NAFLD Update - Chronic Liver Disease · PDF fileBACKGROUND • Nonalcoholic fatty liver...

NAFLD Update

Highlights from AASLD 2012

Nonalcoholic fatty liver disease without

cirrhosis is an emergent and independent risk

factor of hepatocellular carcinoma: A

population based study

Rubayat N. Rahman, Jamal A. Ibdah

Highlights of AASLD 2012

NAFLD

Abstract #97, AASLD 2012

BACKGROUND • Nonalcoholic fatty liver disease (NAFLD) including, nonalcoholic

steatosis and steatohepatitis (NASH), is the most common liver

disease with increasing incidence. NAFLD without cirrhosis is

rapidly evolving as a significant risk factor for primary

hepatocellular carcinoma (HCC) but the magnitude of this risk

has not been analyzed at a population level.

OBJECTIVE • Our goal is to analyze the association between HCC and NAFLD

with and without cirrhosis at national level.


Nonalcoholic fatty liver disease without cirrhosis is an emergent

and independent risk factor of hepatocellular carcinoma

Rahman, R. M., et al. Abstract 97; AASLD 2012


METHODS

• HCC cases reported between 1993-2007 in

Surveillance, Epidemiology, and End Results (SEER)-

Medicare database were identified. Demographics,

incidence, stage and grade of HCC due to

histopathologically confirmed NAFLD with and without

cirrhosis were compared with infection, alcohol and

other risk factors of HCC using SAS. Cases with more

than one risk factor were excluded. Logistic regression

for odds ratios adjusted for covariates and survival

analysis (age adjusted Kaplan Meier) were performed.





RESULTS SUMMARY

• A total of 17,895 cases of HCC were identified for analysis

• Among them 2,863 (16%) HCC were due to confirmed

NAFLD without evidence of other etiologies; 1,832 (64%)

with cirrhosis and 1,031 (36%) without cirrhosis.

• Among those without cirrhosis, 18% had steatosis without

NASH.

• Overall NAFLD was the third most common risk factor for

HCC after infection and alcohol etiologies.

• However, in US Asian/Pacific Islanders, it was the second

most common risk factor after infection.





RESULTS

* P value <0.01; NAFLD, Nonalcoholic fatty liver disease; HCC, Hepatocellular carcinoma; Fav., Favorable; USW, US Whites; Hisp, Hispanic; PI, Pacific Islander.

Comparison of cirrhotic and non-cirrhotic NAFLD HCC: SEER-

Medicare database1993-2007




NAFLD HCC (2,863)

N (%)

Sex (M/F)

%

Race Early Stage (I/II)

Fav. Grade (I/II) USW Black Hisp Asian/

PI

With Cirrhosis 1,832 (64%)

68/32 65% 14% 6% 12% 44% 56%

Without Cirrhosis

Total 1,031 (36%)

61/39 63% 15% 7% 11% 62%* 76%*

Steatosis Only

186 (18%)

59/41 59% 20% 6% 11% 64% 77%


RESULTS

a Includes only patients with ALT>ULN at baseline. b HBeAg-positive patients only. c No anti-HBs observed.

Trend of NAFLD Related HCC 1993-2007




1993-2007 Average Cases

per Year (N=2,863)


per Year (N=1,393)


per Year (N=1,470)

P value

NAFLD HCC with cirrhosis without Cirrhosis

191 122 69

174 123 51

210 122 88

<0.01 NS

<0.01

Steatosis Only 12 4 22 <0.01

CONCLUSIONS

• NAFLD HCC is significantly increasing over time

• NAFLD is independently associated with HCC without cirrhosis

• NAFLD HCC without cirrhosis is increasing more than NAFLD

HCC with cirrhosis

• Simple steatosis may be a significant risk factor of HCC without

NASH or cirrhosis

• Our data suggest unique underlying pathophysiology for

development of HCC in non-cirrhotic NAFLD





Association between statin use and

Nonalcoholic Fatty Liver Disease in a

population-based study

Edith M. Koehler, Catherine E. de Keyser, Jeoffrey N. Schouten, Bettina E. Hansen, Harry L. Janssen, Bruno H. Stricker


NAFLD


AIM

• To study the association of statin therapy with presence of

NAFLD, and elevated alanine aminotransferase (ALT)

concentrations in a large cross-sectional population-based study,

accounting for dose and duration of statin therapy and history of

cardiovascular disease (CVD).


