EFFECT OF CHRONIC LIVER DISEASE ON LIPID PROFILE – AN ANALYTICAL STUDY - PowerPoint Presentation

Slide1

EFFECT OF CHRONIC LIVER DISEASE ON LIPID PROFILE – AN ANALYTICAL STUDY

DR

. THINAKAR MANI

B

DM SENIOR RESIDENT

INSTITUTE OF MEDICAL GASTROENTEROLOGY

MADRAS MEDICAL COLLEGE

CHENNAI,TAMILNADU

INDIA

Slide2

INTRODUCTION

Lipids are an integral part of the body, providing structural support to cell membranes, myelin coating to neurons besides their use as a biological fuel source(1

).

They also appear to play a significant role in cell

signaling

as well as mitochondrial oxidative functions. Disruptions in their metabolism most commonly manifest as atherosclerotic vascular disease which can have serious clinical implications.

Slide3

The Liver is well established as a major site of lipid metabolism.

It

contributes to nearly every step right from the initial digestion and absorption of fats through biliary metabolism, on to

apolipoprotein

production, fatty acid synthesis and finally even in elimination of cholesterol from the body.

Hence

it is a logical assumption that perturbations of hepatic parenchymal function can have a profound effect on lipoprotein synthesis and lipid metabolism as a consequence.(2)

Slide4

Although studies have been previously carried out to assess the effect of cirrhosis on lipid profiles, they have generally been of much smaller cohorts and without the help of a larger healthy control group.

The

general consensus of these studies has been that the level of plasma lipids and lipoproteins tend to decrease with increasing severity of liver disease (3,4).

Slide5

In this study we have

analyzed

the effect of liver dysfunction as determined by Child-

Turcotte

-Pugh(CTP) or Model for end stage liver disease(MELD) scores will have on the extent of lipid profile alterations(5,6

).

Additionally we have also looked at the effect of the etiological cause of CLD on lipid profiles as a result of their varied effects on hepatic parenchyma. Finally we have

slected

250 age-and sex-matched healthy individuals, lipid parameters compared with CLD patients.

Slide6

MATERIALS AND METHODS

This analytical cross sectional study was conducted at a tertiary care referral

center

– Madras Medical College, Institute of Gastroenterology, from 2015 to 2017.

250

consecutive patients were enrolled after excluding those with potential confounders that could affect lipid levels.

These

included patients with diabetes mellitus, cancer, renal failure, acute pancreatitis, and those with a history of

hyperlipidemia

, recent parenteral nutrition or use of glucose or lipid lowering drugs

Slide7

Personal specifics as well as details regarding the

etiology

of cirrhosis were collected for each patient via questionnaire.

Liver

assessment was then performed using a combination of clinical signs and symptoms along with imaging modalities like

sonography

, CT(Computed tomography) or MRI(Magnetic Resonance imaging) Abdomen and rarely liver biopsies

Slide8

The next part of the questionnaire elaborated on details of ascites and/ or encephalopathy grading using a 3-point scale as per Child’s criteria. Serum TG, Total Cholesterol, HDL, VLDL and LDL cholesterol levels were then measured as part of the lipid profile assessment.

Finally

, the extent of liver compromise was estimated using Child-

Turcotte

-Pugh and MELD criteria.

Slide9

Furthermore, a control population of 250 age-and sex-matched healthy individuals were selected and lipid parameters

analyzed

.

 

Values were presented as mean values, standard deviation and percentages. Data was analysed with ANOVA, independent

Slide10

sample t-test, fisher’s exact and chi squared tests. Analysis was carried out by using SPSS-16 statistical software. A p value <0.05 was considered statistically significant

.

Present study has been approved by Institutional Ethical Committee.

Slide11

RESULTS

Slide12

Table 1 Causes of Cirrhosis

Slide13

Slide14

Slide15

Table 3: Lipid profiles in patients with liver damage according to MELD score

Lipid

 

 

 

 

 

 

 

profile

 

 

 

 

 

 

 

in

 

 

 

 

 

 

 

patients

 

Total

 

 

 

 

 

with

 

 

 

 

 

 

N

Choleste

HDL

LDL

Triglyceri

VLDL

 

liver

 

o.

rol

mg/dl

mg/dl

des mg/dl

mg/dl

 

damage

 

 

mg/dl

 

 

 

 

 

accor-

 

 

 

 

 

 

 

 

 

 

 

 

 

ding to

 

 

 

 

 

 

 

MELD

 

 

 

 

 

 

 

score

 

