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This article is linked to Gao et al papers. To view these articles, visit
https://doi.org/10.1111/apt.17670
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https://doi.org/10.1111/apt.17710
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This article is linked to Hsu et al papers. To view these articles, visit https://doi.org/10.1111/apt.17614 and https://doi.org/10.1111/apt.17644
Background and Aims
Large‐scale comprehensive studies on HBV RNA in chronic hepatitis B are lacking. We aimed to study the HBV RNA profile and its correlation with other viral markers in patients ...with chronic hepatitis B who are treatment‐naïve and patients receiving nucleos(t)ide analogues (NA).
Approach and Results
Biomarkers, including HBV RNA and hepatitis B core‐related antigen (HBcrAg), were measured in 388 patients. Of these, 246 were treatment‐naïve and were categorized into HBeAg‐positive chronic infection (n = 41), HBeAg‐positive chronic hepatitis (n = 81), HBeAg‐negative chronic infection (n = 39), HBeAg‐negative chronic hepatitis (n = 66), and HBsAg seroclearance (n = 19). These biomarkers were also measured in 142 patients who were NA‐treated receiving tenofovir or entecavir at baseline, week 48, and week 96. The pattern of serum HBV RNA levels mirrored HBV DNA (1‐2 logs higher than HBV RNA) and HBcrAg in patients who were treatment‐naïve. HBV RNA correlated best with HBcrAg (r = 0.84) and to a lesser extent with HBV DNA (r = 0.737) (both P < 0.001). In patients with HBsAg seroclearance, 15.8% and 15.8% had detectable serum HBV RNA and HBcrAg, respectively. NA treatment reduced serum HBV RNA by 1.46 logs and 1.77 logs at weeks 48 and 96, respectively. At week 96 of NA therapy, only 19.1% patients who were tenofovir‐treated and 25.7% patients who were entecavir‐treated had unquantifiable HBV RNA (P > 0.05). In patients who were treated and had undetectable HBV DNA, 77.5% and 30% had quantifiable HBV RNA and HBcrAg, respectively.
Conclusions
HBV RNA showed distinct and corresponding profiles in patients with HBV in different disease phases. HBV RNA and HBcrAg could be used to monitor residual transcriptional activities in patients with HBsAg seroclearance. NA led to reduction of serum HBV RNA. Monitoring of viral activities can still be achieved in patients with undetectable HBV DNA by serum HBV RNA.
Hepatitis D virus (HDV) causes one of the most severe forms of hepatitis in people with chronic hepatitis B (CHB) infection. Timely and accurate assessment of hepatitis delta virus (HDV) and disease ...stratification is mandatory for thorough pre‐therapeutic evaluation for prioritizing treatment and outcome prediction. Viral biomarkers associated with HDV and hepatitis B virus (HBV) are crucial to aid in diagnosis, and monitoring of serum viral nucleic acids for both viruses is recommended. Liver biopsy remains the gold standard for staging of liver fibrosis and grading of histological activity and should remain central for diagnostic purposes, but is also of importance for research to enhance our understanding of HDV. The emergence of novel non‐invasive tests for the assessment of liver fibrosis in HDV patients coupled with the well‐recognized potential complications of liver biopsy has resulted in reduced utility of liver biopsy in clinical practice. Preliminary data suggest that these emerging non‐invasive modalities appear to be reliable, and their use is supported, similar to other viral hepatitis. Nevertheless, further validation is required before their widespread adoption into clinical practice.
The significance of hepatitis B e‐antigen (HBeAg) seroclearance (ESC) in the long term is not well defined. The current study aimed to determine the clinical outcomes, the factors and predictive ...scores for hepatocellular carcinoma (HCC), and hepatitis B surface antigen (HBsAg) seroclearance of a large cohort of patients undergoing ESC. Patients with documented ESC were followed up 3‐ to 6‐monthly. Baseline characteristics and longitudinal laboratory results were recorded. Predictive scores for HCC (HCC‐ESC) and HBsAg seroclearance (HBsAg‐ESC) were derived from multivariate Cox regression models. A total of 723 patients underwent ESC with a median ESC age and follow‐up of 36.0 and 18.3 years, respectively. Only 3.5% and 3.0% had persistently normal alanine aminotransferase (ALT) and HBV DNA <2logs IU/mL, respectively, after ESC. For patients with 100%, 100%‐90%, 90%‐50%, 50%‐10%, 10%‐0%, and 0% normal ALT after HBeAg seroclearance, the rate of HCC was 4.3%, 2.2%, 3.6%, 3.9%, 17.3%, and 37.2% at 20 years after ESC, respectively (P < 0.001). At 20 years after ESC, the cumulative incidence of HCC and HBsAg seroclearance was 7.9% and 13.5%, respectively, with an overall survival of 91.5%. ESC age, male sex, cirrhosis, hypoalbuminemia, viral load, and ALT were significant factors for HCC, whereas ESC age, male sex, viral load, and antiviral therapy were significant factors for HBsAg seroclearance. The area under receiver operating characteristics for HCC‐ESC and HBsAg‐ESC scores to predict HCC and HBsAg seroclearance at 20 years after ESC was 0.92 and 0.74, respectively. Conclusion: Male sex, older age at ESC, ALT, and higher level of HBV DNA were associated with higher rates of HCC after ESC. HCC‐ESC and HBsAg‐ESC predictive scores can determine the likelihood of developing HCC and achieving HBsAg seroclearance. (Hepatology 2018)
Linked ContentThis article is linked to Hosaka et al and Hosaka papers. To view
these articles, visit https://doi.org/10.1111/apt.15108 and https://doi.org/10.1111/apt.15156.