Association between statin use and Nonalcoholic Fatty Liver

Disease in a population-based study

Koehler, E. M., et al. Abstract 825; AASLD 2012

METHODS • Data acquired from the Rotterdam Study, a population-based

cohort study of elderly persons.

• Nonalcoholic fatty liver disease (NAFLD) defined as presence of

fatty liver at ultrasonography (US) in the absence of known

secondary causes of fatty liver.

• Data on statin prescription was derived from automated

pharmacies.

• We used logistic regression analysis, adjusting for age, gender,

dose of statin therapy, alcohol consumption, presence of

metabolic syndrome (use of serum lipid reducing agents was

excluded in 2 criteria) and history of CVD, to investigate the

association of (duration of) current and past statin use with

NAFLD and elevated ALT.






RESULTS




Total (n=2,578)

Statin users (n=990)

Non-statin users (n=1,588)

Age (years) 76.5±5.9 76.8±5.5 76.2±6.2

Gender, female (%) 60.2 57.3 62.0

Drinks weekly 3.7±3.8 3.6±3.7 3.8±3.8

Metabolic syndrome (%) 40.1 52.5 33.8

Serum ALT (U/L) 20.3±10.7 21.6±11.3 19.5±10.2

History of CVD (%) 9.3 20.5 2.3

Baseline characteristics according to (ever) use of statin therapy


RESULTS




OR (95% CI) P value

Full Model

Never Use ref -

>730 days past use 1.14 (0.81-1.59) 0.5

1-730 days past use 1.22 (0.85-1.73) 0.3

1-183 days current use 0.91 (0.61-1.35) 0.6

184-365 days current use 0.98 (0.62-1.55) 0.9

>365 days current use 0.77 (0.47-1.25) 0.2

Logistic regression: the association between use of statin

therapy and presence of NAFLD


RESULTS




OR (95% CI) P value

Full Model

Never Use ref -

>730 days past use 1.28 (0.70-2.34) 0.4

1-730 days past use 1.68 (0.96-2.96) 0.1

1-183 days current use 1.51 (0.77-2.98) 0.2

184-365 days current use 1.16 (0.51-2.64) 0.7

>365 days current use 1.00 (0.41-2.43) 0.9

Logistic regression: the association between use of statin

therapy and elevation of ALT

CONCLUSIONS

• In this cross-sectional population-based study of elderly

persons, current use of statin therapy was associated with a

lower prevalence of NAFLD.

• Both past and current use of statin therapy was not

associated with elevated serum ALT concentrations.

• These findings suggest that statin therapy is safe in NAFLD,

and use of statins may have a beneficial effect on NAFLD.





Long-Term Mortality Outcome of Metabolically

Normal Individuals with Non Alcoholic Fatty

Liver Disease (NAFLD)

Zobair M. Younossi, Munkhzul Otgonsuren, Chapy Venkatesan, Alita Mishra, Fatema Nader


NAFLD


BACKGROUND • Non-alcoholic fatty liver disease (NAFLD) is an important cause

of chronic liver disease and is strongly associated with metabolic

syndrome (MetSynd).

• The long-term outcome for NAFLD patients remains

controversial

AIM • The goal of this study is to determine the long-term outcome of

NAFLD patients based on the presence or absence of

components of MetSynd in the U.S. population.


