|Year : 2016 | Volume
| Issue : 3 | Page : 101-110
Efficacy of Vitamin E supplementation in patients with alcoholic liver disease: An open-label, prospective, randomized comparative study
Bhanu Prakash Kolasani, Prasanand Sasidharan, Adithiya Kumar
Department of Pharmacology, Vinayaka Missions Medical College and Hospital, Karaikal, Puducherry, India
|Date of Submission||08-Feb-2016|
|Date of Acceptance||31-Mar-2016|
|Date of Web Publication||23-Jun-2016|
Dr. Bhanu Prakash Kolasani
Department of Pharmacology, Vinayaka Missions Medical College and Hospital, Kottucherry, Karaikal - 609 609,
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: The evidence that oxidative stress is involved in the pathogenesis of ALD and Vitamin E deficiency being well documented in patients of ALD, an antioxidant like Vitamin E could likely be beneficial in patients with ALD. Methods: This is a prospective, open labeled, randomized comparative study of eight weeks duration, involving a total of 30 adult patients diagnosed with ALD who were randomized into two groups of 15 each and were designated as group A who received standard treatment and group B who received vitamin E along with standard treatment. Biochemical parameters like Liver Function Tests, De Ritis Ratio, Hb and TLC; prognostic parameters like Child Pugh Score and Model for End-Stage Liver Disease score were recorded before and after the treatment period in each group and compared. Results: In group A, the change observed in total protein and child pugh score were significant (P < 0.05) whereas that seen in PT was highly significant (P < 0.001). In group B, the changes observed in total protein, A:G ratio, bilirubin, PT, MELD score, Hb and TLC were significant (P < 0.05) whereas those seen in albumin, PT-INR, Child Pugh Score were highly significant (P < 0.001). When the differences observed in various parameters in Group A were compared with those seen in Group B, the changes in albumin, globulin and A:G ratio observed in Group B were statistically significant compared to their respective changes observed in Group A. Conclusion: These findings suggest that Vitamin E given in adequate dose will be a useful addition for treating alcoholic liver disease, although larger studies involving more number of patients should be done.
Keywords: Antioxidant, Child-Pugh score, liver function tests, model for end stage liver disease
|How to cite this article:|
Kolasani BP, Sasidharan P, Kumar A. Efficacy of Vitamin E supplementation in patients with alcoholic liver disease: An open-label, prospective, randomized comparative study. Int J Nutr Pharmacol Neurol Dis 2016;6:101-10
|How to cite this URL:|
Kolasani BP, Sasidharan P, Kumar A. Efficacy of Vitamin E supplementation in patients with alcoholic liver disease: An open-label, prospective, randomized comparative study. Int J Nutr Pharmacol Neurol Dis [serial online] 2016 [cited 2020 Nov 23];6:101-10. Available from: https://www.ijnpnd.com/text.asp?2016/6/3/101/184582
| Introduction|| |
Alcoholic liver disease (ALD) is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis or cirrhosis.  It remains as a major cause of liver disease worldwide and is responsible for approximately 25% of deaths due to alcohol consumption. 
Despite significant advances in the understanding of the pathogenesis of alcohol-related liver injury and many drugs such as corticosteroids, pentoxifylline being used in this condition, until now there are no Food and Drug Administration-approved treatments for ALD  and so the search for effective and safe drugs is continuing.
Oxidative stress plays a key role in the pathogenesis of ALD.  Alcohol metabolism includes increased synthesis of reduced form of nicotinamide adenine dinucleotide (NAD) hydrogen and suppression of mitochondrial β oxidation and increased lipid peroxidation in liver. This liberates oxygen-free radicals and decrease in mitochondrial glutathione and S-adenosyl-L-methionine levels, thus depleting the endogenous antioxidant capabilities. ,
Vitamin E deficiency has been well documented in ALD. , Alcoholics with cirrhosis often have low Vitamin E levels in the liver.  Some observational studies suggest that Vitamin E deficiency increases the liver's vulnerability to alcohol.  Vitamin E has experimentally (in rats) proven hepatoprotective capabilities including membrane stabilization, reduced nuclear factor-kappa B (NF-κB) activation, reduced tumor necrosis factor (TNF) production, and inhibition of hepatic stellate cell activation ,,, which are the primary pathological factors involved in the development of ALD.
