With a prevalence of 0,95:100.000, PSC is a rarity in Japan. However, there are still approximately 2.500 patients with PSC. What are the differences and the similarities amongst patients compared to other regions? And what kind of PSC research is undertaken in Japan?  Time to meet with Prof Tanaka, MD Department of Medicine, Teikyo University School of Medicine in Tokyo (Japan), representatives of Tokankai (the Japanese liver patient organization) and two local PSC patients.

This is an excellent opportunity to learn more about the questions the PSC Community have, as PSC patients worldwide were given the opportunity to ask questions upfront via various Facebook groups and via email.

The following articles were the starting point for the interview:

1)      Nationwide survey for primary sclerosing cholangitis and IgG4-related sclerosing cholangitis in Japan (pdf)

2)     Clinical profiles of patients with primary sclerosing cholangitis in the elderly (pdf)

Professor Tanaka

On a sunny Saturday in May 2016 I met Professor Tanaka at his office at the Teikyo Hospital in Tokyo, Japan.  Besides International PSC Study Group (IPSCSG) member Prof Tanaka, there are various PSC researchers in Japan, including IPSCSG  member Dr. Nakazawa based in Nagoya, while the Head of the Japanese PSC study group, Prof Tazuma,  is based in Hiroshima. Other important related organisations are The Japanese Biliary Association (JBA)  and the Intractable Hepatobiliary Disease Study Group of Japan  which is supported by the Ministry of Health, Welfare and Labour of Japan.

With a population of 110 million, there are an estimated 2.000 to 3.000 Japanese PSC patients. This is a relative low number, which may be due to either 1. race diversity, 2.  they may form a sub-type of PSC (still to be decided), and 3. the IgG4 misdiagnosed PSCers. Prof Tanaka has approximately. 400 PSCers in his registry.

Last year they conducted a nationwide survey, which was mainly paper-based. Survey patients described in the research consisted of IgG4 patients and PSC patients. IgG4-related sclerosing cholangitis (IgG4-SC, also called as IgG4-associated cholangitis (IAC)) is a different clinical entity of sclerosing cholangitis, with elevated IgG4 levels, and most of them are complicated with autoimmune pancreatitis (AIP). One of the problems in Japan is IgG4-SC patients are often misdiagnosed with PSC. This does explain the broad estimate of Japanese PSCers. Luckily there aren’t any other diseases the patients are misdiagnosed with.

No DNA analysis has taken place up until now, however the Japanese researchers plan to collect DNA in 2017. With these DNAs from Japanese PSC patients, they hope to examine whether there is any difference in genetic background between the East and the West. In European patients several genes have been identified as responsible for developing PSC, and they aim to search these genes are also playing a crucial role in Japanese PSC patients.

In Japan the male:female rate amongst PSC patients is more or less equal, and the medical teams  prescribe the same first line treatment as in Europe, being UDCA (“urso”). If the desired outcome is not reached with this treatment, the patient starts with UDCA and bezafibrate (see paragraph below for details).

Also, in the research article, fatigue isn’t listed as a symptom. Prof Tanaka explains that fatigue doesn’t seem to be a big issue amongst his patients. Possibly we are dealing with a different genotype, or there could also be a cultural explanation in that patients underestimate this phenomenon and do not mention it. Another possibility is that Japanese PSCers do feel fatigue as a symptom but they don’t think it is a symptom of PSC.

Interestingly enough only 50% of the PSC patients have IBD and all are without AIH, which are very different numbers to, for example, Europe where approximately 70% of PSC patients have IBD. Of those Japanese patients with IBD, few have Crohn’s disease (CD) Whether there is a relation to food and/or other lifestyle components still needs to be determined at this stage. Remarkably, there are two peaks in the distribution of PSC in Japan: elderly patients (without IBD) and the second group consisting of young patients, where the IBD figures are the same as in Europe and USA. Possibly the group of older patients have more secondary sclerosing cholangitis.

Another surprising fact was the relatively quick cholangiocarcinoma (CCA) diagnosis after the PSC diagnosis, which is one year. This is due to the fact that health care in Japan offers annual check-ups, as part of their prevention program. This allows relatively early detection of diseases, in this case CCA. Alternatively, the relatively late diagnosis of PSC might also contribute to this. According to Prof Tanaka, biomarkers are needed for PSC!

Patient organisation Tokankai 

The second half of the afternoon was dedicated to a meeting with representatives from the Japanese liver patient organisation Tokankai at their offices:  Mrs. Yonezawa (CEO / Board member) and Mrs. Furukawa (Rare liver disease Dept.). There were also two patients ready to share their ideas and experiences, Kenji and Kazuyuki.

