.001). Regarding liver histology, the grade of lobular activity, periportal activity, and fibrosis in the HBV group was higher than in the NBNC group (P < 0.001, P < 0.001, and P < 0.001, respectively). There were no statistically significant differences in disease-free survival and overall survival between the two groups (P = 0.257 and P = 0.579, respectively). Multivariate analysis showed that increased tumor size, microvascular invasion, and intrahepatic metastasis were associated with tumor recurrence after curative liver resection. For patients with non-cirrhotic liver, clinical outcomes for NBNC-HCC were comparable to those for HBV-HCC after curative hepatectomy.

Lasting immune memory against hepatitis B following challenge 10–11 years after primary vaccination with either three doses of hexavalent DTPa-HBV-IPV/Hib or monovalent hepatitis B vaccine at 3, 5 and 11–12 months of age

BackgroundThe combined hexavalent diphtheria–tetanus–pertussis–hepatitis B-inactivated poliomyelitis – Haemophilus influenzae type b conjugate vaccine (Infanrix hexa™; DTPa-HBV-IPV/Hib: GlaxoSmithKline Vaccines) induces robust responses to the HBV component when administered at 3, 5 and 11–12 months of age. We assessed long term HBV antibody persistence 10–11 years after primary vaccination in infancy. MethodsAntibody persistence and immune memory were assessed post-primary vaccination at 3, 5, 11–12 months with DTPa-HBV-IPV/Hib, or monovalent HBV vaccine (Engerix™ B, GlaxoSmithKline Vaccines) co-administered with DTPa-IPV/Hib (Infanrix™-IPV/Hib, GlaxoSmithKline Vaccines) in 185 children aged 11–12 years. Blood samples were collected before and 1 month after a challenge dose of Engerix™ B (10μg dose). Results10–11 years after primary vaccination the percentage of subjects with persisting anti-HBs antibody concentrations ≥10mIU/ml was 48.4% in the DTPa-HBV-IPV/Hib group and 58.4% in the DTPa-IPV/Hib+HBV group. After the HBV challenge dose, the percentage with anti-HBs ≥100mIU/ml increased from 14.7% to 93.6% in the DTPa-HBV-IPV/Hib group and 19.1% to 94.4% in the DTPa-IPV/Hib+HBV group. Anti-HBs GMCs increased by at least 187-fold in each group. An anamnestic response (≥4-fold increase in initially seropositive or anti-HBs concentration ≥10mIU/ml in initially seronegative subjects) was observed in 96.8% and 96.6% of subjects in the DTPa-HBV-IPV/Hib and DTPa-IPV/Hib+HBV groups, respectively. No serious adverse events occurred that were considered related to challenge vaccination. ConclusionAdministration of HBV as part of a combination vaccine or as a monovalent vaccine induced long lasting immune memory against HBV in children primed at 3, 5 and 11 months of age. Antibody persistence and immune memory were similar, suggesting that protection afforded by DTPa-HBV-IPV/Hib and monovalent HBV vaccines, is likely to be of similar duration. The administration of HBV challenge dose 10–11 years after the 3, 5, 11–12 months primary schedule induced strong anamnestic responses and was well tolerated.This study is registered at www.clinicaltrials.gov NCT01138098.

Association between IL-10 gene promoter polymorphism and hepatitis B viral infection in an Egyptian population.

Cytokines play critical roles in the pathogenesis of hepatitis B virus infection (HBV). This work was designed to study the effect of IL-10 gene polymorphisms (-1082G/A and -819C/T) on susceptibility of Egyptians to HBV. Genotyping was performed using single-stranded polymorphism-polymerase chain reaction in 118 Egyptian hepatitis B patients and 119 healthy controls, and IL-10 serum levels were measured using ELISA. The frequency of IL-10 -1082G/G was significantly higher in HBV patients than in healthy controls, and G/A and A/A were not significantly different between groups. The distribution of IL-10 -819 genotypes was not significantly different between the HBV and healthy control groups. Although AT was significantly different between controls and patients, the distribution of the other haplotypes was not. IL-10 levels were significantly lower among hepatitis B patients. Our data stress the importance of IL-10 gene polymorphism in HBV infection. Depending on our preliminary work, IL-10 -1082G/G may act as a host genetic factor in the susceptibility to HBV infection in Egyptians.

