HBsAg Clearance Research Articles

Changes in liver stiffness in acute hepatitis E and B: Role of fibroscan

Background and Aim: Published data suggest alteration in liver stiffness (LSM) values measured by fibroscan following hepatic inflammation. This study was conducted to asses the effect of elevated transaminases on stiffness of liver and changes during course of illness and post recovery. Methods: A total of 30 cases of acute hepatitis (HBV 10 cases, HEV 20 cases) were prospectively recruited and evaluated for liver stiffness at entry and every fortnight till recovery and post recovery to maximum of six months. Diagnosis of acute heaptiits E and B was based and std. criterion. Results: In patients with acute hepatitis A the mean LSM was 13.6 kPa at diagnosis with decline to 10 kPa after 15 days and to 7 kPa after 30 days with mean value of 5.2 kPa after complete recovery. Normal value of age and sex matched controls was 4.8 kPa. This decline correlated significantly with fall in ALT (P <0.004), INR (P <0.005) but not with bilirubin values (P <0.02). In acute heaptitis B LSM values had similar trend 14.3 kPa at entry, 12 kPa at 15 days but 6 out of ten cases had elevated kPa values (9.3 kPa) at time of complete recovery and on follow up showed gradual decline to normal in 4 cases alongwith HbsAg clearance. 2 out 6 cases had elevated kPa values (8.2 and 8.1 kPa) after six months with normal LFT. There was significant correlation with ALT (P <0.004) INR (P < 0.005) values but not with serum bilirubin. Conclusion: Liver stiffness values in acute hepatitis should be seen in context to ALT and INR values. In acute Hepatitis B persistent high LSM values with normal LFT may indicate progress towards chronic hepatitis. Larger studies are required

Correlation of hepatitis B surface antigen levels with HBV DNA on antiviral therapy

S 21 ANNUAL CONFERENCE —2013 V ra lH ep a itis not with bilirubin values (P <0.02). In acute heaptitis B LSM values had similar trend 14.3 kPa at entry, 12 kPa at 15 days but 6 out of ten cases had elevated kPa values (9.3 kPa) at time of complete recovery and on follow up showed gradual decline to normal in 4 cases alongwith HbsAg clearance. 2 out 6 cases had elevated kPa values (8.2 and 8.1 kPa) after six months with normal LFT. There was significant correlation with ALT (P <0.004) INR (P < 0.005) values but not with serum bilirubin. Conclusion: Liver stiffness values in acute hepatitis should be seen in context to ALT and INR values. In acute Hepatitis B persistent high LSM values with normal LFT may indicate progress towards chronic hepatitis. Larger studies are required Corresponding author. Punil Mehrotra. E-mail: punmel@yahoo.com ROLE OF THE BYSTANDER LIVER TISSUE IN DOCUMENTING OCCULT HEPATITIS B IN SURGICAL BIOPSY MATERIAL Kim Vaiphei Rajesh Kumar Department of Histopathology, Post Graduate Institue of Medical Education and Researc, Chandigarh, India Background: Hepatitis B virus (HBV) is important cause of chronic liver disease and one third world population is infected. A poorly recognised entity Occult HBV is presence of HBV DNA in liver or in serum in absence of detectable HBsAg in serum by current detectable assay. Objective: to study liver histology in biopsies detected to be HBV positive in patients with serology negative for HBsAg. Case selection criteria: Cases included in the study were those who were negative for serum HBsAg with no obvious clinical features of hepatitis and liver tissue was incidentally detected to be positive for HBV surface or/and core antigens by immunohistochemistry. Methods: Liver tissue obtained in resected specimen or in wedge biopsy in non-hepatitic conditions like extra-hepatic portal vein obstruction (EHPVO), hypersplenism, tumor metastasis, biliary obstruction or chronic cholecystitis. Sections bearing liver tissue were available for the study. Routine staining and immunohistochemistry were performed in all cases. Result: Forty three cases were studied.M: F=22:21,mean age inmale 43.3 and in female 40 years. All cases were positive for cytoplasmic HBcAg, 10 also showed nuclear HBcAg and 12 for HBsAg. Histological features: normal in 7, chronic hepatitis with activity in 22, metastasis in 14, changes consistent with EHPVO, 3 each of Budd Chiary and cholangitis, and 1 each of NCPF, HCC, granuloma and VOD. Histological features included steatosis, steatohepatitis, portal tract fibrosis with bridging, variable degree of portal tract inflammation, S64 interface hepatitis, lobular inflammation, cholangitis, angioma like portal vein and periductal fibrosis. Conclusion:Occult HBV cases exhibiting positivity for HB surface and/or core proteins with histological features of hepatitis is not a rare phenomenon. Hence, the present study further reiterates the statement of the noblest sample to document infection by hepatotrophic virus being the liver tissue itself. Corresponding author. Kim Vaiphei. E-mail: kvaiphei2009@gmail.com IL-28B GENOMIC POLYMORPHISM AS PREDICTOR OF TREATMENT RESPONSE TO INTERFERON BASED THERAPY FOR CHRONIC HCV INFECTIONEXPERIENCE FROM TERTIARY REFERRAL CENTRE FROM SOUTH INDIA K. A. Anoob John, S. Anil Kumar, P. Pradeep Kumar, Abhilash Haridas, N. Premletha, Vinayakumar Kattoor Ramakrishnan Department of Gastroenterology, Govt Medical College Trivandrum,