Based on this background, it was thought that an antioxidant like Vitamin E could likely be beneficial in patients with ALD. As Vitamin E is economical and having least adverse effects, if its usefulness can be proved in patients with ALD, it can be utilized in these patients in a resource poor country like India and also in other developing countries of the world. In two previous studies which tested the efficacy of Vitamin E in ALD patients, there were no significant results in liver indices as one employed Vitamin E as monotherapy alone  and the other used a lower dose.  Hence, this study was aimed to evaluate whether Vitamin E supplementation in adequate doses for 8 weeks will have any advantage over standard treatment regarding biochemical parameters and prognostic indicators in patients with ALD.
| Methodology|| |
The study is an open label, prospective, randomized, comparative study of 8 weeks duration that extended from May 17 of 2014 to July 16 of 2014 conducted at our institute which is a Tertiary Care Teaching Hospital. The study includes thirty patients clinically diagnosed with ALD and all these patients are in-patients of Department of Medicine of our hospital. Patients who are stable and conscious, above 18 years of age, of either sex who met the clinical and biochemical criteria of severe alcoholic hepatitis characterized by a history of chronic and heavy alcohol intake (>80 g/day for the previous 5 years), rapid onset of jaundice in the absence of a biliary tract obstruction, painful hepatomegaly and ascites, transaminases ≥2 times above the normal value, an aspartate aminotransferase/alanine transaminases (AST/ALT) ratio ≥1.2, neutrophilia and a total bilirubin >2.5 mg/dL admitted in the Department of Medicine, were included in this study. The sample size was determined based on prevalence of ALD in this part of the region and a simple random sampling was done. Patients who did not abstain from alcohol consumption and those who did not consent for the treatment prescribed were excluded. Patients with renal failure, lung or any other organ disease, severe hypertension, malignancy, sepsis, bleeding diathesis and those with poor prognostic factors are excluded from this study. Pregnant and lactating patients were excluded from this study. A written informed consent to participate in the study was obtained from all the patients. The study protocol confirmed to the ethical guidelines of the 1975 Declaration of Helsinki and ethical clearance was obtained from Institutional Ethical Committee before commencing the study. All the patients were included in the study after explaining the patient's diagnosis, the nature and purpose of the proposed treatment, the risks and benefits of the proposed treatment, alternative treatment and the risks and benefits of the alternative treatment.
All the patients included in this study were requested to abstain from alcohol consumption. A total of thirty patients were randomized into two groups each of 15. One group (of 15 patients) designated as Group A, received the standard treatment for ALD and the other group (of 15 patients) designated as Group B, received Vitamin E as a capsule (one capsule-twice daily) along with the standard treatment. The standard treatment for the patients with ALD in our institute includes hepatoprotective drugs such as ursodeoxycholic acid or Liv 52 or both together, a diuretic like spironolactone or furosemide for treating ascites, an antibiotic like cephalosporin or metronidazole, an anti-ulcer drug like pantoprazole or ranitidine, an intravenous fluid like 25% dextrose or ringer lactate, drugs like lactulose or l-ornithine l-aspartate for prevention/treatment of hepatic encephalopathy, a beta blocker like propranolol for prevention/treatment of variceal bleeding and chlordiazepoxide for treating symptoms of alcohol withdrawal. Vitamin E (Evion ® -400 IU) capsules were used for this study.
Patient's details were collected and verified. Their present clinical severity and features of alcohol-induced liver disease were noted. The following demographic details of age, sex, present and history, duration of alcohol consumption were obtained, and the presence of co-morbid factors such as hypertension, diabetes, cerebrovascular disease, coronary artery disease, peptic ulcer disease, and chronic pulmonary disease was noted. The body mass index, body temperature, blood pressure, heart rate, and respiratory rate were recorded for all the patients. Details of clinical examination were duly noted down. Use of concurrent allopathic and alternative medications for other systemic issues was noted and excluded based on their reported interactions. Patient's clinical data are maintained confidentially.