Long-Term Mortality Outcome of Metabolically Normal Individuals

with Non Alcoholic Fatty Liver Disease (NAFLD)

Younossi, Z. M., et al. Abstract 1472; AASLD 2012

METHODS • Data were obtained from the National Health and Nutrition Survey

(NHANES) III; 6,709 participants, 64% males, 76% white, 8% black,

16% other ethnicities, ages 20-74.

• NAFLD was defined as significant steatosis on hepatic ultrasound and

exclusion of other chronic liver diseases (N=1,448). Patients were

classified as metabolically normal vs. abnormal. Mortality in this cohort

(N=377) was determined through December 31, 2006.

• Laboratory profiles, body measurement examinations, and mortality

data were linked to self-reported questionnaires of demographic and

health risk information.

• Cox models were used to estimate hazard ratios and 95% confidence

intervals for all-cause, cardiovascular and liver-specific mortality

differences between metabolically abnormal and metabolically normal

cohorts.









• The study cohort included 1,448 (22%) NAFLD participants: of those

1,243 (79%) had MetSynd, 305 (21%) did not have metabolic syndrome

(MetSynd).

• NAFLD patients with MetSynd were 10 yrs older, less likely to be black,

and more likely to have DM, IR, hypertension, and central obesity than

metabolically normal NAFLD patients.

• The risk for liver-specific mortality was independently associated with

obesity, having the diagnosis of MetSynd, and elevated liver enzymes.

• The risk of cardiovascular mortality was independently associated with

older age and the diagnosis of NAFLD with MetSynd.

• In comparison to individuals without liver disease, metabolically normal

NAFLD patients showed no difference in all-cause, liver-related, or

cardiovascular mortality.

RESULTS




Factors Factors HR (95% CI)

OVERALL Age (years) 1.07 (1.06-1.09)

Metabolic syndrome 2.16 (1.15-4.03)

Race Black Other

1.42 (1.04-1.95) 0.37 (0.12-1.12)

Smoking status Never Current Former

Reference 54.66 (25.44-117.43)

1.24 (0.77-2.01)

WHITE Person-Years 19,728

Number of deaths 288

Age 1.08 (1.07-1.10)

Metabolic syndrome 2.57 (1.24-5.32)

BLACK Person-Years 8,382

Number of deaths 77

Age 1.07 (1.06-1.09)

Male 2.16 (1.15-4.03)

Factors associated with overall mortality in NAFLD

CONCLUSIONS • Diagnosis of having metabolic syndrome and NAFLD is an

independent predictor of all-cause, liver-specific, and

cardiovascular mortality.

• In contrast, mortality of metabolically normal NAFLD patients is

similar to the cohort without liver disease.





Dietary changes in patients with non-alcoholic

fatty liver disease are independently

associated with improvement in liver function

tests

Francisco Barrera, Jacob George, David van der Poorten, Alexis St. George


NAFLD


BACKGROUND • Non-alcoholic fatty liver disease (NAFLD) is the hepatic

manifestation of the metabolic syndrome.

• Clinical and laboratory data support the role of dietary

interventions for treating NAFLD).

• However, the specific dietary modifications that benefit these

patients have not been thoroughly examined.

AIM • To investigate the relationship between changes in diet and

improvement in liver function tests in NAFLD subjects

participating in a lifestyle intervention program.


Dietary changes in patients with NAFLD are independently

associated with improvement in liver function tests

Barrera, F., et al. Abstract 1484; AASLD 2012

METHODS

• Data was analyzed from 106 NAFLD patients with abnormal liver

enzymes who participated in a 3 month lifestyle intervention.

• Alanine aminotransferase (ALT), aspartate aminotransferase (AST),

gamma glutamyl transpeptidase (GGT), and 3 day food records at

baseline, 3 and 6 months were analyzed.

• Pearson correlation analysis between changes in diet and liver enzymes

were undertaken at 3 and 6 months adjusted for weight and total

physical activity change. Dietary changes with significant correlations at

p <0.1 were included in multi-linear regression analysis.





