What to Do Before Referring Patients With IBD to a Hepatologist

Christina Ha, MD, gastroenterologist at the Mayo Clinic in Scottsdale, Arizona, admitted “to me, the liver is actually very intimidating” and that she is tempted to get the hepatologist involved all the time. In her session at the Advances in Inflammatory Bowel Disease 2022 virtual regional meeting on Saturday, March 5, Dr Ha offered advice on 5 scenarios involving the liver with inflammatory bowel disease (IBD) patients, and when to refer to the hepatologist in those instances.

The first scenario Dr Ha posited was that of a patient with ulcerative colitis (UC) that is well-controlled on mesalamine and is in endoscopic remission. At an annual follow-up, the patient’s labs show an abnormal liver chemistry—elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT).

For this patient, Dr Ha stated it is not yet time to call the hepatologist. The first thing to do is recheck the liver chemistries. “You never want to send them to hepatology with just 1 time-point of an abnormal liver chemistry.” Additionally, the patient should be assessed for risk factors for liver injury, such as supplements being taken, alcohol or substance use, body mass index (BMI), and any associated nonalcoholic fatty liver disease (NAFLD) conditions. Consider running autoimmune labs, and whether there are any associated conditions like celiac disease, thyroid disorders, or instances of hepatitis. If there is a persistent and increasing elevation of the liver chemistry, Dr Ha also suggested an abdominal ultrasound to look for any structural abnormalities, fatty liver, or any masses/nodules.

From there, Dr Ha advised eliminating any potential causative agents, and then reassess the liver enzymes. She also cautioned, “Just because they have IBD doesn’t mean it’s going to be an autoimmune- or a medication-related issue, because NAFLD, or MAFLD [metabolic associated fatty liver disease], is the most common cause for elevated liver enzymes.”

There are 2 clinical decision aids that Dr Ha called out when assessing for advanced fibrosis for NAFLD patients: the Fibrosis 4 Score and the NAFLD Fibrosis Score. Both tools stratify a patient into low, high, or indeterminate risk. For patients who are low risk, a hepatology consult is not necessary. Rather, patients should work with their primary care physician and a registered dietician to improve diet, exercise, and weight. Patients with indeterminate or high risk will likely require a hepatology consult for additional imaging.

In this scenario, Dr Ha stated a hepatology consult should be sought out if there is a suspicion of advanced fibrosis based on clinical decision aids for NAFLD; the autoimmune serologies are equivocal or suspicious for autoimmune hepatitis; there is an abnormal ultrasound; or the liver chemistries are persistently elevated or increasing over a 3- to 6-month period without an identifiable cause. On this last point, Dr Ha offered the caveat that she will consider involving the hepatologist earlier if she is planning “to start an agent that may be associated with abnormal liver chemistries” (eg, thiopurines, biologics, small molecules, methotrexate).

The next scenario involved a patient with active UC who comes in for a week 10 follow-up after starting a combination therapy of infliximab and azathioprine. The patient’s liver chemistries (AST, ALT) have been increasing with each lab (weeks 2, 6, and 10). Because all IBD treatments can be associated with increased liver chemistries, especially immunomodulators, biologics, and small molecules, Dr Ha stated, “It’s very important, if you’re going to initiate these therapies, that you’re going to routinely monitor not only their blood counts, but also their liver chemistries.”

When dealing with thiopurines, Dr Ha pointed out that thiopurine S-methyltransferase (TPMT) drives production of a hepatotoxic metabolite, and so TPMT enzyme activity should be measured, as well as thiopurine metabolites. If these levels are high, “thiopurine is likely the culprit.” Then, the dosing of the thiopurine should be adjusted, or discontinued, and the liver chemistries should be rechecked every 2 to 4 weeks.

For patients being treated with methotrexate, Dr Ha reminded, “elevated liver chemistries can be quite common,” as is hepatotoxicity. In this case, it is important that the patient is taking their folic acid, as this reduces methotrexate-associated hepatotoxicity.

If a patient is being treated with biologics and small molecules, Dr Ha stated that the hepatitis status should be reassessed. She also pointed out that elevated liver enzymes are more common with combination therapies involving an anti-TNF agent, “likely driven by the thiopurines. However, anti-TNF-associated liver injury may present as an autoimmune-hepatitis-like picture.”

The rule of thumb for patients who have just been initiated on a treatment and are experiencing liver abnormalities is to discontinue the treatment and monitor for decreasing trends. If there are persistent elevations in liver chemistries, a liver biopsy specimen may be required.

The third scenario involved a patient with a liver condition associated with IBD, such as primary sclerosing cholangitis (PSC). If there is a suspicious of PSC, Dr Ha advises to first check the family history, “there is an 80-fold increased risk among first-degree relatives.” She also stated that checking autoimmune serologies “is not always helpful, because they’re not always positive.” Most patients with PSC are asymptomatic at diagnosis, which is why it is important to periodically check metabolic profiles that include the alkaline phosphatase (alk phos) and the total bilirubin (T bili), “because the first sign [of PSC] may actually be this rise in alk phos.”

