patient care perspectives

Fibrosis and Cirrhosis: Multispecialty Care and Optimizing the Referral Pathway

by Arun J. Sanyal, MD

Overview

Across different health care settings, there is a move to risk stratify patients with nonalcoholic fatty liver disease (NAFLD) using clinical factors and simple tests. The goal is to identify those individuals with NAFLD who are at high risk for fibrosis and cirrhosis so that they can be followed in a multidisciplinary fashion.

Expert Commentary

Arun J. Sanyal, MD

Interim Chair
Division of Gastroenterology, Hepatology, and Nutrition
Professor of Medicine, Physiology, and Molecular Pathology
Virginia Commonwealth University School of Medicine
Richmond, VA

“There is a huge unmet need to identify high-risk individuals before they progress to decompensated cirrhosis and to develop effective therapeutics to treat liver fibrosis. The best way to screen patients with NAFLD across multiple specialties is to use simple tests.”

Arun J. Sanyal, MD

Liver fibrosis can be very advanced, yet still completely silent. In fact, the fibrosis does not result in any symptoms until an individual starts developing decompensated cirrhosis. Rather, it is the portal hypertension and the loss of liver function with disease progression that result in recognizable symptoms. Waiting until the signs of liver decompensation start to emerge to initiate treatment, however, limits the options since, at that point, the aim becomes to delay a liver transplant by using various therapies to treat the complications of portal hypertension.

There is a huge unmet need to identify high-risk individuals before they progress to decompensated cirrhosis and to develop effective therapeutics to treat liver fibrosis. The best way to screen patients with NAFLD across multiple specialties is to use simple tests. The Fibrosis-4 (FIB-4) index is one such test, and, if an individual’s FIB-4 is less than 1.3, then the likelihood of that patient dying from liver disease is extremely low. If the FIB-4 is greater than 2.6, then the chance of being at risk for poor liver outcomes is significantly higher; the higher it is above that 2.6 threshold, the greater the risk for poor liver outcomes. Indeed, data show a strong association between fibrosis stages F3 and F4 and hepatic decompensation and death in patients with NAFLD.

It is this high-risk population that should be triaged to a gastroenterologist or hepatologist for further work-up. Clinicians may want to follow individuals who fall somewhere in the middle (ie, FIB-4 1.3-2.6) a bit more closely and reassess their FIB-4, and possibly get a vibration-controlled transient elastography (FibroScan [Echosens]) and/or other types of tests (eg, an Enhanced Liver Fibrosis test or a PRO-C3 test). If the patient has a strong family history of liver-related deaths, cirrhosis, or liver cancer, or if their vibration-controlled transient elastography results are elevated, it may be reasonable to refer them out for further evaluation. Most patients whose FIB-4 levels are low can be treated with lifestyle interventions and/or management of their obesity and diabetes with sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists.

The efficacy of novel glucose-lowering drugs in the treatment of NAFLD continues to be investigated. The impact of the SGLT2 inhibitors in NAFLD is less well characterized in studies than the GLP-1 agonists. Early clinical data indicate that GLP-1 agonists may have a beneficial effect on the resolution of nonalcoholic steatohepatitis, in addition to their glucose-lowering activity in type 2 diabetes. A synergistic effect may also be observed when SGLT2 and GLP-1 agents are combined, but further investigation is required.

Patients with liver fibrosis who are at risk for cirrhosis need to be followed in a multidisciplinary fashion, simply because no single group has all of the answers. For example, hepatologists may not always be comfortable with directing the use of drugs to manage glycemia. Further, diabetologists may not be comfortable with managing the patient’s liver disease, and cardiologists may not be comfortable with managing either the liver or the diabetes aspect, just as the hepatologist will not necessarily be comfortable with managing the patient’s unstable angina. Depending on the patient’s comorbidity profile, we therefore need all of these different specialties (ie, primary care physicians, cardiologists, diabetologists, and hepatologists), along with nutritionists and clinical psychologists, to provide patient care—not siloed, but in an integrated manner in which the same information is conveyed in a clear and implementable way for the patient.

References

Dougherty JA, Guirguis E, Thornby K-A. A systematic review of newer antidiabetic agents in the treatment of nonalcoholic fatty liver disease. Ann Pharmacother. 2021;55(1):65-79. doi:10.1177/1060028020935105

Lazarus JV, Anstee QM, Hagström H, et al. Defining comprehensive models of care for NAFLD. Nat Rev Gastroenterol Hepatol. 2021;18(10):717-729. doi:10.1038/s41575-021-00477-7

Moolla A, Motohashi K, Marjot T, et al. A multidisciplinary approach to the management of NAFLD is associated with improvement in markers of liver and cardio-metabolic health. Frontline Gastroenterol. 2019;10(4):337-346. doi:10.1136/flgastro-2018-101155

Newsome PN, Buchholtz K, Cusi K, et al; NN9931-4296 Investigators. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384(12):1113-1124. doi:10.1056/NEJMoa2028395

Ruissen MM, Mak AL, Beuers U, Tushuizen ME, Holleboom AG. Non-alcoholic fatty liver disease: a multidisciplinary approach towards a cardiometabolic liver disease. Eur J Endocrinol. 2020;183(3):R57-R73. doi:10.1530/EJE-20-0065

Sanyal AJ, Van Natta ML, Clark J, et al; NASH Clinical Research Network (CRN). Prospective study of outcomes in adults with nonalcoholic fatty liver disease. N Engl J Med. 2021;385(17):1559-1569. doi:10.1056/NEJMoa2029349

Steggerda JA, Mahendraraj K, Todo T, Noureddin M. Clinical considerations in the management of non-alcoholic steatohepatitis cirrhosis pre- and post-transplant: a multi-system challenge. World J Gastroenterol. 2020;26(28):4018-4035. doi:10.3748/wjg.v26.i28.4018

Targher G, Tilg H, Byrne CD. Non-alcoholic fatty liver disease: a multisystem disease requiring a multidisciplinary and holistic approach. Lancet Gastroenterol Hepatol. 2021;6(7):578-588. doi:10.1016/S2468-1253(21)00020-0

Unger LW, Berlakovich GA, Trauner M, Reiberger T. Management of portal hypertension before and after liver transplantation. Liver Transpl. 2018;24(1):112-121. doi:10.1002/lt.24830

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