Hepatitis B virus infection among first-time blood donors in Italy: prevalence and correlates between serological patterns and occult infection.

A prospective, 1-year study was performed among Italian first-time, volunteer blood donors, who account for 12% of all donations, in order to assess the frequency and serological patterns of hepatitis B virus infection and the presence of occult infection. Consecutive donors (n=31,190) from 21 blood transfusion centres, from age classes not subjected to universal HBV vaccination, were tested for HBsAg and anti-HBc by commercial immunoassays. Other HBV serological markers were searched for and qualitative and quantitative assessments of HBV-DNA were made in HBsAg and/or anti-HBc-positive individuals. Of the 31,190 donors studied, 100 (0.32%) were positive for both HBsAg and anti-HBc, 2 for HBsAg (0.01%) alone, and 2,593 (8.3%) for anti-HBc. Of these last, 86.7% were also positive for anti-HBs (with or without anti-HBe), 2.9% were positive for anti-HBe without anti-HBs and 10.4% had no other HBV markers (anti-HBc alone). A general north-south increasing gradient of HBV prevalence was observed. Circulating HBV-DNA was found in 96.8% of HBsAg-positive subjects as compared to 0.55% (12/2,186) of anti-HBc-positive/HBsAg-negative subjects, with higher frequencies among anti-HBs-negative than among anti-HBs-positive ones (1.68% vs. 0.37%; p <0.01) and among the 57 cases positive for both anti-HBc and anti-HBe (7%). HBV-DNA levels were significantly higher in HBsAg-positive subjects than in HBsAg-negative ones (median: 456 IU/mL vs. 38 IU/mL). The prevalence of HBV infection among Italian first-time blood donors is much lower than in the past. The presence of occult infections in this group was confirmed (frequency: 1 in 2,599), supporting the hypothesis of long-term persistence of HBV infection after clearance of HBsAg. HBsAg and nucleic acid amplification testing for blood screening and vaccination against HBV are crucial in order to further reduce the risk of transfusion-transmitted HBV towards zero.

Clinical utility of quantitative HBsAg in natural history and nucleos(t)ide analogue treatment of chronic hepatitis B: new trick of old dog

Using commercial quantitative assays, quantitative hepatitis B surface antigen (qHBsAg) has improved our understanding and management of chronic hepatitis B (CHB). The HBsAg level is highest in the immune tolerance phase, starts to decline during the immune clearance phase, and decreases slowly but progressively after hepatitis B e antigen (HBeAg) seroconversion. The HBsAg level is lowest in individuals with an inactive carrier state but higher in those who develop HBeAg-negative hepatitis. It has been shown that a reduction of HBsAg by 1 log IU/mL or more reflects improved host immune control of HBV infection. A combination of HBsAg <1000 IU/mL and HBV-DNA <2000 IU/mL can identify a 3-year inactive state in a genotype D HBeAg-negative carrier population. In the Asian-Pacific region, where HBV genotypes B and C are dominant, HBsAg levels of ≤10–100 IU/mL predict HBsAg loss over time. As to the prediction of disease progression, low-viremic carriers with HBsAg >1000 IU/mL have been shown to be at higher risks of HBeAg-negative hepatitis, cirrhosis, and hepatocellular carcinoma than those with HBsAg <1000 IU/mL. Although qHBsAg has been widely used in CHB patients receiving pegylated interferon therapy, the HBsAg decline is slow and does not correlate with HBV-DNA levels during nucleos(t)ide analogue (NUC) therapy. However, a rapid HBsAg decline during NUC therapy may identify patients who will finally clear HBsAg. A 6- to 12-monthly assessment of HBsAg level could be considered during NUC therapy. Taking these lines of evidence together, qHBsAg can complement HBV-DNA levels to optimize the management of CHB patients in our daily clinical practice.

