29 Mar 2018

Research needed for autoimmune hepatitis patients' salvage therapy

Autoimmune hepatitis is a chronic inflammatory liver disease
not readily treatable for 20% of patients
by Anne Crawford

Autoimmune hepatitis is a chronic inflammatory liver disease. The condition is treatable for the large majority of patients. The 20 per cent or so of patients who don’t respond well to standard medicines are treated with “salvage therapies”, but until now these have been inadequately scrutinised for their efficiency and safety, a new paper says.

Monash University researchers in the Department of Gastroenterology at The Alfred Hospital have conducted a rare, comprehensive review of salvage therapies resulting in findings that could benefit clinicians and their patients with the disease globally.

Professor Stuart Roberts, Director of Hepatology at The Alfred, was invited to write the review by the journal ‘Seminars in Liver Disease’, which focusses on critical analysis of key topics relevant to hepatology.

“There is a low level of evidence in the area and most of the data we use for deciding these agents, especially as frontline or first-line therapy, involves a few clinically controlled trials performed back in the 1970s,” Professor Roberts said.

Salvage therapies, used for patients who don’t respond well to, or who are intolerant of conventional therapy, are designed to bring them into remission and prevent more serious liver disease complications such as liver failure and the patient having to undergo transplantation.

High-dose prednisolone, a steroid, is often used as a frontline salvage therapy, with alternative immunosuppressive therapies reserved for continuing treatment failure. But none of the latter have undergone rigorous clinical evaluation via randomised clinical trial, the review says. Prednisolone is frequently used with a combination treatment aimed to reduce steroid-related side-effects including cosmetic changes such as acne and facial roundness, diabetes, high blood pressure, osteoporosis and cataracts.

“There isn’t a perfect or ideal salvage therapy treatment because there haven’t been sufficient clinical trials performed,” Professor Roberts said. “We don’t have any good, randomised controlled trials which offer higher levels of evidence to ascertain the efficiency and safety of salvage therapy.”

This was partly because the disorder wasn’t common and there weren’t the large populations of patients needed to run clinical trials efficiently, he said.

Professor Roberts and colleague Adjunct Clinical Associate Professor William Kemp, analysed data and conducted a critical evaluation of all treatment options from data published in 213 papers, looking at factors such as the popularity of a treatment, how effective it was and its safety profile.

They then made recommendations based on the available evidence (drug regime, dosage, treatment outcomes and side effects etc.) gauging what a reasonable algorithm for treatment of disease for individual patients might be as they come to the clinic.

“This would be helpful for someone with a difficult-to-treat patient who isn’t responding as well who wants to maintain control of that patients rather than refer them to centres such as ours,” Professor Roberts said.  

“It’s a very comprehensive review,” he said. “I think it gives the reader a far better appreciation of what’s out there, how it can be used and what the expectations are in relation to individual treatments being offered in terms of the likelihood of response and the likely safety profile of the drug used,” he said.

“It increases the take-home messages for readers.”

The review recommended that patients with progressive liver failure should undergo liver transplantation evaluation.

It points to several potent immunosuppressive therapies that have been developed for other autoimmune diseases that may hold promise as new options for autoimmune hepatitis in the future.

The review was well-received when submitted for peer review in the last edition of the quarterly journal and is expected to be commonly cited in its area. Professor Roberts said he thinks he was approached to write it after a national study he led looking at the outcome of the salvage therapy Mycophenolate Mofetil (see below).

Roberts SK, Kemp W. Salvage Therapies for Autoimmune Hepatitis: A Critical Review. Semin Liver Dis. 2017 Nov;37(4):343-362. doi: 10.1055/s-0037-1607453. Epub 2017 Dec 22.

Roberts SK et al; ALA Clinical Research Network. Mycophenolate Mofetil In Autoimmune Hepatitis Patients With Suboptimal Outcomes To Standard Therapy: The Tapestry Study. Clin Gastroenterol Hepatol. 2017 Oct 16. pii: S1542-3565(17)31238-7. doi: 10.1016/j.cgh.2017.09.063. [Epub ahead of print]

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