The ABCs of viral hepatitis that define biomarker signatures of acute viral hepatitis

Viral hepatitis is the leading cause of liver disease worldwide and can be caused by several agents, including hepatitis A (HAV), B (HBV), and C (HCV) virus. We employed multiplexed protein immune assays to identify biomarker signatures of viral hepatitis in order to define unique and common responses for three different acute viral infections of the liver. We performed multianalyte profiling, measuring the concentrations of 182 serum proteins obtained from acute HAV- (18), HBV- (18), and HCV-infected (28) individuals, recruited as part of a hospital-based surveillance program in Cairo, Egypt. Virus-specific biomarker signatures were identified and validation was performed using a unique patient population. A core signature of 46 plasma proteins was commonly modulated in all three infections, as compared to healthy controls. Principle component analysis (PCA) revealed a host response based upon 34 proteins, which could distinguish HCV patients from HAV- and HBV-infected individuals or healthy controls. When HAV and HBV groups were compared directly, 34 differentially expressed serum proteins allowed the separation of these two patient groups. A validation study was performed on an additional 111 patients, confirming the relevance of our initial findings, and defining the 17 analytes that reproducibly segregated the patient populations. This combined discovery and biomarker validation approach revealed a previously unrecognized virus-specific induction of host proteins. The identification of hepatitis virus specific signatures provides a foundation for functional studies and the identification of potential correlates of viral clearance.

Insulin resistance and steatosis in HBV-HCV co-infected patients: Role of PNPLA3 polymorphisms and impact on liver fibrosis progression.

To evaluate steatosis, insulin resistance (IR) and patatin-like phospholipase domain-containing 3 (PNPLA3) and their relation to disease progression in hepatitis B and C viruses (HCV-HBV) co-infected patients. Three hundred and thirty patients with biopsy proven chronic hepatitis were enrolled: 66 had HBV-HCV, 66 HBV and 198 HCV infection. Prevalence of steatosis, IR and PNPLA3 polymorphisms and their relation to anthropometric, biochemical, virological and histological parameters were evaluated. Prevalence of steatosis in group HBV-HCV was similar to that in HCV (47.0% vs 49.5%, respectively); group HBV showed the lowest steatosis (33.3%). Group HBV-HCV had a lesser degree of steatosis than HCV (P = 0.016), lower HCV RNA levels (P = 0.025) and lower prevalence and degree of IR (P = 0.01). PNPLA3 polymorphisms were associated with steatosis. Group HBV-HCV showed higher levels of liver fibrosis than group HCV (P = 0.001), but similar to that observed in HBV group. In HBV-HCV group, liver fibrosis was not associated with steatosis, IR or PNPLA3. HBV infection was the independent predictor of advanced liver fibrosis. HBV-HCV co-infected patients have lower degree of hepatic steatosis, IR and HCV RNA than HCV mono-infected; co-infected patients showed a more rapid liver fibrosis progression that seems to be due to the double infection and/or HBV dominance.

Association of interferon-alpha gene polymorphisms with chronic hepatitis B virus infection

In this study, the association between the risk of chronic hepatitis B virus infection and the polymorphisms within promoter regions of IFN-α1 and five genes was explored. This association study was performed on 180 Thai patients with chronic HBV infection [hepatocellular carcinoma (HCC)=65 and non-HCC=115], 173 individuals with self-limited HBV infection and 140 healthy controls. Our results showed that the A allele of -1823G/A SNP within IFNA1 gene was significantly associated with an increased risk of chronic HBV infection as compared to healthy individuals and self-limited HBV group [OR (95% CI)=2.20 (1.51-3.19), P=0.000014 and OR (95% CI)=1.61 (1.12-2.33), P=0.0073, respectively]. The effect of A allele was similar to autosomal recessive in which the presence of AA genotype when compared to GG and GA conferred the OR of 2.79 (95% CI=1.72-4.52, P=0.0000085). By multifactor dimensionality reduction analysis, we found the interaction between IFNA5 (-2529) and IFNA1 (-1823) genes that gave the risk to chronic HBV infection, with the OR (95% CI) of the high-risk to low-risk group was 2.79 (1.77-4.40), P<0.0001. However, further study in functional significance is required.

