Effect of diet based on the principles of Iranian traditional medicine on cirrhosis (a clinical trial)

Complementary Therapies in Medicine 29 (2016) 35–41

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Effect of diet based on the principles of Iranian traditional medicine on cirrhosis (a clinical trial) Mohammad Javad Ehsani a , Jamileh Mahdavi Jafari b , Jale Aliasl c , Mohammad Kamalinejad d , Latif Gachkar e , Rasool Choopani (M.D, Ph.D, Assistant Professor) b,∗ a

Department of Gastroenterology and Hepatology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Department of Traditional Medicine, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran c Traditional Medicine Clinical Trial Research Center, Shahid University, Tehran, Iran d School of Pharmacology, Shahid Beheshti University of Medical Sciences, Tehran, Iran e Tropical and Infectious Diseases Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran b

a r t i c l e

i n f o

Article history: Received 31 May 2015 Received in revised form 14 February 2016 Accepted 7 September 2016 Available online 9 September 2016 Keywords: Iranian traditional medicine Diet Liver cirrhosis Weight changes

a b s t r a c t Objectives: Cirrhosis is associated with morbidity and mortality worldwide. Iranian traditional medicine (ITM) focused on nutritional intervention in order to improve liver function. The aim of this study was to assess the effectiveness of a diet designed based on ITM and current dietary recommendations. Design: This controlled trial study was performed on 57 subjects with cirrhosis in 5 tertiary hospitals in Teharn, Iran. Setting: Subjects were included if they were diagnosed with class A or B cirrhosis between October 2013 and December 2014. Interventions: Subjects were randomly allocated into intervention (28 subjects) who received dietary and lifestyle recommendations based on ITM and controls (29 subjects) who received routine dietary and lifestyle recommendations for 3 months. Subjects were assessed at baseline and at the end of the intervention for anthropometric measures, liver function tests and cirrhosis severity scoring. Main outcome measures: Model for End-Stage Liver Disease (MELD), anthropometric measures, serum albumin, liver function tests, International Normalized Ratio and alkaline phosphatase as well as subjective findings. Results: Mean age of the subjects was 51.19 ± 11.88 years. Weight reduction was observed in 41 subjects (22 subjects in intervention and 19 in control group). Dietary intervention resulted in a significant decrease in alanine aminotransferase (AST) (p = 0.04) and significant resolution of icterus in sclera (p = 0.02) in weight loss group and increase serum albumin in weight gain group (p = 0.02). Conclusions: ITM recommendations could be beneficial for cirrhotic patients both for the purpose of weight reduction and weight gain. © 2016 Published by Elsevier Ltd.

1. Introduction Cirrhosis is the common complication of end-stage liver disease, which is considered as a worldwide problem and is associated with a substantial economic burden.1,2 Decompensating liver failure may result in a tremendous decrease in life expectancy, from approximately 97%–40% at one year.3 Cirrhosis is defined

∗ Corresponding author at: Department of Traditional Medicine, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, P.O. Box 1516745811, Tehran, Iran. E-mail address: [email protected] (R. Choopani). http://dx.doi.org/10.1016/j.ctim.2016.09.006 0965-2299/© 2016 Published by Elsevier Ltd.

as progressive diffused fibrosis along with the development of regenerative nodules in liver.4 Cirrhosis due to liver failure is associated with various and even life threatening complications including portal hypertension, spontaneous bacterial peritonitis, hepatic encephalopathy and hepatorenal syndrome.5 Therefore, various assessments and models are used in order to predict the prognosis of chronic liver disease. Malnutrition is the most common, reversible complication.1,6 The prevalence of malnutrition in cirrhotic patients is reported to be 50%–90% 7 . Malnutrition adversely affects response to other complications, and quality of life.8,9 and is associated with poor survival and increased mortality 10,11

