Occult Hepatitis BNCT04356404
Risk of Hepatitis Flare in Patients With Previous Hepatitis B Virus Exposure Amongst Patients
An observational study of Occult Hepatitis B and Biological Substance; Adverse Effect, run by Chinese University of Hong Kong at 1 site in Hong Kong.
Trial summary
The purpose of this study is to study the risk of hepatitis flare in patients with previous hepatitis B virus exposure amongst patients on immunosuppressive and biological modifier therapies Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Occult Hepatitis B, Biological Substance; Adverse Effect, Immunosuppression
- How many people
- 68 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 May 2020to 12 Jan 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All patients with previous HBV exposure who are already on biological modifier therapies and who will be newly started on biological modifier therapies in the Department of Medicine and Therapeutics, Prince of Wales Hospital and Department of Medicine, University Malaya Medical Centre will be recruited.
Who may be able to join
- Age ≥ 18 years old at the time of starting biological modifier therapies or at the time of recruitment
- Positive for anti-HBc OR
- Positive for anti-HBs and born before year 1988
Who cannot join
- Known HBV carrier with HBsAg positive
- Concomitant HCV and/ or HIV infection
- Already on HBV anti-viral
- Refuse to consent
- Baseline ALT > 80 IU/ml
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Risk of Hepatitis Flare in Patients With Previous Hepatitis B Virus Exposure Amongst Patients on Immunosuppressive and Biological Modifier Therapies Exposure
The purpose of this study is to study the risk of hepatitis flare in patients with previous hepatitis B virus exposure amongst patients on immunosuppressive and biological modifier therapies
Read the detailed description
Chronic hepatitis B infection remains a global health threat despite vaccination program.[1] Nearly 3 billion population are infected with chronic hepatitis B infection globally. In China, the pooled prevalence of chronic hepatitis B infection was around 7% in year 2018, making an estimated 84 millions of population living with chronic hepatitis B infection. Hepatitis B virus infection is the leading cause of liver cirrhosis and hepatocellular carcinoma, leading to significant morbidity and mortality. Patients with hepatitis B infection can present with a wide range of clinical presentation, ranging from inactive carrier to fulminant hepatitis, cirrhosis or development of hepatocellular carcinoma. Besides, a significant proportion of patients are suffering from occult hepatitis B infection (OBI), which is defined as a state of undetectable serum HBsAg yet detectable serum and/ or intrahepatic HBV DNA. Report from the European Association for the Study of the Liver (EASL) in 2008 has revealed that around one-third of the global population has serological evidence of past or present HBV infection. Disappearance of HBsAg, also known as HBsAg seroclearance, can occur either spontaneously or after anti-viral treatment. However, patients with past or resolved HBV infection are still at risk of development of hepatocellular carcinoma, liver cirrhosis and liver-related mortality.The reported prevalence of OBI amongst patients with non-alcoholic fatty liver disease in Hong Kong was 35% (submitted to American Journal of Gastroenterology, under review). It is well known that there is risk of HBV reactivation after chemotherapy or immunosuppressive therapy which can lead to fulminant liver failure or even death. Short course of high dose corticosteroid could increase the risk of hepatitis flare in patients with chronic hepatitis B infection. Even in patients with OBI, a high daily dose of corticosteroid (>40mg prednisolone equivalents) increased risks of hepatitis flare. It is thus important to know the hepatitis B virus status before start of chemotherapy, immunosuppressive therapy or corticosteroid.