Cure for immune‐tolerant hepatitis B in children: is it an achievable target with sequential combo therapy with lamivudine and interferon?

We prospectively studied the HBsAg seroconversion with sequential combination therapy of lamivudine (LAM) and interferon (IFN) in hitherto untreatable 'immune-tolerant' chronic hepatitis B in children. In this case-control study, 28 children with immune-tolerant hepatitis B [HBsAg positive for >6months with near normal aminotransferase level, minimal/no inflammation in liver histology and high viral load (HBV DNA>10(7) copies/mL)] were treated with LAM alone at 3mg/kg/day for 8weeks followed by LAM plus IFN alpha (5MU/m(2) three times a week) for another 44weeks. They were compared with 34 untreated children. HBV markers (HBsAg, HBeAg, anti-HBe, quantitative HBV DNA) were carried out at baseline, at the end of therapy and 6monthly thereafter. The mean age was 5.9±3.2years and 24 were boys. End therapy response: HBe seroconversion was achieved in 11, and of these, five had complete response (HBsAg clearance), 11 did not respond and six had virologic response (DNA undetectable but no HBe seroconversion). Six months after therapy, 10 of the 11 (91%) originally seroconverted children remained seroconverted while one seroreverted. Six of the 28 (21.4%) children lost HBsAg and they remained HBsAg negative and anti-HBs positive on follow-up. After a mean follow-up of 21.1±11.9months, the status remained same in the responders but one of the nonresponders HBe seroconverted (39.3%). There were no serious side effects of therapy. It is possible to achieve a cure in more than one-fifth of immune-tolerant children with hepatitis B with the sequential combination of LAM and IFN.

Interferon-based Therapy for e-antigen Negative Chronic Hepatitis B Virus Infection

The prevalence of the hepatitis B e antigen (HBeAg)-negative form of chronic hepatitis B (CHB) has increased over the years and is generally more difficult to treat. Pegylated interferon (PEG-IFN) offers a durable response, finite treatment duration and absence of viral resistance. On the other hand, the risk of viral relapse for patients discontinuing nucleos(t)ide analogues remains a major concern for this form of treatment, raising the spectre of drug resistance and safety with long-term use. PEG-IFN remains one of the first-line drugs for a select group of CHB patients, and with its dual immunomodulatory and antiviral effect offers a realistic chance of durable off-treatment response and HBsAg clearance. PEG-IFN could be offered to patients with a high pre-treatment likelihood of response. In this article we aim to discuss the indications and goals of antiviral therapy in HBeAg-negative patients, the safety and efficacy of IFN-based therapy, the predictors of response, and its potential future directions.

Hepatitis B Surface Antigen Concentrations in Patients with HIV/HBV Co-Infection

HBsAg clearance is associated with clinical cure of chronic hepatitis B virus (HBV) infection. Quantification of HBsAg may help to predict HBsAg clearance during the natural course of HBV infection and during antiviral therapy. Most studies investigating quantitative HBsAg were performed in HBV mono-infected patients. However, the immune status is considered to be important for HBsAg decline and subsequent HBsAg loss. HIV co-infection unfavorably influences the course of chronic hepatitis B. In this cross-sectional study we investigated quantitative HBsAg in 173 HBV/HIV co-infected patients from 6 centers and evaluated the importance of immunodeficiency and antiretroviral therapy. We also compared 46 untreated HIV/HBV infected patients with 46 well-matched HBV mono-infected patients. HBsAg levels correlated with CD4 T-cell count and were higher in patients with more advanced HIV CDC stage. Patients on combination antiretroviral therapy (cART) including nucleos(t)ide analogues active against HBV demonstrated significant lower HBsAg levels compared to untreated patients. Importantly, HBsAg levels were significantly lower in patients who had a stronger increase between nadir CD4 and current CD4 T-cell count during cART. Untreated HIV/HBV patients demonstrated higher HBsAg levels than HBV mono-infected patients despite similar HBV DNA levels. In conclusion, HBsAg decline is dependent on an effective immune status. Restoration of CD4 T-cells during treatment with cART including nucleos(t)ide analogues seems to be important for HBsAg decrease and subsequent HBsAg loss.

