Liver Fibrosis

Our research is at the intersection of two novel timelines

1. Liver Fibrosis

2. Interpretable Machine Learning w/ Shapely Additive Explanations

But let's focus on liver fibrosis :)

SHAP ML model in NHANES data for Advanced Fibrosis (F3/F4) using VCTE

https://journals.lww.com/ajg/fulltext/2023/10001/s1416_the_visualization_of_the_importance_of.2377.aspx

Ty Dr. Kwo

TOC

History why liver fibrosis is important

Methods for assessing liver fibrosis 

- Liver Biopsy

- Alternatives (indirect biomarkers, elastography, new scores)

New paradigm shift

HISTORY and WHY FIBROSIS IS IMPORTANT

• Historically utilized as multiple stages variable now binary, transition from specific fibrosis staging using the Ishak, METAVIR, Knodell stages and now just absence or presence of advanced fibrosis
• Degree of fibrosis aids in diagnosis and treatment
• Occur in steatotic liver disease (MASLD, MetALT, ALD), viral hepatitis
• steatosis vs steatohepatitis is distinguished by stage 2 or higher and is associated w/ hepatic events
• For cirrhosis stage 4 fibrosis is when you screen for HCC w/ US and AFP
• HBV w/ stage 2 fibrosis is when you start treatment

METHODS for Assessing liver fibrosis

• Liver bx: gold standard, declining use, heterogeneous not all areas of liver equally fibrosed, requires biopsy needles ideally 3cm w/ 16gauge needle > 10 portal tracts
• Serum tests / biomarkers: APRI, Fib-4, AST/ALT ratio, fibrosure/fibrotest, fibrospect-II, ELF, others
• Elastography: VCTE: vibration controlled transient elastography - fibroscan, shear wave, acoustic radiation force impulse. MRI elastography: expensive

Indirect biomarkers / serum markers

AST/ALT ratio > 0.8 suggests advanced fibrosis if no alcohol

platelet count < 150,000 suggests ptl htn

U/S / axial imaging w/ CT or MRI

splenomegaly or PV diameter >= 13 mm suggests ptl htn

Blood based biomarkers

Fib4 formula: age * AST / [Pltlt * sqrt(ALT)]

- < 1.45 exludes severe fibrosis (F3-F4) w/ high NPV

APRI = AST / AST (ULN) / pltlt * 100

APRI < 0.5 r/o cirrhosis

NAFLD / MASLD Fibrosis scores: -1.675 + (0.037 * age[years] + 0.094 * BMI + 1.13 * IFG/diabetes + 0.99 * AST/ALT ratio - 0.013 * pltlt count - 0.66 * albumin

F0: no cirrhosis, F1 mild fibrosis, F2, moderate fibrosis, F3 severe fibrosis, F4 Cirrhosis

SAFE score = 2.97 * age + 5.99 * BMI w/UL40 + 62.85 * diabetes + 154.85 * lnAST - 58.23*lnALT + 195.48 * ln globulins - 141.61 * lnplatelets - 75

Elastography: two types Vibration controlled transient elastography point of care test with steatosis assessment and MRI

noninvasive, safe, less expensive and can be used serially at the cost of unreliable results or test failure in those BMI > 30, operator dependent, no information on inflammation, cutoffs vary by etiology

VCTE kPa: F0-1: <7, F2 7-9.4, F3 9.5-12.4 or 14, F4 > 12.5 or 14

MRE kPa: F0-1: <3.65, F2 3.66-4.1, F3 4.11-12.4.7 or 14, F4 > 4.7

New scores: Fibroscan-AST score (FAST) compositive score w/ liver stiffness + CAP

MRI-aspartate aminotransferase score (MAST)

MRE + Fib-4 (MEFIB) index

New paradigm shift (simplified)

Start w/ blood based biomarkers that have high NPV to r/o fibrosis (Fib-4, APRI, NFS, SAFE score or VCTE)

then do fibroscan (VCTE)

MRI elastography

then liver biopsy