Clinical Case

Presentation
 • 65-year-old man

Case 1 • Arterial Hypertension, HLD, BMI 34 kg/m2, no alcohol consumption

• Current treatments: Olmesartan and Rosuvastatin
• Clinical Examination: Nothing Relevant

Patient • AST 42 IU/L; ALT 57 IU/L; GGT 149 IU/L; ALP 230 G/L
• HbA1c 5.4%
Medical File • No Hepatitis B, no Hepatitis C, Transferrin Saturation 24%
• US: Bright Liver
• FIB-4 Results: 1.57, in the grey zone
• FibroScan®: LMS 10.1 kPa; CAP 394 dB/m (IQR: 20 dB/m)

Boursier, J. & Nouredin M. (2021, Jun. 24) Enhancing the Management of NAFLD Patients by Using FibroScan® Based Scores. EASL
 How would you interpret these results on FibroScan®?

Is this a patient at risk for NASH?

Would you send this patient back to his GP for follow up or

would you do something else?

Questions What other NIT’s would you order to confirm NASH?

Would you order a liver biopsy?

Do you think the patients has significant fibrosis?

Is he eligible for a NASH clinical study?

Does he have
fibrotic NASH (F2
or higher)? • FAST Score was performed: 0.72
Would you do
another test to
confirm advance à Presence of active fibrotic NASH
disease? Liver biopsy was performed to confirm diagnosis:
Liver Lesion Scoring (NASH CRN)
Steatosis Grade 2 (50%)
Lobular Inflammation 2
Ballooning 2
NAS 6
Portal Inflammation 1
Fibrosis 2

Boursier, J. & Nouredin M. (2021, Jun. 24) Enhancing the Management of NAFLD Patients by Using FibroScan® Based Scores. EASL
1. De Franchis et al. J. Hepatology 2015 – PMID 26047908; 2 Papatheodoridi et at. J. Hepatology 2021 – PMID 33307138
 • 52-year-old Hispanic female complains of fatigue
• Weight gain of 18 lbs. in the last 6 months
• Previously healthy
• On examination: BP is 176/98; BMI 34
Case 2 • Laboratories:
• Hgb – 13 gm/dL
• WBC – 6500/mm3
• Platelets – 230,000

Patient •
•
•
Fasting blood sugar – 105 mg/dL
HbA1c – 7.2
Creatinine – 1.1 mg/dL (eGFR 62 mL/min)
Medical File •
•
AST – 24 IU/L
ALT – 19 IU/L
• Alk Phos – 122 IU/L
• FIB-4 – 1.2
• NFS – -1.23
• NAFL on historical US
• FibroScan®: LSM 5.9 kPa; CAP 364 dB/m (IQR: 14 dB/m)
• MRI-PDFF – 14%
 Do you consider this patient to
be at risk for NASH?

Which clinical features make you

suspect NASH?
Questions
Would you perform a liver
biopsy on this patient ?

How would you manage this

patient?
Risk Stratification Algorithm for NAFLD/NASH

Adapted from F Kanwal et al, Gastroenterology July 2021

 Case 3 • 44-year-old male
• No remarkable medical history

Patient • Referred by hematologist due to thrombocytopenia

• No family history of liver disease

Medical File • Not a habitual drinker and did not take other drugs
• BMI 39.4
• PE
• Hepatosplenomegaly
• Neurological findings were not remarkable

Adapted from Honma, Y., Sumida, K., Ogino, N., Kusanaga, M., Minami, S., Kumei, S., Matsuoka, H., Watanabe, T., Hiura, M., Abe, S., Shibata,
M., & Harada, M. (2018). A Young Adult Patient with Nonalcoholic Steatohepatitis Developed Severe Gastroesophageal Varices Associated
with Severe Obesity and Diabetes Mellitus. Case reports in gastroenterology, 12(2), 487–496. https://doi.org/10.1159/000492423
What labs would
you order?
 • WBC – 15,100
• Platelet count – 122,000
• Total bilirubin – 0.8 mg/dL
• Albumin – 2.9 g/dL
• AST – 37 UI/L
• ALT – 36 IU/L
Laboratories • Alk Phos – 135 IU/L
• GGT – 65 IU/L
• HBsAg, anti-HBc, and HCV-Ab were all negative
• HbA1c – 8.1%
• Fasting plasma glucose – 298 mg/dL
• HOMA-IR – 10.7