Effect of the Cellular-Type Artificial Oxygen Carrier Hemoglobin Vesicle as a Resuscitative Fluid for Prehospital Treatment

The hemoglobin vesicle (Hb-vesicle) is a cellular-type artificial oxygen carrier showing a resuscitative effect comparable to that of blood transfusion in several animal models. However, the efficacy of Hb-vesicles for resuscitation when the hemorrhage cannot be controlled remains unclear. Therefore, we used Hb-vesicles in a rat hemorrhagic shock model caused by continuous bleeding. For inducing uncontrolled hemorrhage, animals were heparinized and bled from the caudal artery. Fluid resuscitation was subsequently performed with five materials: Hb-vesicle suspension in a 5% albumin (Alb) solution (HbV), washed red blood cells (wRBC) in a 6% hydroxyethyl starch (HES) solution, 5% Alb, 6% HES, and saline (Sal). During the experiment, all animals in the HbV and wRBC groups survived, whereas all those in the Alb and HES groups died. In the Sal group, five of seven animals died. In the HbV and wRBC groups, the heart rate, mean arterial pressure, and blood lactic acid levels were stabilized during resuscitation. Meanwhile, the hematocrit levels of the HbV, Alb, and HES groups showed sharp decreases (HbV: 6.8% ± 1.7%, Alb: 6.8% ± 0.8%, HES: 5.5% ± 0.7% at 100% total circulated blood volume; final hematocrit of the HbV group: 1.5% ± 0.5%). These results suggest that shocked animals can survive longer when the Hb-vesicle supply is maintained and that HbV showed a similar effect to wRBC in maintaining the circulating volume and oxygen metabolism. Continuous infusion of Hb-vesicles may extend the survival of trauma victims with uncontrolled hemorrhage until they have reached a trauma center.

Study on type I interferon and phospho-IRF3 in murine liver dendritic cells after intervened by HBV

To detect the secretions of type I interferon and the expressions of phospho-IRF3 in murine liver dendritic cells intervened by HBV. The murine liver dendritic cells were isolated via anti-CD11c microbeads and were incubated in the presence of GM-CSF and IL-4 to induce the DC generation and proliferation in 24-well cell culture plates. HBV virions were isolated via ultracentrifugation and were detected by quantitative Realtime-PCR. The DCs were divided into two groups: one group was cultured with HBV virions for 24 hours, the other group was cultured without HBV as control group. The cells were harvested at Oh, 1h, 2h, 6h and 24h after being stimulated with poly I:C and the expressions of p-IRF3 and the concentration of IFN beta in supernatants were detected with western blot and ELISA respectively. The IFN beta concentrations at 0 h, 6 h and 24 h in the supernatants of the HBV group and the control group were (12.38 +/- 3.71) pg/ml, (88.67 +/- 9.01) pg/ml and (69.89 +/- 5.80) pg/ml vs (10.83 +/- 4.11) pg/ml, (137.68 +/- 12.28) pg/ml and (72.25 +/- 8.61) pg/ml, respectively. No statistical differences found at 0 h (t = 0.8398, P > 0.05) and 24 h (t = 0.6820, P > 0.05) between the two groups except that at 6 h (t = 9.653, P < 0.01). The expressions of phospho-IRF3 in HBV group were lower than that in control group. The type I interferon secretion and the phospho-IRF3 expression were decreased in murine liver dendritic cells when intervened by HBV.