Laboratory parameters such as total protein, albumin, globulin, albumin: Globulin ratio (A:G ratio), total bilirubin, conjugated and unconjugated bilirubin, ALT, AST, alkaline phosphatase (ALP) (i.e., patient's liver function test [LFT]), De Ritis ratio (AST: ALT ratio), prothrombin time (PT), hemoglobin (Hb), total leukocyte count (TLC) and blood urea and serum creatinine (i.e., patient's-renal function test [RFT]) were measured before and 8 weeks after treatment.
Venous blood samples were collected from the patients. Becton Dickinson-franklin lakes NJ USA vacutainer tubes (buffer - 3.2% sodium citrate) with capacity of 2.7 ml were used for collecting blood samples for PT/PT-international normalized ratio (INR) estimation. CDRICH, China vacutainertubes (ethylenediaminetetraacetic acid - K 3 ) with capacity for 3 ml (lavender) were used for collecting blood samples for hematological investigation PT, TLC.
Empty glass tubes were employed for serum collection and the serum obtained is used for performing LFT and RFT. Semi auto-analyzer BTS 350 (Biosystems) is used for laboratory analysis. Genius CA 5I Coagulometer is used for PT and PT-INR estimation.
The total protein level was measured using Biuret method colorimetry using Biuret reagent. The albumin level was calculated using bromocresol green (BCG) albumin assay colorimetry using BCG reagent. The direct and the indirect bilirubin levels were measured using dimethylsulfoxide method-colorimetry using total/direct bilirubin reagent and activator kit. The ALP was measured by p-nitrophenyl phosphate (pNPP) ALP assay-colorimetry using pNPP substrate and 2-amino-2-methyl-1-propanol buffer. The ALT/serum glutamate pyruvate transaminase (SGPT) was calculated using ALT/SGPT test calorimetry with SGPT enzyme and substrate reagent. The AST/SGOT was calculated using AST/SGOT test colorimetry with serum glutamate oxaloacetate transaminase enzyme and substrate reagent. The blood urea level was measured using Berthelot method-colorimetry using urease enzyme reagent and chromogen reagent. The serum creatinine level was analyzed using alkaline picrate method (Jaffe's method) using creatinine buffer and creatinine picrate reagent. All the above mentioned investigational reagents were manufactured by Beacon Diagnostics Pvt. Ltd., India. The PT and PT-INR were calculated using LIQUIPLASTIN ® -liquid calcified thromboplastin reagent which was manufactured by Tulip Diagnostics Pvt. Ltd., India [Table 1].
|Table 1: Laboratory parameters and their standard investigation techniques with the reagents used |
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Child-Pugh score and model for end-stage liver disease (MELD) were used to monitor prognosis for these patients. Both are calculated at the time of admission and 8 weeks after the treatment. Child-Pugh score/Child-Turcotte-Pugh score is used to assess the prognosis of chronic liver disease, mainly cirrhosis. The score employs five clinical measures of liver disease such as Total bilirubin in mg/dl (<2:1; 2-3:2; >3:3), serum albumin in g/dl (>3.5:1; 3.5-2.8:2; <2.8:3), PT-INR (<1.7:1; 1.7-2.3:2; >2.3:3), ascites (none: 1; mild: 2; moderate to severe: 3), and hepatic encephalopathy (none: 1; supressed with medication: 2; refractory to treatment: 3). Each measure is scored 1-3, with 3 indicating most severe derangement. , Interpretation classifies chronic liver disease into Child-Pugh Class A (5-6), B (7-9) and C (10-15), employing the added score from above. Survival after 1 year for Class A is 100%, Class B is 81%, and for Class C is 41% whereas survival after 2 years for Class A is 85%, Class B is 57%, and for Class C is 35%. MELD is a scoring system for assessing the severity of chronic liver disease using the patient's values for serum bilirubin, serum creatinine and the INR for PT to predict survival. It is calculated according to the following formula: 
MELD = 3.78 × ln (serum bilirubin [mg/dL]) + 11.2 × ln (INR) + 9.57 × ln (serum creatinine [mg/dL]) + 6.43 × etiology (0: Cholestatic or alcoholic, 1: Otherwise)
United Network for Organ Sharing has made the following modifications to the score:  If the patient has been dialyzed twice within the last 7 days, then the value for serum creatinine used should be 4.0. Any value < 1 is given a value of 1 (i.e., if bilirubin is 0.8, a value of 1.0 is used) to prevent the occurrence of scores below 0 (the natural logarithm of 1 is 0, and any value below 1 would yield a negative result). In interpreting the MELD score in hospitalized patients,  the 3 months mortality is: >40: 71.3% mortality, 30-39: 52.6% mortality, 20-29: 19.6% mortality, 10-19: 6.0% mortality and <9:1.9% mortality.