 

 

 

 

 

 

MELD

 

148.94±

32.50

99.61

120.83±

23.28±2

 

18

±

 

≤10

13.89

± 4.41

8.08

.93

 

 

11.53

 

 

 

 

 

 

 

 

11≤

10

143.27±

31.75

93.19

111.52±

22.54±3

 

MELD

±

 

7

10.89

± 3.05

9.63

.11

 

≤18

12.82

 

 

 

 

 

 

 

19 ≤

 

134.35±

30.57

85.20

104.40±

21.11±2

 

MELD

82

±

 

12.10

± 2.73

10.37

.72

 

≤24

 

12.27

 

 

 

 

 

 

 

MELD

43

115.93±

29.35

75.37

100.95±

18.00±2

 

≥25

19.24

± 2.52

± 9.82

8.97

.64

 

 

 

P value One

 

<0.00

<0.00

 

 

 

Way

 

<0.0001

<0.0001

<0.0001

 

 

01

01

 

ANOVA

 

 

 

 

 

 

 

 

 

 

Slide16

Table 2 and 3 highlight the lipid profile distribution among patients of increasing severity of cirrhosis as determined by Child and MELD scores respectively

.

A statistically significant drop in all lipid parameters with increasing severity of cirrhosis is clearly noted with a p value of <0.05 as per one way ANOVA

.

 

Slide17

A significant negative correlation was observed between the severity of liver damage and all fractions of cholesterol (p < 0.05).

Though most apparent with LDL and Total cholesterol, this inverse correlation was clearly observed with serum TG levels as well.

This was interesting as previous studies had failed to find a statistically significant correlation between TG levels and severity of hepatic compromise.

Slide18

Table 4: Mean values of lipid profiles in cirrhotic patients in comparison with the control

group

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

                TotalHDLLDLTriglyceridVLDL Mean lipid profile in cirrhotic VsHealthy control NoCholester  mg/dlmg/dles mg/dlmg/dl   ol mg/dl                        I                                Cirrhotic patients       CCCIRRRRR  18136.39±31.03±88.15±108.23±21.37±  16.703.1213.9911.073.33            Controls 10194.91±41.71±130.30157.71±30.39±  ±  727.342.6815.052.26  63.66         P value <0.000<0.000 <0.000 Unpaired t test<0.0001<0.0001             

Slide19

Lipid profile when compared between patients with liver damage and controls table shows that there is a statistically significant difference in relation to lipid profile parameters distribution between cirrhotic patients and healthy control subjects with a p value of

<0.05

as per unpaired t test

.

The evidence showed that cholesterol and its fractions showed a significant decrease in cirrhotic patients compared to healthy control group subjects

(30-32% decrease)

Slide20

Slide21

Finally it was interesting to note that the underlying

etiology

of liver disease seemed to affect lipid parameters to different degrees, perhaps a result of differential damage patterns to the hepatic parenchyma

.

We hope to make further conclusions in this regard in the near future by expanding the study population and re-

analyzing

the data

Slide22

A subgroup analysis of

cirrhotics

, looking at the effects of individual liver

etiologies

on the lipid profile is depicted in the table above (TABLE

5

).

Ethanol

appears to contribute to the majority of patients while HBV is the second most common etiological cause.

Presently

, there are insufficient numbers of patients in the other subgroups to make conclusive statistical statements

Slide23

DISCUSSION

Our study indicates that a decline in hepatic dysfunction is associated with a statistically significant drop in lipid levels.

All

components of the lipid profile which were evaluated, namely HDL, LDL, TG, Total cholesterol and VLDL were significantly lower in

cirrhotics

than age matched healthy controls.

Furthermore

a clear linear correlation was noted between the decline in hepatic function and the reduction in lipid levels, i.e. patients with higher MELD and CHILD scores were found to have significantly lower lipid levels

Slide24

A number of previous studies (7,8) demonstrate a similar decline in lipid parameters with a progressive increase in severity of liver disease(9).

Habib

et al proposed that the HDL-cholesterol fraction is the best functional predictor of survival in cirrhotic patients.(10)

Slide25

These findings are not very surprising when considering the integral role the liver plays in lipid metabolism. Saponification and micelle formation, processes integral to dietary lipid digestion and absorption are largely carried out through the action of biliary fluid which is produced by the liver

.