Independent associations between changes in diet and liver

function tests




A

LT

at

6 M

(% r

esp

ect

of b

ase

line)

100

50

0

-50

-100-300 -200

Carbohydrate intake at 3 m (g/day)

-100

r = 0.25

p = 0.02

0 100

A

100

50

0

-50

-100-30 -20 -10

Carbohydrate intake at 6 m

(% of total kjle per day)

0

r = 0.39

p = 0.01

10 20 30

C

100

50

0

-50

-100-10 -5

PUFA intake at 3 m

(%of total kjle per day)

0 5

r = -0.24

p = 0.02

10 15

B

GG

T a

t 6 m

(%

)

100

50

0

-50

-100-60 -40 -20

MUFA Intake at 6 m (g/day)

0

r = -0.32

p = 0.01

20 40

D

AS

T a

t 6 M

(% o

f b

ase

line

)

200

150

100

50

0

-50

-100-30 -20 -10

Carbohydrate intake at 6m

(% of total kjle per day)

0

r = 0.26

p = 0.03

2010 30

E

% %





β 95% CI P value

Change of GGT at 3 months follow up Carbohydrate intake (gr/d) PUFA intake (% of total kjle per day)

0.2

-0.19

0.03

0.006

0.03 0.04

Change of GGT at 6 month follow up Carbohydrate intake (% of total kjle per day)

0.42

0.347

0.001

Change of ALT at 6 month follow up Carbohydrate intake (% of total kjle per day)

0.31

0.531

0.01

Change of AST at 6 month follow up MUFA intake (gr/day)

-0.33

0.3

0.01

Multivariate analysis correlates dietary changes with

improvement in metabolic parameters and liver function tests.

GGT, gamma glutamyl transpeptidase, ALT, alanine aminotransferase , AST, aspartate aminotransferase (AST), MUFA, monounsaturated fatty acid.

CONCLUSIONS

• Specific dietary modifications were associated with

improvements in liver tests independent of physical activity and

weight loss changes.

• Decreases in carbohydrate intake and increases in PUFA intake

were independently associated with a reduction of GGT at 3

months.

• Decreases in carbohydrate and increases in MUFA intake were

independently associated with a decrease in ALT and AST

respectively at 6 months.

• These reports are important for the future development of

specific dietary recommendations for the treatment of NAFLD.





Non-alcoholic fatty liver disease (NAFLD)

influences on cardiovascular disease:

Meta-analysis

Javier Ampuero, Rocío Gallego-Durán, Manuel Romero-Gómez


NAFLD


AIM • To perform a meta-analysis to evaluate the influence of NAFLD in the

promotion of subclinical cardiovascular disease.

METHODS • We reviewed and identified studies in Pubmed and EMBASE to

September 2012. According to inclusion and exclusion criteria, we

selected 15 studies which were classified in 2 subgroups.

• NAFLD was evaluated by ultrasound in all studies. To assess subclinical

atherosclerosis, we selected studies (6) with carotid intima-media

thickness (CIMT), and to determine CVD, we selected studies (9) with

ischaemic heart disease.

• The random effect model of der Simonian and Laird method were used

for heterogeneous studies using the Meta-Disc 1.4 software, Madrid

Spain.


Non-alcoholic fatty liver disease (NAFLD) influences on

cardiovascular disease: Meta-analysis

Ampuero, J., et al. Abstract 1485; AASLD 2012





RESULTS

• In the subclinical atherosclerosis group (6 studies, 1599

patients), data analysis showed subjects with NAFLD presented

34% (282/832) of subclinical atherosclerosis; in patients without

NAFLD, it was detected in 19.3% (148/767), with odds ratio 2.15

(95% CI: 1.69-2.73).

• In the CVD subgroup (9 studies, 25,658 patients), subjects with

NAFLD presented 19.8% (1,594/8,065) of CVH, while in patients

without NAFLD, CVD was detected in 8.15% (1,433/17,593),

with odds ratio 2.99 (95% CI: 1.95-4.60).