Biologics is one of the mainstay treatments for many autoimmune diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), psoriasis etc. The incidence of IBD has increased rapidly in Hong Kong over the past 30 years. The age-adjusted incidence of IBD in Hong Kong has rose from 0.10 per 100,000 individuals in 1985 to 3.12 per 100,000 individuals in 2014. The reported prevalence of RA in Hong Kong was 0.35% while the reported prevalence of SLE in Hong Kong was 0.1% with annual incidence of 6.7 per 100,000 individuals. It is well known that treatment with biological agent like anti-CD20 monoclonal antibody (rituximab) in patients with OBI can lead to fulminant hepatitis B flare. Recently, anti-tumor necrosis factor alpha (TNF α) has been widely used in patients with inflammatory bowel disease and various rheumatological diseases. Risk of hepatitis B reactivation after anti-TNF α has been reported, but actual risk remains controversial. In a report from Japan including 135 rheumatoid arthritis patients with previous HBV infections, 17/135 (12.6%) had HBV reactivation after receiving immunosuppressants and patients who were treated with biologics were more frequent to develop HBV reactivation compared to those who were not on biologics. In another study, 9/168 (5%) anti-HBc positive patients developed HBV reactivation after receiving anti-TNF α and one patient died due to fulminant liver failure.However, another three studies revealed low rates of HBV reactivation (0-2%) amongst rheumatology patients with previous HBV infections receiving anti-TNF α. The European Crohn's and Colitis Organisation (ECCO) suggested routine antiviral prophylaxis for patients with previous HBV infection starting biologics is not recommended. Instead, regular monitoring of ALT/ AST, change in HBV serology and HBV DNA every 1 to 3 months should be performed. In 2015, the American Gastroenterology Association (AGA) has developed guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive therapy. It classifies patients receiving anti-TNF α as moderate risk of developing HBV reactivation and antiviral prophylaxis is preferred over monitoring alone, but it is a weak recommendation. Therefore, it is now still uncertain whether prophylactic anti-viral should be given for patients with previous HBV exposure before starting anti-TNF α.
With the advancement of technology, there are now more biological agents and small molecules for the treatment of IBD and various rheumatological conditions. These include anti-integrin, cytokine inhibitors, and small molecules e.g. JAK inhibitors. Cytokine inhibitor, ustekinumab (anti-IL12/23), has been reported to be leading to hepatitis reactivation in a psoriasis patient who has past HBV infection.[26] Whether these agents can lead to hepatitis flare in patients with past HBV exposure remains largely unknown.
Based on the compelling data, the investigators hypothesize that use of biologic modifier therapies in patients with occult hepatitis B infection will lead to hepatitis flare. The investigators aim to assess the rate of hepatitis flare while on biological modifier therapies in both retrospective population-based database and prospectively in patients who are on biological modifier therapies.
- Keywords
- Occult Hepatitis B infection, Biologics, Immunosuppressants
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Prospective group | Patients will be followed up until development of hepatitis flare or at 2 years after study recruitment. We plan to recruit 150 patients for the prospective cohort. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of hepatitis flare
Hepatitis flare, defined as ALT >2xULN IU/L, according to the Asia Pacific Association for the Study of the Liver (APASL) definition while on biological modifier therapy. The upper limit of normal (ULN) was defined as 40 IU/L by APASL.
Measured: 24 months
Secondary outcomes (4)
Rate of severe hepatitis flare
Severe hepatitis flare, defined as ALT > 5xULN or > 10xULN, as defined by the APASL definition, while on biological modifier therapy
Measured: 24 months
Rate of icteric flare
Icteric flare, defined as ALT raised >3xULN together with serum total bilirubin >2xULN (i.e. >38 µmol/L), while on biological modifier therapy
Measured: 24 months
Rate of HBsAg seroreversion
HBsAg seroreversion, defined as reappearance of HBsAg
Measured: 24 months
Risk factors associated with development of hepatitis flare
Risk factors associated with development of hepatitis flare, Including concomitant use of steroid and immunosuppressants
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2020
- Study start1 May 2020
- Primary completion12 Jan 2022
- Study completion12 Jan 2022
Why it stopped: No suitable case identified
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (26)Papers the sponsor has linked to this study.
- Other trials for Occult Hepatitis BStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- University of Malaya
- Responsible party
- Principal investigator, Mak Wing Yan, Chinese University of Hong Kong
- Investigators
- WingYan Mak, MRCP, Principal investigator, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04356404
- Sponsor's protocol ID
- HEP-FLARE_Protocol_20210604_V5
- Status last verified
- Jan 2022
- First submitted
- 19 Apr 2020
- Last updated
- 28 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Polaris Observatory Collaborators. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol. 2018 Jun;3(6):383-403. doi: 10.1016/S2468-1253(18)30056-6. Epub 2018 Mar 27.
PubMed 29599078Wang H, Men P, Xiao Y, Gao P, Lv M, Yuan Q, Chen W, Bai S, Wu J. Hepatitis B infection in the general population of China: a systematic review and meta-analysis. BMC Infect Dis. 2019 Sep 18;19(1):811. doi: 10.1186/s12879-019-4428-y.