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The etiology of malnutrition is multifactorial and primarily related to reduced liver function; poor oral intake and complications of cirrhosis such as ascites as well as increased protein catabolism and insufficient synthesis, mal digestion and malabsorption associated with portal hypertension.3,7 Due to the association between nutrition and the outcome of patients with end-stage liver disease, it is important to accurately assess nutritional status and provide timely nutritional support studies have shown that early detection and treatment of malnutrition is imperative to improve patient outcomes.7 Assessment of the nutritional state of liver cirrhosis patients has a wide spectrum.12 Alanine transaminase (ALT) and aspartate aminotransferase (AST) are considered as sensitive markers for hepatobiliary disease and liver injury.13 However, it was shown that these markers are influenced by inflammation and therefore might not necessarily indicate the amount of fibrosis and thus produce false information regarding liver function.14 Increased blood levels of ALP usually occur in liver or bone disorders. Increased hepatic fraction of ALP is a sensitive indicator of intra- or extra-hepatic cholestasis.15 If other liver tests such as Bill, AST, ALT are also high, usually the ALP from the liver. If the treatment is successful, the ALP is reduced or returned to normal so decrease ALP in patients is good result from this clinical trial.15 Increased Albumin and decreased total bilirubin have recently attracted attention in the assessment of the progression of cirrhosis.16 Due to the error of each of the discussed markers in predicting the function and therefore prognosis of end-stage liver disease, combination of various markers has been suggested in the assessment of the prognosis of end-stage liver disease. The Child-Pugh score is used to assess the prognosis of chronic liver disease, mainly cirrhosis, and is based on total bilirubin, serum albumin, INR, presence of ascites and hepatic encephalopathy.17 Serum albumin concentration is the most frequently used laboratory measure of nutritional status. Although non-specific, it has been used to assess changes in nutritional status and identifying the risk of malnutrition.18 It has been shown that increased serum albumin level is associated with reduced risk of malnutrition in cirrhosis patients.19 Another indicator for severity of liver disease is the model for end-stage liver disease (MELD). MELD is a scoring system for assessing the severity of chronic liver disease, which is calculated based on total bilirubin, serum Cr and INR.17 Lower MELD score is related to lower severity and fewer complications of cirrhosis.20 All these indicators can be changed with nutritional intervention, therefore nutrition and diet are considered as an important factor in the management of end stage liver disease and cirrhosis.20 Nutrition received special attention in Iranian traditional medicine (ITM) since it was believed that quality of nutrition and the types of food play a substantial role in survival of the patients.21 Based on the Iranian Traditional Medicine (ITM) theories, management of ascites, as similar to most other ailments, is achievable by lifestyle modification, dietary intervention and administration of medicinal foods. Avicenna, as a leading practitioner in ITM, used dietary interventions in the treatment of cirrhosis.21 Avicenna believed that the quantity and quality of diet should be considered in treatment of patients presenting with ascites. Avicenna’s dietary recommendations included water restriction, eating food at small amounts and consumption of small amount of soft diet. Ascitic patients were advised to be fed with porridge of chicken fat, Partridge (Ammoperdix griseogularis) with warm spice or chicken and lamb with cooked chick peas (Cicer arietinum L.) and sumac (Rhus coriaria L.), which is considered as a hepatoprotective agent. Some of the dietary recommendations of Avicenna included stewed meals and feeds with the following ingredients; chicken breast or wing or lamb with celery, onion and olive oil, tarragon leaves or fenugreek leaves, peas, pumpkin, garlic as well as break-

fasts or deserts with barberry, cumin, pomegranate juice, lentils and oat meal, cinnamon, mint, honey syrup, quince jam without molasses, barley bread and almonds. The importance of the liver was also recognized in ITM. Based on ITM theories liver involves in almost all human life pathways including growth, nutrient supply, and energy provision and reproduction.22 In the viewpoint of ITM nutritional tonics can improve liver function when liver function, for any reason, is disrupted.23,24 Therefore specific foods were recommended to modify and improve liver function.25,26 Despite its long history, traditional medicine is of interest to its believers, especially in Asia and Africa, to cure ailments in human diseases.27–29 The main reasons for this preference were cultural acceptability, low cost and efficacy to cure some diseases.29–31 Therefore, new interventions were performed incorporating traditional medicine in promoting health in societies with traditional beliefs.27,32 Therefore, the present study was performed to determine the effect of a diet based on the principles of the ITM in patients with liver cirrhosis classes A and B.

