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Autoimmune pancreatitis is ‘a significant challenge’
Dealing appropriately with autoimmune pancreatitis (AIP) is a significant challenge for both surgeons and gastroenterologists, the Irish Society of Gastroenterology (ISG) 2016 Annual Summer Meeting heard.
Giving a comprehensive update on the condition, Dr Laurent Palazzo, Consultant Gastroenterologist, Paris, France, explained that AIP type I is more a disease of older males, presenting with jaundice in 80 per cent of cases, generally with no pain, and IgG4 in the serum. On the other hand, type II is more common in younger, female patients, with jaundice in less than a third of patients, but they are much more likely to have pain and sexual issues.
Dr Palazzo advised that clinicians should only treat AIP when it is symptomatic, ie, as it frequently resolves, particularly the jaundice, and particularly type II (80 per cent). Treatment-wise, he said “steroids always work”, adding that “the best treatment is rituximab”. The risk of recurrence of AIP is high in type I (20-50 per cent) but low in type II, he said
Also speaking during the pancreato-biliary session was Prof Thierry Ponchon, Consultant Gastroenterologist, Lyon, France, who discussed the best treatment options for ‘Large stones, intrahepatic stones — ERCP/ cholangioscopy?’.
Looking at mechanical lithotripsy, he said that it “mainly works” but the failure rate is 5-30 per cent, “which is mainly due to stone capture”, ie, poorly-accessible stones, very large stones, impacted stones and ones that completely fill the duct. However, stone fragmentation is “rarely an issue”.
Prof Ponchon compared mechanical lithotripsy to fishing. “Like fishing, you should go very slowly, if you go fast, you can break things, though not the stones, you need to go slow, and apply enough pressure but not too much, and then it works.” However, he acknowledged that his “younger colleagues” prefer newer approaches.
“Extracorporeal lithotripsy is better indicated in cases of limited numbers of stones; extrahepatic bile duct stones; and absence of underlying disease,” he said.
Meanwhile, Mr John Connelly, Consultant Surgeon, Mater Hospital, Dublin, gave an update on laparoscopic surgery. “Beware of absolutes” in practice, Dr Connelly stressed, pointing put that laparoscopic surgery is no longer new and is just a different approach, which is about far more “than just a small scar”.
“There is a wealth of data over the last 30 years that demonstrates a very significant amelioration of the systemic inflammatory response within [laparoscopic] patients, no matter what… we’ve gotten better, slicker and I feel, from my experience, that laparoscopy is as good as open surgery and in a lot of cases, a lot better.”
Discussing surgical training, he said high-volume bariatric units are the best place to learn advanced lower and upper abdomen laparoscopy.
“The advantage of doing it in the benign setting is you can now do it in the oncological setting or the severe disease state, like advanced Crohn’s, etc… The future is fat and the future is bariatrics. If you want to be an advanced laparoscopic surgeon, you’ve got to go and learn bariatrics,” Dr Connelly stated.
Briefly touching upon robotic surgery, he said its potential had been exaggerated “and it is not the revolution we thought it would be”.
“It’s a very cool thing to have and in North America if your hospital does not have one, you are just not at the races. It is a wonderful marketing tool… However, there is no benefit in any field of surgery, with the exception of prostatectomy, for the use of an extremely expensive device.”
Treating more difficult-to-cure hepatitis C
While the vast majority of hepatitis C patients can be cured by the new direct-acting antivirals (DAAs), some patients are more complex and require a more targeted approach, with re-treatment options available for non-responders, a special AbbVie satellite symposium on the topic heard.
Opening the ‘Hot topics in hepatitis C: Treatment success and failure’ symposium at the ISG 2016 Annual Summer Meeting, Dr John Lee, Consultant Gastroenterologist, Bon Secours Hospital, Galway, discussed how hepatitis C treatment has revolutionised from the early days of interferon treatment in the 1990s, which cured only a small percentage and was very difficult for patients to tolerate.
Looking at the results of the Irish early-access treatment programme for hepatitis C patients using the new DAAs, he reported that for those with decompensated cirrhosis, the sustained virologic response (SVR) at 12 weeks was 73 per cent (107 started).
“The second phase of treatment was those with cirrhosis without necessarily being decompensated. SVR at 12 weeks was 90 per cent [342 started], so it still does leave a small number of patients who are not cured, so that is one of the challenges with these medications. The other one is making them available to everybody with hepatitis C on a worldwide basis.”
Next to speak was Prof Jean-Michel Pawlotsky, Professor of Medicine, Hospital Henri Mondor, Paris, and Director of the National Reference Centre for Viral Hepatitis B, C, and Delta, who gave a comprehensive overview of the results to date with the new DAAs, which can cure in the region of 96 per cent of patients with oral, interferon-free, 12-week regimens.
