Chronic Hepatitis B Infection: New insights in therapy and predictors of response

__Abstract__ The hepatitis B virus (HBV) was discovered by dr. Baruch Samuel Blumberg when he identified the ‘Australia antigen’ among an aboriginal in the 1960s. The ‘Australia antigen’ is nowadays known as the hepatitis B surface antigen (HBsAg). For his work dr. Blumberg was awarded the 1976 Nobel Prize in Medicine. Despite the introduction of safe and effective vaccines in the eighties, HBV infection still constitutes a major burden of disease. Currently, about one third of the world’s population has evidence of past or current HBV infection and over 350 million people still being chronically infected.1 Approximately 45% of the infected population lives in high endemic areas (HBV prevalence over 8%) including Asia and sub-Saharan Africa. Chronic HBV infection remains one of the most serious infectious diseases worldwide with 0.5-1.2 million deaths every year due to longterm sequelae of hepatitis B related chronic liver disease, such as liver cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC)

Abdominal Wound Dehiscence in Adults: Development and Validation of a Risk Model

Background: Several studies have been performed to identify risk factors for abdominal wound dehiscence. No risk model had yet been developed for the general surgical population. The objective of the present study was to identify independent risk factors for abdominal wound dehiscence and to develop a risk model to recognize high-risk patients. Identification of high-risk patients offers opportunities for intervention strategies. Methods: Medical registers from January 1985 to December 2005 were searched. Patients who had primarily undergone appendectomies or nonsurgical (e.g., urological) operations were excluded. Each patient with abdominal wound dehiscence was matched with three controls by systematic random sampling. Putative relevant patient-related, operation-related, and postoperative variables were evaluated in univariate analysis and subsequently entered in multivariate stepwise logistic regression models to delineate major independent predictors of abdominal wound dehiscence. A risk model was developed, which was validated in a population of patients who had undergone operation between January and December 2006. Results: A total of 363 cases and 1,089 controls were analyzed. Major independent risk factors were age, gender, chronic pulmonary disease, ascites, jaundice, anemia, emergency surgery, type of surgery, postoperative coughing, and wound infection. In the validation population, risk scores were significantly higher (P < 0.001) for patients with abdominal wound dehiscence (n = 19) compared to those without (n = 677). Resulting scores ranged from 0 to 8.5, and the risk for abdominal wound dehiscence over this range increased exponentially from 0.02% to 70.1%. Conclusions: The validated risk model shows high predictive value for abdominal wound dehiscence and may help to identify patients at increased risk

Real life adherence of chronic hepatitis B patients to entecavir treatment

BACKGROUND: Real-life prospective data on adherence to nucleos(t)ide analogues in chronic hepatitis B patients are scarce. AIMS: We investigated adherence to entecavir in relation to virological response. METHODS: In this prospective study, we provided 100 consecutive chronic hepatitis B patients with a medication dispenser that monitored entecavir intake during 16 weeks therapy. Hepatitis B virus (HBV) DNA was measured at baseline and after 16 weeks. Beliefs about medicines were evaluated using a questionnaire. RESULTS: Adherence over 16 weeks averaged 85 ± 17%, with 70% of patients exhibiting good (i.e. ≥ 80%) adherence. Patients with poor (i.e. 20 IU/mL (n=18) and ≤ 20 IU/mL (n=81) averaged 83% and 91% respectively (p=0.19). In multivariate analysis, adherence was not a significant predictor of HBV DNA negativity (adjusted OR 1.02; p=0.34), after adjustment for duration of entecavir treatment (p<0.001) and HBe-status (p=0.001). CONCLUSIONS: 70% of chronic hepatitis B patients exhibited good adherence to entecavir, with younger age and an indifferent attitude being risk factors for poor adherence. Poor adherence was not an independent predictor of virological response

Presence of anti-interferon antibodies is not associated with non-response to pegylated interferon treatment in chronic hepatitis B

Background: Several factors have been related to response to pegylated interferon (PEG-IFN) in chronic hepatitis B (CHB). The occurrence of anti-IFN antibodies is associated with non-response to PEG-IFN in chronic hepatitis C. This study investigated the association between anti-IFN antibodies and response to PEG-IFN in CHB. Methods: Presence of anti-IFN antibodies was assessed at baseline and at 3 and 6 months post-treatment in 323 CHB patients treated with PEG-IFN for 1 year. Results: At baseline, anti-IFN antibodies were detected in 112 (35%) patients. Prevalence was higher in HBeAg-negative compared to HBeAg-positive CHB (43% versus 31%, respectively; P=0.03). Detection of anti-IFN antibodies was not associated with age, sex or HBV genotype. Presence of anti-IFN antibodies at baseline was associated with previous IFN therapy failure (P=0.04), which remained after adjustment for HBeAg status (OR 2.0, 95% CI 1.1, 3.7; P=0.03). Presence of anti-IFN antibodies at baseline was not associated with response, nor with HBV DNA or HBsAg decline (all P-values >0.3). Overall, 56 of 211 (27%) patients without anti-IFN at baseline developed anti-IFN antibodies after PEG-IFN treatment. Response rates did not differ between patients who developed anti-IFN antibodies and patients who did not develop anti-IFN antibodies during treatment (P=0.1). Conclusions: Anti-IFN antibodies may frequently be detected in CHB patients, and presence is associated with previous IFN therapy. However, presence or development of anti-IFN antibodies after PEG-IFN therapy is not associated with non-response to PEG-IFN treatment in CHB. There appears to be no future role for anti-IFN antibodies in predicting response to PEG-IFN in CHB

