Now hepatitis B and hepatitis C are the most important cause of chronic liver diseases in Asia-pacific region, especially China. Due to the similar mode of transmission, co-infection with HBV and HCV is common, especially in high-risk populations and in HBV endemic area. For example, co-infection of HBV in patients with chronic HCV infection has been estimated to be as high as 8.4% in Chinese. To date, no standard-of-care recommendation exists for HBV/HCV co-infection.

 

　　In general, HCV can suppress the replication of HBV, probably via indirect immune mechanism. Hence, eradication or suppression of HCV could lead to HBV reactivation.  This is somewhat not a big issue in the past when IFN was the main therapy for hepatitis C because IFN can inhibited HCV and HBV simultaneously, Even though, successful treatment of chronic hepatitis C infection with pegylated interferon-α and ribavirin has been related to HBV reactivation in patients co-infected with both virus.

 

　　"Up to 30% of patients co-infected with HBV/HCV might experience hepatitis flare after their HCV infections controlled by DAA."

 

　　But now with the use of pan-oral DAAs that solely target HCV (Professor Lau and his colleagues are among the first and the largest group to make use of the brand name DAA treatment of hepatitis C in China), HBV reactivation in HBV/HCV co-infected patients after cure of HCV should not be neglected anymore.  In APASL 2016, Professor George Lau, Humanity & Health Medical Centre, Hong Kong, Hong Kong SAR, China, and his colleagues present a breakthrough finding of increase incidence of hepatitis due to HBV reactivation in HBV/HCV co-infected patients, treated with pan-oral DAAs therapy. Professor Lau told APASL Daily: "we see a phenomenon which has not been observed previously and that is HBV reactivations when the patients who are co-infected both viruses and treated with DAAs for hepatitis C, the patient can have reactivations of hepatitis B. This is a novel observation and if is important that we notice this phenomenon and manage them appropriately."

 

　　They prospectively studied 355 consecutive CHC Chinese treated with 8-24 weeks pan-oral DAAs. Among these patients, 10（2.8%）were HBsAg positive. Eleven (3.1%) CHC patients suffered from hepatitis during DAAs therapy at week 8, with three due to HBV reactivation (one of them developed liver failure). They also identified that HBsAg positive patients not treated with anti-HBV NAs is the most significant factor associated with hepatitis in CHC patients treated with pan-oral DAAs (HR: 12.28, P=0.001).

 

　　Prof. Lau addressed that up to 30% of untreated (by NA) patients co-infected with HBV/HCV might experience hepatitis flare after their HCV infections controlled by DAA. In severe cases, hepatitis flare even can lead to liver failure. He thinks it's reasonable that in HBV high-epidemic area, all patients with hepatitis C get test for HBV infection before DAA therapy initiated. For patients confirmed co-infection should anti HBV therapy with potent NAs start at the same time of DAA therapy.

 

　　"With HBsAg loss or seroconversations, it means that we are able to restore the host immune control on the viral."

 

　　Another thing Professor Lau would discuss in his another lecture is how we are going to move forward from 2015 and onwards and that is a cure for hepatitis B.

 

　　A cure would mean either a functional cure or a complete cure. A functional cure means HBsAg conversations or loss and then these patients can still be reactivated. For a complete cure it means a complete elimination of all of DNA, even that has integrated with the normal DNA, so the patient will be completely cured.

 

　　The current management for hepatitis B so far is only control but not cure the disease.

 

　　Most of the patients can get control of the virus with prolonged medication such as treatment with entecavir and tenofovir but we cannot take the patients off of the drugs.

 

　　However, when a functional cure achieved the therapy can be stopped safely and the patient will not have the problem any more. To this aspect, so far the only certain way to stop a patient from therapy is HBsAg loss or s seroconversion. The problem is it is very difficult to achieve HBsAg loss or HBsAg seroconversion using current therapies with the nucleoside analoges or with interferon-based therapy. In order to improve this, many different approaches are under study, such as combinations of interferon plus entecavir or tenofovir and more promising new therapies.

 

　　Prof. Lau said: " We have small molecules which block the viral replication cycles at different steps such as the entry site, capsid and assembly, and to prevent the formations of cccDNA. On the other hand we also have miRNA to interfere with the replication cycle. Also we have immune modulation methods, such as Toll like receptors and therapeutic vaccinations and also the very exciting is the TCR engineering of the T cells because a functional cure can only happen when we restore the immune control of the viral replication gene. This is based on actually my paper in 1994 published in Gastroenterology. We are the first group to make the observations that restoration of the host immune control on hepatitis B can result in a functional cure but these patients can still have reactivations because they still have cccDNA and this will be a very difficult task."

 

　　Professor Lau believes that in the next 5 to 10 years we will be able to see new molecules coming into practice. At the same time, they are working on achieving immune control of the viral replication.

 

Symposium 7: Treatment of HBV for a Cure - “Nucleotide”

 

15:05 - 15:25