Alcoholism is one of the most frequent substances of abuse among people leading to increased mortality. Alcohol intake causes a number of metabolic changes and disturbs homeostasis of macro- and micro-elements in the body. [1]

Alcohol dependence syndrome (ADS) is described as a cluster of physiological behavioral and cognitive phenomena in which the use of alcohol takes a much higher priority for a given individual than other behaviors that once had a greater value.

A National House hold survey conducted in India for estimating the extent of substance dependence for alcohol and opiates between March 2000, showed the prevalence of alcohol to be 21.4%, opium 0.4%, other opiates 0.1%, cannabis 3.0% and heroin 0.2%.[2] Although the prevalence of alcohol use in India has been calculated at 30% there has been a rapid and noticeable increase in the rates of alcohol use in the Indian population as a whole.[3]

Chronic alcoholism is the most psychoactive substance abuse after caffeine. Chronic alcoholism is a major public health problem and causes multi-organ diseases and toxicity. Although the liver metabolizes the majority of alcohol ingested, it has intoxicating effects in the brain. Chronic alcohol intake is associated with several degenerative and inflammatory processes in the central nervous system. Evidence is accumulating that intermediates of oxygen reduction may be associated with the development of alcoholic diseases.[4]

Alcohol consumption is associated with the number of changes in cell functions, oxidant-antioxidant system, body weight, BMI, percentage body fat. Hematological and biochemical parameter are also effected. Enzyme AST/ALT are protein that helps cells do their works, when cells are injured, enzyme tends to leak into the blood stream to produce higher than normal levels, in various clinical conditions like liver disease, jaundice, hepatitis, necrosis, cirrhosis, nephritic syndrome and malnutrition. Studies have also found that alcohol dependence syndrome patients without alcohol liver disease do not have high AST/ALT ratio.[5] We would like to study this hypothesis in our patient’s population.

Physician have long sought for an accurate and inexpensive means to distinguish alcoholic liver disease from the non-alcoholic one as it has important implication for treatment and management. Several markers for high alcohol consumption per se have been studied example: carbohydrate deficiency transferrin (CDT), gamma glutamyl transferase (GGT) and Aspartate aminotransferase (AST) most have fairly low sensitive.[6]

The study of AST, ALT and their ratio in alcohol dependence syndrome with and without alcoholic liver disease was performed on blood sample from inpatients department of psychiatry in St. John’s Medical College Hospital.

Patients were selected based on criteria. Blood samples were collected by venipuncture. The serum was separated and evaluated for total serum AST and ALT, GGT on Dade RxL System.

The data was not normally distributed. Hence median and interquartile ranges were used. Descriptive statistics was used to describe the sociodemographic data Independent sample t test (Mann Whitney U test) was used to show the difference between the groups. Spearman’s Correlation was used for correlation analysis. SPSS version 15 software was used for the analysis. Probability value less than 5% was considered as statistically significant.

There was a significant difference in the BMI of both the groups (Table no.1) and hence, the data was controlled for the same.

Table 2. Shows the difference in LFT between the ADS groups with and without ALD

Mann Whitney U test was used to evaluate the difference in the LFT between the ADS with ALD group and without ALD group. The analysis revealed a significantly elevated AST, AST/ALT ratio and GGT in ADS with ALD group than without ALD group; however there was no significant difference in ALT between both the groups as shown in Table 2.

Table: - 3 showing the correlation of variables in ADS without ALD group

In the ADS without ALD group (Table no.3), AST correlated positively with Deritis ratio (r = .677, P =0.001). ALT correlated positively with GGT (r = .471, P =0.009) and quantity of alcohol use (r = 0.372, P =0.043); while it correlated negatively with Deritis ratio (r = - .489, P =0.006). Deritis ratio correlated positively AST (r = .677, P =0.001)

In the ADS with ALD group (Table no.4), AST correlated significantly with ALT (r = 0.829, P =0.001) and, GGT (r = 0.395, P =0.001) using Spearman correlation; while ALT correlated significantly with GGT (r = 0.463, P =0.001). There was also a significant correlation between GGT and quantity of alcohol (r = .387, p =0.034) and a negative correlation with age of starting alcohol use (r = - .531, p = 0.003).