Metabolic syndrome and severity of fibrosis in patients with chronic viral hepatitis B infection or non-alcoholic fatty liver disease

To investigate the prevalence of metabolic syndrome (MS) in patients with chronic viral hepatitis B (HBV) infection or non-alcoholic fatty liver disease (NAFLD), and to determine the relationship between MS and the risk of fibrosis in those patients, 136 patients with chronic HBV infections and 110 NAFLD patients were analyzed retrospectively between January 2008 and June 2009. The results showed that the prevalence of MS in the NAFLD group was significantly higher that of the HBV infection group (49.1 and 11.8%, respectively; P < 0.01). In HBV group, severity of fibrosis was associated with increased body mass index (BMI), higher aspartate aminotransferase (AST) and gamma-glutamyl-transpeptidase (GGT), severity of necroinflammation and MS. However, in NAFLD group, MS was more prevalent in patients with non-alcoholic steatohepatitis (NASH) than that of simple fatty liver (55.4 and 40%, respectively; P < 0.01). Severity of fibrosis was associated with MS, higher alanine transarninase (ALT), AST, GGT, and severe necroinflammation. We concluded that MS might be more prevalent in NAFLD patients, and associated with the severity of fibrosis in patients with chronic HBV infection or NAFLD. Key words: Metabolic syndrome, viral hepatitis B, non-alcoholic fatty liver disease, fibrosis.

The association of HBV-DNA change with cytokines levels in chronic HBV carriers superinfected with measles virus

Objective To investigate the HBV-DNA changes in HBV carriers superinfected with measles virus and its relation with cytokines. Methods HBV-DNA loads were detected by PCR in 23 chronic HBV carriers superinfected with measles virus (superinfection group), 27 chronic HBV carriers (HBV group), and 27 measles patients (measles group). Serum levels of cytokines (IL-2, 4, 5, and 10, IFN-r, TNF-a, and RANTES) were measured by Luminex Liquichip technology. Reaults The HBV-DNA loads were significantly lower in superinfection group than in HBV group (P＜0.05). There were significant differences in levels of IL-4, IL-5, IFN-r, and TNF-a between the three groups (P＜0.05); but there were no significant differences in IL-2, RANTES, and IL-10 (P＞0.05). The change of HBV-DNA loads were negatively related with levels of IFN-r and TNF-a, but positively related with levels of IL-4 and IL-5 (P＜0.05). Conclusions The elevated levels of IFN-r and TNF-a and the decreased levels of IL-4 and IL-5in chronic HBV carriers superinfected with measles virus can probably lead to the inhibition of HBV-DNA replication. Key words: Chronic hepatitis B; Measles virus; Cytokines; Viral interference

The biomarker N-terminal pro-brain natriuretic peptide and liver diseases

NT-proBNP has emerged as a powerful diagnostic and prognostic biomarker in heart disease. Studies showed that NT-proBNP is a sensitive biomarker for identifying patients with heart failure caused by hepatitis C virus (HCV) related myocarditis. The purpose of this study was to evaluate the correlation between the serum concentration of NT-proBNP and hepatitis virus infection/liver disease. 223 serum samples from blood donors (aged 19~50 years old) were collected as a control group, and 644 samples were obtained from patients infected by hepatitis viruses including 493 HBV: 364 chronic hepatitis (CH), 86 hepatocellular carcinoma (HCC) and 43 liver cirrhosis (LC) and 151 HCV (85 CH, 14 HCC, 52 LC). All samples were assayed with an Elecsys immunoassay analyzer for NT-proBNP concentration. The mean concentration of NT-proBNP in the control group was 21.77 pg/ml and showed no significant variation with either age or gender. Both the mean value and the rate of abnormality of NT-proBNP were significantly higher for the HBV- and HCV-infected groups in comparison with the control group. The mean NT-proBNP value (380.24 pg/ml) and abnormality rate (38.41%) in the HCV group were higher than that of the HBV group. For samples from patients with HBV/HCV-related hepatic disease/pathology, the mean NT-proBNP value (517.19 pg/ml/597.18 pg/ml) were the highest in the liver cirrhosis group. Hepatic pathologic lesions, particularly cirrhosis, may contribute to the elevation of NT-proBNP in subjects with HBV/HCV infection.