Significance of liver histology in HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B virus‐related hepatitis

The natural course of HBsAg-positive, IgM anti-HBc-negative acute hepatitis B virus (HBV)-related hepatitis is unclear. The aim of this study was to evaluate the prognostic significance of histological features and hepatic expression of HBV antigens in such patients. Fifty patients with HBsAg-positive, IgM anti-HBc-negative acute hepatitis B who underwent liver biopsy during the acute hepatitis episode were studied [HBeAg seroconversion (n = 16), persistently positive for HBeAg (n = 9), and persistently negative for HBeAg (n = 25)]. Twenty-six cases had features of typical acute hepatitis only (group A), and 24 cases had changes suggesting pre-existing chronic hepatitis (group B). HBcAg and/or HBsAg immunoreactivity was detected less frequently in group A than in group B (31% versus 79%, P = 0.01). HBsAg clearance was observed in 24% of patients, almost exclusively in cases with HBeAg seroconversion. HBsAg loss was significantly more frequent in group A than in group B (52% versus 0%, P < 0.001), and in cases without rather than with immunohistochemical expression of HBV antigens (55% versus 0%, P < 0.001). In group A, HBsAg clearance was observed in 80%, 54% and 0% of patients with mild, moderate or severe acute hepatitis, respectively (P < 0.034). Histological information is very important for the prognosis of HBsAg-positive, IgM anti-HBc-negative acute hepatitis B. HBeAg seroconversion with underlying typical acute hepatitis changes of mild to moderate severity without hepatic expression of HBV antigens strongly predicts subsequent HBsAg loss.

Randomised study comparing 48 and 96 weeks peginterferon α-2a therapy in genotype D HBeAg-negative chronic hepatitis B

ObjectiveTreatment with peginterferon α-2a (PegIFN) for 48 weeks is the standard of care for selected HBeAg-negative patients chronically infected with hepatitis B virus (HBV), but with limited treatment efficacy. A...

A Multicentre Molecular Analysis of Hepatitis B and Blood-Borne Virus Coinfections in Viet Nam

Hepatitis B (HBV) infection is endemic in Viet Nam, with up to 8.4 million individuals estimated to be chronically infected. We describe results of a large, multicentre seroepidemiological and molecular study of the prevalence of HBV infection and blood-borne viral coinfections in Viet Nam. Individuals with varying risk factors for infection (n = 8654) were recruited from five centres; Ha Noi, Hai Phong, Da Nang, Khanh Hoa and Can Tho. A mean prevalence rate of 10.7% was observed and levels of HBsAg were significantly higher in injecting drug users (IDUs) (17.4%, n = 174/1000) and dialysis patients (14.3%, n = 82/575) than in lower-risk groups (9.4%; p<0.001). Coinfection with HIV was seen in 28% of HBV-infected IDUs (n = 49/174) and 15.2% of commercial sex workers (CSWs; n = 15/99). HCV infection was present in 89.8% of the HBV-HIV coinfected IDUs (n = 44/49) and 40% of HBV-HIV coinfected CSWs (n = 16/40). Anti-HDV was detected in 10.7% (n = 34/318) of HBsAg positive individuals. Phylogenetic analysis of HBV S gene (n = 187) showed a predominance of genotype B4 (82.6%); genotypes C1 (14.6%), B2 (2.7%) and C5 (0.5%) were also identified. The precore mutation G1896A was identified in 35% of all specimens, and was more frequently observed in genotype B (41%) than genotype C (3%; p<0.0001). In the immunodominant ‘a’ region of the surface gene, point mutations were identified in 31% (n = 58/187) of sequences, and 2.2% (n = 4/187) and 5.3% (n = 10/187) specimens contained the major vaccine escape mutations G145A/R and P120L/Q/S/T, respectively. 368 HBsAg positive individuals were genotyped for the IL28B SNP rs12979860 and no significant association between the IL28B SNP and clearance of HBsAg, HBV viral load or HBeAg was observed. This study confirms the high prevalence of HBV infection in Viet Nam and also highlights the significant levels of blood-borne virus coinfections, which have important implications for hepatitis-related morbidity and development of effective management strategies.

