What to do about the high ALT picked up at the annual .../media/website/gps... · Source:...
Transcript of What to do about the high ALT picked up at the annual .../media/website/gps... · Source:...
![Page 1: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/1.jpg)
What to do about the high ALT picked up
at the annual review
Dr Michael Yee Consultant in Diabetes and Endocrinology
![Page 2: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/2.jpg)
Mrs DC
![Page 3: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/3.jpg)
HPC
![Page 4: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/4.jpg)
PMH
Type 2 Diabetes (decades)
Regular retinal screening
No foot complications/neuropathy
No significant nephropathy
Obesity
Psoriasis
Never had methotraxate
Hypertension
Carpal Tunnel Syndrome
![Page 5: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/5.jpg)
DH
Aspirin 75mg od
Irbesartan 300mg od
Doxazosin MR 8mg od
Indapamide MR 1.5mg od
Amlodipine 10mg od
Glimepiride 1mg od (previously 4mg od)
Exenatide 10ug bd
Simvastatin 40mg od
![Page 6: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/6.jpg)
O/E
![Page 7: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/7.jpg)
Investigations
Na 138
K 4.4
Ur 6.0
Cr 55
ALT 30
AST 25
gGT 24
Bil 12
ALP 65
Alb 40
INR 1.0
HbA1c 7.1 (54)
Chol 5.33
HDL 1.06
TG 1.82
WCC 6.0
Hb 14.0
Plts 148
![Page 8: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/8.jpg)
Investigations
USS (08/07/09):
1.3cm calculus in neck of
gallbladder
Normal liver parenchyma
Normal echotexture and
contour
CLD screen:
Hep B sAg Neg
Hep C Ab Neg
LAA Neg
a1AT 1.3
Ferritin 8
TSH 1.9
![Page 9: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/9.jpg)
Angulo et al. Hepatology 2007
![Page 10: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/10.jpg)
• Fibroscan 25.1kPa
![Page 11: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/11.jpg)
NAFLD • Non-Alcoholic Fatty Liver Disease
is an increasingly recognised
condition that may progress to
end-stage liver failure
• Ludwig in 1980 introduced the
term “Non-Alcoholic
Steatohepatitis”
• Prevalence is increasing
worldwide with increasing obesity
![Page 12: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/12.jpg)
Prevalence of abnormal LFT’s
• Abnormal LFT’s – 8% population
(NHANES III)
• An identifiable cause was found in 31%
• Remainder probably had NAFLD
Clark et al Am J Gastroenterol 2003:98 960-7
![Page 13: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/13.jpg)
Prevalence
• Using traditional upper limits for ALT 3-5%
of populations
• New lower ALT limits (men < 30; women
<19) 12-14%
• Using ultrasound 20%
• (In obesity and diabetics 60-70%)
Prati et al Ann Intern Med 2002:137 1-10
Ruhl et al Gastroenterology 2003:124 71-9
![Page 14: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/14.jpg)
Prevalence of NAFLD in NHANES over
1988 – 2008
02468
1012141618
All chronicliver
disease
Hepatitis B Hepatitis C ALD NAFLD
1988-94
1999-04
2005-08
Younossi et al. Clin Gastro Hepatol. 2011(9)
524-30
![Page 15: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/15.jpg)
(Day, Liver Int., 2006)
NORMAL
STEATOSIS
NASH
CIRRHOSIS
12-20%
5-15%
0-12%
![Page 16: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/16.jpg)
(Day, Liver Int., 2006)
NORMAL
STEATOSIS
NASH
CIRRHOSIS
12-20%
5-15%
0-12%
GENES
Steatosis
Genes
Oxidative Stress,
Cytokine,
Endotoxin-related
Genes
Fibrosis Genes
![Page 17: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/17.jpg)
Genotypes
• PNPLA3 variant I148M
• TM6FS2 variant E167k
![Page 18: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/18.jpg)
(Day, Liver Int., 2006)
NORMAL
STEATOSIS
NASH
CIRRHOSIS
12-20%
5-15%
0-12%
ENVIRONMENT Diet, Obesity, DM
SIBO,
Endotoxin,
TNFa,
ROS
SIBO,
Endotoxin,
TNFa,
ROS
![Page 19: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/19.jpg)
Environment
• Fructose
• Processed foods
![Page 20: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/20.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 1985
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14%
![Page 21: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/21.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 1986
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14%
![Page 22: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/22.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 1987
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14%
![Page 23: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/23.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 1988
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14%
![Page 24: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/24.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 1989
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14%
![Page 25: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/25.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 1990
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14%