Data collected under each group was summarized as mean ± standard deviation. Statistical analysis was carried out using paired t-test for within the group comparisons and unpaired t-test for between the group comparisons. A P < 0.001 is considered statistically highly significant whereas a P < 0.05 is considered statistically significant and a P > 0.05 was considered statistically not significant. The IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp (International Business Machines Corporation-Statistical Package for Social Science program version 21.0) software was used for statistical analysis of data.
| Results|| |
A total of 41 patients with ALD were assessed for eligibility, of which thirty patients were selected based on inclusion and exclusion criteria, and also based on their willingness to participate in the study. Three patients did not meet the inclusion or exclusion criteria, whereas eight patients declined to participate in the study. The remaining thirty patients were randomized into two groups of fifteen each and were designated as Group A (received standard treatment) and Group B (received standard treatment and Vitamin E). One patient was lost during the follow-up in Group B and 29 patients - 15 in Group A and 14 in Group B were followed up after the treatment duration of 8 weeks. [Figure 1] shows the flow of participants of this study through its various phases.
|Figure 1: Consort flow diagram of patients of the study through its various phases|
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The two groups were homogenous with respect to most of the baseline demographic data, including patient's age, duration of alcohol consumption and all the biochemical parameters except for total protein, globulin, A:G ratio, and bilirubin levels [Table 2]. All the patients in our study belonged to the low socioeconomic status.
|Table 2: Baseline demographic data and other parameters of the patients |
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In Group A, when the changes in the LFT parameters were compared before and after the treatment, only the total protein value was significantly (P < 0.05) increased [Table 3]. There is an improvement in the other LFT parameters indicated by an increase in the levels of albumin and globulin, a decrease in the levels of total bilirubin, conjugated and unconjugated bilirubin values. There is also a decrease in the serum levels of ALT and ALP, as well as A:G ratio and De Ritis ratio, but these changes were not statistically significant.
|Table 3: Student paired t-test results for within the group comparison of Group A |
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There was a decrease of PT value observed in Group A after the treatment which was statistically highly significant (P < 0.001). Even though, there was a decrease in the PT-INR in the same group after the treatment, the change was not statistically significant. There was a statistically significant decrease in the Child-Pugh score after the treatment. A decrease in the -MELD score was also observed after the treatment in Group A, but the change was not statistically significant. As far as renal parameters such as serum creatinine and blood urea are concerned, there was an improvement in both the parameters, but it was not statistically significant. Even hematological parameters such as Hb and TLC showed improvement but not significant [Table 3].
In Group B, to whom Vitamin E was given in addition to standard treatment, the improvement in albumin was highly significant (P < 0.001) and most of the other LFT parameters such as total protein, A:G ratio, total bilirubin, conjugated and unconjugated bilirubin showed a statistically significant (P < 0.05) improvement. There was an improvement in the globulin, ALP, ALT, AST and De Ritis ratio, but these changes were not statistically significant [Table 4].
|Table 4: Student paired t-test results for within the group comparison of Group B |
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In contrast to Group A, where the change in the PT-INR was not statistically significant, the change in the PT-INR value in Group B was highly significant and that of PT was statistically significant. Even the decrease in the Child-Pugh score was highly significant. In relation to MELD score, the decrease in the score after treatment in Group B was statistically significant which contrasts with that in Group A, where the decrease in the score after the treatment was not statistically significant. There was a statistically significant (P < 0.05) improvement in the hematological parameters like TLC. The renal parameters such as serum creatinine and blood urea showed improvement but were not statistically significant [Table 4].