Mo1906 Anti-Thymocyte Globulin (ATG) in Severe Acute Cellular Graft Rejection (ACGR) After Liver Transplantation (LT)

Background/Aims: Hepatitis B virus (HBV) genotypes B and C are common in Japan and have been demonstrated as one of the predictive factors associated with the progression of liver diseases. The aim of this study was to examine the changes over time in genotypes of HBV carriers in the hyperendemic area for HBV genotype B infection in Japan as well as in genotypes responsible for acute hepatitis B. Methods: We evaluated HBV genotypes in 430 HBsAg-positive HBV carriers and 34 patients with acute hepatitis B who had a medical examination at our university hospital between 1990 and 2010. The subjects were divided into two time-period groups (1990-1999 and 2000-2010) and analyzed the distribution of genotypes. In addition, the clinical and virological characteristics; ALT value, HBeAg, antiHBe antibody, IgM-HBc antibody, HBVDNA, were compared between subjects with genotype A infection and those with non-genotype A infection. Results: Of the 430 HBsAg-positive carriers, 45% had genotype B and 35% had genotype C in both time-period groups, indicating no changes in genotypes over time. Among 34 acute hepatitis B patients, the prevalence of genotype B was lower in the 2000-2009 group (1/17; 5.9%) than in the 1990-1999 group (10/17; 58.8%, p=0.012), while that of genotype A tended to have increased from 11.8% (2/17) to 29.4% (5/17) in the last 10 years. One of 7 patients with acute HBV genotype A infection did not clear HBsAg and developed to chronic infection. When Kaplan-Meier analysis was used to compare HBsAg clearance phase between the patients with or without genotype A infection, the phase was significantly longer in the genotype A patients (49 wks vs. 8 wks; p < 0.05). HBV DNA negative phase was also significantly longer in the genotype A patients (45 wks vs. 4.9 wks; p < 0.05), while the both groups showed no difference in HBeAg negative phase, anti-HBe positive phase, IgM-HBc antibody negative phase, and ALT normalization period. Conclusion: In a hyperendemic area for HBV genotype B infection in Japan, there was no large change of HBV genotypic distribution in carriers, while genotype A infection was increased in acute hepatitis B in the last 10 years. Compared to patients with acute HBV non-genotype A infection, patients with genotype A infection took a longer duration for HBsAg clearance and for achievement of HBV DNA negative status. Infection became chronic in some of the patients with infected with genotype A, suggesting that genotype distribution in HBV carriers will change in Japan in the future. It is necessary to re-examine the nation-wide study of clinical course of acute hepatitis B patients, especially infected with genotype A.

Mo1904 Treatment Evaluation of Chronic Hepatitis B (CHB) Patients at Tertiary Care and Community Centers

Background/Aims: Hepatitis B virus (HBV) genotypes B and C are common in Japan and have been demonstrated as one of the predictive factors associated with the progression of liver diseases. The aim of this study was to examine the changes over time in genotypes of HBV carriers in the hyperendemic area for HBV genotype B infection in Japan as well as in genotypes responsible for acute hepatitis B. Methods: We evaluated HBV genotypes in 430 HBsAg-positive HBV carriers and 34 patients with acute hepatitis B who had a medical examination at our university hospital between 1990 and 2010. The subjects were divided into two time-period groups (1990-1999 and 2000-2010) and analyzed the distribution of genotypes. In addition, the clinical and virological characteristics; ALT value, HBeAg, antiHBe antibody, IgM-HBc antibody, HBVDNA, were compared between subjects with genotype A infection and those with non-genotype A infection. Results: Of the 430 HBsAg-positive carriers, 45% had genotype B and 35% had genotype C in both time-period groups, indicating no changes in genotypes over time. Among 34 acute hepatitis B patients, the prevalence of genotype B was lower in the 2000-2009 group (1/17; 5.9%) than in the 1990-1999 group (10/17; 58.8%, p=0.012), while that of genotype A tended to have increased from 11.8% (2/17) to 29.4% (5/17) in the last 10 years. One of 7 patients with acute HBV genotype A infection did not clear HBsAg and developed to chronic infection. When Kaplan-Meier analysis was used to compare HBsAg clearance phase between the patients with or without genotype A infection, the phase was significantly longer in the genotype A patients (49 wks vs. 8 wks; p < 0.05). HBV DNA negative phase was also significantly longer in the genotype A patients (45 wks vs. 4.9 wks; p < 0.05), while the both groups showed no difference in HBeAg negative phase, anti-HBe positive phase, IgM-HBc antibody negative phase, and ALT normalization period. Conclusion: In a hyperendemic area for HBV genotype B infection in Japan, there was no large change of HBV genotypic distribution in carriers, while genotype A infection was increased in acute hepatitis B in the last 10 years. Compared to patients with acute HBV non-genotype A infection, patients with genotype A infection took a longer duration for HBsAg clearance and for achievement of HBV DNA negative status. Infection became chronic in some of the patients with infected with genotype A, suggesting that genotype distribution in HBV carriers will change in Japan in the future. It is necessary to re-examine the nation-wide study of clinical course of acute hepatitis B patients, especially infected with genotype A.

