Clinical Programs

Determining liver fibrosis is an important element in the evaluation of patients with chronic liver disease. For example, for patients with non-alcoholic fatty liver disease, currently the most common cause of liver abnormality, stage of liver fibrosis is the single most important predictor of future outcomes. Staging of liver fibrosis is traditionally done by liver histology. It ranges from stage 0 (normal) to stage 1-2 (localized fibrosis) to stage 3-4 (advanced fibrosis, stage 4 being cirrhosis). More recently, elastography to measure liver stiffness is widely used in place of liver biopsy to estimate liver fibrosis.

The most commonly used device to measure liver stiffness is vibration controlled transient elastography (Fibroscan®), which was approved by the US FDA in 2013. It reports two data points including liver stiffness and a gauge of liver steatosis (called controlled attenuation parameter [CAP]). In the next figure, the device in our Redwood City is shown, which displays a liver stiffness value of 8.9 kPa (stage 2 fibrosis) and a CAP score of 325 dB/m (moderate steatosis).

In practice, elastography is helpful to make clinical decisions in the context of (1) clinically significant liver fibrosis (stage 2 or higher), which signals the need for an intervention to prevent further progression and (2) advanced fibrosis, which triggers preventive measures such as evaluation for portal hypertension and surveillance for hepatocellular carcinoma. The next figure shows the “rule of five,” translating liver stiffness data to clinical assessment of patients with advanced liver fibrosis. Liver stiffness >15 kPa is associated with compensated cirrhosis and >25kPa with portal hypertension. In a patient with liver stiffness < 20 kPa and platelets > 150,000, endoscopic screening for varices has a low yield and may be avoided.

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The good news is that we have now set up Fibroscan to be available via open access. In order to request it, please go to: https://stanfordhealthcare.org/medical-clinics/digestive- health-center.html. Scroll to the very bottom and find the link to ‘digestive health referral form,’ which brings up a form that offers a number of procedures.

Heart defects are the most common congenital defect at birth. These cardiac defects can range from simple defects requiring monitoring and pharmacotherapy, to more complex congenital defects such as a functional single ventricle, Hypoplastic Left Heart Syndrome as an example, which can require multiple surgeries to correct hypoxia and allow for ‘normal’ life and growth.

The final palliation surgery for single ventricle patients over the past 5 decades is the creation of a Fontan circuit. This circuit is characterized by loss of the subpulmonic ventricle resulting in non-pulsatile flow in the pulmonary circulation, elevated caval system pressure, and reduction in cardiac output.

As such, the number of adults living with congenital heart disease in the United States is growing, and although the repairs in childhood allow patients to live a ‘normal’ life, complications develop as a result of this passive cardiac pump physiology. Not only do patients develop cardiac failure and life-threatening arrhythmias, these complications can affect every organ system including, but not limited to the liver with the development of congestive hepatopathy and cirrhosis, liver cancer, and portal hypertension.

Specialists from the Stanford Adult Congenital Heart Disease (ACHD) and Hepatology departments have teamed up to create a special program for these patients. In addition to regular visits with their congenital heart team, all patients with Fontan physiology are seen in the Fontan Associated Liver Disease (FALD) clinic. They undergo standard lab work and imaging to assess for fibrosis and for HCC screening. Additionally, all patients’ data, including cardiac function, lab work, liver biopsy, and cross-sectional imaging are reviewed at our monthly multidisciplinary Fontan working group consisting of radiologists, pathologists, cardiologists, and hepatologists with special experience with this patient population. This group aims to monitor the patients with Fontan physiology to maximize their cardiac and hepatic function, screen for liver cancer, determine the timing for a heart transplant in those with failing physiology, and determine if the patient needs a combined organ transplant.

Once patients begin to experience these symptoms, they need to undergo evaluation for Heart and sometimes combined Heart and Liver Transplant. Stanford is one of the premier centers in the US specializing in the care of patients with Congenital heart disease and Fontan related liver disease and combined heart liver transplants.

At Stanford, we have completed 20 combined heart liver transplants for patients with complex congenital heart disease with liver cirrhosis since 2017. These patients ranged from the ages of 15 to 49 years of age. We are unique in using an en-bloc approach in which the donor heart and liver are not separated when harvested, and are implanted together. During this transplant, the Cardiac and Liver surgeons are operating simultaneously, decreasing organ ischemia and thereby reducing the potential risk of liver dysfunction. Additionally, simultaneous reperfusion of both organs while on cardiopulmonary bypass can decrease the strain on a newly transplanted heart and allow control of venous congestion of the liver. (Transplantation 2021).

Citations:

• Khairy et al, Univentricular Heart, Circulation, 115 (6): 800-812. 2007
• Gabbert et al, Heart beat but not respiration is the main driving force of the systemic venous return in the Fontan circulation, Scientific Reports Nature Research, 9: 2034. 2019
• Elde et al, Operative Technique of Donor Organ Procurement for En Bloc Heart-liver Transplantation, Transplantation, 105 (12): 2661-2665. 2021

If you are outside of Stanford Health Care, there are several ways to refer your patients. Please visit our website for links and details: https://stanfordhealthcare.org/medical-clinics/ digestive-health-center.html.

1) Refer electronically through our online portal PRISM (Physician Referral Information at Stanford Medicine). https://prism.stanfordhealthcare.org/prism/login/PRISM_User_FAQ.pdf

2) Fax referrals. From the website, you can scroll down to the section “How To Refer”, download the form and fax your request to (650)320-9443.