The mean percentage changes of various parameters in Group A and Group B are shown in [Table 5]. On the whole, the mean percentage changes observed were more in Group B compared to Group A, except in the cases of total protein, globulin, conjugated bilirubin, AST, ALT, PT and Hb where we observe a higher change in mean percentage in Group A compared to Group B. In Group A, the highest change was observed in conjugated bilirubin (49.82%) followed by change in ALT (45.83%), whereas in Group B, highest change was observed in A:G ratio (67.2%) followed by change in albumin (49.03%) [Figure 2]. The mean percentage changes in PT, PT-INR, Child-Pugh score and MELD score are shown in [Figure 3]. In relation to Child-Pugh score, the mean percentage change in Group B was 36.57% which is more than that in Group A of 20.29%. Similarly in MELD score, the mean percentage change in Group B was 31.36% which is more than that in Group A of 16.79%.
|Figure 2: Mean percentage change observed in both the groups for biochemical parameters. A:G ratio = Albumin to globulin ratio; ALP = Alkaline phosphatase; AST/SGOT = Aspartate aminotransferase also known as serum glutamate oxaloacetate transaminase; ALP/SGPT = Alanine aminotransferase also known as serum glutamate pyruvate transaminase; De-ritis ratio = Ratio of AST to ALT|
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|Figure 3: Mean percentage changes observed in both the groups for prothrombin time, prothrombin time-international normalized ratio, Child-Pugh score and MELD score. PT = Prothrombin time; PT-INR = Prothrombin time-international normalized ratio; MELD = Model for end-stage liver disease|
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| Discussion|| |
To the best of our knowledge, there is no study evaluating clinical efficacy of Vitamin E on Indian patients with ALD. This study for the 1 st time assessed the effect of Vitamin E supplementation to the standard treatment in patients with ALD.
The two groups were homogenous with respect to most of the baseline demographic data, including patient's age, duration of alcohol consumption and all the biochemical parameters except for total protein, globulin, A:G ratio and bilirubin levels [Table 2]. Nonsignificance of the demographic variables between Group A and B indicates that the two groups were properly randomized [Table 2]. Even though, there are several studies demonstrating that women develop liver disease after exposure to lower quantities of alcohol and over shorter time periods, , in our study, all the thirty patients who were included in the study were males. This may be due to sociocultural aspects of this country, where almost exclusively males are involved in alcohol intake. Furthermore, we observe that, at a very early age only, people of this region are suffering from ALD. This may be ascribed to the habit of consuming the alcohol from a very early age compared to other parts of the country. Furthermore, as our hospital is located in a union territory, the reduced cost of alcohol beverages due to the reduced tax compared to other parts of the country, also is contributing here to the increased prevalence of alcoholism and subsequently ALD in this region.
The normal range of various parameters that were analyzed as a part of this study are as follows: Total protein is 6.7-8.6 g/dl; albumin is 3.5-5.5 g/dl; globulin is 2.0-3.5 g/dl; A:G ratio is 1.2-1.5:1; total bilirubin is 0.3-1.3 mg/dl; conjugated bilirubin is 0.1-0.4 mg/dl; unconjugated bilirubin is 0.2-0.9 mg/dl; ALP is 45-115 U/L; AST is 12-38 U/L; ALT is 7-41 U/L; PT is 12.7-15.4 s; De Ritis ratio: 1.1:1; PT-INR is 0.8-1.2; TLC is 3.54-9.06 × 10 3 /mm 3 ; blood urea is 7-20 mg/dl; serum creatinine is 0.6-1.2 mg/dl; Hb for adult males is 13.3-16.2 g/dl and for adult females is 12.0-15.8 g/dl. 