Mo1903 Transition in Hepatitis B Virus Genotypes Responsible for Acute Hepatitis B in a Hyperendemic Area for Genotype B Infection – 20 Years Follow-up Study in Japan

Background/Aims: Hepatitis B virus (HBV) genotypes B and C are common in Japan and have been demonstrated as one of the predictive factors associated with the progression of liver diseases. The aim of this study was to examine the changes over time in genotypes of HBV carriers in the hyperendemic area for HBV genotype B infection in Japan as well as in genotypes responsible for acute hepatitis B. Methods: We evaluated HBV genotypes in 430 HBsAg-positive HBV carriers and 34 patients with acute hepatitis B who had a medical examination at our university hospital between 1990 and 2010. The subjects were divided into two time-period groups (1990-1999 and 2000-2010) and analyzed the distribution of genotypes. In addition, the clinical and virological characteristics; ALT value, HBeAg, antiHBe antibody, IgM-HBc antibody, HBVDNA, were compared between subjects with genotype A infection and those with non-genotype A infection. Results: Of the 430 HBsAg-positive carriers, 45% had genotype B and 35% had genotype C in both time-period groups, indicating no changes in genotypes over time. Among 34 acute hepatitis B patients, the prevalence of genotype B was lower in the 2000-2009 group (1/17; 5.9%) than in the 1990-1999 group (10/17; 58.8%, p=0.012), while that of genotype A tended to have increased from 11.8% (2/17) to 29.4% (5/17) in the last 10 years. One of 7 patients with acute HBV genotype A infection did not clear HBsAg and developed to chronic infection. When Kaplan-Meier analysis was used to compare HBsAg clearance phase between the patients with or without genotype A infection, the phase was significantly longer in the genotype A patients (49 wks vs. 8 wks; p < 0.05). HBV DNA negative phase was also significantly longer in the genotype A patients (45 wks vs. 4.9 wks; p < 0.05), while the both groups showed no difference in HBeAg negative phase, anti-HBe positive phase, IgM-HBc antibody negative phase, and ALT normalization period. Conclusion: In a hyperendemic area for HBV genotype B infection in Japan, there was no large change of HBV genotypic distribution in carriers, while genotype A infection was increased in acute hepatitis B in the last 10 years. Compared to patients with acute HBV non-genotype A infection, patients with genotype A infection took a longer duration for HBsAg clearance and for achievement of HBV DNA negative status. Infection became chronic in some of the patients with infected with genotype A, suggesting that genotype distribution in HBV carriers will change in Japan in the future. It is necessary to re-examine the nation-wide study of clinical course of acute hepatitis B patients, especially infected with genotype A.