Trends in mortality after diagnosis of hepatitis B or C infection: 1992–2006

Chronic hepatitis B (HBV) or C (HCV) virus infection has been associated with increased risk of death, particularly from liver- and drug-related causes. We examined specific causes of death among a population-based cohort of people infected with HBV or HCV to identify areas of excess risk and examine trends in mortality. HBV and HCV cases notified to the New South Wales (NSW) Health Department between 1992 and 2006 were linked to cause of death data and HIV/AIDS notifications. Mortality rates and standardised mortality ratios (SMRs) were calculated using person time methodology, with NSW population rates used as a comparison. The study cohort comprised 42,480 individuals with HBV mono-infection and 82,034 with HCV mono-infection. HIV co-infection increased the overall mortality rate three to 10-fold compared to mono-infected groups. Liver-related deaths were associated with high excess risk of mortality in both HBV and HCV groups (SMR 10.0, 95% CI 9.0-11.1; 15.8, 95% CI 14.8-16.8). Drug-related deaths among the HCV group also represented an elevated excess risk (SMR 15.4, 95% CI 14.5-16.3). Rates of hepatocellular carcinoma (HCC)-related death remained steady in both groups. A decrease in non-HCC liver-related deaths was seen in the HBV group between 1997 and 2006, but not in the HCV group. After a sharp decrease between 1999 and 2002, drug-related mortality rates in the HCV group have been stable. Improvements in HBV treatment and uptake have most likely reduced non-HCC liver-related mortality. Encouragingly, HCV drug-related mortality remained low compared to pre-2002 levels, likely due to changes in opiate supply, and maintenance or improvement in harm reduction strategies.

E0239 N-terminal pro-brain natriuretic peptide (NT-proBNP): a potential diagnostic biomarker for predicting cardiac dysfunction in patients with liver diseases

BackgroundNT-proBNP has emerged as a powerful diagnostic and prognostic biomarker in heart disease. Studies showed that NT-proBNP is a sensitive biomarker for identifying patients with heart failure caused by hepatitis...

392 LONGITUDINAL ASSESSMENT OF LIVER FIBROSIS USING TRANSIENT ELASTOGRAPHY AND FOUR BIOMARKERS IN HCV PATIENTS WITH F3–F4 FIBROSIS: RELATIONSHIP WITH ANTIVIRAL TREATMENT RESPONSE AND CLINICAL OUTCOME

accelerated in HCV patients with significant steatosis and/or insulin resistance (IR). There is little data regarding the impact of these factors on the accuracy of TE. Aim: To evaluate the influence of metabolic variables on the performance of TE for predicting fibrosis in HBV/HCV subjects. Methods: This study enrolled treatment-naive subjects with positive HBsAg or detectable HCVRNA ≥6 months, submitted to liver biopsy (LB) and TE on the same day. METAVIR score was used for histological analysis. Steatosis ≥30% was considered significant. TE cut-offs: 7.2 (F ≥ 2) and 8.1 (F ≥ 3) kPa for HBV; 7.1 (F ≥ 2) and 9.5 (F ≥ 3) kPa for HCV. IR was defined by HOMA-IR ≥3 and obesity by a BMI ≥30kg/m. Results: After excluding 48 cases (7.8%) with unreliable/unsuccessful TE measurement, 565 patients were analyzed (HBV = 202; HCV = 363). Mean age was 46.1±11.2 years, 67% male. Obesity and diabetes were identified in 6% and 5%, respectively. Significant steatosis was observed in 118 cases (21%) and 141 (25%) had IR. METAVIR F ≥2 was seen in 42% and 54% in HBV and HCV groups, respectively (P = 0.005). Higher TE values were observed in diabetics (P < 0.001), subjects with significant steatosis (P < 0.001), and in those with IR (P < 0.001). Obesity had no influence on TE values (P = 0.607). There was no correlation between TE and BMI (r = 0.108; P = 0.11) and positive but weak correlations were found between TE and HOMA-IR (r = 0.213; P = 0.001) and glucose (r = 0.217; P < 0.001). Discordant results between LB and TE were observed in 117/565 cases (21%). Discordant cases were comparable to concordant ones regarding age, etiology, gender, ALT, AST, GGT, A2/3 METAVIR grade, and all metabolic factors. TE overestimation of fibrosis was identified in 33/565 cases (6%). Among these, none had diabetes or obesity and no association was found between overestimation and metabolic factors. Conclusions: Higher TE values are observed in chronic viral hepatitis patients with metabolic disorders (IR, diabetes, significant steatosis). However, this seems not to exert a significant negative impact on the diagnostic performance of TE for predicting liver fibrosis.