PubMed 31533643Maynard JE. Hepatitis B: global importance and need for control. Vaccine. 1990 Mar;8 Suppl:S18-20; discussion S21-3. doi: 10.1016/0264-410x(90)90209-5.
PubMed 2139281Torbenson M, Thomas DL. Occult hepatitis B. Lancet Infect Dis. 2002 Aug;2(8):479-86. doi: 10.1016/s1473-3099(02)00345-6.
PubMed 12150847Raimondo G, Allain JP, Brunetto MR, Buendia MA, Chen DS, Colombo M, Craxi A, Donato F, Ferrari C, Gaeta GB, Gerlich WH, Levrero M, Locarnini S, Michalak T, Mondelli MU, Pawlotsky JM, Pollicino T, Prati D, Puoti M, Samuel D, Shouval D, Smedile A, Squadrito G, Trepo C, Villa E, Will H, Zanetti AR, Zoulim F. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepatol. 2008 Oct;49(4):652-7. doi: 10.1016/j.jhep.2008.07.014. Epub 2008 Jul 31. No abstract available.
PubMed 18715666Yip TC, Chan HL, Wong VW, Tse YK, Lam KL, Wong GL. Impact of age and gender on risk of hepatocellular carcinoma after hepatitis B surface antigen seroclearance. J Hepatol. 2017 Nov;67(5):902-908. doi: 10.1016/j.jhep.2017.06.019. Epub 2017 Jun 24.
PubMed 28652084Yip TC, Wong GL, Chan HL, Tse YK, Lam KL, Lui GC, Wong VW. HBsAg seroclearance further reduces hepatocellular carcinoma risk after complete viral suppression with nucleos(t)ide analogues. J Hepatol. 2019 Mar;70(3):361-370. doi: 10.1016/j.jhep.2018.10.014. Epub 2018 Oct 25.
PubMed 30367899Yip TC, Wong GL, Wong VW, Tse YK, Lui GC, Lam KL, Chan HL. Durability of hepatitis B surface antigen seroclearance in untreated and nucleos(t)ide analogue-treated patients. J Hepatol. 2017 Oct 6:S0168-8278(17)32332-2. doi: 10.1016/j.jhep.2017.09.018. Online ahead of print.
PubMed 28989093Chung SM, Sohn JH, Kim TY, Yoo KD, Ahn YW, Bae JH, Jeon YC, Choi JH. [Fulminant hepatic failure with hepatitis B virus reactivation after rituximab treatment in a patient with resolved hepatitis B]. Korean J Gastroenterol. 2010 Apr;55(4):266-9. doi: 10.4166/kjg.2010.55.4.266. Korean.
PubMed 20389182Khan ZH, Ilyas K, Ghazanfar H, Khan HH, Hussain Q, Hammad S, Munir A, Asim R. Fatal Fulminant Hepatitis from Rituximab-induced Hepatitis B Reactivation in a Patient with Follicular Lymphoma: A Case Report and a Brief Review of Literature. Cureus. 2018 Mar 2;10(3):e2257. doi: 10.7759/cureus.2257.
PubMed 29725560Ng SC, Leung WK, Shi HY, Li MK, Leung CM, Ng CK, Lo FH, Hui YT, Tsang SW, Chan YK, Loo CK, Chan KH, Hui AJ, Chow WH, Harbord M, Ching JY, Lee M, Chan V, Tang W, Hung IF, Ho J, Lao WC, Wong MT, Sze SF, Shan EH, Lam BC, Tong RW, Mak LY, Wong SH, Wu JC, Chan FK, Sung JJ. Epidemiology of Inflammatory Bowel Disease from 1981 to 2014: Results from a Territory-Wide Population-Based Registry in Hong Kong. Inflamm Bowel Dis. 2016 Aug;22(8):1954-60. doi: 10.1097/MIB.0000000000000846.
PubMed 27416041Ho CTK, Mok CC, Cheung TT, Kwok KY, Yip RML; Hong Kong Society of Rheumatology. Management of rheumatoid arthritis: 2019 updated consensus recommendations from the Hong Kong Society of Rheumatology. Clin Rheumatol. 2019 Dec;38(12):3331-3350. doi: 10.1007/s10067-019-04761-5. Epub 2019 Sep 4.
PubMed 31485846Mok CC. Epidemiology and survival of systemic lupus erythematosus in Hong Kong Chinese. Lupus. 2011 Jun;20(7):767-71. doi: 10.1177/0961203310388447. Epub 2010 Dec 10.