CONCLUSIONS

• NAFLD increases the risk of subclinical atherosclerosis and

cardiovascular disease.

• This result provides a new dimension in clinical practice, as the

correct management of this kind of patients will enable to modify

the natural history both non-alcoholic fatty liver disease and

cardiovascular disease.





Hypovitaminosis D associated with more

advanced non-alcoholic fatty liver disease

Jaividhya Dasarathy, Pranav Periyalwar, Sanath Allampati, Carol A. Hawkins, Patricia T. Brandt, Amer Khiyami, Arthur J. McCullough , Srinivasan Dasarathy


NAFLD


BACKGROUND • Non Alcoholic Fatty Liver Disease (NAFLD) is the most common form of

liver disease. One of the nutritional abnormalities recognized in these

patients is hypovitaminosis D.

• Animal studies have suggested that hypovitaminosis D results in more

advanced forms of NAFLD.

• Hypovitaminosis D is also common in obesity and is believed to

contribute to insulin resistance: an important underlying factor in the

pathophysiology of NAFLD.

AIM • We therefore performed a prospective study to determine the

associations among plasma vitamin D concentration, severity of disease

in NAFLD and body composition


Hypovitaminosis D associated with more advanced non-alcoholic

fatty liver disease

Dasarathy, J., et al. Abstract 1486; AASLD 2012

METHODS

• Plasma concentrations of vitamin D3 were quantified in 87

biopsy proven patients with NAFLD:51 patients with NASH and

36 subjects with hepatic steatosis alone.

• Healthy subjects (n=32) without disease formed the control

group.

• Body composition was quantified by bioelectrical impedance

analysis.



fatty liver disease



RESULTS • Plasma vitamin D3 concentration were significantly lower in NAFLD

(24.0±10.7 ng/ml) compared to healthy controls (28.3±10.6 ng/ml).

• Higher NAFLD activity scores were associated with lower plasma

concentration of vitamin D3. Subgroup analysis amongst patients with

NAFLD showed that patients with NASH had significantly lower vitamin D3

levels than those with steatosis alone (21.9±9.0 vs. 26.9±12.2 ng/ml).

• Low concentrations of vitamin D were associated with greater severity of

steatosis, hepatocyte ballooning and fibrosis (p<0.05). Although body fat

mass was inversely correlated (p=0.008) with vitamin D concentration, on

multivariate regression analysis, severity of hepatic steatosis (p=0.01) and

inflammation (p=0.04) were independently associated with low vitamin D

concentrations.

• Plasma vitamin D (p=0.002) and insulin concentrations (p=0.048) were

independent predictors of the NAFLD activity score on biopsy.


fatty liver disease


CONCLUSIONS

• Plasma vitamin D3 concentration were significantly lower in

NAFLD and correlated inversely with severity of liver disease.

• Subjects with NAFLD had significantly higher whole body fat

mass and fat/fat free mass ratios compared to controls.

• Whole body fat mass correlated inversely with plasma vitamin

D3 concentration in both NAFLD and control patients.

• Routine screening for hypovitaminosis D3 supplementation in

NAFLD and replacement therapy should form part of good

clinical practice and standard of care.



fatty liver disease


The natural history of nonalcoholic fatty liver

disease in children and adolescents assessed

in placebo recipients in the TONIC trial

Joel E. Lavine, Katherine P. Yates, Elizabeth M. Brunt, David E. Kleiner, Jeffrey B. Schwimmer, Karen F. Murray, Jean P. Molleston, Stephanie H. Abrams, Philip

Rosenthal, Rohit Loomba, Aynur Unalp, James Tonascia


NAFLD


BACKGROUND • Nonalcoholic fatty liver disease is the most prevalent chronic pediatric

liver disease.

• Very little is published on the natural history of NAFLD in children and

adolescents. Given the increased genetic and environmental penetrance

likely associated with early onset, factors influencing consequence and

rate of progression need to be identified.

