Large spontaneous HBV DNA fluctuations and potential usefulness of a single point measurement of combined HBV DNA and quantitative HBsAg for the exclusion of HBeAg negative chronic hepatitis B: A prospective Tunisian cohort study

Background/Aims: We aimed to describe spontaneous short-term hepatitis B Virus (HBV) DNA level fluctuations and to assess the usefulness of quantitative HBsAg (qHBsAg) in Tunisian patients with HBeAg-negative chronic HBV infection.Patients and methods: We included 174 treatment-naïve patients with chronic HBeAg-negative HBV. A one-year prospective follow-up was carried out with serial determinations of HBV DNA, alanine aminotransferase levels and qHBsAg. Patients were classified into three groups: inactive carriers (G1), patients with HBeAg negative chronic hepatitis B (CHB) (G2) and patients with indeterminate state (G3). For this latter group, a liver biopsy was indicated.Results: Only genotype D was detected. During the follow-up, 21.6% and 19.5% of patients with low initial (<2000 IU/mL) and intermediate viral load (2000-20000 IU/mL), experienced a subsequent increase in their HBV DNA levels above 2000 and 20000 IU/mL, respectively. Significant variations of HBV DNA levels (≥0.5 log10 IU/mL) were observed in 61.1% of patients at 6 months-interval. Among the 174 patients, 89 (51.1%) belonged to G1, 33 (19%) to G2 and 52 (29.9%) to G3. Fourteen patients have undergone liver biopsy, among whom 7 (50%) showed moderate to severe liver disease. Combination of HBV DNA <2000 IU/mL and qHBsAg <832 IU/mL excluded CHB in 98.4% of cases.Conclusions: This study highlights the large short-term HBV DNA fluctuations in Tunisian patients with HBeAg negative chronic HBV of genotype D. HBV DNA < 2000 IU/mL along with qHBsAg < 832 IU/mL excluded CHB in 98.4% of cases. Significant proportion of patients with indeterminate state within genotype D would have HBeAg negative CHB.

The Potential of Serum IFN-γ for Determining the Progression of Chronic Hepatitis B

Background: A persistent infection of hepatitis B virus (HBV) can cause liver cirrhosis and hepatocarcinoma even though the virus itself is non-cytopathic and does not cause cell injury. It has been asserted that liver injury in chronic HBV infection is attributed to the host immune system responding to HBV infection. Cytokines have a critical role in mediating immune responses to viral infection. This study aimed to determine the correlation between the levels of serum IFN-γ, IL-2, IL-17, and TNF- α with the progress of chronic HBV infection that was determined through provisional diagnosis, patient’s age, and the levels of serum transaminases.Method: Blood samples were collected from patients with chronic hepatitis B and the levels of serum IFN-γ, IL-2, IL-17, and TNF-α were measured by using ELISA. The correlation between each cytokine levels and the provisional diagnosis, patient’s age, and serum transaminases were analyzed by using the Spearman correlation test with a p value of 0.05 is considered as statistically significant.Results: A total of 47 samples were collected from patients with chronic hepatitis B (n=38), chronic hepatitis B with liver cirrhosis (n = 6), and chronic hepatitis B with hepatocellular carcinoma (nc = 3). A significant correlation was found between the levels of serum IFN-γ and aspartate aminotransferase (AST) (p = 0.04).Conclusion: The increase of serum IFN-γ and AST levels may highlight the importance of these particular cytokine and liver transaminase in the immune response to chronic HBV infection since IFN-γ is capable to induce apoptotic cell death which promotes AST release and facilitates liver injury.

Vagaries of the Host Response to Chronic Hepatitis B Virus Infection: What is the Ultimate Outcome of So-called “Asymptomatic HBV Carriers” Observed Over Several Decades?

