People diagnosed with autoimmune hepatitis, but who show no symptoms, may not need therapy, say doctors in a clinical trial whose findings were published this month.¹ That's because they may not do any worse than those with symptomatic autoimmune hepatitis on treatment.

"Although the natural history of autoimmune hepatitis (AIH) has been characterized, little is known about patients who present asymptomatically," wrote physicians at the University of Toronto in Canada.

AIH: A Genetic Origin?
Autoimmune hepatitis is characterized by an immune attack on the liver's cells. This causes liver inflammation. More than two-thirds of those afflicted by this disease are women, mostly between the ages of 15 and 40. Autoimmune hepatitis, which is believed to be associated with some inherited factor, can be very serious and can become worse over time if not treated. It is usually chronic, meaning it lasts a long time, and can lead to liver cirrhosis, and eventually, liver failure.²

Autoimmunity—the process whereby the immune system mistakenly attacks the body's own tissues—may be caused by certain bacteria, viruses, toxins, or drugs that trigger such a response in those who are genetically susceptible to developing the disorder. Symptoms may include the following:

• Fatigue
• Jaundice
• Itching
• Skin rashes
• Joint pain
• Abdominal discomfort
• Spider angiomas on the skin
• Nausea and vomiting
• Loss of appetite
• Dark urine
• Pale or gray colored stools.²

Does Therapy Help?
While the disease can become seriously advanced if not treated, it's unclear if those who don't have symptoms need therapy, wrote chief study investigator Jordan Feld, MD, and his colleagues. Treatment such as immunosuppressants can potentially slow the progress of the disease, they explained, but can also present side effects that can be potentially toxic in some cases.

In fact, it's become more common to diagnose AIH in those with no symptoms due to rapidly advancing forms of tests used to detect the illness, experts say, including those that uncover liver enzymes in the bloodstream, as well as antibodies—immune system cells whose presence indicates autoimmune disease.

"For many years, it was always thought that AIH was symptomatic," explained Feld, with the Liver Diseases Section at the NIH in Bethesda, Maryland and the departments of Medicine and Pathology of the University Health Network at the University of Toronto. "But with increased use of 'routine' liver tests, we are now picking it up in people that are entirely asymptomatic."

This latter group, presumably, has a milder form of the disease, Feld told Priority Healthcare. "It remains unclear whether this is just the mild end of a broad spectrum of disease or whether, ultimately, these patients will develop symptomatic, more aggressive AIH," he said.

Further, asymptomatic AIH is much more non-specific. As such, there are no definitive indicators that physicians can use to alert them of the disease's presence in these individuals, Feld stated.

Combing Through Data
To find out whether therapy in asymptomatic patients is necessary, Feld's team collected medical records of 124 patients at a Toronto-area hospital diagnosed with autoimmune hepatitis between 1970 and 2002. Each had been followed, on average, for eight years. The patients were classified as being symptomatic or asymptomatic at the time therapy began, and thirty-one of these were the latter. This was defined as those who were free of all symptoms, even the non-specific ones such as fatigue or abdominal pain.

Treatment prescribed for patients presenting with symptoms involved immunosuppressive therapy, while those without symptoms were not treated, unless treatment had already been started previously by a referring physician. Any patient who developed symptoms during the study period was also prescribed immunosuppressive therapy. If he or she remained in remission with no relapse for two years, therapy was then halted, but restarted at any time that the disease recurred.

Prognoses Compared
After analyzing all of the patient data collected, Feld and his colleagues found that three-quarters of the asymptomatic patients never developed symptoms. The rest who progressed to active disease were prescribed immunosuppressive treatment with good results. The study team also determined that most of those without symptoms during this period had lower levels of liver enzymes, as well as antibodies. They also had lower levels of liver inflammation, but otherwise did not differ from those with confirmed symptoms.

Survival rates were similar between non-treated asymptomatic AIH patients and treated symptomatic individuals, Feld and his colleagues learned. The 5-year and 10-year survival rates for those with asymptomatic disease were about 87% and 80%, respectively, compared with approximately 90% and about 84%, respectively, for those with symptomatic AIH.

Conclusion: No Treatment, But Close Monitoring
In conclusion, the researchers suggested that treatment may be unnecessary for those with no symptoms, but may need to be prescribed once symptoms emerge. "Our data suggest that it may be safe to follow asymptomatic patients with a strategy to institute immunosuppressive treatment if symptoms develop over time," they wrote. But they added that patients who had no symptoms initially were less likely to respond to immunosuppressive therapy once it was prescribed compared to those who initially presented with symptoms.

Feld and his colleagues also underscored the fact that those with cirrhosis at diagnosis had worse outcomes, including certain complications and/or death, compared to those without the liver condition. Treatment is typically started in asymptomatic patients because it's believed it can help prevent cirrhosis, the study team stated, though that has yet to be confirmed. For now, patients with this condition are advised to avoid alcohol and certain medications, and they should be screened for esophageal varices and hepatocellular carcinoma. However, while there are no specific treatments for cirrhotic patients currently, many are in development, Feld said.

Thus, based on this study's findings, the authors wrote: "Most [asymptomatic] patients will not develop symptoms during follow-up, and they appear to do well without immunosuppressive therapy, at least for as long as they remain asymptomatic."

Further Confirmation Needed
Feld was quick to point out, however, that a randomized, controlled clinical trial is necessary to directly compare treatment efficacy in symptomatic versus asymptomatic patients.

"If others reported similar results to ours, or if possible, did a controlled trial of treating or not treating patients with asymptomatic AIH, our conclusions would be much more robust," he said. "Although this would be ideal, it would be very difficult, as these patients are relatively hard to come by (a variant form of an uncommon disease), and in order to draw strong conclusions about outcome, long follow-up is required."

1. Feld JJ, Dinh H, Arenovich T, Marcus VA, Wanless IR, Heathcote EJ. Autoimmune hepatitis: effect of symptoms and cirrhosis on natural history and outcome. Hepatology 2005 Jul;42(1):53-62.
2. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). National Institutes of Health (NIH). Autoimmune Hepatitis. Available at: http://digestive.niddk.nih.gov/
ddiseases/pubs/autoimmunehep/index.htm. Accessed June 29, 2005.

John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.