PubMed 21148605Sera T, Hiasa Y, Michitaka K, Konishi I, Matsuura K, Tokumoto Y, Matsuura B, Kajiwara T, Masumoto T, Horiike N, Onji M. Anti-HBs-positive liver failure due to hepatitis B virus reactivation induced by rituximab. Intern Med. 2006;45(11):721-4. doi: 10.2169/internalmedicine.45.1590. Epub 2006 Jul 3.
PubMed 16819252Koo YX, Tay M, Teh YE, Teng D, Tan DS, Tan IB, Tai DW, Quek R, Tao M, Lim ST. Risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen negative/hepatitis B core antibody positive patients receiving rituximab-containing combination chemotherapy without routine antiviral prophylaxis. Ann Hematol. 2011 Oct;90(10):1219-23. doi: 10.1007/s00277-011-1241-0. Epub 2011 Apr 26.
PubMed 21520001
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Risk of Hepatitis Flare in Patients With Previous Hepatitis B Virus Exposure Amongst Patients on Immunosuppressive and Biological Modifier Therapies Exposure
- ClinicalTrials.gov ID
- NCT04356404
- Acronym / sponsor ID
- HEP-FLARE_Protocol_20210604_V5
- Keywords
- Occult Hepatitis B infection, Biologics, Immunosuppressants
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: No suitable case identified
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Collaborators
- University of Malaya
- Study start
- 1 May 2020 (actual)
- Primary completion
- 12 Jan 2022 (actual)
- Study completion
- 12 Jan 2022 (actual)
- First posted
- 22 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to study the risk of hepatitis flare in patients with previous hepatitis B virus exposure amongst patients on immunosuppressive and biological modifier therapies
Detailed description
Chronic hepatitis B infection remains a global health threat despite vaccination program.[1] Nearly 3 billion population are infected with chronic hepatitis B infection globally. In China, the pooled prevalence of chronic hepatitis B infection was around 7% in year 2018, making an estimated 84 millions of population living with chronic hepatitis B infection. Hepatitis B virus infection is the leading cause of liver cirrhosis and hepatocellular carcinoma, leading to significant morbidity and mortality. Patients with hepatitis B infection can present with a wide range of clinical presentation, ranging from inactive carrier to fulminant hepatitis, cirrhosis or development of hepatocellular carcinoma. Besides, a significant proportion of patients are suffering from occult hepatitis B infection (OBI), which is defined as a state of undetectable serum HBsAg yet detectable serum and/ or intrahepatic HBV DNA. Report from the European Association for the Study of the Liver (EASL) in 2008 has revealed that around one-third of the global population has serological evidence of past or present HBV infection. Disappearance of HBsAg, also known as HBsAg seroclearance, can occur either spontaneously or after anti-viral treatment. However, patients with past or resolved HBV infection are still at risk of development of hepatocellular carcinoma, liver cirrhosis and liver-related mortality.The reported prevalence of OBI amongst patients with non-alcoholic fatty liver disease in Hong Kong was 35% (submitted to American Journal of Gastroenterology, under review). It is well known that there is risk of HBV reactivation after chemotherapy or immunosuppressive therapy which can lead to fulminant liver failure or even death. Short course of high dose corticosteroid could increase the risk of hepatitis flare in patients with chronic hepatitis B infection. Even in patients with OBI, a high daily dose of corticosteroid (>40mg prednisolone equivalents) increased risks of hepatitis flare. It is thus important to know the hepatitis B virus status before start of chemotherapy, immunosuppressive therapy or corticosteroid.
