Exploration of Digestive Diseases

Special Issue Topic

Chronic Hepatitis B and C

Submission Deadline: April 30, 2025

Guest Editor

Prof. Ching Lung Lai E-Mail

The University of Hong Kong, State Key Laboratory of Liver Research, Hong Kong, China

About the Special Issue

The World Health Organization (WHO) has set the target for the global elimination of viral hepatitis since 2016. It aims to reduce new infections and death due to viral hepatitis by 30% and 10% respectively in 2020, and 90% and 65% respectively in 2030.
However of the four top infectious diseases in the world, including malaria, tuberculosis, human immunodeficiency virus (HIV) and viral hepatitis, WHO reports that the incidence of mortality in the first 3 diseases are dropping but the mortality due to viral hepatitis is rising. Despite the wide spread use of neonatal vaccination against the hepatitis B virus (HBV) including in countries of the Third World, WHO reported in 2019 that there were 296 million people with chronic HBV, with 1.5 million new infections per year. The problem is even more serious with the hepatitis C virus (HCV) since there is no vaccine to prevent the infection. The incidence of HCV mainly depends on the people who injects drugs (PWID) using needles which have been used by others. Both HBV and HCV can lead to cirrhosis and hepatocellular carcinoma (HCC). Antiviral treatment for both HBV and HCV can reverse, to a certain degree, the severity of cirrhosis and the development of HCC. Whereas HCV, being a RNA virus, requires only an 8-12 week course of antiviral treatment to induce sustained virologic response, HBV, being a DNA virus, still requires life-long treatment. With HBV infection, if the patients manage to lose the hepatitis B surface antigen (HBsAg seroclearance) there is a reduction in the development of HCC. HBsAg seroclearance is now termed as “functional cure” for HBV and newer agents are being studied to increase the proportion of patients with HBsAg seroclearnace.
To complicate matters, there is a rising incidence of steatotic liver disease (STD, formerly known as non-alcoholic steatohepatitis) globally. STD can also cause cirrhosis and HCC. The effect of co-existence of STD with HBV or HCV is still not clearly defined.
The aim of the present issue is to clarify some of the issues raised in this Introduction.

Keywords: chronic hepatitis B, chronic hepatitis C, cirrhosis, hepatocellular carcinoma, HBsAg seroclearance

Call for Papers

Published Articles

Open Access

Review

Hepatocellular carcinoma surveillance after HBsAg seroclearance
Hepatitis B surface antigen (HBsAg) seroclearance is considered the functional cure and the optimal treatment endpoint for chronic hepatitis B (CHB). Patients with CHB who cleared HBsAg generally ha [...] Read more.

Hepatitis B surface antigen (HBsAg) seroclearance is considered the functional cure and the optimal treatment endpoint for chronic hepatitis B (CHB). Patients with CHB who cleared HBsAg generally have a favorable clinical course with minimal risk of developing hepatocellular carcinoma (HCC) or cirrhotic complications. Nevertheless, a minority of patients still develop HCC despite HBsAg seroclearance. While patients with liver cirrhosis are still recommended for HCC surveillance, whether other non-cirrhotic patients who achieved HBsAg seroclearance should remain on HCC surveillance remains unclear. This review provides an overview of the incidence of HBsAg seroclearance, the factors associated with the occurrence of HBsAg seroclearance, the durability of HBsAg seroclearance, the risk of developing HCC after HBsAg seroclearance, the risk factors associated with HCC development after HBsAg seroclearance, the role of HCC risk scores, and the implications on HCC surveillance. Existing HCC risk scores have a reasonably good performance in patients after HBsAg seroclearance. In the era of artificial intelligence, future HCC risk prediction models based on artificial intelligence and longitudinal clinical data may further improve the prediction accuracy to establish a foundation of a risk score-based HCC surveillance strategy. As different novel hepatitis B virus (HBV) antiviral agents aiming at HBsAg seroclearance are under active development, new knowledge is anticipated on the natural history and HCC risk prediction of patients treated with new HBV drugs.

