How to optimize referral timing for severe liver disease

Feb. 12, 2022

Referral timing is crucial for the health of patients with advanced liver disease to avoid missing the window that would allow for successful transplantation. If transplant evaluation occurs too soon, patients may unnecessarily undergo transplant center referral with testing and consultations they don't yet need, though this can usually be minimized if it's recognized that the patient doesn't yet require transplantation. Impact of referral too late can be far more significant, potentially causing patients to no longer qualify for transplant or lack sufficient strength for surgery.

El momento de la derivación es crucial El momento de la derivación es crucial

Dr. Bashar A. Aqel, Gastroenterología y Hepatología en Mayo Clinic en Phoenix y Scottsdale, Arizona, habla con un paciente sobre un trasplante de hígado.

Nota: Este contenido se creó antes de la pandemia de la enfermedad por coronavirus 2019 (COVID-19) y no describe los protocolos adecuados para la pandemia. Respeta todas las pautas recomendadas por los Centros para el Control y la Prevención de Enfermedades relativas al uso de mascarillas y al distanciamiento físico.

Because patient status can change quickly with liver disease, monitoring patients carefully to ensure stability is important. Disease trajectory determines monitoring frequency. Patients with cirrhosis require hepatocellular carcinoma (HCC) screening, typically conducted with liver ultrasound or another imaging technique plus a blood test measuring alpha-fetoprotein level.

"A patient can mow the lawn in May and by June have a complication and become bedridden and fatigued with muscle wasting," says Julie K. Heimbach, M.D., a liver transplant surgeon at Mayo Clinic's campus in Minnesota.

Referral criteria

Hometown physicians are critical guides regarding transplant timing for patients with severe liver disease, says Dr. Heimbach. Several criteria demonstrating need for specialty center referral follow:

Progression of symptoms

Despite significant symptoms, it's easy to postpone referring patients with low model for end-stage liver disease scores. Nevertheless, when symptoms such as ascites, encephalopathy or sarcopenia escalate, Dr. Heimbach recommends referral.

Decompensated liver signs

Care providers should watch for decompensated liver indications, such as encephalopathy, ascites, gastrointestinal bleeding, muscle wasting, edema or disabling itching.


Physicians must screen patients with cirrhosis biannually to identify cancer early. HCC is a common indication for liver transplantation, says Kymberly D. Watt, M.D., a transplant hepatologist at Mayo Clinic's campus in Minnesota. She encourages physicians to avoid following tumors till they grow too large for transplant eligibility and to refer at tumor identification.

Inability to carry out life duties

When patients with liver disease experience multiple hospital stays and can no longer work, these are signs that referral for consultation, including transplant discussion, is appropriate.

Overall, Dr. Watt recommends referring sooner rather than later. If transplant is warranted, earlier surgery may offer patients a greater chance of full function post-transplant. "If there's a question about a patient, reach out and ask," says Dr. Watt. "With any mass — even if small — we'd be happy to discuss or see the patient in person or by telemedicine. Even if someone has concerns that it's futile, call us first."

In Mayo Clinic Gastroenterology, rotating hepatologists take external physician calls all day.

Challenges for liver transplant and overcoming barriers

It's crucial that physicians review patients' histories of other medical conditions beyond liver disease, such as stroke or advanced heart or lung disease. The key issue is whether they have other life-threatening conditions such as malignancy or heart disease that won't be addressed with liver transplant and often will worsen with transplantation.

Some conditions physicians previously considered to make patients inappropriate for transplantation may actually be suitable, such as:

Severe obesity

Mayo Clinic will accept selected patients with severe obesity (often defined as BMI greater than 40) — including those who may have been declined at other centers — offering a noninvasive weight loss program or liver transplant with sleeve gastrectomy.

"If the local transplant center says no to transplant because of BMI, we may consider transplant at Mayo Clinic," says Dr. Heimbach. "We've found that by fixing obesity, the liver returns patients to full function."

She says the liver transplant program at Mayo Clinic in Minnesota has experienced multiple patient self-referrals from hospice because providers assumed transplant was not possible due to morbid obesity. Now these patients are alive and well after liver transplant combined with sleeve gastrectomy.

Alcohol-associated liver disease

Active alcohol use is contraindicated in most circumstances. The traditional approach with alcohol addiction and liver disease secondary to alcohol use is requiring a fixed abstinence period, typically six months. Mayo Clinic's approach is to ensure the patient has undergone alcohol addiction treatment and enrolled in aftercare pretransplant.

This approach may require more or less than six months to complete. Recently, evidence has suggested that a highly select patient group with severe liver failure secondary to alcohol use can be considered for transplant with addiction treatment post-transplant, though identifying which patients are most likely to benefit from this approach is difficult and requires careful assessment.

Severe frailty

Patients with liver disease who are debilitated or frail lack strength to survive and recover from transplant. Yet sometimes Mayo Clinic liver transplant specialists can help strengthen frail patients, facilitating transplant.

Early-stage fibrosis

Though often cirrhosis is not reversible, early-stage fibrosis is potentially reversible, even with 10% weight loss.

Transplant may also be unnecessary or undesirable for some patients with severe liver disease.

Liver supply challenges

While physicians can consider their patients' options with severe liver disease, access to transplantable livers remains difficult. "Fourteen thousand patients are awaiting liver transplant yearly," says Dr. Heimbach. "We can only transplant 8,000 due to supply."

If physicians follow patients listed for liver transplant over three years, 20% to 25% will die, she says, noting that the deceased donor liver shortage also demonstrates need for living donor transplant, accelerating the process.

Liver transplant goals and Mayo Clinic's program

Dr. Heimbach considers the goal of liver transplantation to be restoration of patients' full function. "Return to active life should be the expectation," she says. "We've seen kids we've transplanted become firefighters when they grow up, farmers returning to their roles and athletes able to participate in sports again."

Dr. Watt says most patients fare well with liver transplant. Mayo Clinic's one-year liver transplant survival is 94%; five-year survival is 80%. The transplant program is long-standing, founded in 1985, with substantial experience and transplant research and publication.

For more information

Refer a patient to Mayo Clinic.