Biologics is one of the mainstay treatments for many autoimmune diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), psoriasis etc. The incidence of IBD has increased rapidly in Hong Kong over the past 30 years. The age-adjusted incidence of IBD in Hong Kong has rose from 0.10 per 100,000 individuals in 1985 to 3.12 per 100,000 individuals in 2014. The reported prevalence of RA in Hong Kong was 0.35% while the reported prevalence of SLE in Hong Kong was 0.1% with annual incidence of 6.7 per 100,000 individuals. It is well known that treatment with biological agent like anti-CD20 monoclonal antibody (rituximab) in patients with OBI can lead to fulminant hepatitis B flare. Recently, anti-tumor necrosis factor alpha (TNF α) has been widely used in patients with inflammatory bowel disease and various rheumatological diseases. Risk of hepatitis B reactivation after anti-TNF α has been reported, but actual risk remains controversial. In a report from Japan including 135 rheumatoid arthritis patients with previous HBV infections, 17/135 (12.6%) had HBV reactivation after receiving immunosuppressants and patients who were treated with biologics were more frequent to develop HBV reactivation compared to those who were not on biologics. In another study, 9/168 (5%) anti-HBc positive patients developed HBV reactivation after receiving anti-TNF α and one patient died due to fulminant liver failure.However, another three studies revealed low rates of HBV reactivation (0-2%) amongst rheumatology patients with previous HBV infections receiving anti-TNF α. The European Crohn's and Colitis Organisation (ECCO) suggested routine antiviral prophylaxis for patients with previous HBV infection starting biologics is not recommended. Instead, regular monitoring of ALT/ AST, change in HBV serology and HBV DNA every 1 to 3 months should be performed. In 2015, the American Gastroenterology Association (AGA) has developed guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive therapy. It classifies patients receiving anti-TNF α as moderate risk of developing HBV reactivation and antiviral prophylaxis is preferred over monitoring alone, but it is a weak recommendation. Therefore, it is now still uncertain whether prophylactic anti-viral should be given for patients with previous HBV exposure before starting anti-TNF α.
With the advancement of technology, there are now more biological agents and small molecules for the treatment of IBD and various rheumatological conditions. These include anti-integrin, cytokine inhibitors, and small molecules e.g. JAK inhibitors. Cytokine inhibitor, ustekinumab (anti-IL12/23), has been reported to be leading to hepatitis reactivation in a psoriasis patient who has past HBV infection.[26] Whether these agents can lead to hepatitis flare in patients with past HBV exposure remains largely unknown.
Based on the compelling data, the investigators hypothesize that use of biologic modifier therapies in patients with occult hepatitis B infection will lead to hepatitis flare. The investigators aim to assess the rate of hepatitis flare while on biological modifier therapies in both retrospective population-based database and prospectively in patients who are on biological modifier therapies.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Prospective group | – | –Patients will be followed up until development of hepatitis flare or at 2 years after study recruitment. We plan to recruit 150 patients for the prospective cohort. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All patients with previous HBV exposure who are already on biological modifier therapies and who will be newly started on biological modifier therapies in the Department of Medicine and Therapeutics, Prince of Wales Hospital and Department of Medicine, University Malaya Medical Centre will be recruited.
Key inclusion criteria (3 listed)
- Age ≥ 18 years old at the time of starting biological modifier therapies or at the time of recruitment
- Positive for anti-HBc OR
- Positive for anti-HBs and born before year 1988
Key exclusion criteria (5 listed)
- Known HBV carrier with HBsAg positive
- Concomitant HCV and/ or HIV infection
- Already on HBV anti-viral
- Refuse to consent
- Baseline ALT > 80 IU/ml
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Rate of hepatitis flare
Time frame: 24 months
Hepatitis flare, defined as ALT >2xULN IU/L, according to the Asia Pacific Association for the Study of the Liver (APASL) definition while on biological modifier therapy. The upper limit of normal (ULN) was defined as 40 IU/L by APASL.
4 secondary outcomes
Rate of severe hepatitis flare
Time frame: 24 months
Rate of icteric flare
Time frame: 24 months
Rate of HBsAg seroreversion
Time frame: 24 months
Risk factors associated with development of hepatitis flare
Time frame: 24 months
Results and safety
The study was stopped early (reason given: No suitable case identified). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2022.
- Background: PubMed 29599078Polaris Observatory Collaborators. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol. 2018 Jun;3(6):383-403. doi: 10.1016/S2468-1253(18)30056-6. Epub 2018 Mar 27.
- Background: PubMed 31533643Wang H, Men P, Xiao Y, Gao P, Lv M, Yuan Q, Chen W, Bai S, Wu J. Hepatitis B infection in the general population of China: a systematic review and meta-analysis. BMC Infect Dis. 2019 Sep 18;19(1):811. doi: 10.1186/s12879-019-4428-y.
- Background: PubMed 2139281Maynard JE. Hepatitis B: global importance and need for control. Vaccine. 1990 Mar;8 Suppl:S18-20; discussion S21-3. doi: 10.1016/0264-410x(90)90209-5.