Mother's educational level and fetal growth: the genesis of health inqualities

Background Women of low socio-economic status (SES) give birth to lighter babies. It is unknown from which moment during pregnancy socio-economic differences in fetal weight can be observed, whether low SES equally affects different fetal-growth components, or what the effect of low SES is after taking into account mediating factors. Methods In 3545 pregnant women participating in the Generation R Study, we studied the association of maternal educational level (high, mid–high, mid–low and low) as a measure of SES with fetal weight, head circumference, abdominal circumference and femur length. We did this before and after adjusting for potential medi-ators, including maternal height, pre-pregnancy body mass index and smoking. Results In fetuses of low-educated women relative to those of high-educated women, fetal growth was slower, leading to a lowe

Reduced risk of relapse after long-term nucleos(t)ide analogue consolidation therapy for chronic hepatitis B

BackgroundBefore stopping nucleos(t)ide analogue (NA) treatment in chronic hepatitis B (CHB), 6-12months of consolidation therapy is recommended. AimTo investigate the effect of consolidation therapy on off-treatment outcomes in CHB patients. MethodsWe included 94 patients who stopped NA after at least 1year of therapy. Patients could be HBeAg-positive or HBeAg-negative at start-of-treatment, but were HBeAg-negative and had undetectable HBV DNA at time of discontinuation. Consolidation therapy was defined as treatment after the first undetectable HBV DNA (and HBeAg loss for HBeAg-positive patients) until NA cessation. ResultsAt 3years, 74% of the start-of-treatment HBeAg-positive and 75% of the start-of-treatment HBeAg-negative patients developed HBV DNA >2000IU/mL at a single time point, whereas a persistent virological relapse (2 tests of HBV DNA >2000IU/mL 6months apart within 1year) developed in 49% of the start-of-treatment HBeAg-positive and 53% of the start-of-treatment HBeAg-negative patients. For both HBeAg-positive and HBeAg-negative patients, consolidation therapy of 3years was associated with lower persistent virological relapse rates compared to <1year (1-year relapse rate: 25% vs. 54%; P=0.063 and 24% vs. 57%; P=0.036, respectively). At 3years, 9% of the HBeAg-positive and 14% of the HBeAg-negative patients became HBsAg-negative. Prolonged consolidation therapy increased the likelihood of HBsAg loss. Two cirrhotic patients developed hepatic decompensation but both recovered. ConclusionsAfter nucleos(t)ide analogue discontinuation, relapse was common in patients with chronic hepatitis B. Prolongation of consolidation therapy beyond 3years decreased the risk of persistent virological relapse and increased the likelihood of HBsAg loss

Repeated Measurements of Hepatitis B Surface Antigen Identify Carriers of Inactive HBV During Long-term Follow-up

BACKGROUND & AIMS: Measurements of hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA might help to identify carriers of inactive HBV. We assessed the performance of repeated measurements of HBsAg over a median time period of 8 years. METHODS: We performed a retrospective study of 292 HBe antigen-negative patients with chronic HBV infection, normal levels of alanine aminotransferase (ALT), levels of HBV DNA 2000 IU/mL and/or abnormal levels of ALT) after each year of follow-up. Patients were followed for a median time of 8 years (range, 4-9 years). Dynamic regression analysis was used to study changes in level of HBsAg and HBV phase and to update the risk of HBV activity. RESULTS: One year after study enrollment, 189 patients (65%) had inactive HBV and 103 patients (35%) had HBV activity. Based on dynamic analysis, the probability that a patient would have HBV at any following year differed according to level of HBsAg; odds were 97% for patients with initial level of HBsAg 1000 IU/mL (P 100 IU/mL had HBV activity in the third year. The combination of HBsAg level <100 IU/mL and HBV DNA level <2000 IU/mL identified patients whose virus remained inactive for the entire follow-up period, with 98% specificity and a positive predictive value of 97%, for all HBV genotypes. Patients with HBV activity who had levels of HBV DNA < 5000 IU/mL and decreases in HBsAg of 0.5 log IU/mL or more for 1 year had a high probability of becoming carriers of inactive HBV in the next year. CONCLUSIONS: In a retrospective, dynamic analysis of almost 300 patients with chronic HBV infection, we found that levels of HBsAg <100 IU/mL identify patients with inactive virus with a high level of specificity. HBsAg levels should therefore be used to define phases of HBV infection in HBe antigen-negative patients