1381 INDICATION OF MRI LIVER IRON CONCENTRATION DETERMINATION WITHIN THE HIGH LIVER IRON OVERLOAD DIAGNOSTIC ALGORITHM

Introduction: Natural history studies show that the risk of development chronic HBV infection is inversely proportional with age of acquisition: 25% of children infected at <5 years develop chronic infection, versus <10% adults. In Romania, treatment of HBV infection in children is limited to lamivudine (until 2009) and alpha2b standard interferon. Treatment of all children with chronic B hepatitis must be tempered by studying the natural history in children. Spontaneous HBeAg clearance is influenced by mode of transmission, viral load, necroinflammatory activity, immunocompetence, genotype. Aim: To investigate the rate of HBeAg/HBsAg seroconversion during childhood, spontaneous and after antiviral treatment. Methods: We retrospectively studied 176 children with chronic HBV infection and +HBeAg diagnosed between 2003–2011. The route of transmission was vertical in 92 and parenteral/unknown in 84 children. The mean age at diagnosis was 7.5 years (6 months to 16 years). In the lot with vertical transmission, 64 children emerged from HBe+Ag mothers with high viral load and 28 from HBe−/HBs+Ag mothers with low viral load. 112 children were diagnosed in the first 4 years of life. HBVmarkers, viral load, clinical and liver function were tested at least once every 6 months. Results: 24 (21%) of the 112 infected infants seroconvert in “e” system before 4 years without treatment. 3 (12%) infants with spontaneous HBeAg seroconversion emerged from HBe+Ag mothers compared to 6 (25%) from HBe−Ag mothers and 15 (63%) from noninfected mothers (p < 0.005).No spontaneous “s system” seroconversion was detected.58 children older than 4 years (HBs+Ag/HBe+Ag, hypertransaminasemia, detectable viral load, necroinflamatory activity) started antiviral treatment. HBe+Ag seroconversion and virusologic respond rate were 48% after 12 months of Interferon and 24%, respectively 45% after 12 months, respectively 24 months of Lamivudine (p < 0.005 at one year). HBsAg clearance was obtained in 2 cases (3%) after one year of Interferon and in 1 case (1.7%) after 2 years of Lamivudine. Conclusions: Maternal carrier status is very important: children of HBeAg seropositive mothers have lower rates of HBeAg seroconversion. Due to the possibility of spontaneous HBeAg seroconversion, antiviral treatment shouldn’t be initiated in the first 4 years of life. HBsAg clearance rate was higher but not statistic significant in children who had anti-HBeAb achieved under Interferon treatment.

1380 HYPERFERRITINEMIA: PHENOTYPIC CHARACTERISTICS, RELEVANCE OF HFE MUTATIONS AND MAGNETIC RESONANCE AMONG OUTPATIENT REFERRALS FOR ELEVATED SERUM FERRITIN

Introduction: Natural history studies show that the risk of development chronic HBV infection is inversely proportional with age of acquisition: 25% of children infected at <5 years develop chronic infection, versus <10% adults. In Romania, treatment of HBV infection in children is limited to lamivudine (until 2009) and alpha2b standard interferon. Treatment of all children with chronic B hepatitis must be tempered by studying the natural history in children. Spontaneous HBeAg clearance is influenced by mode of transmission, viral load, necroinflammatory activity, immunocompetence, genotype. Aim: To investigate the rate of HBeAg/HBsAg seroconversion during childhood, spontaneous and after antiviral treatment. Methods: We retrospectively studied 176 children with chronic HBV infection and +HBeAg diagnosed between 2003–2011. The route of transmission was vertical in 92 and parenteral/unknown in 84 children. The mean age at diagnosis was 7.5 years (6 months to 16 years). In the lot with vertical transmission, 64 children emerged from HBe+Ag mothers with high viral load and 28 from HBe−/HBs+Ag mothers with low viral load. 112 children were diagnosed in the first 4 years of life. HBVmarkers, viral load, clinical and liver function were tested at least once every 6 months. Results: 24 (21%) of the 112 infected infants seroconvert in “e” system before 4 years without treatment. 3 (12%) infants with spontaneous HBeAg seroconversion emerged from HBe+Ag mothers compared to 6 (25%) from HBe−Ag mothers and 15 (63%) from noninfected mothers (p < 0.005).No spontaneous “s system” seroconversion was detected.58 children older than 4 years (HBs+Ag/HBe+Ag, hypertransaminasemia, detectable viral load, necroinflamatory activity) started antiviral treatment. HBe+Ag seroconversion and virusologic respond rate were 48% after 12 months of Interferon and 24%, respectively 45% after 12 months, respectively 24 months of Lamivudine (p < 0.005 at one year). HBsAg clearance was obtained in 2 cases (3%) after one year of Interferon and in 1 case (1.7%) after 2 years of Lamivudine. Conclusions: Maternal carrier status is very important: children of HBeAg seropositive mothers have lower rates of HBeAg seroconversion. Due to the possibility of spontaneous HBeAg seroconversion, antiviral treatment shouldn’t be initiated in the first 4 years of life. HBsAg clearance rate was higher but not statistic significant in children who had anti-HBeAb achieved under Interferon treatment.