Jimmy Che-To Lai ... Terry Cheuk-Fung Yip

Published: May 11, 2024 Explor Dig Dis. 2024;3:175–189
DOI: https://doi.org/10.37349/edd.2024.00046

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Hepatitis B surface antigen (HBsAg) seroclearance is considered the functional cure and the optimal treatment endpoint for chronic hepatitis B (CHB). Patients with CHB who cleared HBsAg generally have a favorable clinical course with minimal risk of developing hepatocellular carcinoma (HCC) or cirrhotic complications. Nevertheless, a minority of patients still develop HCC despite HBsAg seroclearance. While patients with liver cirrhosis are still recommended for HCC surveillance, whether other non-cirrhotic patients who achieved HBsAg seroclearance should remain on HCC surveillance remains unclear. This review provides an overview of the incidence of HBsAg seroclearance, the factors associated with the occurrence of HBsAg seroclearance, the durability of HBsAg seroclearance, the risk of developing HCC after HBsAg seroclearance, the risk factors associated with HCC development after HBsAg seroclearance, the role of HCC risk scores, and the implications on HCC surveillance. Existing HCC risk scores have a reasonably good performance in patients after HBsAg seroclearance. In the era of artificial intelligence, future HCC risk prediction models based on artificial intelligence and longitudinal clinical data may further improve the prediction accuracy to establish a foundation of a risk score-based HCC surveillance strategy. As different novel hepatitis B virus (HBV) antiviral agents aiming at HBsAg seroclearance are under active development, new knowledge is anticipated on the natural history and HCC risk prediction of patients treated with new HBV drugs.

Open Access

Original Article

Impact of the direct acting antivirals on chronic hepatitis C prevalence on the Swiss organ transplantation list: a retrospective analysis
Aim: In Switzerland, the first access to interferon-free direct-acting antivirals (DAAs) for hepatitis C virus (HCV) treatment was in 2014. This study aimed to analyze the effects of DAAs on the [...] Read more.

Aim:

In Switzerland, the first access to interferon-free direct-acting antivirals (DAAs) for hepatitis C virus (HCV) treatment was in 2014. This study aimed to analyze the effects of DAAs on the yearly listed numbers of HCV RNA-positive (RNA+) patients and their mortality on the Swiss organ transplantation waiting list (SOWL).

Methods:

In this retrospective secondary time series analysis of yearly aggregated data on listed and delisted patients from a subset of HCV RNA+ patients on the SOWL, listed patients were grouped by the requested organ, and delisted patients by reason. Time series were split into two periods of equal length, the phases before and after DAA implementation, and the mean difference was tested using the Mann-Whitney U test.

Results:

From 2008 to 2019, 328 HCV RNA+ patients were listed on SOWL, 86.6% requesting liver, 11.6% kidney, and 1.8% other organ transplantations. A total of 285 RNA+ patients were delisted from SOWL: 14.7% died, 75.4% had been transplanted, and 9.8% were delisted without surgery. There were significant reductions of patients listed for requesting any organ (–21.7, P = 0.004), liver (–18.3, P = 0.004), or kidney (–3.0, P = 0.031) comparing the periods before and after DAA launch. The mean number of delistings after transplantation (–11.2, P = 0.010), or death (–4, P < 0.001) show a significant reduction.

Conclusions:

With DAAs, the rising trend of HCV RNA+ people waiting for organs was broken, as was the increasing trend of mortality on the SOWL among HCV RNA+ individuals.

Luis Falcato ... Franz Immer

Published: December 25, 2023 Explor Dig Dis. 2023;2:297–304
DOI: https://doi.org/10.37349/edd.2023.00032

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Aim:

In Switzerland, the first access to interferon-free direct-acting antivirals (DAAs) for hepatitis C virus (HCV) treatment was in 2014. This study aimed to analyze the effects of DAAs on the yearly listed numbers of HCV RNA-positive (RNA+) patients and their mortality on the Swiss organ transplantation waiting list (SOWL).

Methods:

In this retrospective secondary time series analysis of yearly aggregated data on listed and delisted patients from a subset of HCV RNA+ patients on the SOWL, listed patients were grouped by the requested organ, and delisted patients by reason. Time series were split into two periods of equal length, the phases before and after DAA implementation, and the mean difference was tested using the Mann-Whitney U test.

Results:

From 2008 to 2019, 328 HCV RNA+ patients were listed on SOWL, 86.6% requesting liver, 11.6% kidney, and 1.8% other organ transplantations. A total of 285 RNA+ patients were delisted from SOWL: 14.7% died, 75.4% had been transplanted, and 9.8% were delisted without surgery. There were significant reductions of patients listed for requesting any organ (–21.7, P = 0.004), liver (–18.3, P = 0.004), or kidney (–3.0, P = 0.031) comparing the periods before and after DAA launch. The mean number of delistings after transplantation (–11.2, P = 0.010), or death (–4, P < 0.001) show a significant reduction.

Conclusions:

With DAAs, the rising trend of HCV RNA+ people waiting for organs was broken, as was the increasing trend of mortality on the SOWL among HCV RNA+ individuals.

Guest Editor

About the Special Issue

Call for Papers

Published Articles

Aim:

Methods:

Results:

Conclusions:

Aim:

Methods:

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