“I think clinical trials demonstrated that these treatments work very well, but I think it was very important to show that these therapies were safe and efficacious in the real world, and there were several [real world] studies presented at the last meeting of the European Association for the Study of the Liver (EASL),” he said, citing the results of a number of studies from different countries, which showed very high SVR rates.
Prof Pawlotsky focused on the small number of patients who do not achieve a successful SVR, and how best to treat them with specific regimens. He noted that because of “the different genotypes, subtypes and comorbidities, etc,” in hepatitis C patients, treatment is not as simple as was hoped with the advent of the new DAAs. Genotype 3 patients, for example, still pose a challenge, “and the choice is limited”. Re-infection and resistance are issues that need to be monitored, he acknowledged.
Discussing the use of ribavirin, he said, looking at the results from the last few years, the guidance has changed so it is now recommended for treatment-experienced hepatitis C patients (who have failed to achieve SVR) with or without cirrhosis, “but this may change in the next guidelines”.
Noting that decompensated cirrhosis patients remain difficult to cure, Prof Pawlotsky said that the addition of ribavirin and longer treatment durations improve results. “So our good friend ribavirin that everyone wants to kill is still around, and will remain.”
He also looked at attempts to shorten DAA treatment duration, which he was critical of, as he feels it is driven by commercial reasons. He said that it appears that eight weeks is the minimum, and that most patients clear in 12 weeks.
An update of the current EASL hepatitis C recommendations will be presented in Paris in September, he confirmed, adding that the update will most likely include that “systematic HCV resistance testing prior to first-line therapy is not recommended”.
Summarising his main points, Prof Pawlotsky said that re-treatment options for patients who fail to achieve an SVR with the latest DAAs do exist and more will be available in the near future. However, optimising first-line therapy in order to avoid treatment failure remains the best option.
Speaking to the Medical Independent (MI), Prof Pawlotsky said: “We have very good treatments now, efficacy and safety have been confirmed in the real world, unlike previous treatments where the results were not as good in the real world. There are patients who fail; they are in a minority, but when they fail they select resistant viruses. There are re-treatment options but it is always better to optimise treatment from the beginning.”
Meanwhile, a separate session on hepatitis C at the meeting had a debate-style format asking the question,‘HCV eradication — A public health measure we can’t afford?
Dr Will Gelson, Addenbrooke’s Hospital, Cambridge, UK, was the main speaker of this session and while he praised the effectiveness of the new DAAs, he raised concern about the cost of treatment, as well as re-infection risk in the more chaotic hepatitis C patient population, such as injecting drug users, and the fact that many of these patients will actually die from other comorbidities. He noted that in the UK, the majority of cirrhotic hepatitis C patients have been treated but the NHS is now “clamping down”and placing a limit on how many patients are treated per month.
Dr Diarmaid Houlihan, Consultant Hepatologist, St Vincent’s University Hospital, Dublin, co-chairing the session, made a number of contributions in favour of treating all hepatitis C patients and eradicating the disease as soon as possible.
He pointed out that hepatitis C treatment is the only “capped” treatment budget in the health service, as far as he was aware, and asked how people would react if access to cancer drugs or biologics was capped in the same manner as hepatitis C treatments.
He confirmed to MI that approximately 700 Irish patients have been treated to date with the new DAAs under the early-access scheme and the National Hepatitis C Treatment Programme. Last week, the HSE announced that, under new clinical guidelines, approximately 1,500 new patients will be eligible for DAA therapy over the next 12-to-18 months.
“We’re relaxing the criteria, which means many more patients are going to be eligible for treatment, which effectively means the budget [€30 million] is going to be burnt out before the end of the year. So that presents the scenario where we have an eligible patient coming into a clinic that you’ve got to turn down, and say ‘wait til next year’,” Dr Houlihan told MI.
Speaking to MI at the end of the two-day event, ISG President Prof Padraic MacMathuna said hepatitis C treatment access is a hot topic in Ireland.
“Hepatitis C is controversial, as we now have the drugs to cure the disease but the amount of people with the disease is huge. And a lot of the people have other health issues and the drugs are very expensive, and they could die from other diseases like alcoholic liver disease. In the chaotic population, where you have injecting drug users and they re-infect themselves, that means resources have been wasted, so allocation of limited resources is an issue. We make choices about who has a liver transplant, heart transplant, etc, everyone is on the list but not everyone can have one and society accepts you cannot do everything for everybody.
“I think the other issue is that it can’t be the Department of Health and HSE responding to those who shout loudest.”