Adapted from Honma, Y., Sumida, K., Ogino, N., Kusanaga, M., Minami, S., Kumei, S., Matsuoka, H., Watanabe, T., Hiura, M., Abe, S., Shibata, M., & Harada, M. (2018). A Young Adult Patient with Nonalcoholic Steatohepatitis
Developed Severe Gastroesophageal Varices Associated with Severe Obesity and Diabetes Mellitus. Case reports in gastroenterology, 12(2), 487–496. https://doi.org/10.1159/000492423
Do you suspect
cirrhosis?
What other NIT’s would
you order?
Would you order a liver
biopsy to confirm
diagnosis?
 FIB-4 APRI FibroScan ® Agile 4

• 3.48 • 1.9 • kPa 21 • 0.61

• CAP 302
Agile 4 score: Identify cirrhosis in NAFLD patients. Echosens. (2021, July 9). Retrieved September 27, 2021, from https://www.echosens.com/products/agile-4/.
Boursier J. et. al. (2021). Prognostic Value of Agile Scores in Patients with Non Alcoholic Fatty Liver Disease. Paris NASH Meeting
 Imaging
• Abdominal ultrasonography:
• Showed brightness
• Mild hepatorenal echo contrast
• Surface irregularity
• Dullness of the edge of the liver
• Splenomegaly
• CT
• Enlargement of the left hepatic lobe
and splenomegaly

Adapted from Honma, Y., Sumida, K., Ogino, N., Kusanaga, M., Minami, S., Kumei, S., Matsuoka, H., Watanabe, T., Hiura, M., Abe, S., Shibata,
M., & Harada, M. (2018). A Young Adult Patient with Nonalcoholic Steatohepatitis Developed Severe Gastroesophageal Varices Associated with
Severe Obesity and Diabetes Mellitus. Case reports in gastroenterology, 12(2), 487–496. https://doi.org/10.1159/000492423
 • 61-year-old male
• F3 hepatic fibrosis
• Biopsy-confirmed NASH
Case 4 • T2D
• Obesity
• Dyslipidemia
Patient Adipose
Overload

Medical File Dislipide Obesi

Dyslipidemia
mia/CVD ty
CVD
Obesity T2D
T2D NASH
NAS
H
Future: How might
we treat based on
Current: No FDA
data generated to
approved
date and agents
treatments
currently being
studied?
 Fibrosis Puts Him at High Risk for Liver Outcomes

Severe Liver Disease[1] Liver-related Mortality[2]

120 50
104.5
Hazard Ratio vs Controls

42.3

Mortality Rate Ratio

100
40
80
30
60
20 16.69
40
9.57
20 14.3 10
1.9 1.7 5.5 1.41
REF
0 0
F0 F1 F2 F3 F4 F0 F1 F2 F3 F4

Hagström. J Hepatol. 2017;67:1265.

 Potential Targets: Bringing Him Back From the Brink

• F3 hepatic fibrosis Regress or prevent progression of fibrosis

• Biopsy-confirmed NASH Reverse NASH, a driver of fibrosis
• Obesity
• T2D
Improve metabolic state
• Dyslipidemia

1. Chalasani. Hepatology. 2018;67:328. 2. Angulo. Gastroenterology. 2015;194:389.

This patient’s
NASH Puts Him
at High Risk for • Patients with NAFLD more likely to
have morbidity and mortality from
Death CVD than from liver causes[1,2]
• The ideal NASH treatment must
also be heart healthy

1. Chalasani. Hepatology. 2018;67:328. 2. Angulo. Gastroenterology. 2015;194:389.

 Potential Targets: Managing Glycemic and CV Risk

• F3 hepatic fibrosis Regress or prevent progression of fibrosis

• Biopsy-confirmed NASH Reverse NASH, a driver of fibrosis
• Obesity Improve metabolic state
• T2D
Address glycemic control
• Dyslipidemia
Address—or at least do not worsen—
atherogenic risk

1. Chalasani. Hepatology. 2018;67:328. 2. Angulo. Gastroenterology. 2015;194:389.

Thank you