Histologic Changes in Liver Tissue From Patients With Chronic Hepatitis B and Minimal Increases in Levels of Alanine Aminotransferase: A Meta-analysis and Systematic Review

Hoang

et al. 2016

Aliment Pharmacol Ther

BACKGROUND Hepatitis B surface antigen (HBsAg) positivity is associated with increased risk for cirrhosis and hepatocellular carcinoma (HCC). HBsAg seroclearance is thought to be rare in general, but cohort data from U.S. patients is limited. AIM: Our objective is to determine the incidence of HBsAg seroclearance in a real-life U.S. cohort. METHODS In total, 4,737 consecutive chronic hepatitis B (CHB) patients from five primary care, gastroenterology, and multispecialty centers, and a university medical center were retrospectively enrolled between 2001-2014 with data obtained by manual review of individual patient medical records. Seroclearance was determined by loss of HBsAg seropositivity. Persistent HBsAg was confirmed by direct serology or by proxy with positive hepatitis B e-antigen (HBeAg) or HBV DNA levels. RESULTS HBsAg seroclearance occurred in 52 patients over 16,844 person-years (0.31% annually, 1.2% overall). Median follow-up was 32 months, and mean age 45±14 years. Incidence of HBsAg seroclearance was higher in non-Asians, age>45, males, and those with baseline HBV DNA ≤ 10,000 IU/mL. On multivariate Cox proportional modeling, non-Asian ethnicity (HR 2.8), male sex (HR 2.1), baseline HBVDNA≤10,000 (HR 2.0), and age>45 (HR 1.8) were significant independent predictors of seroclearance. DISCUSSION HBsAg seroclearance rates were lower than previously described in in this real-life cohort of CHB patients, especially among Asian, female, and younger patients.

Section: Introductionmentioning

confidence: 99%

Ethnic differences in incidence of hepatitis B surface antigen seroclearance in a real‐life multicenter clinical cohort of 4737 patients with chronic hepatitis B infection

Hoang

et al. 2016

Aliment Pharmacol Ther

“…The only factor in our study associated with the presence of signi cant brosis activity was the high level of transaminases. The predictive nature of transaminases for the presence of signi cant hepatic brosis is recognized by several authors [10,12,22,23].…”

Section: Discussionmentioning

confidence: 99%

Biological Profile of Chronic Hepatitis B Infection and Its Predictive Factors According to Liver Histological Activity at the Renaissance Hospital, N’djamena, Chad

Mahamat-Saleh

Moussa

Bolti

et al. 2020

Preprint

Background: the profile of chronic viral hepatitis B has been little studied in Chad. The factors predictive of the presence of hepatic fibrosis are not well known. The aim of the study was to determine the biological profile of chronic HBsAg carriers according to the new European classification of chronic hepatitis B.Method: This is a prospective cross-sectional study carried out in the gastroenterology outpatient department at the Renaissance Hospital in N’Djamena from January, 2018 to July, 2019. All patients with chronic HBsAg were included and documented for at least one year. Patients with hepatitis C, hepatitis D or HIV are known alcoholic patients and were excluded from the study. The biological profile was determined according to four forms; HBeAg positive chronic infection, HBeAg positive chronic hepatitis, HBeAg negative chronic infection, HBeAg negative chronic hepatitis and HBsAg negative phase. Factors associated with presence of significant liver fibrosis were founded by logistical regression.Results: The average age of the patients were 42.4 years old. The sex ratio was 1.43 in favor of men and a total number of 106 patients were included. The median of the transaminase concentrations were 24 IU/ml (AST) and 21 IU/ml (ALT). 61 patients had HBeAg negative chronic infection (59.8%) and 37 patients had HBeAg negative chronic hepatitis (36.2%). HBeAg positive chronic infection and HBeA positive chronic hepatitis were both seen in 2% of the cases. Significant liver fibrosis was independently associated with the ALT levels (Odds ratio=1.038 [1.009-1.068]; p=0.009).Conclusion: Chronic HBeAg-negative B infection is the main form found in chronic HBeAg-positive carriers. Transaminases are a predictive factor for the presence of hepatic fibrosis.

