Cystic Fibrosis Screening, Evaluation and Management of Hepatobiliary Disease

Publication Date: October 26, 2023
Last Updated: November 10, 2023

Screening

  • The CFF recommends that annual labs (total bilirubin, AST, ALT, alkaline phosphatase, GGT, Platelet Count) should be performed, at a time of clinical stability, for identification of hepatobiliary involvement in all persons with CF starting at CF diagnosis.
  • CFF recommends annual abdominal physical examination for hepatosplenomegaly for identification of advanced liver disease in all persons with CF starting at CF diagnosis.
  • CFF recommends abdominal ultrasound to assess the liver and spleen at least every two years in persons with CF from childhood until late adolescence, starting at age 3 or at diagnosis, if diagnosed after age 3.
  • In adults with CF, there is value in baseline screening for CFHBI, but the optimal frequency of subsequent imaging for those with normal baseline findings is unknown and a specific recommendation cannot currently be made.
  • CFF recommends that persons with CF who are found to have hepatobiliary involvement (abnormal physical exam, persistently elevated liver enzymes, or abnormal abdominal ultrasound findings), should undergo baseline liver elastography, when available, for the identification of advanced liver disease.
  • CFF recommends that persons with CF and hepatobiliary involvement should receive a standardized evaluation for other causes of liver disease.
  • CFF recommends that all persons with CF who have cholestatic liver test (Direct Bilirubin, GGT, and/or alkaline phosphatase) elevation, abdominal pain consistent with a biliary cause and inconclusive abdominal ultrasound should undergo magnetic resonance cholangiopancreatography (MRCP) to detect hepatolithiasis, choledocholithiasis, biliary strictures, and/or biliary obstruction.

Monitoring

  • CFF recommends that in persons with CF and liver involvement, a liver specific physical examination be performed at least annually and at each in-person visit to monitor for the progression of disease.
  • CFF recommends that for persons with CF and hepatobiliary involvement at least one liver fibrosis index be calculated and followed at least annually.
  • CFF recommends for persons with CF and hepatobiliary involvement an abdominal US be performed at least every 2 years to monitor for the progression of disease.
  • CFF recommends that persons with CF and hepatobiliary involvement or advanced liver disease undergo evaluation of liver stiffness with elastography at least annually, if available, to monitor for the progression of disease.
  • CFF recommends that persons with CF hepatobiliary involvement or advanced liver disease receive consultation with a pharmacist with experience in CF and hepatobiliary disease to identify high risk medications, polypharmacy, therapy modifications, and risk based on their hepatobiliary disease every 6 months, unless there have been no medication changes, to improve morbidity and mortality.
  • CFF recommends that persons with CF and advanced liver disease undergo liver specific physical examination and measurement of AST, ALT, GGT, alkaline phosphatase, conjugated (or direct) bilirubin, albumin, platelets, and international normalized ratio (INR) at least every 6 months to detect progression of liver disease.
  • CFF recommends that persons with CF and advanced liver disease, receive a nutritional assessment for malnutrition and liver specific macro- and micronutrient deficiencies every 6 months by a dietitian experienced in CF. When abnormalities are identified a treatment plan and monitoring of nutritional rehabilitation should be developed.
  • The CFF recommends, for persons with CF and advanced liver disease, beginning CF beginning CF beginning CF beginning CF beginning CF related diabetes (CFRD) screening at the diagnosis of advanced liver disease, even if earlier than age 10 and then annually thereafter, to provide early diagnosis and treatment of CFRD (using methodologies described in the most current CFRD Guidelines).
  • CFF recommends that persons with CF and advanced liver disease receive multidisciplinary care from pulmonology, gastroenterology/hepatology, endocrinology and when appropriate, a transplant center, to optimize liver outcomes.
  • CFF recommends that adults with CF and advanced liver disease with esophageal varices be managed according to the relevant most current published guidelines, such as those from the American Association for the Study of Liver Diseases or the Baveno group.
  • The CFF cannot provide a recommendation for or against endoscopic variceal surveillance in children with advanced liver disease, due to insufficient evidence.
  • CFF recommends that all CF children with cirrhosis or suspected cirrhosis, are screened annually for hepatocellular carcinoma with abdominal US and serum alphafetoprotein.
  • CFF recommends that all CF adults with cirrhosis or suspected cirrhosis are screened for hepatocellular carcinoma using the most current screening guidelines as per American Association for the Study of Liver Diseases or European Association for the Study of Liver Disease.