Randomised clinical trial: the benefit of combination therapy with adefovir and lamivudine for chronic hepatitis B

Combination antiviral therapy holds the promise of increasing response rates while decreasing antiviral resistance, but has yet to be shown to be beneficial or necessary in chronic hepatitis B. To evaluate the benefit of combination therapy with adefovir and lamivudine versus adefovir alone in maintaining virological, biochemical and histological responses. Patients with chronic hepatitis B with and without previous lamivudine therapy were randomised to receive adefovir alone (10 mg/daily) or adefovir and lamivudine (100 mg/daily) for up to 192 weeks. Study endpoints were (i) maintained virological (HBV DNA <500 copies/mL), biochemical and histological response, (ii) loss of HBeAg and (iii) loss of HBsAg. A total of 41 patients were enrolled, including 31 HBeAg -positive and 31 treatment-naïve subjects. 30 patients remained on assigned therapy at 192 weeks. The percentage of patients achieving a combined maintained response was higher in the combination than the monotherapy arm, both at week 48 (59% vs. 26%, P = 0.06) and 192 (68% vs. 31%, P = 0.03). At week 192, 76% of the combination vs. 36% of the monotherapy group had loss of HBeAg (P = 0.03). One patient receiving adefovir cleared HBsAg. Adefovir resistance developed in 6 of 19 (32%) monotherapy but none of 22 combination treated patients (P = 0.03). Extended combination therapy with lamivudine and adefovir is associated with a high rate of long-term virological and biochemical response. Adefovir monotherapy appears to be less effective mainly because of poor initial response and the ultimate development of antiviral resistance (www.Clinical. Trials.gov NCT00023309).

Clinical analysis of HBsAg clearance in ten chronic hepatitis B patients treated with nucleoside analogs

本研究对10例用核苷(酸)类似物(NUCs)治疗出现HBsAg阴转或血清学转换的病例资料进行了回顾性分析,现报道如下.一、资料与方法1.病例资料:收集2005年2月至2010年8月于沈阳市第六人民医院入院的10例慢性乙型肝炎(CHB)患者应用NUCs治疗出现HBsAg阴转或血清学转换的患者资料.临床诊断符合2005年慢性乙型肝炎防治指南[11标准. 关键词：肝炎;乙型;慢性;核苷(酸)类似物;治疗;抗病毒

HBV DNA suppression and HBsAg clearance in HBeAg negative chronic hepatitis B patients on lamivudine therapy for over 5years

In long-term responder patients, it is unclear whether lamivudine (LAM) monotherapy should be continued or switched to a high-genetic-barrier analogue. This study aims at assessing LAM efficacy over a 5-year period and the residual risk of drug resistance. The rate of HBsAg clearance and LAM long-term safety profile were also evaluated. One hundred and ninety-one patients with chronic HBeAg-negative hepatitis B successfully treated with LAM monotherapy for at least 5 years were included. Biochemical and virological tests were assessed every 3 months in all patients and HBsAg quantification was performed in 45/191. Reverse-transcriptase (RT) region was directly sequenced in virological breakthrough patients. One hundred and ninety-one patients (148 males, median age 53 years, 72 with compensated cirrhosis) responding to 60-month LAM monotherapy continued to receive LAM monotherapy beyond the initial 5 years and were followed for an additional 36-month median period (range 1-108). Virological response was maintained in 128/191 patients (67%) and HBsAg clearance was observed in 15/128 (11.7%) after a 32-month median period (range 1-65). The 63 remaining patients (33%) showed virological breakthrough after a 15-month median treatment (range 1-78). RT region analysis was performed in 38/63 breakthrough patients and LAM resistant mutations were found in 37/38. No significant side effects were observed. In long-term responder patients, continuation of LAM monotherapy resulted in persistent viral suppression in most cases with undetectable HBV DNA by real-time PCR; moreover, 11.7% of these patients cleared HBsAg. Selection of LAM resistance, however, can still occur even after successful long-term therapy, thus emphasising the importance of a careful virological monitoring.

OC-11 IL28B polymorphism in chronic HBV infection: the CC allele does not correlate with the phase of the infection nor with HBsAg clearance in IFN treated patients

OC-11 IL28B polymorphism in chronic HBV infection: the CC allele does not correlate with the phase of the infection nor with HBsAg clearance in IFN treated patients

Genetic variation in IL28B and treatment outcome in HBeAg-positive and -negative chronic hepatitis B patients treated with Peg interferon alfa-2a and adefovir

In a cohort of 95 chronic hepatitis B patients, who were treated with peg-interferon and adefovir for 1 year, and who had 15% HBsAg loss (overall), no association was found between IL28B polymorphisms and HBeAg seroconversion or HBsAg clearance. These findings suggest that any association with outcome, if present, is less than that seen in chronic hepatitis C. Additional studies are needed to enlarge sample size and to refine our understanding of IL28B biology in the context of chronic hepatitis B response to immunomodulatory and direct antiviral therapy.