2. Methods This clinical trial was conducted on sixty cirrhotic patients (aged 20–70 years) between October 2013 and December 2014. Subjects were diagnosed with cirrhosis between 2012 and 2014 and were hospitalized in 5 hospitals (Taleghani, Imam Hussein, Imam Khomeini, Shohada and Modarres) in Tehran, Iran. Subjects were approached by phone and the information regarding the study as well as the intervention was provided for the subjects. Subjects who agreed to participate in the study were randomly assigned in intervention or control group. All subjects gave written informed consent prior to participating in the study. This study was approved by the independent Ethics Committee of the Shahid Beheshti University and conducted in accordance with the Declaration of Helsinki (approval number: 144) and was registered in the Iranian Registry of Clinical Trials (No: IRCT2013122415864N1). Subjects did not receive any payment for the participation in the study. Subjects were included in this study if they were class A and B cirrhotic patients, aged between 20 and 70 years and were not ill two weeks prior to the study commencement. Subjects with documented diagnosis of diabetes mellitus, Hepato cellular carcinoma, hepatic encephalopathy, and chronic renal failure, as well as subjects who failed to follow instructions for two weeks and those with complications that lead to hospitalization and intolerance of diet plan were excluded.

2.1. Determination of the severity of cirrhosis The Model for End-Stage Liver Disease (MELD) score, a scoring system for assessing the severity of chronic liver disease, was computed based on total bilirubin, serum Cr and INR.17 MELD was calculated based on the following formula.33 : MELD = 9.57 × loge (totalbilirubin) + 11.2 × loge (INR) + 6.43 The Child-Pugh score (or Child-Turcotte-Pugh score) was used to assess the prognosis of chronic liver disease, mainly cirrhosis, and is based on five clinical measures of liver disease total bilirubin, serum albumin, international normalized ratio for pro thrombin time (INR), ascites and hepatic encephalopathy.17 Based on these calculations patients are divided into three classes based on prognosis ranging from class A as good prognosis to class C as poor prognosis.17

M.J. Ehsani et al. / Complementary Therapies in Medicine 29 (2016) 35–41 Table 1 Diet based on the principles of ITM. Early morning

a cup of boiling water with a tablespoon Oxymel

Breakfast

Quince jam, Without molasses with Barley bread Citron jam Without molasses with Barley bread apple jam Without molasses with Barley bread 5 currant with 5 Almonds Celery stew with barley bread Containing: celery, chicken breast half, half a small onion and a teaspoonful of olive oil Stew contain 50 g lamb sheep, One teaspoon dried tarragon leaves, One teaspoon dried fenugreek leaves, 10 peas and half a small onion with barley bread Pumpkin stew with barley bread: A medium pumpkin, one garlic, a teaspoonful of olive oil, 50 g lamb sheep and a tablespoon of barberry Chicken feed: chicken breast half, half a small onion, a teaspoon of cumin half beaten, a quarter teaspoon dried thyme Feed meat with Barley bread And two Olive Pickle containing 50 g of lamb meat and two garlic Fresh pomegranate juice Food Lentils: 3 tablespoons of lentils, 2 tablespoons of oatmeal, a tablespoon of olive oil Feed almonds: chicken breast half, 7 peeled almonds, A quarter teaspoon cinnamon Chicken feed: chicken breast half or Chicken wings and neck, 5 currant, half a teaspoon of cinnamon, half a teaspoon of dried mint Honey syrup: One tablespoon of honey and a cup of boiling water

Snack Lunch

Snack Dinner

Bedtime

2.2. Measurements Body weight was measured in light clothes with a non electronic scale and height was measured with specific measuring apparatus. Weight and height were used to calculate Body Mass Index (BMI) (weight [Kg]/height [m]). Patients were considered malnourished if the BMI was below 18.5 kg/m2 according to the recommendation of the WHO.34 Laboratory tests included AST, ALT, ALP, total bilirubin, serum albumin, INR and serum creatinine (Cr). 2.3. Designing diet plan In order to provide a dietary recommendation, an extensive review of literature in ITM was performed. The extracted food modifications and liver tonic foods were used to design a diet (Table 1). Furthermore, current dietary recommendations regarding protein (1–2 g/kg/day) and salt (not more than 2.3 g/day) intake were taken into consideration in the meal plan due to ethical considerations.11,35,36 The experimental group received diet plan that included early morning, breakfast, snack, lunch, snack, dinner and bedtime meals based on the principles of ITM along with lifestyle commands to improve health based on the principles of ITM. The lifestyle commands included regulation of sleep and food habits. The control group was asked to follow the diet prescribed by their physician along with commands to improve health.