“…The latest guideline for CHB issued by the European Association for the Study of the liver (EASL) has thus changed the nomenclature of these four phases although the major criteria for classification remained the same(23). Though the patients in IT phase in general have much lower fibrosis scores, a substantial portion of them showed significant fibrosis(24, 25). It is tempting to speculate that the extent of HBV DNA ISH signal in comparison with HBsAg IHC signal would also be indicative of further progression of liver disease considering the close ties between fibrogenesis and the DNA-rich state.…”

Section: Discussionmentioning

confidence: 99%

Spatial and functional links between cellular virological state and progression of liver fibrosis in chronic hepatitis B

Zhang

Liu

et al. 2020

Preprint

Abbreviations: 38 HBV, Hepatitis B Virus; CHB, chronic hepatitis B; ECM, extracellular matrix; HepPar-1, 39 hepatocyte Paraffin 1; HNF4a, Hepatocyte nuclear factor 4 alpha; hepatitis B e 40 antigen (HBeAg); covalently closed circular DNA (cccDNA); IT, immune tolerant; IA, 41 immune active; ENH, hepatitis B e antigen negative hepatitis; ISH, in situ 42 hybridization; HSC, hepatic stellate cells; HBsAg, Hepatitis B Surface Antigen; AgNOR, 43 argyrophilic nucleolar organizer region, IP-10, Interferon gamma-induced protein 10. 44 45 46 3 Abstract 47 Chronic Hepatitis B Virus (HBV) infection is strongly associated with the progression of 48 liver fibrosis, cirrhosis and hepatocellular carcinoma. Despite intensive study, the 49 detailed mechanisms leading to HBV induced liver disease have not been fully 50 elucidated. Previously, we reported a mosaic distribution of viral antigens and nucleic 51 acids at single-cell level in liver tissues of chronic hepatitis B (CHB) patients and 52 proposed a 'three-stage model' of HBV infection in vivo. Here, we explored whether 53 the different stages at cellular level is functionally linked with fibrogenesis. We 54 observed a tight spatial relationship between the invasion of collagen fibers and 55 transitions from S-rich to DNA-rich stage. While S-rich cells mainly localized within 56 minimally fibrotic tissue, DNA-rich cells were often closely surrounded by a milieu of 57 stiffened extracellular matrix (ECM). cDNA microarray and subsequent validation 58 analyses revealed that S-rich cells manifested elevated ribosomal proteins and 59 oxidative phosphorylation genes in a disease phase-dependent manner. On the other 60 hand, DNA-rich cells exhibited gradually deteriorated expression of hepatocyte-61 specific antigen and transcriptional regulator in parallel with the progression of hepatic 62 fibrosis. Finally, during fibrogenesis, inflammatory genes such as IP-10 were found to 63 be expressed in both portal infiltrated cells and surrounding parenchymal cells which 64 resulted in suppressed antigen expression. Taken together, we propose that liver 65 inflammation and accompanying fibrogenesis is spatially and functionally linked with 66 the transition of virological stages at cellular level. These transitions occur possibly due 67 to an altered hepatocyte transcription profile in response to a transformed ECM 68 4 environment. The collective viral and host activities shape the histological alterations 69 and progression of liver disease during CHB infection. (262 words) 70 71 72 5 Introduction 73 Globally, hepatitis B virus (HBV) chronically infects over 240 million people. Patients 74 with chronic hepatitis B (CHB) often develop liver fibrosis, cirrhosis and hepatocellular 75 carcinoma, which results in over 780,000 deaths annually(1). Currently available 76 antivirals such as nulceot(s)ide analogs and pegylated interferon can effectively control 77 viremia and lower the risk of CHB related liver disease, but sustained off-treatment 78 responses are still rare(2). Novel therapies a...