• The placebo arm of the NASK CRN TONIC trial offers a unique

opportunity to study the histological disease progression using repeat

biopsies in a cohort of children provided uniform standard of care (SOC).

AIM • This study characterizes placebo subjects in the “Treatment of NAFLD in

Children” (TONIC) trial, assessing factors associated with histological

and clinical improvement and worsening (JAMA 2011; 305:1659-68).


The natural history of nonalcoholic fatty liver disease in children

and adolescents assessed in placebo recipients in the TONIC trial

Lavine, J., et al. Abstract 1520; AASLD 2012

METHODS

• The cohort consisted of 58 subjects ages 8-17 years with biopsy-proven

NAFLD.

• Assessments included changes in histology in relation to age, gender,

race, and changes in BMI z-score, insulin resistance, body composition,

diet, activity and routine laboratory assessments in children provided

uniform, standard-of-care advice on lifestyle.

• BMI z-scores were based on the sex-specific 2000 CDC population

reference curves.





RESULTS

• Of 58 enrollees, 47 underwent repeat liver biopsy at 96 weeks. Of these

47, 8 initially had NAFLD without NASH, 22 borderline NASH and 17

definite NASH with a NAFLD Activity Score (NAS) mean of 4.6.

• Only 26% of children with NAFLD had a histological response (NAS

decrement of ≥2 with no worsening of fibrosis) after 96 weeks of SOC

treatment.

• Responders had greater decreases in ALT and AST levels and

improved insulin resistance as measured by HOMA-IR. The most

significant association with change in NAS was change in BMI z-score

(p=0.001).





RESULTS (cont’d)

• Resolution of NASH was found in 28% and improvement in steatosis,

inflammation and ballooning in 40%, 43% and 21%, respectively.

Forty% had an improvement in fibrosis by at least one point and 26%

had worsening; none developed cirrhosis.

• Factors associated with improvement in fibrosis stage were non-white

race (white versus non-white, p=0.02), lower baseline BMI z-score (≥2.5

versus <2.5, p=0.06) and lower baseline serum LDL-cholesterol.

• Five of the 58 children developed diabetes and these 5 had significantly

higher baseline BMI z-scores (≥2.5 vs. <2.5, p=0.04), higher baseline

HbA1c levels (5.6% vs. 5.2%, p=0.01) and higher baseline ballooning

scores (1.7 vs. 0.7, p=0.02).





CONCLUSIONS

• About one-quarter of children with NAFLD demonstrated histological

response and resolution of NASH with standard-of-care management.

Those with lower BMI z-score at baseline and decrease in scores during

follow-up were more likely to demonstrate “response” and diminished

fibrosis stage. Responders demonstrated larger decrements in serum

aminotransferases, HOMA-IR, alkaline phosphatase and BMI z-score

over the study interval. The incidence of diabetes in 10% of this cohort

suggests that children with NASH should be followed closely for this

problem.





Factors Predict Normal Histology in Patients

at High Risk for Non-Alcoholic Fatty Liver

Disease

Kathleen E. Corey, Joseph Misdraji, Hui Zheng, Kyle Malecki, Jacob Kneeman, Louis G. Gelrud, Raymond T. Chung


NAFLD


BACKGROUND

• Non-alcoholic fatty liver disease (NAFLD) is the most common cause of

liver disease in the United States.

• NAFLD is associated with increased all cause mortality.

• No screening guidelines for NAFLD exist.

AIM

• This study was designed to identify predictors of normal liver histology in

a high risk population to guide future screening.


Factors Predict Normal Histology in Patients at High Risk for Non-

Alcoholic Fatty Liver Disease

Corey, K.E., et al. Abstract 1524; AASLD 2012

METHODS

• Patients undergoing weight loss surgery at Bon Secours Healthcare in

Richmond, Virginia, from August 2009 through July 2011 were included.