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All patients were closely monitored for clinical signs and symptoms including subjective complaints of the subjects, objective findings in physical examination along with compliance with the study medication every two weeks. Biochemical and hematological assessments were performed at baseline and at the end of 12 weeks at Dey Hospital Laboratory, Tehran, Iran. A total of 74 subjects were approached but 14 subjects (23%) were excluded. Exclusions were due to losing follow up (1 subject in intervention and 3 control groups), death (2 subjects in the control group), addiction during the follow up (1 subject in control group), hospital admission due for angiography (1 subject in intervention group) and gastrointestinal bleeding (1 subject in control group) and refusing to follow dietary advice due to the difficulty in maintaining the recommended diet (4 subjects in intervention and 1 in control groups) while 3 subjects were excluded during statistical analysis due to extremely high or low laboratory test results (outliers). In a clinical trial fifty seven (36 male, 21 female) with cirrhosis received diet based on the principles of ITM (n = 28) or routine health care (n = 29) for 3 months. 2.4. Statistical analysis The statistical package for social sciences (SPSS) software version 21.0 (IBM Inc, Chicago, Il) was used for the statistical analysis. Variables were assessed for normality based on the Shapiro-Wilk test and the outliers were removed. Baseline characteristics of the intervention and control groups were compared using independent t-test for continuous variables and chi-square test for categorical variables. The Fisher exact test was used to assess the association between weight category of subjects (normal/underweight and overweight/obese) and weight loss. Two-way repeated measures analysis of variance (ANOVA) was used to assess the effect of intervention on continuous variables including BMI, AST, ALT, ALP, total bilirubin, INR, creatinin and model of end stage liver disease. Generalized linear model was used to assess the effect of intervention on liver related symptoms including bloating, feeling of fullness after eating, drooling after eating, sleepiness and etc. In order to select the categorical variables for the model, chi square test was used. Variables that with chi square p value lesser than 0.1 were selected for inclusion in the model. P value smaller than 0.05 was considered statistically significant. 3. Results The mean age of the subjects was 51.19 ± 11.88 years. Mean age for subjects in the intervention group was 53.46 ± 11.03 and for subjects in control group was 49.07 ± 12.42 years. There was no significant difference between study groups in terms of age (p = 0.16). In both groups males dominated females (17 males and 11 females in intervention group and 19 males and 10 females in control group) but there was no significant association between study group and gender ␹2 (1, N = 57) = 0.58, p = 0.92. The most prevalent underlying cause of cirrhosis was cryptogenic in 28 (48.3%) subjects (16 subjects in intervention and 12 subjects in control groups) followed by hepatitis C virus (HCV) in 11 (19.0%) subjects (4 subjects in intervention and 7 subjects in control groups), autoimmune hepatitis in 6 (10.3%) subjects (4 subjects in intervention and 2 subjects in control groups), hepatitis B virus (HBV) in 5 (8.6%) subjects (2 subjects in intervention and 3 subjects in control groups), alcoholic liver disease in 3 (5.2%) subjects (1 subject in intervention and 2 subjects in control groups),primary biliary cirrhosis in 2 (3.4%) subjects (in 2 subjects in control group) and fatty liver disease in 2 (3.4%) (one subject in each group). There was no significant association between study groups and cause of liver cirrhosis (alcoholic liver disease, non-alcoholic liver disease

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Table 2 Mean and standard deviation of continuous variables as per intervention and control groups. Variable

Intervention

Control

p

BMI ALT AST ALP Total bilirubin INR Creatinine Albumin MELD

26.26 ± 4.39 31.50(22.75) 38.00(16.5) 139.50173.75) 1.33(1.05) 1.42 ± 0.39 0.80 ± 0.27 3.89 ± 0.66 11.89 ± 3.86

26.39 ± 5.43 26.00(17.00) 49.00(43.00) 155.00(137.50) 1.46(1.40) 1.46 ± 0.34 0.91 ± 0.37 3.54 ± 0.58 13.03 ± 4.10

0.92 0.100.250.720.350.65 0.92 0.05 0.28

BMI = Body Mass Index, ALT = Alanin Transaminase, AST = Aspartate Aminotransferase, ALP = Alkaline Phosphatase, INR = International Normalized Ratio, MELD = Model for End-stage Liver Disease. Mean and SD was used to describe variables. The independent t-test was used for the comparison. BMI = Body Mass Index, ALT = Alanine Transaminase, AST = Aspartate Transaminase, INR = International Normalized Ratio Median and interquartile range (IQR) was used to describe variables. The MannWhitney U test was used for the comparison.

