1. Jun Yu,1,2 Joseph Jao-Yiu Sung,1,2 Henry Lik-Yuen Chan1,2
Original article
Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years
Vincent Wai-Sun Wong,1,2 Grace Lai-Hung Wong,1,2 Paul Cheung-Lung Choi,3
Anthony Wing-Hung Chan,3 Mia Ka-Po Li,1,2 Hoi-Yun Chan,1,2 Angel Mei-Ling Chim,1,2
Jun Yu,1,2 Joseph Jao-Yiu Sung,1,2 Henry Lik-Yuen Chan1,2
Gut :
Presented by Cho, Chang-hyun

2. Background
NAFLD
NASH
Esophageal varices for high bleeding rates and mortality , primary prevention indication.
BB and EVL are used for primary prevention of VB in patients for LC with EV.
The author sought to determine whether and under what condition of BB Tx or EVL more `cost effective `.

3. 3.5 years later: Cirrhosis Hepatocellular cancer
NASH progression
3.5 years later: Cirrhosis
NASH
Hepatocellular cancer

4. The Natural History of NAFLD
9-46%PREVALENCE
Stable
NASH
6-13%PREVALENCE
NASH/
Cryptogenic
Cirrhosis
related
complications
including
HCC
Progression
of Fibrosis
Stable or
Regression
Majority
9-20%
26-37%
52-79% ?%
40-60% over
5-7 years
The Natural History of NAFLD

5. Aims
To investigate disease progression in Pts with different degrees of NAFLD activity
Prospective study with paired liver Bx 3 years apart
Factors associated with disease
Adipokines were also studied
Esophageal varices for high bleeding rates and mortality , primary prevention indication.
BB and EVL are used for primary prevention of VB in patients for LC with EV.
The author sought to determine whether and under what condition of BB Tx or EVL more `cost effective `.

6. Mechanisms of Hepatic Steatosis in Obesity
NASH
Adipose tissue
Obesity
Type 2 diabetes
Insulin resistance
ROS
PAI-1
FFA
MCP-1
Leptin
ETOH
TNF
Adiponectin
ACC
FAS
SCD
Resistin
 Glucose
ChREBP
SREBP-1c
SREBP-2
FFA
 Insulin
Liver steatosis
ApoB+ TG CH
Steatohepatitis
ROS
Inflammation
Apoptosis/necrosis
Fibrosis
GSH
Liver
VLDL
Fernandez-Checa, Int Hepatol Update 2007;21

7. NAFLD activity score

8. Simple steatosis ; fatty liver alone without necroinflammation
Borderline NASH ; lobular inflammation but not to the degree of NASH
NASH ; hepatocytes ballooning or intralobular hepatocyte necrosis

9. Patients and methods 54 Pts from Prince of Wales Hospital, Hong Kong
Inclusion ; aged over 18 years with biopsy-proven NAFLD
Exclusion
men who consumed more than 20 g of alcohol / day
women who consumed more than 10 g/day
Patients with positive HBs Ag or anti-HBC Ab, ANA titre >1/160 or histological features of other liver diseases were excluded.
Pts with secondary causes of liver steatosis

10. Results

11. Table 1 Clinical characteristics of 52 Pts with NAFLD at baseline and month 36

12. (HEPATOLOGY 2009;50: )

13. Table 2 Distribution of disease activity at baseline and month 36
16/29 (58%)
Table 3 Distribution of fibrosis stage at baseline and month 36
25 (48%)
14 (27%)
13 (25%)

14. Table 4 Factors associated with increased NAFLD activity score from baseline to month 36

15. By multivariate analysis
Increase in BMI remained as an independent factor associated with worsened NAS (OR for each 1 kg/m2 increase, 1.9; 95% CI 1.2 to 3.1; p=0.012)
CK-18 ; correlated with NAS both at baseline and month 36
The change in NAS had correlation with change in serum CK-18 fragment levels (R=0.51, p<0.001).

16. Table 5 Factors associated with fibrosis progression

17. By multivariate analysis
Increase in waist circumference (adjusted OR for each 1 cm increase, 1.3; 95%CI 1.1 to 1.5; p=0.002)
High baseline LDL (adjusted OR for each 1 mmol/l increase, 2.7; 95% CI 1.2 to 6.1; p=0.019)
 Independent factors associated with a worsened fibrosis stage.

18. Among 13 patients with simple steatosis at baseline
2 (15%) had a normal liver at month 36,
3 (23%) continued to have simple steatosis
5 (39%) developed borderline NASH
3 (23%) developed NASH
Among 22 patients with borderline NASH at baseline
4 (18%) had simple steatosis
13 (59%) had borderline NASH at month 36
5 (23%) developed NASH
Among 17 patients with NASH at baseline
10 (59%) continued to have NASH
6 (35%) had borderline NASH at month 36
1 (6%) patient regressed to simple steatosis

19. Conclusions
Patients with simple steatosis may still develop NASH and fibrosis progression
Weight reduction is associated with non-progressive disease
All patients with NAFLD should undergo periodic assessment and lifestyle modification