• Exclusion criteria: patients with other chronic liver disease (assessed by

viral serologies, autoimmune markers, iron studies and liver biopsy),

with excess alcohol use (defined as >2 drinks per day for men and >1

drink per day for women).

• All subjects underwent liver biopsy at the time of weight loss surgery;

reviewed by a single blinded pathologist (JM) and scored according to

the NASH CRN scoring system.









• 159 patients were included in the study.

• Forty nine patients (30.8%) had normal liver histology, while 110

patients met criteria for NAFLD.

• Liver histology characteristics for NAFLD group:

Study Population Clinical Characteristics

NAFLD (n=110) n, (%)

Fibrosis stage 0 1 2 3 4

51 (46.8) 46 (42.4)

8 (7.3) 1 (0.9) 3 (2.8)

NASH Activity Score 0-2 3-4 5-8

45 (46.3) 35 (32.4) 28 (25.9)





Normal NAFLD P Value

Mean ALT, Units/mL (SD) 16.9 (7.9) 28.3 (27.1) 0.0042

Mean glucose, mg/dL (SD) 105.8 (35.3) 126.1 (41.1) 0.004

Mean insulin, µU/mL (SD) 20.8 (15.1) 32.4 (29.0) 0.01

HOMA-IR, (SD) 2.5 (1.6) 3.5 (1.7) 0.001

C Reactive Protein (SD) 1.1 (0.96) 1.0 (0.75) 0.64

Mean Total Cholesterol, mg/dL 170.6 (32.7) 161.3 (40.2) 0.16

Mean HDL, mg/dL 49.5 (14.5) 42.3 (11.1) 0.009

Mean LDL, mg/dL 98.2 (24.3) 94.2 (32.7) 0.45

Mean Triglycerides, mg/dL 114.6 (64.8) 133.4 (90.2) 0.19

Mean Non-HDL Cholesterol, mg/dL 121.1 (30.4) 119.0 (36.5) 0.73

Metabolic Characteristics of Patients with Normal

Histology and NAFLD





• Absence of obstructive sleep apnea - OR of 5.6 (95% CI 2.0-16.1)

• Black race - OR of 6.8 (95% CI 2.4-18.9)

• Low HOMA-IR – OR of 1.4 (95% CI 1.03-1.9)

• Low ALT – OR of 1.4 (95% CI 1.01-1.1)

• Low HDL was associated with decreased likelihood of normal liver

histology - OR of 0.38 (95% CI 0.05-0.83)

Factors that Predicted Absence of NAFLD





• Race, obstructive sleep apnea, HOMA-IR, and ALT predicted the presence of

normal histology with an area under the ROC curve of 0.85

• Addition of diabetes mellitus, glucose, insulin, age, gender, the presence of

hyperlipidemia or HDL did not improve this model.

• Our predictive score is: Healthy Liver Score=

1.8 (race) – 1.8 (sleep apnea) – 0.35 (HOMA-IR) – 0.05 (ALT) + 1.5

• The Healthy Liver Score ranged from -12 to 3 in our cohort

Score to Predict Normal Histology

NAFLD Histology Normal Histology -12 3 0

• A score of ≥0 maximized the combined sensitivity and specificity for predicting

normal liver histology (sensitivity 59.5%; specificity, 92.7%).

• High specificity minimizes the risk of falsely predicting normal liver histology,

suggesting it’s value as a tool to refer patients for NAFLD screening.

CONCLUSIONS

• Our study identified a new factor associated with normal histology in a

group at high risk for NAFLD: absence of OSA

• Our study confirmed previously identified factors protective against the

development of NAFLD, including: black race, low HOMA-IR, low ALT.

• The identification of protective factors offers a unique insight into the

forces that ameliorate or modulate the driving forces underlying NAFLD.

• Identification of the mediators of protection in time could lead to rational

approaches to prevention or treatment of patients at high risk for

NAFLD.





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