Table 3 Baseline frequency of signs and symptoms as per intervention and control groups. Variable Thirst Sleep discomfort Sleepiness Anxiety Head ache Bloating Oral malodour Drooling during sleep Dry mouth Feeling of heaviness in stomach after eating Pain in RUQ Constipation

and infectious liver disease) ␹2 (2, N = 57) = 1.88, p = 0.39. Subjects were similar at baseline in terms of weight, BMI, alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, creatinin (Cr), serum albumin and international normalized ratio (INR) (Table 2). Among the baseline clinical signs and symptoms, icteric sclera was found significantly more frequent in control group compared with intervention group (22 subjects in control group vs 12 subjects in intervention group, p = 0.01) while leg cramps was found significantly more frequent in intervention group compared with control group (20 subjects in intervention group vs 13 subjects in control group, p = 0.04) (Table 3). Based on baseline BMI, 32 subjects (56.1%) were overweight or obese (BMI > 25 kg/m2) and 25 subjects (43.9%) were normal or underweight (BMI < 25 kg/m2). No significant association was found between study groups and being overweight/obese or normal weight/underweight ␹2 (1, N = 57) = 0.47, p = 0.45. At the end of the 3 months course of this study, a total of 41 subjects (71.9%) reduced weight while 16 subjects (28.1%) increased weight (6 subjects (21.4%) in the intervention group and 10 subjects (34.5%) in the control group). Among the intervention group weight loss was observed in 22 subjects (78.6%) while 19 subjects (65.5%) reduced weight in control group. There was no relationship between groups and frequency of weight loss in this study ␹2(1, N = 57) = 1.20, p = 0.27). Mean percentage of weight change in all subjects was −1.22 ± 3.5% after 3 months. Mean percentage of weight loss was −2.51 ± 3.12% and for weight gain was +2.10 ± 1.90%. Among the overweight/obese subjects (32 subjects), 28 (87.5%) reduced weight while 4 subjects (12.5%) gained weight while among the normal/underweight subjects (25 subjects), 13 (52.0%) lost weight and 12 (48.0%) gained weight. Weight loss was significantly associated with being overweight/obese ␹2 (1, N = 57) = 8.76, p = 0.006. Due to the effect of weight change on serum albumin level and liver function tests, assessment of the effect of intervention on study variables was performed separately on subjects who lost weight and those who gained weight during the study period (Table 4). Two-way repeated measures ANOVA analysis revealed that intervention resulted in a significant decrease in AST (p = 0.04) among subjects who lost weight and a significant increase in serum albumin (p = 0.02) in subjects who gained weight (Table 4). Generalized linear model analysis revealed that intervention resulted only in a significantly higher improvement in scleral icterus (p = 0.02) (Table 5).

Inability to pass stool Dark face color Facial icterus Scleral icterus Coated tongue Cold extremities Edema Leg cramps Nausea Fatigue

Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No

Intervention

Control

p-

10 18 13 15 23 5 7 21 7 21 13 15 2 26 12 16 16 12 12 16 10 18 7 21 7 21 20 8 15 13 12 16 16 12 16 12 12 16 20 8 6 22 28 0

12 17 14 15 26 3 11 18 14 15 13 16 1 28 16 13 23 6 15 14 11 18 8 21 7 22 22 7 20 9 22 7 21 8 18 11 6 23 13 16 6 23 29 0

0.66 0.89 0.33 0.29 0.07 0.90 0.49 0.35 0.07 0.50 0.86 0.82 0.94 0.70 0.23 0.01a 0.23 0.70 0.07 0.04a 0.94 –

RUQ = Right Upper Quadrant. Chi square test was used to assess the association between study variables and study groups. a Significant association.