Introduction: Chronic hepatitis B virus (HBV) infection is prevalent worldwide and up to 40% is known to progress to serious complications including cirrhosis and hepatocellular carcinoma (HCC). The outcome of the remaining infected individuals is not well documented. Our case series describes a longer cohort of chronic HBV infections that have remained asymptomatic with no progression of liver disease. Case Series: Thirty-three patients (ages 31-84) with chronic HBV infection were identified. All patients had no significant elevations in transaminase levels and were followed over 32 years, collectively. 18/33 had a fluctuating greater magnitude of HBV viral load with no elevations in tumor marker or significant radiographic changes to their liver. Discussion/Conclusion: Chronic HBV infection can lead to serious complications over time, the mechanism of which are not well understood. The variation in patients that do and do not develop these complications stresses the importance of the individual response to the virus and may highlight host immune response differences.

Liver Histological Abnormalities Were Better Reflected by Virus Level in Chronic Hbv Infected Patients Aged ≤ 30 Years, Hbeag-Positive and Persistently Normal Alt

Background: We analyzed correlations between significant liver histological characteristics and clinical variables in HBV-infected patients and provided recommendations on treatment decisions for patients age younger than 30-year-old.Methods: Liver biopsy was performed on 161 chronic HBV-infected patients with ALT ≤ 40 U/L from July, 2000 – November, 2019. Median age was 39(18-70) years old. Histologic assessment was based on the Scheuer scoring system. Results: Significant necroinflammation and fibrosis were observed in 65.2% (105/161) and 52.2% (84/161) patients of all cases. The pathological abnormality was significantly negatively correlated with viral level in HBeAg-positive subjects, and based on ROC curve analysis, the viral level to predict obvious liver pathological changes was 6.7 log10 IU/ml in those patients. Threshold value of ALT (25 U/L) based on the distribution of ALT and virus levels. Patients younger than 30 years old, almost all had significant pathological alteration with HBV-DNA < 6.7 log10 IU/ml; However, the ratio of insignificant liver’s inflammation and fibrosis were 65% and 70% with HBV-DNA levels ≥ 6.7 log10 IU/ml respectively, on that basis, it could have a further rising, reaching 67.5% and 75% combining with ALT ≤ 25 U/L. Conclusion: Viral load was a better factor to reflect hepatic histological abnormality in Chronic HBV-infected patients with HBeAg-positive and persistently normal ALT whose age ≤ 30 years, 5000000 IU/ml was a suitable threshold.

Large spontaneous HBV DNA fluctuations and potential usefulness of a single point measurement of combined HBV DNA and quantitative HBsAg for the exclusion of HBeAg negative chronic hepatitis B: A prospective Tunisian cohort study

Background/Aims: We aimed to describe spontaneous short-term hepatitis B Virus (HBV) DNA fluctuations and to assess the usefulness of quantitative HBsAg (qHBsAg) in Tunisian patients with HBeAg-negative chronic HBV infection.Methods: We included 174 treatment-naïve patients with chronic HBeAg-negative HBV. A one-year prospective follow-up was carried out with serial determinations of HBV DNA, alanine aminotransferase (ALT) levels and qHBsAg. Patients were classified into three groups: inactive carriers (G1), patients with HBeAg negative CHB (G2) and patients with “indeterminant state” (G3). For this latter group, a liver biopsy was indicated.Results: Genotype D was the only detected. During the follow-up, 21.6% and 19.5% of patients with low initial (<2000 IU/mL) and intermediate viral load (2000-20000 IU/mL), experienced a subsequent increase in their HBV DNA levels above 2000 and 20000 IU/mL, respectively. Significant variations of HBV DNA levels (≥0.5 log10 IU/mL) were observed in 61.1% of patients at 6 months-interval. Among the 174 patients, 89 (51.1%) belonged to G1, 33 (19%) to G2 and 52 (29.9%) to G3. Fourteen patients have undergone liver biopsy, among whom 7 (50%) showed moderate to severe liver disease. Combination of HBV DNA <2000 IU/mL and qHBsAg <832 IU/mL excluded CHB in 98.4% of cases.Conclusions: This study highlights the large short-term HBV DNA fluctuations in Tunisian patients with HBeAg negative chronic HBV of genotype D. HBV DNA < 2000 IU/mL along with qHBsAg < 832 IU/mL excluded CHB in 98.4% of cases. Significant proportion of patients with “indeterminant state” within genotype D would have HBeAg negative CHB.