Additionally, synthesis of

apolipoproteins

which are the major carriers of lipids in the circulation occurs largely in the liver. Finally the majority of enzymes required for cholesterol biosynthesis,

interconversion

of HDL,LDL as well as receptor modulation are produced by the hepatic parenchyma

Slide26

A compromise of this parenchymal functioning likely therefore results in a decline in lipid metabolism at multiple levels leading to a drop in lipid levels

.

Interestingly the

dyslipidemia

encountered in CLD appears to be very distinct from the regular forms encountered in clinical practice.

i.e

cirrhotic patients with the same numerical values of lipid levels as non-

cirrhotics

appear to have varied outcomes.

Slide27

This is in large part a result of the abnormal composition and structure of

apolipoproteins

as a result of impaired hepatic synthetic mechanisms.

The extent of clinical consequence as a result of this alteration needs to be

analyzed

in future studies.

Slide28

Our study included patients with a number of different

etiologies

of CLD. We hypothesized that the underlying pathological processes of each

etiology

might affect varying parts of the hepatic parenchyma to different degrees which in turn could affect the lipid metabolism in distinctive ways.

In

our study, ethanol induced cirrhosis comprised the majority of subjects with HBV accounting for the second most prevalent group.  

Slide29

With the existing data we can conclusively surmise that the decline in lipid and lipoprotein levels is much greater in patients with alcohol related cirrhosis as compared to those with non-alcoholic disease.

However we do not have sufficient patient numbers to make conclusions regarding the effects on lipid levels among individual

etiologies

.

We are presently collecting more patient data to study the other subgroups more accurately and hope to make generalizable conclusions in the near future.

Slide30

 

It is now well understood that lipids are an integral part of cell membranes, an extremely important energy source and also play a role in intracellular signalling pathways.

Whether

this decline in lipid levels translates into a clinically significant compromise of the aforementioned functions and as a result poorer outcomes is as yet undetermined.

Slide31

Also unclear is whether the poorer outcomes are a result of an already worse baseline hepatic status or the systemic consequences of lower lipid levels

.

Further studies are needed to

analyze

whether lipid replacement in any form might yield any benefit in these patients and also to look at the

the

prognostic utility of the extent of reduction in lipid levels.

Slide32

REFERENCES

1.Chiang JY, Nuclear receptor regulation of lipid metabolism: potential therapeutics for

dyslipidemia

, diabetes, and chronic heart and liver diseases.

Curr

Opin

Investing Drugs. 2005; 6:994-1001

2.Studenik P. [Lipid disorders in liver diseases].

Vnitr

Lek

. 2000;46(9):547-8

3.Selimoglu MA,

Aydogdu

S,

Yagci

RV. Lipid parameters in childhood cirrhosis and chronic liver disease.

Pediatr

Int. 2002;44:400–403.

doi

: 10.1046/j.1442-200X.2002.01590.x.

4.Ooi K,

Shiraki

K,

Morishita

Y,

Nobori

T. Clinical significance of abnormal lipoprotein patterns in liver diseases.

Int

J

Mol

Med. 2005;15:655–660.

Slide33

5.Santoyo J, Suarez MA, Fernandez-Aguilar JL, et al. True impact of the indication of cirrhosis and the MELD on the results of liver transplantation. Transplant Proc. 2006;38(8):2462-4.

6.Siagris D,

Christofidou

M,

Theocharis

GJ,

Pagoni

N, Papadimitriou C,

Lekkou

A,

Thomopoulos

K,

Starakis

I,

Tsamandas

AC,

Labropoulou-Karatza

C. Serum lipid pattern in chronic hepatitis C: histological and

virological

correlations. J Viral

Hepat

. 2006;13(1):56–61.

7.MEHBOOB F., RANJHA F.A., MASUD

S.Changes

in Serum Lipid Profile Among Patients Suffering From Chronic Liver

Disease.ANNALS

VOL. 2007;13(3): 209-211

Slide34

8.Cicognani C,

Malavolti

M,

Marselli-Labate

AM, Zamboni L,

Sama

C, Barbara L. Serum lipid and lipoprotein patterns in patients with liver cirrhosis and chronic viral hepatitis. Arch Intern Med. 1997;157:792–796.

doi

: 10.1001/

archinte

. 1997. 00440280120012

9.Habib A, Mihas AA,

Abou-Assi

SG, Williams LM,

Gavis

E,

Pandak

WM,

Heuman

DM. High-density lipoprotein cholesterol as an indicator of liver function and prognosis in

noncholestatic

cirrhosis.

Clin

Gastroenterol

Hepatol

. 2005;3:286–291.

doi

: 10.1016/S1542-3565(04)00622-6.