4. Discussion The findings of this study revealed that among the subjects who lost weight, dietary intervention resulted in reduction in AST, ALT and increase in serum albumin from baseline while only AST was found to be reduced significantly more in intervention group compared to the control group. It was previously shown that high fat-high protein diet could result in increased liver transaminases, serum albumin, ALP and total protein.42,43 The reason why this study failed to identify a significant difference in other liver function markers might be due to the heterogeneity of the subjects in this study. In this study, subjects had varied AST, ALT, ALP and total bilirubin levels. Moreover, this study recruited subjects who had cirrhosis regardless of the underlying cause. Although no significant difference was observed in total bilirubin levels throughout the study duration, the frequency of scleral icterus decreased significantly in intervention group compared to the controls. In the study by Duarte et al. no significant effect was found for dietary intervention on total bilirubin levels.39 Of the subjects who gained weight, dietary intervention resulted in a significant reduction in ALP, INR while these markers increased

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Table 4 Two-way repeated measure s ANOVA analysis for the effect of treatment and group on the liver function tests in subjects with weight gain and subject with weight loss. Variable

Weight BMI ALT AST ALP Total bilirubin INR Creatinine Albumin MELD

Group

Intervention Control Intervention Control Intervention Control Intervention Control Intervention Control Intervention Control Intervention Control Intervention Control Intervention Control Intervention Control

Weight loss

Weight gain

Baseline

Follow up

Baseline

Follow up

75.03 ± 13.98 79.05 ± 14.75 26.49 ± 4.22 28.29 ± 4.99 36.95 ± 19.20 39.63 ± 36.05 42.59 ± 28.00 55.05 ± 27.44 195.77 ± 130.45 190.10 ± 127.08 1.63 ± 1.22 2.03 ± 0.97 1.42 ± 0.37 1.53 ± 0.36 0.89 ± 0.30 0.84 ± 0.33 3.80 ± 0.65 3.53 ± 0.73 12.18 ± 3.84 13.95 ± 3.99

72.29 ± 13.29a 77.95 ± 14.52 25.52 ± 3.86a 27.88 ± 4.83 27.73 ± 10.25a 41.53 ± 38.34 37.59 ± 16.46b 57.68 ± 31.59 139.50 ± 86.16a 209.63 ± 175.43 1.50 ± 1.10 2.13 ± 0.85 1.37 ± 0.35 1.50 ± 0.34 0.82 ± 0.35 1.38 ± 2.10 4.04 ± 0.60a 3.53 ± 0.65 11.73 ± 3.60 14.00 ± 3.68

72.58 ± 21.59 63.50 ± 11.78 25.40 ± 5.29 22.77 ± 4.46 36.50 ± 13.85 27.60 ± 24.52 39.67 ± 12.01 40.60 ± 17.56 170.00 ± 110.96 188.90 ± 74.08 1.26 ± 1.12 1.12 ± 0.42 1.43 ± 0.49 1.33 ± 0.25 0.94 ± 0.12 1.04 ± 0.43 4.19 ± 0.65 3.57 ± 0.60 10.83 ± 4.12 11.30 ± 3.95

74.33 ± 21.07 64.57 ± 11.89 26.05 ± 5.15 23.16 ± 4.45 30.50 ± 7.99 42.90 ± 32.91 35.17 ± 12.58 53.20 ± 24.06 103.50 ± 47.87a 199.30 ± 85.88 1.42 ± 0.49 1.56 ± 0.98 1.37 ± 0.45a 1.51 ± 0.29 0.84 ± 0.16 0.99 ± 0.37 4.21 ± 0.49b 3.54 ± 0.34 11.00 ± 3.95 13.50 ± 3.69

BMI = Body Mass Index, ALT = Alanin Transaminase, AST = Aspartate Aminotransferase, ALP = Alkaline Phosphatase, INR = International Normalized Ratio, MELD = Model for End-stage Liver Disease. Median and IQR were used to describe the variables. a Significant main effect of time with Greenhouse-Geisser correction. The calculated p value for within subject effect in weight loss group was p = 0.03 for weight, p = 0.04 for BMI, p = 0.02 for ALT, p = 0.01 for ALP and p = 0.02 for serum albumin. The calculated p value for within subject effect was p = 0.03 for ALP and p = 0.04 for INR in weight gain group. b Significant main effect of time and intervention. The calculated p value for between subject effects in weight loss group was p = 0.04 for AST. The calculated p value for between subject effect in weight gain group was p = 0.02 for serum albumin. Table 5 Generalized linear model for the effect of categorical variables on the liver related symptoms in subjects with weight gain and weight loss. Variable

