Patients often show symptoms of autoimmune hepatitis along with symptoms of other autoimmune diseases that affect the liver. When this overlap syndrome occurs, treatment decisions are not so clear-cut. Doctors often opt to treat the disease showing the strongest features. When test results show that two autoimmune liver diseases coexist in more or less equal intensity, they will combine treatment therapies to address both diseases.
Three autoimmune liver diseases commonly overlap with AIH: primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune cholangitis. Viral hepatitis, particularly hepatitis B and C (HBV and HCV), may also show features similar to AIH.
The blood of AIH patients suspected of having PBC (about 10 percent of AIH patients) contains the antimitochondrial antibody (AMA), which is present almost invariably in PBC. A small proportion of AIH patients, about 6 percent, also show symptoms of PSC, marked by narrowing and dilation in both the intrahepatic and extrahepatic bile ducts. Primary sclerosing cholangitis occurs most often in men, while AIH is most often found in women, so AIH patients—especially men and especially those suffering from ulcerative colitis, which is linked to PSC—should be tested for PSC. Patients with AIH and PSC overlap syndrome are often the youngest AIH patients, but PSC can also develop in older AIH patients who have been able to control their illness for years. If the AIH treatment loses efficacy, testing for PSC should be considered.
Another autoimmune disease that inflames the liver (as well as injuring the bile ducts and showing ANA or SMA) is autoimmune cholangitis (autoimmune cholangiopathy). This condition is sometimes treated with steroids. Autoimmune hepatitis also fre- quendy overlaps with chronic hepatitis B and hepatitis C. Patients displaying this syndrome may require careful assessment of both conditions. A liver biopsy determines whether patients need to be treated with antivirals or with medications to treat the autoimmune process. In this situation, patients are treated according to the progression of their HBV or HCV, including with a program of interferon when appropriate.
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Like most autoimmune diseases, autoimmune hepatitis is a chronic condition, but the good news is that once diagnosed, it can usually be controlled with a low dose of prednisone (a corticosteroid) or a synthetic steroid. Another common prescription for AIH is azathioprine (brand name Imuran). Both drugs suppress the overactive immune system, thereby keeping AIH under control.
Some patients must take prednisone for the rest of their lives, starting with a higher initial dose and tapering off once AIH is in remission, usually less than two years after the diagnosis. For most, though, it is best to switch to azathioprine when possible because of prednisone’s side effects, which include weight gain, osteoporosis, thinning hair and skin, diabetes, high blood pressure, cataracts, glaucoma, anxiety, and confusion. More than 40 percent of patients taking prednisone long-term will experience at least one of those side effects. Azathioprine is not without side effects, including nausea, loss of appetite, pancreatitis, allergic reaction, and a lower white blood cell count, although side effects are overall uncommon and rarely severe.
In spite of the unpleasant side effects associated with these two drugs, some combination of them effectively controls AIH about 75 percent of the time. Many patients feel stronger and better after only two weeks of drug treatment. When the drugs succeed, a liver biopsy will show decreased inflammation and scarring.
For patients who don’t respond well to drug therapy for AIH, other immunosuppressive drugs (including mycophenolate mofetil, cyclosporine, and tacrolimus) may be effective. If these substances also fail and the liver deteriorates, the best option may be a liver transplant.
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Patients with autoimmune hepatitis should plan on long-term therapy, which will probably call for a lifetime commitment. If patients stop treatment, about 50 percent relapse within six months after discontinuing their medication. Those who don’t relapse have an 80 percent chance of remaining AIH-free, but the others usually go back to a low dosage of prednisone, azathioprine, or both.
A minority of patients on drug therapy (up to 20 percent) never respond positively to the treatment. But drugs may not be recommended in all cases, particularly for patients with mild AIH, which is defined as having near-normal transaminases and minimal inflammation on biopsy. Nor are drugs always recommended for patients diagnosed with cirrhosis but without inflammation in the liver, or for patients with mild hepatitis. As a rule, the more severe the symptoms, the greater the expected benefit from drug therapy for AIH.
Postmenopausal women are often cautioned against taking prednisone because of the risk of developing osteoporosis. In addition, severe AIH can cause a woman to stop menstruating, so female patients of childbearing age who do not undergo drug therapy might not be able to become pregnant. The menstrual cycles usually normalize, however, with corticosteroids and azathioprine, and the patient once again becomes able to conceive.
So many factors influence the management of autoimmune hepatitis that it is difficult to make generalizations about long-term prognosis. Studies have shown, though, that patients who do not seek treatment for severe AIH have only a 30 percent chance of surviving beyond five years. Those who undergo drug therapy have an 11 percent risk of seeing their AIH progress to cirrhosis during the first three years of treatment. Once the three-year milestone has passed, the risk shrinks dramatically to 1 percent each year.
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