Coeliac disease incidence on the rise
Almost a third of Irish coeliac patients assessed under a new study had a coexisting autoimmune disorder, the ISG Summer Meeting heard.
Ms Patricia Dominguez-Castro, Trinity College Dublin, presented the findings of a new Irish study exploring the co-existence of other autoimmune conditions in a cohort of coeliac disease patients (n=564) attending five Irish referral centres, which won second prize in the Oral Presentation category.
The retrospective analysis of medical charts (median age 57 years, range 16-88 years) showed that almost a third of the coeliac patients (134, 30.9 per cent) had a co-existent autoimmune disorder, the most prevalent being thyroid disease (20.6 per cent), followed by type 1 diabetes (3.2 per cent) and psoriasis (3.2 per cent).
Type 1 diabetes presented prior to coeliac disease in most cases, however presentation of thyroid disorders and psoriasis occurred equally prior or after coeliac disease diagnosis, she said.
Thyroid disorders were more prevalent in women than in men (ratio 6.7:1, p<0.001). Patients with thyroid disease were diagnosed later in life with this condition (median 47 years) compared to those with type 1 diabetes or psoriasis (median 33 years) (p=0.003).
Coeliac disease patients thus seem to be predisposed to developing other co-existent autoimmune conditions and the presentation of the disease has changed in Ireland, Ms Dominguez-Castro concluded.
Also speaking during the session on coeliac disease was Prof Joseph Murray, Mayo Clinic, US, originally from Ireland, who gave a comprehensive overview on how to accurately diagnose coeliac disease and discussed the huge rise in incidence in western Europe and the US.
“Adult coeliac disease has now outstripped paediatric disease in terms of prevalence and incidence,” he said, adding that there has also been an increase in overweight and obese patients being diagnosed and non-classical/subclinical presentation.
Prof Murray also noted that coeliac disease continues to be significantly under-diagnosed, is common in close relatives of those already diagnosed, and is associated with type 1 diabetes and a number of other genetic disorders.
Discussing the best ways to accurately diagnose patients, he explained that older coeliac disease tests, including exclusion tests, are being phased out due to lack of efficacy. Newer serologic testing, despite its limitations, has made evaluation for coeliac disease less complicated and more reliable, he noted. Tissue transglutaminase antibody (tTG-IgA) is perhaps the most accurate test for diagnosing coeliac disease and has high sensitivity and reasonably high specificity “in the 90 per cent range”.
However, Prof Murray warned that, in regards to testing, “once the patient reduces or avoids gluten in their diet, the sensitivity in the test drops dramatically and can happen very quickly, even within weeks, so the important clinical point is that when the patient comes to the doctor to ask for a test, they are often already on a gluten-free diet”.
Continuing, he said gastroenterologists could recognise some of the signs of coeliac disease endoscopically. Microscopic signs include loss of folds in the duodenum and fissuring/scalloping of the folds, “a mosaic pattern in that area between the folds and then nodularity, which is probably due to Brunner gland hyperplasia”.
“These findings can trigger the suspicion of coeliac disease in someone undergoing endoscopy who has not been previously considered,” Prof Murray told the meeting.
Later in his talk, he noted that an increasing number of people are removing gluten from their diets, often unnecessarily.
“People have started to assume that gluten is the new ‘devil’ that causes everything, from not only GI problems, to chronic depression, liver disease to whatever,” Prof Murray commented.
Meanwhile, Dr Valerie Byrnes, Consultant Gastroenterologist, University Hospital Galway, spoke about treating challenging cases of coeliac disease, specifically refractory coeliac disease (RCD), which accounts for an estimated 1-2 per cent of cases.
She noted that while rare, RCD II has high mortality rates — five-year survival of 40-58 per cent — with significant progression to enteropathy-associated T cell lymphoma (33-52 per cent within five years).
“These patients have a much poorer prognosis, which is why we try to nail the diagnosis early and are very aggressive in our treatment of those patients,” she said, explaining that treatment includes steroids and cladribine therapy.
Speaking to the Medical Independent (MI), Dr Byrnes said: “Certainly, 1 per cent of patients with coeliac disease fail to respond to a gluten-free diet and in many situations, this may be because of inadvertent gluten ingestion, so we do rely on a vigorous dietician review to check for cross-contamination.
“There are a small percentage of patients in whom the condition becomes autonomous to gluten ingestion and who require other therapies than the gluten-free diet. Some patients will require a short course of steroids to help the small bowel recover and a smaller subset of patients may require more rigorous therapy and these newer therapies such as autologous stem cell transplantation and a trial drug of anti-IL-15 are out there; the study is open for enrolment and we are enrolling some patients in it, so clinicians should be aware there are newer therapeutic options.”