Sleep comfort Sleepiness Anxiety Drooling during sleep Facial icterus Scleral icterus Coated tongue Cold extremities *

Group

Intervention Control Intervention Control Intervention Control Intervention Control Intervention Control Intervention Control Intervention Control Intervention Control

Weight loss group

Weight gain group

Baseline

Follow up

Baseline

Follow up

13 15 – – – – 11 12 – – 10 15 13 15 – –

7 13 – – – – 5 10 – – 6* 14 7 11 – –

1 5 6 10 0 4 – – 3 7 – – 3 6 2 7

0 5 2 8 0 4 – – 1 7 – – 0 5 1 6

Significant relationship between intervention group and presence of scleral icterus p = 0.02.

in the control group and increase in serum albumin in intervention group compared with control group. Among these markers, there was a significant difference between intervention and control groups only in serum albumin. In a study by Duarte et al., low caloric-high protein diet resulted in increased serum total protein level.39 The improved serum albumin level might be due to improved nutrition rich diet and increased protein intake.39 The findings of this study revealed that dietary intervention resulted in different outcomes in cirrhotic subjects who gained weight compared to those who lost weight. This finding was in line with the findings of the study conducted by Duarte et al.39 . MELD was not significantly affected by nutrition intervention in this study. MELD is a scoring system that predicts long term and short term prognosis of cirrhosis.44,45 On the other hand this tool may not be used as an indicator of nutrition due to the lack of nutrition parameters in the formula.44,45

While a high protein diet is recommended to be prescribed for compensated cirrhosis, branched chain amino acids (BCAA) should be provided in case of complicated cirrhosis with encephalopathy to reduce the ammonium production.46,47 Furthermore, compensated cirrhotic patients may also benefit from BCAA administration due to the observed effects of BCAAs in delaying the process of hepatic failure through the improvement in regeneration and immunity of the liver.48,49 ITM provides meals with high BCAA content by prescribing food comprised of BCAAs including asparagus, broccoli, cauliflower, whey and casein proteins, egg, meat, poultry.46,47 Avicenna advised ascetic patients to consume meat and chicken frequently, which provides a high calorie-high protein diet with high BCAA content.50 These dietary recommendations are similar to the modern dietary recommendations for the management of cirrhotic patients.51

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Moreover, the effect of ITM recommendation on liver function might be due to the usage of medicinal foods of plant sources which contain hepatoprotective compartments including alkaloids, phenols and xanthenes.52,53 In this study the leading underlying cause of cirrhosis was cryptogenic followed by HCV infection, autoimmune hepatitis and HBV infection. In a previous study in European countries alcohol was found to be the leading cause of cirrhosis followed by cryptogenic cirrhosis, HCV and other causes.37 Since alcohol consumption is prohibited by the Islam religion, alcohol consumption is significantly lower in Iran compared to the western countries. The mean age of subjects was 51.19 ± 11.88. Previous studies reported the incidence of non-alcoholic liver disease in younger age compared to this study.38 Since the leading cause of cirrhosis in a large number of subjects in this study was cryptogenic, the mean age of subjects in this study mostly follows the trend of non-alcoholic liver disease mainly cryptogenic cirrhosis. Previous studies showed that cryptogenic cirrhosis was found in older subjects compared with other types of non-alcoholic liver disease.39–41 One of the limitations of this study was the small number of subjects with weight gain. It is recommended for further studies to assess larger number of subjects in order to reach more subjects in each sub-group. On the other hand subjects in this study focused more on anthropometry and serum bilirubin as indicators of nutritional status and but no nutrition intake assessment was performed to monitor the compliance to diet. It is recommended for further researchers to conduct randomized controlled trials with nutritional assessment tools to control for compliance to diet. The findings of this study indicate that the ITM recommendations may be used safely for weight reduction and weight gain of uncomplicated cirrhotic patients by providing medicinal foods that improve the function of liver.

Conflict of interest None.

Source of grant This study was not funded by any source.

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