- Background: PubMed 12150847Torbenson M, Thomas DL. Occult hepatitis B. Lancet Infect Dis. 2002 Aug;2(8):479-86. doi: 10.1016/s1473-3099(02)00345-6.
- Background: PubMed 18715666Raimondo G, Allain JP, Brunetto MR, Buendia MA, Chen DS, Colombo M, Craxi A, Donato F, Ferrari C, Gaeta GB, Gerlich WH, Levrero M, Locarnini S, Michalak T, Mondelli MU, Pawlotsky JM, Pollicino T, Prati D, Puoti M, Samuel D, Shouval D, Smedile A, Squadrito G, Trepo C, Villa E, Will H, Zanetti AR, Zoulim F. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepatol. 2008 Oct;49(4):652-7. doi: 10.1016/j.jhep.2008.07.014. Epub 2008 Jul 31. No abstract available.
- Background: PubMed 28652084Yip TC, Chan HL, Wong VW, Tse YK, Lam KL, Wong GL. Impact of age and gender on risk of hepatocellular carcinoma after hepatitis B surface antigen seroclearance. J Hepatol. 2017 Nov;67(5):902-908. doi: 10.1016/j.jhep.2017.06.019. Epub 2017 Jun 24.
- Background: PubMed 30367899Yip TC, Wong GL, Chan HL, Tse YK, Lam KL, Lui GC, Wong VW. HBsAg seroclearance further reduces hepatocellular carcinoma risk after complete viral suppression with nucleos(t)ide analogues. J Hepatol. 2019 Mar;70(3):361-370. doi: 10.1016/j.jhep.2018.10.014. Epub 2018 Oct 25.
- Background: PubMed 28989093Yip TC, Wong GL, Wong VW, Tse YK, Lui GC, Lam KL, Chan HL. Durability of hepatitis B surface antigen seroclearance in untreated and nucleos(t)ide analogue-treated patients. J Hepatol. 2017 Oct 6:S0168-8278(17)32332-2. doi: 10.1016/j.jhep.2017.09.018. Online ahead of print.
- Background: PubMed 20389182Chung SM, Sohn JH, Kim TY, Yoo KD, Ahn YW, Bae JH, Jeon YC, Choi JH. [Fulminant hepatic failure with hepatitis B virus reactivation after rituximab treatment in a patient with resolved hepatitis B]. Korean J Gastroenterol. 2010 Apr;55(4):266-9. doi: 10.4166/kjg.2010.55.4.266. Korean.
- Background: PubMed 29725560Khan ZH, Ilyas K, Ghazanfar H, Khan HH, Hussain Q, Hammad S, Munir A, Asim R. Fatal Fulminant Hepatitis from Rituximab-induced Hepatitis B Reactivation in a Patient with Follicular Lymphoma: A Case Report and a Brief Review of Literature. Cureus. 2018 Mar 2;10(3):e2257. doi: 10.7759/cureus.2257.
- Background: PubMed 27416041Ng SC, Leung WK, Shi HY, Li MK, Leung CM, Ng CK, Lo FH, Hui YT, Tsang SW, Chan YK, Loo CK, Chan KH, Hui AJ, Chow WH, Harbord M, Ching JY, Lee M, Chan V, Tang W, Hung IF, Ho J, Lao WC, Wong MT, Sze SF, Shan EH, Lam BC, Tong RW, Mak LY, Wong SH, Wu JC, Chan FK, Sung JJ. Epidemiology of Inflammatory Bowel Disease from 1981 to 2014: Results from a Territory-Wide Population-Based Registry in Hong Kong. Inflamm Bowel Dis. 2016 Aug;22(8):1954-60. doi: 10.1097/MIB.0000000000000846.
- Background: PubMed 31485846Ho CTK, Mok CC, Cheung TT, Kwok KY, Yip RML; Hong Kong Society of Rheumatology. Management of rheumatoid arthritis: 2019 updated consensus recommendations from the Hong Kong Society of Rheumatology. Clin Rheumatol. 2019 Dec;38(12):3331-3350. doi: 10.1007/s10067-019-04761-5. Epub 2019 Sep 4.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
WingYan Mak, MRCP principal investigator
Chinese University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Occult Hepatitis B and Biological Substance; Adverse Effect, run by Chinese University of Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: No suitable case identified). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of hepatitis flare (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04356404, which also lists 26 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2022.