Prof Trautwein is a professor at University Hospital RWTH Aachen, Department of Medicine III, in Germany. Here he comments on the importance of early intervention in primary biliary cholangitis, the challenges around diagnosis, the Check-up 35 programme, the medical challenges in primary biliary cholangitis (PBC), the improved prognosis for patients today and the unmet needs

 

 

Why was the name change for PBC so important?

In primary biliary cholangitis (PBC), patients have an immune response within the small bile ducts, which means the ducts are destroyed over time. Histologically^* we differentiate between four different stages of the disease. At the end stage, we have cirrhosis. PBC was originally named as primary biliary cirrhosis, but that was changed to cholangitis some five or six years ago. This was really through the work of patients’ organisations, who did not want the focus to be on cirrhosis because that only happens in the late stages. PBC is a good example of where we must intervene in the early stages of a disease. Our improved understanding over time means that patients have a better prognosis.

*Histology is the study of tissue

What are the diagnostic challenges around PBC?

Many liver diseases are not recognised because they may be asymptomatic for a very long time. So a patient can have PBC for a very long time without having a specific symptom. But maybe if a liver doctor or a normal doctor investigated it further, they would see increased alkaline phosphatase (ALP) or gamma-glutamyl transferase (GGT) values. That is a typical landmark situation for PBC patients, especially having increased ALP. Seeing this, especially if the patient is a woman, a doctor has to think about PBC or another cholestatic liver disease.

The specific diagnostic test would be to look for antimitochondrial antibodies (AMA). Increased alkaline phosphatase and AMA positivity is, basically, how the diagnosis of PBC is made. To have AMA-negative PBC is a very rare disease and, therefore, if you see AMA-negative disease, you may potentially have a patient who has another cholestatic liver disease.

Is fatigue a helpful symptom in terms of making a diagnosis of PBC?

It is hard to distinguish tiredness from everyday fatigue and say what is liver disease and what is not. I think this is the problem. Some people, for example, may have thyroid problems or are not active, so they are a little bit fatigued from that. So, the problem of fatigue is that the symptom is not specific. It may also happen in any liver disease; for example in PBC, PSC, NASH and viral hepatitis, you may have fatigue syndrome.

I think the primary detection of a patient who has a liver disease is strongly dependent on both the patient and the doctor. Firstly, patients may not go to the doctor to check a concern, and secondly doctors who see a little increase in liver values may not worry and think it is fine.

I think the German legislation saying we need to do the Check-up 35 is important, because to understand if somebody has liver disease, the best you can do is to look for biochemical parameters. Fatigue is not a very useful diagnostic marker.

 

What is the Check-up 35 system that is used in Germany?

In Germany we have the Check-up 35, which is paid for patients through statutory insurance; it entitles patients to a general health check-up from the age of 35. Liver values are included in this so that we can understand if a patient potentially has a liver disease such as viral hepatitis, but also, of course, any rare disease, which are very important to detect.

What are the potential benefits of the Check-up 35 for patients with liver diseases, including PBC?

I think there were very strong efforts to introduce the programme as a prophylactic measure to prevent disease progression. We know that when you detect any liver disease early, you can intervene and treat the patients, and then the long-term costs are much lower.

Of course, this programme has not been specifically implemented for PBC but for different diseases in general, including viral hepatitis or non-alcoholic steatohepatitis (NASH), which have a much bigger impact for society. But as a side effect, rare diseases are more easily detected too: doctors see increased liver values and look at patients in more detail to understand what the cause of the liver disease is. So, this may lead to a higher percentage of patients in the PBC population being detected and diagnosed.

 

What other medical challenges, other than PBC itself, do patients face?

We conducted a survey together with Deutsche Leberstiftung (the German liver foundation) to look for the different diseases which are linked with PBC. Thyroiditis was the most frequently found, besides rheumatoid arthritis, psoriasis, colitis, sprue and Sjögren’s syndrome.

Around 30% of patients with PBC also have thyroid diseases. So, this is quite a high number and for these patients the disease burden may be more severe. And in any cholestatic liver disease, especially with females, you also have to be careful about the risk of osteoporosis.

What are the unmet needs in PBC from your perspective?

Most importantly, we need to have programmes to detect PBC patients earlier and then to treat them. Because we know when we start treatment earlier, the impact on inhibiting disease progression is much higher than when you start very late. When we detect patients early and get them under treatment, we can save a lot more patients from progression. We still have this small proportion of patients which do not respond, but even then, the prognosis of these patients improves when treated.

Of course, it’s important that we have novel drugs for those patients who do not respond to current treatment, and we have a lot of studies going on to increase the treatment options further.

 

Prof Trautwein is a professor at University Hospital RWTH Aachen, Department of Medicine III, in Germany. His expertise lies in the treatment of liver and metabolic disorders as well as gastrointestinal tumours. His research focus is liver diseases, pathophysiology of tumour diseases of the gastrointestinal tract and endoscopic examination methods.

 

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