The effect of hydroalcoholic extract of artichoke leaf (Cynara scolymus) on liver alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes in patients with non-alcoholic steatohepatitis (NASH).

Dissertation for Master's Degree in Health Sciences in Nutrition

Abstract

Context: Recent clinical studies have shown that the extract of conifer leaves (Cynara scolymus) has a protective effect on the liver. Therefore, this study was designed and carried out with the aim of investigating the therapeutic effects of conifers on liver biomarkers in patients with non-alcoholic steatohepatitis (NASH). Materials and methods: In this double-blind clinical trial, 60 patients with NASH of both sexes were randomly divided into two groups. 30 patients in the intervention group received 2700 mg per day of hydroalcoholic extract of conifer leaves equivalent to 6 tablets (2 tablets with breakfast, 2 tablets with lunch and 2 tablets with dinner) for 2 months and 30 patients in the placebo group received 2700 mg per day of placebo equivalent to 6 tablets (2 tablets with breakfast, 2 tablets with lunch and 2 tablets with dinner) for 2 months. Blood was taken and the data was analyzed using spss software.

Findings: The results of the study showed that two months of intervention with artichoke leaf extract significantly reduced ALT and AST liver enzymes (P < 0.001). Also, this extract caused a significant decrease in total cholesterol and triglyceride serum levels (P < 0.05) in the intervention group. The amount of fasting blood sugar (FBS), LDL cholesterol and HDL cholesterol did not show a significant difference in the comparison between the intervention group and the placebo group. Conclusion: This study showed the effect of artichoke leaf extract on the reduction of ALT and AST liver enzymes and blood lipids (total cholesterol and triglyceride) in patients with NASH.

Key words: non-alcoholic steatohepatitis, Cinara scolymus, liver enzymes, lipids

-1 Introduction

In recent decades, with the rapid development of technology and lifestyle changes, the face of common diseases has changed from infections to newly emerging diseases. are a way of life and are associated with inactivity, weight gain and sometimes the occurrence of autoimmune responses, they are so dangerous that it seems that in the near future the debilitation and disability resulting from them will be equal to the debilitation and disability caused by contagious infectious diseases in the past ages. One of these non-infectious diseases that has attracted the attention of medical researchers in recent years is "non-alcoholic fatty liver" and cirrhosis and liver failure resulting from it, which is certainly in In the coming years, even viral hepatitis will have more serious consequences. Therefore, familiarity with the various aspects of diagnosis, treatment and prevention of this disease is very necessary and it prevents not only liver damage but also important cardiovascular complications which are the most important cause of death in patients with fatty liver (Dyson, 2014).

1-1-1 Non Alcoholic Fatty Liver Disease is known today as an important health threatening problem and is one of the most common chronic liver diseases. This disease was first identified in 1980 by Ludwig et al. and included patients who had no history of alcohol consumption, but their liver biopsy findings were indistinguishable from alcoholic hepatitis, and thus it was introduced with the term non-alcoholic fatty liver disease (NAFLD) (Ludwig, 1980). Non-alcoholic fatty liver disease includes a wide range of liver problems, the first of which is simple steatosis, which is called type 1. In simple steatosis, fat accumulation is seen in the liver tissue, but there is no inflammation in the liver tissue. Simple steatosis is the first detectable stage of non-alcoholic fatty liver disease. Type 2 of this disease is steatosis with inflammation. Type 3 steatosis is accompanied by damage to liver cells. Type 4 is steatosis with fibrosis of the sinusoids. (NASH) Non Alcoholic Steatohepatitis includes types 3 and 4 and is actually a condition between steatosis and cirrhosis.Most studies show that 10-20% of patients with non-alcoholic fatty liver disease will develop NASH, and 30-40% of patients with NASH may develop advanced fibrosis, and cirrhosis is found in 10-15% of patients. Many patients diagnosed with "cryptogenic" cirrhosis actually have liver disease based on NASH and enter a catabolic phase with worsening steatosis, which is the cause of their cirrhosis. These patients may suffer from liver failure and require a liver transplant, and some suffer from hepatocellular carcinoma (Machado, 2014, Takahashi, 2014).

Since this disease often does not have obvious symptoms, many people suffering from it are not aware of their disease. And most patients with NASH are diagnosed by the incidental discovery of elevated liver enzymes ALT and AST (these aminotransferases are mildly elevated, about 2.5-1.5 times higher than the upper limit of normal, and ALT is generally higher than AST). If the disease is symptomatic, the symptoms include weakness and vague discomfort in the upper right quadrant of the abdomen. Imaging methods show the characteristics of fatty liver, but the final diagnosis of fatty liver or NASH requires a liver biopsy. Liver biopsy shows macrovesicular characteristic of steatosis and sometimes microvesicular fat, and mixed inflammatory infiltrate is seen in lobular distribution. The diagnosis of non-alcoholic fatty liver disease requires a detailed history to determine the amount of alcohol consumed. Most researchers in the field of fatty liver disease focus on consuming less than 20 grams of alcohol per day to rule out alcoholic fatty liver disease. The results of laboratory tests for hepatitis B and C, iron and autoimmune serology should also be done (Fauci, 2012 Chalasani, 2012).

Although the importance of this disease is increasing day by day, epidemiological information about it is very limited, the main reason of which is the lack of safe and accurate criteria for screening this disease. So far, many studies have been conducted in the world on the prevalence of non-alcoholic fatty liver disease in different age groups and its relationship with other diseases, specific physical conditions and the use of drugs. The prevalence of non-alcoholic fatty liver disease increases with age. It is worth mentioning that fatty liver disease can be seen at any age, but its highest prevalence is between the ages of 40-60, and the prevalence of this disease in men is twice that of women, and with increasing age, the prevalence in women approaches that of men. Especially after menopause, the prevalence of fatty liver disease in women is increasing (Williams, 2011, Arun, 2006).

In a study titled the prevalence of non-alcoholic steatohepatitis in Iran in 2010 by Dr. Sohrabpour and colleagues, the prevalence of NASH in the study population was estimated at 2.9% (Sohrabpour, 2010). Studies conducted in eastern countries have stated that its prevalence is increasing due to lifestyle changes (high-fat diet, low physical activity, central obesity, and type 2 diabetes mellitus). In industrialized countries, non-alcoholic fatty liver disease affects 20 to 40% of people and is the most prevalent among chronic liver diseases. The prevalence of non-alcoholic fatty liver disease is estimated at 18% in Japan and 34% in America. This increased prevalence is directly related to the obesity epidemic seen in these populations. In the United States, NASH is thought to occur in about 3% of the general population, and NASH-related fibrosis is seen significantly in more than 40% of obese patients. In 40-90% of cases, obesity leads to non-alcoholic fatty liver (Corrado, 2014, Veena, 2014).

NASH is commonly seen in association with other components of the metabolic syndrome, "high blood pressure, diabetes mellitus, increased lipid levels and obesity", and NASH is considered as the liver manifestation of this syndrome (Marchesini, 2005). Recent studies have focused on the existence of insulin resistance as the main pathophysiological mechanism of NASH. Studies have also shown that abnormal ferritin levels are seen in 50% of patients with NASH, and increased ferritin levels can be a marker for insulin resistance in NASH. According to a theory known as the "double hit" theory, the transformation and progression of simple steatosis to steatohepatitis and advanced fibrosis is the result of two separate processes. In the first attack, insulin resistance causes the accumulation of fat in the liver cells