In patients with ALD, the albumin levels will be deceased because of decrease in the synthetic function of the liver, globulin levels will be increased in response to antigenic stimulation reflecting the immune changes associated with ALD, A:G ratio reversed obviously. Total bilirubin and especially the conjugated bilirubin levels will rise, levels of ALP, AST, and ALT will rise and because AST will be much more raised compared to ALT, the De Ritis ratio will also be increased. PT and PT-INR are increased as there is reduced synthesis of clotting factors. Hb is decreased due both to loss of synthetic function and to hemolysis and TLC is increased because of the inflammation.
In relation to the LFT parameters, in Group A, only the total protein value was significantly (P < 0.05) improved [Table 3], whereas in Group B, to whom Vitamin E was given in addition to standard treatment, in addition to total protein, A:G ratio, total bilirubin, conjugated and unconjugated bilirubin showed a statistically significant (P < 0.05) improvement and also the improvement in albumin and PT-INR values were highly significant (P < 0.001) indicating that addition of Vitamin E has actually improved the outcome of many more LFT parameters compared to standard treatment given alone [Table 4]. This was in accordance with a previous study carried out by Mahmood et al., where Vitamin E supplementation (500 mg/d) for 3 months in 17 chronic hepatitis C patients resulted in modest reduction of serum ALT levels to 63 IU/l from baseline levels of 73 IU/l.  Similar results were reported in another study with a prospective randomized double-blind cross over design in 23 chronic hepatitis C patients who were refractory to interferon. Vitamin E supplementation (800 IU/day) for 12 weeks reduced serum ALT from 90 to 68 IU/l at the end of treatment.  However, both the above studies evaluated the effect of Vitamin E in patients of chronic hepatitis C and not in those having ALD.
In relation prognostic scores, the decrease in the Child-Pugh score was highly significant in Group B, whereas it was just significant in Group A [Table 3] and [Table 4]. The decrease in the MELD score Group B was statistically significant, whereas in Group A, it was not statistically significant [Table 5] and [Table 6]. Both these results indicate an improved chance of survival with addition of Vitamin E to the treatment.
|Table 6: Independent t-test results for comparison of differences in both the groups |
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In relation to hematological parameters, in Group B, there was a statistically significant (P < 0.05) reduction of TLC and increase in Hb which were not significant in Group A [Table 3] and [Table 4] which indicate that supplementing Vitamin E has caused a reduction in the hepatic inflammation and an improvement in the synthetic function of the liver, which resulted in an increase in the synthesis of the protein part-globin of Hb.
When the differences observed in various parameters in Group A were compared with those seen in Group B using independent Student's t-test, the changes observed in albumin, globulin and A:G ratio in Group B were statistically significant (P < 0.05) when compared to the respective changes in Group A [Table 6]. Even though, the remaining parameters have improved better in Group B compared to Group A, these changes were not statistically significant [Table 6]. Increase in albumin indicates the improved synthetic function of the liver. Globulin levels increased following treatment in Group A but decreased in Group B. As mentioned earlier, the globulin levels will increase during liver disease in response to antigenic stimulation reflecting the immune changes associated with ALD. The decrease in globulin levels in Group B signifies the improvement because of addition of Vitamin E which being an antioxidant decreases the antigenic stimulation and thus reducing the immunological damage. These results indicate that addition of Vitamin E improved the liver function in comparison to the standard treatment given alone. This is in contrast to the results seen in a previous study of Vitamin E in ALD patients, in which some normalization of serum hyaluronic acid levels was observed, but without significant changes in indices of liver function.  This may be due to the use of Vitamin E as monotherapy only, in that study. However in our study, we used it only as a supplementation to standard treatment for ALD patients.
In a previous study which was carried out with Vitamin E alone in ALD patients, has showed no benefit which might be due to an inadequate dose (500 mg/day)  used in that study. In this study, we have used a recommended and an adequate dose of Vitamin E of 800 mg/day.