The association between Fc gamma RIIb expression levels and chronic hepatitis B virus infection progression

Background Fc gamma receptor IIb (FcγRIIb) is an important inhibitory receptor that plays vital roles in regulating various immune response processes and the pathogenesis of many infectious diseases. The purpose of our research was to evaluate FcγRIIb expression in serum and liver biopsy specimens from hepatitis B virus (HBV)-infected patients and to explore the association of FcγRIIb with chronic HBV infection. Methods Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the serum FcγRIIb levels in 119 HBV-infected patients and 24 healthy controls. An immunohistochemical method was then employed to identify FcγRIIb expression in biopsy specimens from patients with chronic hepatitis B (CHB). The integrated optical density (IOD) value was measured to represent FcγRIIb expression levels. Results Serum FcγRIIb levels were decreased in CHB patients compared to controls (P < 0.001). The FcγRIIb levels in the CHB patient group were remarkably lower than those in the HBV carrier group (P < 0.001). In addition, FcγRIIb levels were negatively associated with AST and ALT (r = −0.3936, P = 0.0063; r = −0.3459, P = 0.0097, respectively). The IOD values of FcγRIIb expression in the moderate and severe CHB groups were significantly lower than those in the control group (P = 0.006 and P < 0.001, respectively). The FcγRIIb level tended to be lower with pathological changes related to hepatitis. Furthermore, correlation analysis revealed that FcγRIIb had negative correlations with AST and ALT (r = −0.688, P = 0.0016; r = −0.686, P = 0.0017, respectively) but a positive association with the platelet count (r = 0.6464, P = 0.0038). Conclusions FcγRIIb levels are significantly related to chronic HBV infection and the progression of CHB. Changes in FcγRIIb may affect the progression of liver inflammation and fibrosis in CHB patients.

Cross-sectional study of chronic hepatitis B virus infection in Rwandan high-risk groups: unexpected findings on prevalence and its determinants

ObjectivesUsing secondary data from 208 079 Rwandans, we determined the prevalence of chronic hepatitis B virus (HBV) infection among high-risk groups and its demographic, geographical and health-related determinants.DesignIn this cross-sectional study, we obtained and analysed data from a national hepatitis B vaccination and screening campaign conducted in Rwanda in 2017. We performed logistic regression to examine associations between chronic HBV infection and related factors such as risk status and geographical characteristics.SettingIndividuals were sampled nationally in all 30 districts across 4 provinces and the city of Kigali and all prisons in Rwanda.ParticipantsThe study involves 208 079 individuals at high risk including prisoners and other high-risk groups (oHRG).Main outcomeThe primary outcome for our study was hepatitis B surface antigens (HBsAg) prevalence.FindingsFrom 208 079 adults participants, 206 517 (99.2%) had valid HBsAg results, 4.3% of 64 944 prisoners and 4.0% of 140 985 oHRG were HBV positive. The prevalence was higher in Northern Province 5.1%, (95% CI 4.8 to 5.4). In multivariate analysis, the odds of infection decreased with increasing age, and hepatitis C antibody positivity reduced the odds for chronic HBV (OR 0.58, 95% CI 0.52 to 0.66 and OR 0.74, 95% CI 0.62 to 0.89 among oHRG and prisoners, respectively). In addition, being female was associated with lower odds of HBV (OR 0.70, 95% CI 0.66 to 0.74 and OR 0.80, 95% CI 0.65 to 0.98 among oHRG and prisoners, respectively).ConclusionWe found that individuals below 55 years of age and individuals who belong to high-risk groups (ie, sex workers, injection drug users, men who have sex with men, etc) have a higher probability of chronic HBV infection. Infection with chronic hepatitis C virus was not correlated with chronic HBV infection in our study population. Potential explanations include differential routes of transmission, specific immunological and pathophysiological factors or different effects of health prevention and control programmes.