![Page 26: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/26.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 1991
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19%
![Page 27: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/27.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 1992
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19%
![Page 28: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/28.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 1993
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19%
![Page 29: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/29.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 1994
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19%
![Page 30: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/30.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 1995
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19%
![Page 31: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/31.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 1996
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19%
![Page 32: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/32.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 1997
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% ≥20%
![Page 33: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/33.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 1998
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% ≥20%
![Page 34: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/34.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 1999
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% ≥20%
![Page 35: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/35.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 2000
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% ≥20%
![Page 36: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/36.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 2001
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% 20%–24% ≥25%
![Page 37: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/37.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
Obesity Trends* Among U.S. Adults BRFSS, 2002
No Data <10% 10%–14% 15%–19% 20%–24% ≥25%
![Page 38: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/38.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 2003
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% 20%–24% ≥25%
![Page 39: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/39.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 2004
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% 20%–24% ≥25%
![Page 40: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/40.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 2005
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
![Page 41: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/41.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 2006
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
![Page 42: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/42.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 2007
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
![Page 43: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/43.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 2008
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
![Page 44: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/44.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 2009
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
![Page 45: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/45.jpg)
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 2010
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
![Page 46: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/46.jpg)
Pathogenesis
![Page 47: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/47.jpg)
Clinical features
• Symptoms
– Asymptomatic – 65%
– Fatique
– Right upper quadrant pain
• Signs
– Hepatomegaly
– Acanthosis nigricans
– Signs of chronic liver disease
![Page 48: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/48.jpg)
Biochemistry
• Usually elevated ALT
• AST/ALT < 1
• GGT variable
• Platelets
• Clotting abnormalities
![Page 49: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/49.jpg)
Diagnosis
![Page 50: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/50.jpg)
Imaging
• Ultrasound – Increased echogenicity to
kidney
• CT – Low density to spleen
• MRI – In and Out Phase ECHO
• MRS – Quantative assessment of steatosis
• No imaging modality can differentiate the
different stages of NAFLD
Saadeh et al Gastroenterology 2002:123 745-50
![Page 51: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/51.jpg)
Liver Biopsy
• Confirm diagnosis
• Staging and Prognosis
• Management
![Page 52: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/52.jpg)
Liver Biopsy – Normal and
Steatosis
![Page 53: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/53.jpg)
Liver Biopsy - Steatohepatitis
![Page 54: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/54.jpg)