AIM To investigate the epidemiology and natural history of Wilson’s disease in the Chinese.METHODS Data were retrieved via electronic search of hospital medical registry of the Hong Kong Hospital ...Authority,which covers all the public healthcare services. We identified cases of Wilson’s disease between 2000 and 2016 by the International Classification of Diseases(ICD)-9 code. We analyzed the incidence rate,prevalence and adverse outcomes of Wilson’s disease.RESULTS We identified 211 patients(male cases 104; female cases 107; median age 27.2 years,IQR: 17.1-38.6 years; duration of follow-up 8.0 years,IQR: 5.0-14.0 years). The average annual incidence rate was 1.44 per million person-years while the prevalence was 17.93 per million. Between 2000 and 2016,there was a decrease in the annual incidence rate from 1.65 to 1.23 per million person-years(P = 0.010),whereas there was an increase in the annual prevalence from 7.80 to 25.20 per million(P < 0.001). Among the 176 cases with hepatic involvement,38(21.6%) had cirrhosis,three(1.7%) developed hepatocellular carcinoma,24(13.6%) underwent liver transplantations,and 26(14.8%) died. Seven patients had concomitant chronic viral hepatitis B or C. The 5-year and 10-years rates of overall survival were 92.6% and 89.5%,and for transplant-free survival rates 91.8% and 87.4%,respectively. Cirrhosis and possibly chronic viral hepatitis were associated with poorer overall survival. CONCLUSION There was a significant increase in the prevalence of Wilson’s disease in Hong Kong. The prognosis was favorable except for those with cirrhosis or concomitant viral hepatitis.
Background
We aimed to assess whether residual hepatitis B virus (HBV) viraemia is associated with HCC development.
Methods
This is a case–control study of 104 patients 52 HCC and 52 non-HCC (matched ...with age, gender, cirrhosis and treatment duration) on ≥ 3 years entecavir (ETV) with unquantifiable HBV DNA by Cobas Taqman assay v2.0 (Roche Diagnostics; lower limit of quantification LLOQ 20 IU/mL). Serial sera within 1, 1–2, and > 2 years prior to HCC diagnosis or last follow-up (LFU) were measured for HBV DNA and pre-genomic (pg) RNA using a highly sensitive semi-quantitative PCR assay with lower limit of detection of 10 IU/mL and LLOQ of 51.5 IU/mL, respectively.
Results
Among the 104 patients (80.8% male, median age 61.2 years old, 38.5% cirrhosis, median duration of ETV 45.5 months), 38.5% and 9.6% HCC patients had undetectable serum DNA and pgRNA, respectively, compared to 65.4% and 36.5% in non-HCC patients;
P
= 0.005 & 0.001, respectively, at the time of HCC diagnosis/LFU. Detectable HBV DNA and pgRNA were associated with a higher 2-year risk of HCC development (HR 2.79, 95% CI 1.424–5.468 & HR 4.544, 95% CI 1.07–19.289, respectively). No significant differences were observed for qHBsAg levels between HCC and non-HCC patients.
Conclusions
More than 50% CHB patients on ETV with HBV DNA < LLOQ by standard assay had persistent viraemia as determined by a more sensitive assay. Detectable HBV DNA or pgRNA by more sensitive assays was associated with HCC development. More potent viral suppression is required to further reduce the risk of HCC.
Treatment cessation in chronic HBV infection may be durable in certain patient subgroups before hepatitis B surface antigen (HBsAg) seroclearance. The role of serum HBV RNA in determining treatment ...cessation suitability has not been well-investigated.
Nucleos(t)ide analogue (NUC) treatment was discontinued in non-cirrhotic patients with chronic HBV with serum HBsAg <200 IU/mL and fulfilling internationally recommended criteria for treatment cessation. Patients were monitored till 48 weeks with baseline and serial measurements of serum HBsAg, HBV RNA and hepatitis B core-related antigen. NUCs were resumed when HBV DNA reaches >2000 IU/mL regardless of alanine aminotransferase (ALT) levels.
114 entecavir-treated patients (median age 58.4 years, median serum HBsAg 54.4 IU/mL) with median treatment duration of 6.7 years were recruited. The 48-week cumulative rate of HBV DNA >2000 IU/mL was 58.1%. End-of-treatment serum HBV RNA and off-treatment serial HBV RNA were both independently associated with HBV DNA >2000 IU/mL (HR 2.959, 95% CI 1.776 to 4.926, p<0.001; HR 2.278, 95% CI 1.151 to 4.525, p=0.018, respectively). Patients with HBV RNA ≥44.6 U/mL had a cumulative 48-week rate of 93.2%, while combining HBV RNA undetectability and HBsAg <10 IU/mL had a cumulative 48-week rate of 9.1%. 24 patients (38.7%) developed off-treatment ALT elevation, highest peak ALT was 1515 U/L. 8 patients (median serum HBsAg 2.6 IU/mL) developed HBsAg seroclearance.
Serum HBV RNA measurement is essential for deciding on entecavir cessation in patients with chronic HBV, especially with low HBsAg levels. Patients can be stratified on their risk of off-treatment relapse based on both viral determinants.
NCT02738554.
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