Dr Ha brought in wisdom from a hepatology colleague of hers at Cedars Sinai, Vinay Sundaram, MD, director of Hepatology Outcomes Research and assistant medical director of Liver Transplantation, who said, “If an elevated alk phos is present, but a MRCP [magnetic resonance cholangio pancreatography] is normal, please refer them to hepatology, because they may need a liver biopsy to rule out small duct PSC.”

The biggest thing for IBD patients, Dr Ha went on, “is the cumulative risk of developing dysplasia or colorectal cancer [CRC].” There is a 9% risk of CRC at 10 years and up to 50% at 25 years, “so it is very important to encourage these patients to get their routine annual surveillance colonoscopies.” Dr Ha added that the severity and duration of the PSC does not influence the CRC risk, and that the CRC risk persists after liver transplant. In addition to CRC, there are other cancers associated with PSC, such as cholangiocarcinoma, gall bladder cancer, colon cancer, and hepatocellular cancer. Annual surveillance exams to monitor for these conditions are equally important.

“At the end of the day,” Dr Ha said, “refer your PSC patients to the hepatologists.” She quoted hepatology colleagues as saying: “Please send all your PSC patients. Seeing them early helps to establish expectations about cholangitis, to make sure they’re getting their cancer surveillances, and also to monitor them in the future if they were to ever progress to needing a liver transplant.”

When it comes to hepatitis B, Dr Ha said all patients with IBD who are starting an immunosuppressive agent, including corticosteroids, should be screened for hepatitis B—including hepatitis B surface antigens (HBsAg), hepatitis B surface antibodies (HBsAb), and hepatitis B core antibodies (HBcAb).

When it comes to patients with IBD who may be positive for hepatitis B, guidelines from 2017 recommend that for any patients who are HBsAb positive, who are going to be starting a medication that has either high or moderate risk of reactivation (which includes nearly all IBD therapies except thiopurines and methotrexate), hepatitis B virus (HBV) DNA testing should be done, and anti-viral treatment should be started. These patients will also need a referral to hepatology, as they will need imaging to check for fibrosis. “In these patients,” Dr Ha said, “it is very important to taper and avoid recurrent courses of [cortico]steroids; and the antiviral needs to stay onboard until 6 months after their IBD treatment is discontinued.”

When the patient is HBsAg negative, but HBcAb positive, “it becomes a little more tricky,” Dr Ha said. The guidelines from Gastroenterology indicate that “high-dose corticosteroids” correlate to a “moderate risk of reactivation” and “moderate- and low-dose prednisone” are “low risk of reactivation.” However, “European and Asian guidelines consider high-dosed [cortico]steroids to be high-risk and moderate-dosed [cortico]steroids to be moderate risk.” Other biologics are all considered to present a moderate risk of reactivation.

For these patients, Dr Ha proposes 2 options: “empirically treat with an antiviral, which is a strategy that most hepatologists would recommend, or you can adopt a watch and wait strategy, where you would monitor the ALT serially and if it starts to increase, you check the HBsAg and the HBV DNA.” Again, Dr Ha stressed the importance of tapering and avoiding recurrent corticosteroid courses for these patients, “because [cortico]steroids are also associated with reactivation.”

Dr Ha went on to state that if patients are negative for hepatitis A and B at screening, they should be vaccinated. While the standard vaccination is at 0, 1, and 6 months, there are risk factors for inadequate response, such as advanced age, immunosuppression, and an incomplete vaccination series. Because of those factors, patients with IBD “may be recommended to have an intensified protocol for vaccinations.” She also stated that titers should be checked 1 to 3 months after the vaccination series is complete, as well as rechecked every 2 years after.

When it comes to assessing hepatitis B reactivation risk, Dr Ha pointed out that this can be a relatively simple telemedicine consult to hepatology colleagues.

The last scenario Dr Ha proposed was that of a patient with IBD and advanced liver disease, being evaluated for liver transplant. Dr Ha first pointed out that random biopsy procedures are not necessary. Instead, she advised the use of enhanced imaging modalities and limited targeted biopsies. If there is a suspicion of dysplastic lesions that are visible, discrete, and resectable, Dr Ha stated that providers should “consider patient factors prior to attempting the EMR [endoscopic mucosal resection],” such as bleeding risks, a need to correct the coagulopathy, and whether the EMR should be attempted by an interventional endoscopist.

If the patient has a multifocal, invisible, or moderate to severe disease activities, Dr Ha stated consideration of the risks of colectomy pretransplant relative to repeated colonoscopy or medication optimization. “Remember,” she said, “posttransplant, they’re going to be on a lot of immunosuppression. So what do you do with their IBD treatment posttransplant?... You have to think about that course and trajectory.” In these cases, the patients require very close, multidisciplinary care with the transplant hepatologists.

Dr Ha concluded, “hepatologists are very smart, and they are always willing to help us out. If there’s a question, we should feel free to ask, but we should do a little bit of the homework ahead of time, so we can prepare them for an adequate consultation."

—Allison Casey


For more content from the Advances in Inflammatory Bowel Disease 2022 Regional Meetings, visit our Meeting Newsroom.

Reference
Ha C. When is it time to consult with a hepatologist about my IBD patient?. Presented at: Advances in Inflammatory Bowel Disease 2022 Regional Meeting; March 5, 2022; Virtual.