Liver Biopsy - Fibrosis
![Page 55: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/55.jpg)
ALT may not be reliable marker
of activity
Mofrad et al Hepatology 2003:37 1286-92
![Page 56: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/56.jpg)
Prognosis based on histology
0
5
10
15
20
25
30
Type 1 Type 2 Type 3 Type 4
Perc
en
tag
e (
%)
Liver Biopsy
Cirrhosis
Liver rel Death
Matteoni et al Gastroenterology 1999:116 1413-19
![Page 57: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/57.jpg)
Survival rates based on liver
histology
Matteoni et al Gastroenterology 1999:116 1413-19
![Page 58: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/58.jpg)
Hepatocellular carcinoma
Wong et al, Hepatology 2014 (59) 2188-95
![Page 59: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/59.jpg)
Hepatic cellular carcinoma
Cirrhosis (7%)
NASH (15-25%)
Simple Steatosis (12-40%)
![Page 60: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/60.jpg)
Non-Invasive Methods of
Staging
• Age > 45
• BMI > 30
• AST:ALT ratio > 1
• T2DM
• Obstructive sleep apnoea
Angulo et al Hepatology 1999:30 1356-62
![Page 61: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/61.jpg)
Non-Invasive Methods of
Staging
• NAFLD Fibrosis score
– Age, AST/ALT ratio, BMI, platelets, albumin,
glycaemia
• ELF Score
– Hyaluronic acid, tissue inhibitor of matrix
metalloproteinase 1, amino terminal peptide of
pro-collagen III
Angulo et al Hepatology 2007:45 846-54
Guha et al Hepatology 2008:47 455-60
![Page 62: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/62.jpg)
Non-Invasive Methods of
Staging
• Imaging techniques have limited use in
early disease
• Transient elastography (Fibroscan) – BMI
< 28
• Controlled attenuation parameter (CAP)
Foucher et al Eur J Gastroenterol Hepatol 2006:18 411-2
![Page 63: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/63.jpg)
Weight management
• Lifestyle modification – Improvement in
LFT’s and a few studies shows histological
improvement with gradual moderate (10%)
wt loss (< 1.6kg/wk)
• Orlistat – Improvements in LFT’s and U/S
![Page 64: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/64.jpg)
Weight management
• Bariatric surgery
– Significant weight loss 60%
– Early techniques of jejuno –ileal bypass were
associated with acute liver failure and massive
steatosis
– Newer surgical techniques are associated with
histological improvements in liver biopsy
![Page 65: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/65.jpg)
Insulin sensitiser
• Metformin – some conflicting evidence
regarding benefits on steatosis
• Thiazolidendione – all studies have
demonstrated improvements in steatosis in
addition to histology.
– Recent rosiglitazone meta-analysis
– Stopping treatment leads to recurrence
Bugianesi et al Am J Gastro 2005:100 1082-90
Belfort et al NEJM 2006:355 2297-307
![Page 66: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/66.jpg)
Lipid Lowering Therapy
• Fibrates – Good animal data but limited
human data. Improvements have been
shown with gemfibrozil, but no significant
changes with clofibrate
• Statins
– No data on statins
– Increased CVD risk
– No evidence of increased hepatoxicity
![Page 67: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/67.jpg)
Anti-hypertensive agents
• Renin-Angiotensin System
– Lorsartan has been demonstrated to improve
liver fibrosis
![Page 68: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/68.jpg)
Liver directed treatment
• Ursodeoxycholic acid – promising data on
LFT’s and histology
• Anti-oxidants – no evidence of benefit from
Vitamin C and E
• Rimonabant – in addition to effects from
weight loss, inhibition of CB-1 receptor anti-
fibrotic actions
• TNF α inhibitors (pentoxyfylline) – promising
results
![Page 69: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/69.jpg)
Liver transplant
• Decompensated cirrhosis
• 50% have recurrence NASH in 4 years
![Page 70: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/70.jpg)
Multidisciplinary clinics – 5 year
follow up data
01020304050607080
Improvementin ALT
Normalisationin ALT
Reduction inweight (5%)
Reduction inweight (10%)
Percentage
Percentage
Cobbold et al Frontline Gastro 2013 (4) 263-9
![Page 71: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/71.jpg)
Clinical Guidelines
![Page 72: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/72.jpg)
Summary
• NAFLD is increasingly prevalence
• It can lead to cirrhosis and HCC
• Treatments are currently limited but likely
to increase
![Page 73: What to do about the high ALT picked up at the annual .../media/website/gps... · Source: Behavioral Risk Factor Surveillance System, CDC. Obesity Trends* Among U.S. Adults BRFSS,](https://reader034.fdocuments.in/reader034/viewer/2022051911/6001eb61a66c8a49a831134c/html5/thumbnails/73.jpg)
Specialist Metabolic and
Hepatology Clinic
• Referrals to Dr Michael Yee (Metabolic
Medicine Unit) or Dr Pinelopi Manousou
(Hepatology Unit)
• Non-alcoholic and viral hepatitis negative