Assessing liver fibrosis without biopsy in patients with HCV or NAFLD

Cleveland Clinic Journal of Medicine. 2019 March;86(3):179-186 | 10.3949/ccjm.86a.17118
March 1, 2019|Cleveland Clinic Journal of Medicine
Tavankit Singh, MD;Daniela S. Allende, MD;Arthur J. McCullough, MD
Author and Disclosure Information

Tavankit Singh, MD
Department of Gastroenterology and Hepatology, Cleveland Clinic

Daniela S. Allende, MD
Director, Hepatobiliary Pathology, Department of Pathology, Cleveland Clinic; Associate
Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Arthur J. McCullough, MD
Departments of Gastroenterology and Hepatology and Pathobiology and Transplantation Center, Cleveland Clinic; Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Address: Arthur J. McCullough, MD, Department of Gastroenterology and Hepatology, A30, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; mcculla@ccf.org

Release date: March 1, 2019
Expiration date: February 29, 2020
Estimated time of completion: 1 hour

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ABSTRACT

Staging of liver fibrosis is increasingly done using noninvasive methods, in some cases obviating the need for liver biopsy. Scores based on laboratory values and demographic variables have been developed and validated for assessing fibrosis in patients with hepatitis C virus (HCV) infection and nonalcoholic fatty liver disease (NAFLD), as have several imaging methods that measure shear-wave velocity, a reflection of fibrosis severity.

KEY POINTS

  • Liver biopsy remains the gold standard for determining fibrosis stage but is expensive and entails risk of complications.
  • For patients infected with HCV, fibrosis stage should be determined with transient elastography, a transthoracic ultrasonographic technique that measures shear-wave velocity.
  • For patients with cirrhosis, transient elastography combined with a platelet count can detect developing portal hypertension and determine whether to screen for esophageal varices.
  • For NAFLD, combined elastography and NAFLD fibrosis score—which incorporates patient characteristics and laboratory test results—should be used to determine the need for liver biopsy.

STAGING BASED ON DEMOGRAPHIC AND LABORATORY VARIABLES

Several scores based on patient characteristics and laboratory values have been developed for assessing liver fibrosis and have been specifically validated for HCV infection, NAFLD, or both. They can serve as inexpensive initial screening tests for the presence or absence of advanced fibrosis.

FIB-4 index for HCV, NAFLD

The FIB-4 index predicts the presence of advanced fibrosis using, as its name indicates, a combination of 4 factors in fibrosis: age, platelet count, and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), according to the formula:

FIB-4 index = (age × AST [U/L]) /
(platelet count [× 109/L] × √ALT [U/L]).

,

The index was derived from data from 832 patients co-infected with HCV and human immunodeficiency virus.24 The Ishak staging system10 for fibrosis on liver biopsy was used for confirmation, with stage 4 to 6 defined as advanced fibrosis. A cutoff value of more than 3.25 had a positive predictive value of 65% for advanced fibrosis, and to exclude advanced fibrosis, a cutoff value of less than 1.45 had a negative predictive value of 90%.

The FIB-4 index has since been validated in patients with HCV infection25 and NAFLD.26 In a subsequent study in 142 patients with NAFLD, the FIB-4 index was more accurate in diagnosing advanced fibrosis than the other noninvasive prediction models discussed below.27

NAFLD fibrosis score

The NAFLD fibrosis score, constructed and validated only in patients with biopsy-confirmed NAFLD, incorporates age, body mass index, presence of diabetes or prediabetes, albumin level, platelet count, and AST and ALT levels.

A group of 480 patients was used to construct the score, and 253 patients were used to validate it. Using the high cutoff value of 0.676, the presence of advanced fibrosis was diagnosed with a positive predictive value of 90% in the group used to construct the model (82% in the validation group). Using the low cutoff score of –1.455, advanced fibrosis could be excluded with a negative predictive value of 93% in the construction group and 88% in the validation group.28 A score between the cutoff values merits liver biopsy to determine fibrosis stage. The score is more accurate in patients with diabetes.29 When used by primary care physicians, the NAFLD fibrosis score is more cost-effective than transient elastography and liver biopsy for accurately predicting advanced fibrosis.30

AST-to-platelet ratio index score for HCV, NAFLD

The AST-to-platelet ratio index (APRI) score was developed in 2003 using a cohort of 270 patients with HCV and liver biopsy as the standard. A cutoff value of less than or equal to 0.5 had a negative predictive value of 86% for the absence of significant fibrosis, while a score of more than 1.5 detected the presence of significant fibrosis with a positive predictive value of 88%.31 The APRI score was subsequently validated for NAFLD.27,32

FibroSure uses a patented formula

FibroSure (LabCorp; labcorp.com) uses a patented mathematical formula that takes into account age, sex, and levels of gamma-glutamyl transferase, total bilirubin, haptoglobin, apolipoprotein-A, and alpha-2 macroglobulin to assess fibrosis. Developed in 2001 for use in patients with HCV infection, it was reported to have a positive predictive value of greater than 90% and a negative predictive value of 100% for clinically significant fibrosis, defined as stage 2 to 4 based on the METAVIR staging system in the prediction model.33 The use of FibroSure in patients with HCV was subsequently validated in various meta-analyses and systematic reviews.34,35 It is less accurate in patients with normal ALT levels.36

FibroSure also has good accuracy for predicting fibrosis stage in chronic liver disease due to other causes, including NAFLD.37

The prediction models discussed above use routine laboratory tests for chronic liver disease and thus are inexpensive. The high cost of additional testing needed for FibroSure, coupled with the risk of misdiagnosis, makes its cost-effectiveness questionable.38