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 2010 59: 969-974 Presented by Cho, Chang-hyun

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 `.

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

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

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 `.

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

NAFLD activity score

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

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

Results

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

(HEPATOLOGY 2009;50:1072-1078.)

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%)

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

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).

Table 5 Factors associated with fibrosis progression

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.

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

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