This was a comparative study of Deritis ratio in alcohol dependence syndrome with and without alcohol liver disease in a hospital based subjects. The mean age of our subjects was 45 yrs and had an age of onset of alcohol use by 20 yrs (early onset of alcoholism). Most of our subjects have studied up to secondary educational level and were married. The average amount of alcohol consumption was increased in the ADS without ALD and lesser in the other group. This reinforces the theory that ADS group who are more vulnerable for liver disease react to even lower levels of alcohol use and leads to liver injury faster. The ADS with ALD group (Chart no. 1) preferred predominantly Whisky (50%) while the other group preferred a mixed type of beverage. This is in consonance with a report by WHO study where the predominant use was Whisky in urban Bangalore [7]

AST was significantly elevated in the ADS with ALD group, while the ALT was not significantly elevated. This leads us to an important question of whether single or multiple lab markers are needed to predict alcohol induced liver disease. Most authors prefer a combination of lab markers rather than single lab markers such as AST, ALT, Mean Corpuscular volume (MCV) and gamma glutamyl transferase (GGT). But most of them have low specificities and low sensitivity (Conigrave et al., 2002)⁶. Hence the important of a combination of markers or ratio’s using the lab markers have been found be very cost effective and useful. Increased AST in relation to ALT has been called as Deritis ratio. The predominance of AST over ALT in alcohol-related liver disease was first reported by Harinasuta et al. in 1967.[8] However, it became more widely recognized only with the paper by Cohen and Kaplan in 1979. The diagnostic significance of a high AST/ALT ratio for alcoholic liver disease was recently underscored in the Practical Guidelines for Alcoholic Liver Disease published by the American College of Gastroenterology in 1998 (McCullough and O’Connor, 1998)[9].

The Deritis ratio of more than 1.5 indicates that the cause of liver disease is mainly due to alcohol (Correia et al., 1981; Salaspuro, 1987)[10, 11]. In our study, only ADS subjects with ALD had Deritis ratio of more than 2.30; which was significantly more compared to those without ALD. This assumes importance of Deritis ratio in ADS with ALD. Increased Deritis ratio is usually seen in advanced stage of alcoholism compared to early use; even though some authors report that it is sensitive during any phase of alcoholism[12]. This assumes importance since the mortality with alcoholic cirrhosis peaked in patients aged 45 to 54 years[13]. Some of the theories for a high AST/ALT ratio are reduced hepatic ALT, depletion of pyridoxal 5-Pyrophosphate in the livers of alcoholics and increased mitochondrial damage leading to increased mitochondrial activity of mitochondrial aspartate (Matloff et al., 1980; Diehl et al., 1984; Nalpas et al., 1984)[14, 15, 16].

Even though there was a significant differences in the Deritis ratio between both the groups; there was no correlation with AST or ALT. AST correlated significantly with ALT (r = 0.829, P =0.001) and GGT (r = 0.395, P =0.001); ALT correlated significantly with GGT (r = 0.463, P =0.001) in the ADS with ALD group. There was also a significant correlation between GGT and quantity of alcohol (r = .387, p =0.034) and a negative correlation with age of starting alcohol use (r = - .531, p = 0.003). Also there was a significant difference in GGT between both the groups, highlighting the importance of GGT as a lab marker of alcoholism.

In the ADS group, AST was correlating with the Deritis ratio but there was no correlation with ALT. However, the ALT was correlating negatively with Deritis ratio, positively with GGT and Quantity of alcohol. This highlights the important of Deritis ratio even in the ADS group without ALD. Not only has a combination of lab markers used but questionnaires also had been combined to improve the sensitivity and specificity. In a study by Dolman et al (2005)[17], they found that using a combination of AUDIT, AST and GGT, the sensitivity increased to sensitivity 70.6%, specificity 98.8%, PPV 54.5% and NPV 99.4% compared to other combinations.

This study has highlighted the importance of not only the individual markers such as AST or ALT but also the ratio of them In the future, a combination of markers should be use to improve the specificity and sensitivity of these markers in identifying early damage of liver in Alcoholism. This will help in prevention of alcoholic cirrhosis which is the end stage of liver damage.