As mentioned earlier, oxidative stress plays a key role in the pathogenesis of ALD. Metabolism of alcohol leads to increased liver oxidative stress via formation of acetaldehyde which can form hybrid-adducts with reactive residues mediating lipid peroxidation and nucleic acid oxidation,  excessive reduction of NAD leading to the transfer of an electron to molecular oxygen to generate reactive species such as superoxide anion  and induction of CYP2E1 which interacts with cytochrome reductase leading to electron leaks in the respiratory chain and reactive oxygen species production.  Even urinary levels of 8-isoprostanes, a marker of oxidative stress and lipid peroxidation are elevated in subjects after alcohol intake compared to normal. 
Alcohol intake also increases the intestinal permeability to a variety of substances that include bacterial endotoxins, such as lipopolysaccharide  that activates the NF-κB in Kupffer cells causing exaggerated transcription of pro-inflammatory cytokines such as TNF-α, interleukin-6 (IL-6), and transforming growth factor-beta (TGF-β). , Whereas TNF-α and IL-6 are mainly involved in cholestasis and synthesis of acute-phase proteins, TGF-β may be critically involved in fibrogenesis through the activation of hepatic stellate cells.
Vitamin E, being an antioxidant has caused a statistically significant improvement in some of the liver function parameters and prognostic indicators in our study which can be explained by its proven hepatoprotective mechanisms mentioned previously which include membrane stabilization, reduced NF-κB activation, reduced TNF production, and inhibition of hepatic stellate cell activation. ,,,
| Conclusion|| |
This study shows that in patients with ALD, Vitamin E supplementation to standard treatment has shown better improvement in liver function parameters and prognostic indicators than standard treatment given alone, although it was not statistically significant in most of them except in albumin, globulin, and A:G ratio. Among the prognostic indicators, even though both the Child-Pugh score and MELD score showed significant improvement, it was the MELD score that showed a very high improvement indicating that short-term mortality is better improved compared to long-term mortality with Vitamin E supplementation. These findings suggest that Vitamin E, given in adequate dose will be a useful addition for treating ALD, although larger studies involving more number of patients should be done.
We would like to thank Indian Council of Medical Research for funding this project under STS-2014 (Reference Id: 2014-00840) and Dr. Sakthivel, Professor and HOD of Department of Medicine for his full support throughout the study without which this study could not be possible.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
O′Shea RS, Dasarathy S, McCullough AJ, Practice Guideline Committee of the American Association for the Study of Liver Diseases and the Practice Parameters Committee of the American College of Gastroenterology. Alcoholic liver disease. Hepatology 2010;51:307-28.
Frazier TH, Stocker AM, Kershner NA, Marsano LS, McClain CJ. Treatment of alcoholic liver disease. Therap Adv Gastroenterol 2011;4:63-81.
Szuster-Ciesielska A, Daniluk J, Kandefer-Szerszen M. Oxidative stress in the blood of patients with alcohol-related liver cirrhosis. Med Sci Monit 2002;8:CR419-24.
Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines: Management of alcoholic liver disease. Clin Mol Hepatol 2013;19:216-54.
Dey A, Cederbaum AI. Alcohol and oxidative liver injury. Hepatology 2006;43 2 Suppl 1:S63-74.
Arteel G, Marsano L, Mendez C, Bentley F, McClain CJ. Advances in alcoholic liver disease. Best Pract Res Clin Gastroenterol 2003;17:625-47.
McClain CJ, Hill D, Kugelmas M, Marsano L. Nutrition and liver disease. In: Bowman B, Russell RM, editors. Present Knowledge in Nutrition. Washington: International Life Sciences Institute; 2001. p. 483-96.
Leo MA, Rosman AS, Lieber CS. Differential depletion of carotenoids and tocopherol in liver disease. Hepatology 1993;17:977-86.
Lieber CS. Relationships between nutrition, alcohol use, and liver disease. Alcohol Res Health 2003;27:220-31.