Tokankai was established in 2001 and is located in Tokyo, the capital of Japan, with approx. 2,000 members. They get an average of 15 phone calls per day during their 10:00 to 16:00 hours availability. Most questions relate to where patients can find hepatologists nearby. The membership fee is relatively low (Yen 3000 p/y (= € 24)), they get 30% of their budget from pharma and currently the Tokyo metropolitan government is supporting the rest of their budget. However unfortunately the latter grant is expected to change soon.

Together with the patients we had a frank conversation about various topics and Prof. Tanaka translated everything for us. One of the patients expressed his interest in the process in which patients are actively participating clinical trials and sharing the results. Organ donation was another topic that was interesting to hear more about. Obviously, the Japanese PSC patients also need liver transplants. The cultural background and the few donors available make it difficult to harvest donors. In general, the family is the only reference point when an organ donation is needed, meaning there’s testing amongst family members to look for a potential candidate for a living donor liver transplant (LDLT).  A transplant from somebody on life support (also known as cadaver organs) is rarely the case in Japan. Until a few years ago, Japanese PSC patients received organs from their family members as LDLT. However, the rate of recurring PSC in a 5-year time frame was sky –high (approx. 80%) and therefore they stopped this procedure.  Even if a Japanese person consents to organ donation after death, according to law it is the family who has the final say and they tend to overrule this decision. If even one family member disagrees, organ donation is not possible any more.


Photo May 2016: Kenji, Mrs Kurukawa, Kazuyuli, Mrs.Yonezawa and Prof Tanaka @ Tokankai office

The patient organisation has quite a few projects coming up. They are looking at providing surveys online, collaborating with researchers and exploring ways to collaborate with other patient organisations, both on a national and international level. Tokankai will also look into possibilities to better inform their members about ongoing PSC-related research and medicine research and development in general. They are also trying to find new ways to financially support their organisation, as governmental support continues to be cut on an annual level, due to budget cuts in general. It was decided that Tonkankai and PSC Patients Europe will strengthen their collaboration and assist one another in future.

Interesting Japanese research: Bezafibrate

Bezafibrate was originally labelled as a drug for hyperlipidaemia and used for prevention of cardiovascular diseases (hyperlipaemia is an abnormal high concentration of fats in the blood).
The drug works as an activator of several receptors in liver cells and bile duct cells. A receptor is a structure of a cell that binds a specific substance.

 Japanese researchers found bezafibrate could improve biochemical markers in patients with primary biliary cholangitis (PBC) and have used bezafibrate as a second-line treatment for PBC. Bezafibrate has been already used in some patients with PSC as well, especially those resistant to UDCA. A Japanese research group demonstrated in a small-size retrospective study that bezafibrate treatment decreases serum ALP levels and is also safe in patients with PSC. Therefore Prof Tanaka and his colleagues aim to examine whether the use of bezafibrate could inhibit or delay the onset of liver-related symptoms and improve the long-term effect of patients with PSC through a multicentre, prospective, randomized and controlled study. Now they are preparing the Phase 2 study of bezafibrate for PSC and seeking a funding source for this clinical trial.

The Japanese research group will keep us posted of their findings in the months to come. First results  at this stage depend mainly on funding.


Activator: To cenvert a certain biological compound into a biologically active derivative

AIH: Autoimmune hepatitis

AIP: Autoimmune pancreatitis

Biomarker: A measurable indicator of a biological state. E.g. X-ray is a biomarker for a broken bone, blood    draw is an indicator if you have an infection etc..

CCA: Cholangiocarcinoma

CD: Crohn’s disease

Cholangitis: Inflammation of the bile ducts

IAC: IgG4-associated cholangitis

IBD: Inflammatory bowel disease

IgG4: Immunoglobulin G4

IPSCSG: International PSC Study Group

JBA: Japanese Biliary Association

PBC: Primary Biliary Cholangitis

Prevalence: Proportion of a certain population found to have a certain condition

Receptor: A structure of a cell that binds a specific substance

Retrospective study: Also known as an historic cohort study –  a study in which participating individuals are classified as either having some sort of outcome (cases) or not. It looks “backwards”

Second-line treatment:Treatment that is given when the initial treatment (aka first-line treatment) doesn’t work, or stop.

Tokankai: The Japanese liver patient organisation


The original (English) version of the above article has been checked and approved by
Prof. Tanaka, MD Department of Medicine,
Teikyo University School of Medicine in Tokyo (Japan)
(August 2016)

Author:  Marleen K
Editor: Dr. Valmae Y

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  1. Mentioning: An article by PSC Patients Europe (PSCPatientsEurope.org)
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