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  5. FP398 : To Correlate Fatty Liver Stages with Corneal Endothelial Parameters in Alcohol Dependence Syndrome

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Dr. (Lt Col) Alok Sati, S09925, Dr. Jaya Kaushik, Dr. (maj) Shankar Sandeep, Dr. (Brig) Parthasarathi Moulick

Introduction:

According to the International classification of diseases (ICD-10), for diagnosis of Alcohol Dependence Syndrome (ADS), three or more of the following criteria should be present for at least one month or if less than one month then together they should be present several times in the past 12 months, like  (a) a strong desire or sense of compulsion to take alcohol, (b) impaired capacity to control alcohol taking behavior in terms of its onset, termination, or levels of use, (c) a physiological withdrawal state when substance use is reduced or ceased, (d) evidence of tolerance to the effects of the substance, (e) preoccupation with the use of alcohol and (f) persistent alcohol use despite clear evidence of harmful consequences. Alcohol related harmful effects often result in chronic health consequences including the liver changes (Fatty live stages I to IV as assessed by Ultrasonography) and ophthalmic complications like corneal endothelial changes. The current study is aimed to correlate the stages of fatty liver with corneal endothelial parameters in ADS.

Material & Methods:

This study adheres to the tenets of the Declaration of Helsinki, and prior approval of the institutional ethical committee was obtained. A total of 161 corneas of 161 subjects with ADS were studied. These patients were examined by noncontact specular microscopy (Topcon Medical Systems, Inc., Paramus, NJ), and their endothelial parameters [central corneal thickness (CCT) in micrometers, endothelial cell density (CD) in cells per square millimeter, coefficient of variation (CV) in percentage, and hexagonality (Hex) in percentage] were analyzed. The ADS group was further analyzed to assess the influence of stages of fatty liver (I to IV diagnosed by ultrasonography) on the corneal endothelium. For the comparison of grades of stages of fatty liver with endothelial cell parameters, Kruskal wallis test was used.  P value < 0.05 was considered as significant.

Results:

The mean age of subjects in ADS and control groups was 36± 7.3 years (range, 23–56 yrs) and 35±9.1 years (range, 20–71 yrs) respectively. The best spectacle-corrected visual acuity (BCVA) in ADS group was 0.01 ± 0.05 (range; 0-0.3) logarithm of the minimum angle of resolution (log MAR) [Snellen equivalent (SE), 20/20.4] in right eye (RE) and 0.01 ± 0.04 (range; 0-0.3) log MAR (SE, 20/20.4) in the left eye (LE).

In Table 1, Kruskal-Wallis test was used to compare the endothelial parameters with different stages of fatty liver. It was found that the four stages differ significantly in terms of CCT (P< 0.001) and CD (P< 0.001), whereas an insignificant difference was seen in terms of CV and % hexa. When pair-wise comparison (using Mann-Whitney U test) was done in terms of CCT, a statistically significant difference was observed between stage I and stage II (P=0.048) and in between stage I and stage IV (P = 0.006) stages of fatty liver. Similarly, a significant difference was observed between stage I and stage II (P=0.004), stage I and stage III (P=0.004), stage I and stage IV (P<0.001), stage II and stage III (P=0.031) and stage II and stage IV (P=0.041); in terms of CD.

Discussion:

The present study has highlighted the endothelial alterations in patients with Alcohol Dependence Syndrome. Among the various endothelial parameters analyzed including CCT, we found that patients with ADS exhibit increased CD as compared to age matched controls. In addition, endothelial parameters do not change significantly with abstinence from alcohol, for a month. Moreover, on eliciting the impact of various variables on corneal endothelium, it was found that the patients with advanced stages of fatty liver exhibit more pronounced endothelial alterations, including CCT.

On assessing the influence of various factors on corneal endothelium as mentioned above, we could find a significant increase in CCT and a significant decrease in ECD with increasing stages of fatty liver only. The stages of fatty liver was assessed by ultrasonography  and comprises of Stage 1 as normal liver echogenicity, stage 2 as grade 1 fatty liver with increased liver echogenicity, stage 3 as grade  2 fatty liver with the echogenic liver obscuring the echogenic walls of the portal venous branches  and grade 4 as grade 3 fatty liver with an obscured diaphragmatic outline. 1

            The above correlation is explained by the known effect of chronic alcohol intake on liver and also on corneal endothelium. Our results indicate that there is an insult to corneal endothelium with chronic alcohol use. We hypothesize that this insult is a result of elevated ethanol levels in blood, which in turn is raised in aqueous humor and leads to endothelial alteration. The second factor could be a prolonged hypoglycemia due to poor nutritional status (as a result of neglect and poor appetite due to alcohol). As a result, there might be a fall in aqueous glucose level, as aqueous humour maintains a specific concentration of glucose (60% of blood glucose concentration) in comparison to the blood glucose level. Since glucose is one of the important nutrients of corneal endothelium, there is a possibility that the reduced aqueous glucose level might result in damage to the corneal endothelium.

Hypovitaminosis, again due to poor nutritional status of ADS patients, has been incriminated as one of the factors in causing corneal endothelial alterations. The fourth factor could be the depressed activity of Na+ K+ ATPase pump in corneal endothelium of ADS patient. This depressed activity may be attributed to both hypoglycemia and hypovitaminosis as evident by increased CCT in our study. This effect of ethanol has earlier been reported in both animal and human studies.2,3 The current study, for the first time, provides data showing an increased corneal endothelial damage with an increase in stages of fatty liver. Because, this study is first of its kind, further studies need to be carried out to confirm or contest these results and to analyze the possible causes of these alterations in greater depth.

References:

  1. Singh D, Das CJ, Baruah MP. Imaging of non alcoholic fatty liver disease: A road less travelled. Indian J Endocr Metab 2013;17:990-995.
  2. Israel Y, Kalant H, Laufer J. Effects of ethanol on (Na+,K+, Mg++) stimulated microsomal ATPase activity. Biochem Pharmacol 1965;14:1803-1814.
  3. Sun A Y, Samorajski T. The eflects of age and alcohol on (Na+ + K+) ATPase activity of whole homogenate and synaptosomes prepared from mouse and human brain. J Neurochem 1965;24:161-164.

Table

Table 1: Comparison of endothelial parameters with Stages of Fatty liver

Stage I (n=83) Stage II (n=33) Stage III (n=12) Stage IV (n=33) p-value
Mean SD Mean SD Mean SD Mean SD
CCT, µm 521 23 533 29 538 30 541 35 0.015*
CV, % 36.8 6.3 38.0 5.2 35.0 6.1 36.2 2.6 0.292
CD, cells/mm2 2653 222 2547 197 2459 179 2431 245 < 0.001*
Hexa, % 48.3 6.5 48.9 8.4 48.2 6.7 50.8 7.2 0.344

*Significant (p<0.05)

 

 

 

 

 

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