Hill DB, Devalaraja R, Joshi-Barve S, Barve S, McClain CJ. Antioxidants attenuate nuclear factor-kappa B activation and tumor necrosis factor-alpha production in alcoholic hepatitis patient monocytes and rat Kupffer cells, in vitro
. Clin Biochem 1999;32:563-70.
Evstigneeva RP, Volkov IM, Chudinova VV. Vitamin E as a universal antioxidant and stabilizer of biological membranes. Membr Cell Biol 1998;12:151-72.
Lee KS, Buck M, Houglum K, Chojkier M. Activation of hepatic stellate cells by TGF alpha and collagen type I is mediated by oxidative stress through c-myb expression. J Clin Invest 1995;96:2461-8.
Mezey E, Potter JJ, Rennie-Tankersley L, Caballeria J, Pares A. A randomized placebo controlled trial of Vitamin E for alcoholic hepatitis. J Hepatol 2004;40:40-6.
de la Maza MP, Petermann M, Bunout D, Hirsch S. Effects of long-term Vitamin E supplementation in alcoholic cirrhotics. J Am Coll Nutr 1995;14:192-6.
Cholongitas E, Papatheodoridis GV, Vangeli M, Terreni N, Patch D, Burroughs AK. Systematic review: The model for end-stage liver disease - Should it replace Child-Pugh′s classification for assessing prognosis in cirrhosis? Aliment Pharmacol Ther 2005;22:1079-89.
Heuman DM, Habib A, Abou-Assi S, Williams L, Mihas A. Rationally derived child-turcotte-pugh (CTP) subclasses permit accurate stratification of near-term risk in cirrhotics patients referred for liver transplantation. Gastroenterology 2005;128: A-734.
Kamath PS, Kim WR; Advanced Liver Disease Study Group. The model for end-stage liver disease (MELD). Hepatology 2007;45:797-805.
Wiesner R, Edwards E, Freeman R, Harper A, Kim R, Kamath P, et al.
Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology 2003;124:91-6.
Becker U, Deis A, Sørensen TI, Grønbaek M, Borch-Johnsen K, Müller CF, et al.
Prediction of risk of liver disease by alcohol intake, sex, and age: A prospective population study. Hepatology 1996;23:1025-9.
Fuchs CS, Stampfer MJ, Colditz GA, Giovannucci EL, Manson JE, Kawachi I, et al.
Alcohol consumption and mortality among women. N Engl J Med 1995;332:1245-50.
Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. editors. Harrison′s Principles of Internal Medicine, 18 th
ed. New York, NY: McGraw-Hill; 2012.
Mahmood S, Yamada G, Niiyama G, Kawanaka M, Togawa K, Sho M, et al.
Effect of Vitamin E on serum aminotransferase and thioredoxin levels in patients with viral hepatitis C. Free Radic Res 2003;37:781-5.
von Herbay A, Stahl W, Niederau C, Sies H. Vitamin E improves the aminotransferase status of patients suffering from viral hepatitis C: A randomized, double-blind, placebo-controlled study. Free Radic Res 1997;27:599-605.
Wu D, Cederbaum AI. Alcohol, oxidative stress, and free radical damage. Alcohol Res Health 2003;27:277-84.
Lieber CS. Microsomal ethanol-oxidizing system (MEOS): The first 30 years (1968-1998) - A review. Alcohol Clin Exp Res 1999;23:991-1007.
Albano E. Oxidative mechanisms in the pathogenesis of alcoholic liver disease. Mol Aspects Med 2008;29:9-16.
Pemberton PW, Smith A, Warnes TW. Non-invasive monitoring of oxidant stress in alcoholic liver disease. Scand J Gastroenterol 2005;40:1102-8.
Tilg H, Diehl AM. Cytokines in alcoholic and nonalcoholic steatohepatitis. N Engl J Med 2000;343:1467-76.
Thurman RG. Mechanism of hepatic toxicity: II. Alcoholic liver injury involves activation of Kupffer cells by endotoxin. Am J Physiol 1998;275:G605-11.
Hoek JB, Pastorino JG. Cellular signaling mechanisms in alcohol-induced liver damage. Semin Liver Dis 2004;24:257-72.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
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