Some people with rheumatoid arthritis (RA) can have elevated liver enzymes. This may be due to the effects of RA on the body, side effects from RA medications, or both.

Rheumatoid arthritis (RA) is an autoimmune disorder where your immune system attacks joint tissue. Estimates suggest that about 1.3 million adults in the United States are living with RA.

Having RA doesn’t always just affect your joints. Sometimes, other areas of the body can be affected as well. One of these areas is the liver. People with RA can have elevated liver enzymes.

Elevated liver enzymes can signal that something is stressing or damaging the liver.

Keep reading to learn more about how RA affects your liver, what causes elevated liver enzymes, and if you should seek treatment if you have RA and elevated liver enzymes.

Many people with RA and liver involvement don’t know it. In fact, a 2020 study of 150 people with RA found that 94% of study participants with liver involvement had no symptoms of liver disease.

Liver alterations in people with RA can be due to different factors, such as RA disease activity and the effects of RA treatment.

RA disease activity

RA is an immune-mediated condition. This means that levels of inflammation can be increased in the body, affecting various organs and tissues.

Research from 2023 looked at the effects of RA on the liver using several different models. It found that:

  • Compared to healthy participants, those with RA had significantly higher markers of inflammation in the body as well as altered markers related to liver disease.
  • Participants with RA were at a higher risk of fatty liver disease. This was associated with levels of inflammation and autoimmune disease activity.
  • Laboratory exposure of liver cells to RA autoantibodies led to an increase in markers of inflammation.
  • In a mouse model of RA, the disease boosted levels of inflammation, fat accumulation, and scarring in the liver.

Effects of RA treatment

Treatment for RA typically includes the use of disease-modifying antirheumatic drugs (DMARDs). These drugs help reduce inflammation in the body and lower RA disease activity.

However, some DMARDs can damage the liver over time. A 2020 study found that liver toxicity of RA medications was the most common cause of liver involvement in study participants.

Methotrexate is a common DMARD used for RA and can affect the liver. Other drugs used for RA that may affect the liver include:

Estimates suggest up to 22% of people taking methotrexate will have abnormal results on liver function tests at some point. This chance increases if you already have liver disease or if you consume alcohol daily.

Methotrexate use also has links to fatty liver disease. As such, obesity or diabetes, two important risk factors for fatty liver disease, also have links with an increased risk of methotrexate liver toxicity.

The effects of increases in inflammation and autoimmune activity in RA can place additional stress on the liver. And the use of some DMARDs for RA can also damage the liver. This may show up as high liver enzymes.

When you have tests to look at liver function, the levels of different liver enzymes are measured. These include:

The levels of these different enzymes can tell your doctor different things. Elevated ALT or AST signals that liver damage is occurring.

Methotrexate is believed to damage the liver directly. Taking methotrexate for RA can increase ALT levels. Having elevated ALT before starting methotrexate boosts the risk of early or recurring high ALT during methotrexate treatment.

High ALP and GGT are associated with cholestasis, a condition where the flow of bile from your liver is reduced or blocked. Over time, chronic cholestasis can lead to liver damage. Researchers have noted elevations of ALP and GGT in people with RA.

Cholestasis is also a sign of the autoimmune disease primary biliary cholangitis (PBC).

Rheumatoid arthritis and nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) can cause elevated liver enzymes and liver damage. There’s a possible link between RA and NAFLD. While this may be due to the effects of RA or its treatment, more research needs to be done.

One study, presented at the American College of Rheumatology Annual Meeting in 2016, found that current methotrexate use was associated with higher rates of NAFLD in people with RA.

However, other than this, the chance of NAFLD in people with RA was linked with similar risk factors for fatty liver disease in the general population, such as metabolic syndrome and diabetes.

Additionally, a 2023 review estimates that one in three (33%) of people with RA have NAFLD. This is only slightly higher than the estimated global prevalence of NAFLD, which is about 30%.

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If you have RA, your doctor will periodically want to monitor your overall health and RA disease activity. It’s possible they may find elevated liver enzymes during this routine blood work.

If you have elevated liver enzymes and are at risk for liver disease or currently have liver disease, your doctor may use a DMARD other than methotrexate to treat your RA. Some examples include biologics or JAK inhibitors.

Your doctor may also recommend lifestyle changes to promote liver health, including:

Other autoimmune disorders that cause elevated liver enzymes

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RA can cause elevated liver enzymes in some people. Having elevated liver enzymes signals that your liver is stressed or damaged.

Elevated liver enzymes may occur due to the effect of RA on the body, the effects of certain RA treatments, or both.

If you have RA and elevated liver enzymes, your doctor may switch you to a medication that doesn’t stress the liver as much. They’ll also recommend that you adopt lifestyle changes that promote liver health.