Treatment

  • CFF recommends against the routine use of ursodeoxycholic acid to prevent advanced liver disease in all persons with CF.
  • Efficacy: The CFLD Guidelines Committee cannot recommend for or against the use of CFTR modulator treatment to improve liver outcomes in persons with CF and hepatobiliary involvement or advanced liver disease when age-appropriate, genotypespecific modulator therapy is available due to insufficient evidence.
  • Safety: The CFLD Guidelines Committee recommends, based upon expert opinion,TR modulator treatment in persons with CF and CF hepatobiliary involvement in the setting of close monitoring by a CF gastroenterologist and/or hepatologist and pharmacist because the benefits to CF lung disease outweigh the liver related risk.
  • Safety: The CFLD Guidelines Committee cannot recommend for or against the use of CFTR modulators in persons with CF with advanced liver disease and portal hypertension without decompensation due to insufficient evidence.
  • Safety: The CFLD Guidelines Committee recommends against CFTR modulator use in persons with CF and decompensated advanced CF liver disease, as determined by a consultant Hepatologist based on thresholds such as sustained INR>1.5, abnormal direct bilirubin, low albumin, refractory ascites or encephalopathy.
  • Transplant: The CFLD Guidelines Committee recommends, based upon expert opinion,TR modulator treatment in persons with CF who have received a liver transplant because the benefits to CF lung disease outweigh the liver related risk. There should be close monitoring and collaboration with the transplant team/pharmacist in these individuals as drug-drug interactions need to be noted and monitored.
  • CFF recommends cholecystectomy for all CF persons with symptomatic gallbladder disease and other interventions (such as ERCP) for all CF persons with symptomatic biliary tract disease.
  • The CFF cannot recommend for or against the use of non-selective beta-blocker treatment for the prevention or treatment of variceal bleeding in persons with CF and advanced liver disease with portal hypertension due to insufficient evidence.
  • CFF cannot recommend for or against primary variceal prophylaxis for children with CF and advanced liver disease with portal hypertension and varices due to insufficient evidence.
  • CFF recommends that for children with CF and advanced liver disease with portal hypertension, varices, and prior variceal hemorrhage, current guidelines for secondary prophylaxis be followed in consultation with a pulmonologist and anesthesiologist with expertise in CF.
  • CFF recommends that adults with CF and advanced liver disease and portal hypertension (with or without prior variceal hemorrhage), should undergo primary or secondary prophylaxis according to current guidelines in consultation with a pulmonologist and anesthesiologist with expertise in CF.
  • CFF recommends that for persons with CF and cirrhotic or non-cirrhotic portal hypertension with INR ≤1.5, normal direct bilirubin and albumin, no encephalopathy and no refractory ascites, portosystemic shunt or liver transplantation be considered as longterm treatment.
  • CFF recommends that for persons with CF and cirrhotic or non-cirrhotic portal hypertension with INR>1.5, abnormal direct bilirubin, low albumin, refractory ascites or encephalopathy, liver transplantation be considered as the appropriate long-term treatment. Portosystemic shunt placement may be a bridge to transplantation for management of intractable variceal bleeding.
  • CFF recommends that for persons with CF and advanced liver disease and advanced lung disease that may be considered for lung or liver transplant, combined lungliver transplantation be considered to optimize long-term treatments.

Recommendation Grading

Abbreviations

  • CF: Cystic Fibrosis
  • CFF: Cystic Fibrosis Foundation
  • CFRD: Cystic Fibrosis-related Diabetes
  • CFTR: Cystic Fibrosis Transmembrane Conductance Regulator
  • INR: International Normalized Ratio

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Cystic Fibrosis Screening, Evaluation and Management of Hepatobiliary Disease

Authoring Organization

Publication Month/Year

October 26, 2023

Last Updated Month/Year

February 14, 2024

Document Type

Consensus

Country of Publication

US

Document Objectives

Cystic fibrosis (CF) may cause a spectrum of hepatobiliary complications, including portal hypertension, multilobular cirrhosis, and liver failure. Current guidelines on the detection and monitoring of hepatobiliary complications in CF were published in 1999. The CF Foundation assembled a committee to evaluate research advances and formulate revised guidelines for CF-associated liver disease. 

Inclusion Criteria

Male, Female, Adolescent, Adult, Child, Older adult

Health Care Settings

Ambulatory, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Assessment and screening, Management

Diseases/Conditions (MeSH)

D003550 - Cystic Fibrosis

Keywords

cystic fibrosis, Hepatobiliary Disease

Source Citation

Sellers ZM, Assis DN, Paranjape SM, Sathe M, Bodewes F, Bowen M, Cipolli M, Debray D, Green N, Hughan KS, Hunt WR, Leey J, Ling SC, Morelli G, Peckham D, Pettit RS, Philbrick A, Stoll J, Vavrina K, Allen S, Goodwin T, Hempstead SE, Narkewicz MR. Cystic fibrosis screening, evaluation and management of hepatobiliary disease consensus recommendations. Hepatology. 2023 Oct 26. doi: 10.1097/HEP.0000000000000646. Epub ahead of print. PMID: 37934656.