Cause Of Cryptogenic Cirrhosis Research Articles

The differences between patients with nonalcoholic fatty liver disease (NAFLD) and those without NAFLD, as well as predictors of functional coronary artery ischemia in patients with NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with metabolic syndrome. It is the most common cause of cryptogenic cirrhosis. The disease is also involved in the occurrence and development of type 2 diabetes and atherosclerosis and can directly affect the outcome of patients with coronary heart disease. Therefore, the focus of treatment of nonalcoholic fatty liver disease has also begun to focus on the treatment of risk factors for atherosclerotic heart disease. In this study, we investigated the difference between patients with coronary artery stenosis combined with NAFLD and those without NAFLD and evaluated the predictive factors and value of functional coronary artery ischemia in patients with NAFLD. Many clinical factors (such as age, BMI, hyperglycemia) and imaging parameters (such as CACS grade) in the NAFLD group were different from those in the non-NAFLD group. The predictive model combined with multiple influencing factors has a good value in predicting coronary artery ischemia in patients with NAFLD. We collected the clinical and imaging data of patients who underwent coronary computed tomography angiographyand coronary artery calcification score (CACS) scans between January and June 2023. A total of 392 patients were included and divided into the NAFLD group and the non-NAFLD group. Based on CT fractional flow reserve (CT-FFR), patients with NAFLD were divided into CT-FFR ≤ 0.08 group and CT-FFR > 0.08 group. Significant differences were observed between the non-NAFLD and NAFLD groups in terms of age, body mass index, hyperglycemia, hyperlipidemia, triglyceride, high-density lipoprotein, coronary artery disease-reporting and data system (CAD-RADS) classification, CACS classification, number of diseased coronary arteries, and CT-FFR ≤ 0.80 ratio (p < .05). The CAD-RADS and CACS classifications can independently predict functional coronary artery ischemia in NAFLD patients. The combined use of CAD-RADS and CACS classifications resulted in an area under the curve of 0.819 (95% confidence interval: 0.761-0.876) for predicting coronary artery ischemia in NAFLD patients, which was higher than the individual classification methods (CAD-RADS: 0.762, CACS: 0.742) (p = .000). There are differences between patients with coronary artery stenosis and NAFLD and those without NAFLD. The CAD-RADS classification and CACS classification can economically and efficiently predict functional coronary artery ischemia in patients with NAFLD, which has crucial value in clinical diagnosis and treatment.

Interleukin 32 as a New Biomarker for Non-Alcoholic Fatty Liver Disease

Abstract Background Nonalcoholic fatty liver disease (NAFLD) now refers to a spectrum of liver diseases that ranges from steatosis (i.e., fatty infiltration of the liver) to Non-alcoholic steatohepatitis (NASH) ie, steatosis with inflammation and hepatocyte necrosis, to fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. NAFLD is the most common cause of cryptogenic cirrhosis, which is cirrhosis that cannot be explained by hepatitis, alcohol abuse, toxin exposure, autoimmune disease, congenital liver disease, vascular outflow obstruction, or biliary tract disease. Objective To study serum levels of interleukin 32 in patients with NAFLD to detect its relation to the incidence and severity of NAFLD. Patients and Methods Type of Study: Case control study. Study Setting: The study will be conducted at Ain Shams University Hospitals. Study Period: The study will take place from January 2019 to October 2019. To obtain this aim, we included 80 persons &amp; divided them into 2 groups: Group I: 40 patients with NAFLD as a case group. Group II: 40 healthy subjects as a control group. We can sum up our results in the following points: Weight, BMI and Waist circumference were significantly higher among case group when compared with the control group (p &amp;lt; 0.001 for all). While there was non statistically significant difference found between two groups regarding Height. Results The best cut off point of Interleukin 32 Concentration (ng\ml) to detect Cases group was &amp;gt; 22.5 with sensitivity of 100%, specificity of 87.50%, PPV of 88.9%, NPV of 100% and total accuracy of 98.2%. The best cut off point of Interleukin 32 Concentration (ng\ml) to detect High group was found ≤165 with sensitivity of 90.91%, specificity of 28.57%, PPV of 85.7%, NPV of 40% and total accuracy of 55.8%. The best cut off point of Interleukin 32 Concentration (ng\ml) to detect Indeterminant group was ≤75 with sensitivity of 48.48%, specificity of 85.71%, PPV of 94.1%, NPV of 26.1% and total accuracy of 62%. Conclusion Interleukin 32 can be considered as a diagnostic marker for nonalcoholic fatty liver diseases with sensitivity of 100% and total accuracy of 98.2%. Interleukin 32 Concentration was found to be negatively correlated with serum Albumin level. Although, We found no correlation between Interleukin 32 Concentration &amp; each of Fatty Liver Index score, nonalcoholic fatty liver diseases Fibrosis Score and PAUS Size.

Study of Serum Lipid Profile and Aminotransferases (ALT and AST) in Non-obese, Non-diabetic Nonalcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of liver diseases characterized by simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. It is the most common cause of cryptogenic cirrhosis. NAFLD is associated with obesity, insulin resistance, hypertension, type 2 diabetes mellitus, and dyslipidemia.&#x0D; Objective: The study aimed to assess the changes in lipid profile and aminotransferases (ALT and AST) in Non-alcoholic fatty liver disease (NAFLD).&#x0D; Methods: This observational cross-sectional study was carried out in the department of Biochemistry, Mymensingh Medical College in cooperation with the Centre for Nuclear Medicine and Ultrasound, Mymensingh from January 2012 to June 2013 after the approval of the protocol. A total of 120 subjects were included through purposive sampling, among them, 60 subjects were with fatty liver disease (group-I) and another 60 were without fatty liver (group-II) with ultrasonography. The sampling method was purposive (non-random). Relevant laboratory investigations were performed by using established methods to achieve the objectives.&#x0D; Results: The majority of the subjects with NAFLD (33.33%) were in 51-60 years (in Group-I). Mean serum total cholesterol, triacylglycerol, LDL-cholesterol, and HDL-cholesterol were 203.33±21.83, 184.41±33.31, 126.28±18.75, and 40.17±6.32 mg/dl in group-I and 167.65±9.83, 128.77±11.65, 101.74±9.29 and 40.16±3.55 mg/dl in group-II respectively. Significant differences were found in the case of total cholesterol (p&lt;0.001), triacylglycerol (p&lt;0.001), and LDL-cholesterol (&lt;0.001), but no significant difference was found in the case of HDL-cholesterol (p&gt;0.05). Serum ALT and AST were 49.43±16.98, 45.20±13.56 U/L in group-I and 32.83±4.54, 28.68±4.31 U/L in the group- II respectively. Significant differences were found in case of ALT (p &lt;0.001) and AST (p &lt;0.001).&#x0D; Conclusion: Nonalcoholic fatty liver disease is associated with dyslipidemia and with the elevation of serum ALT and AST.&#x0D; J Rang Med Col. September 2022; Vol. 7, No. 2:35-39

Pathologic Diagnosis of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) encompasses steatosis and steatohepatitis. The cause may be multifactorial, and diagnosis requires correlation with clinical information and laboratory results. To provide an overview of the status of histology diagnosis of steatosis, steatohepatitis, and associated conditions. A literature search was performed using the PubMed search engine. The terms ''steatosis,'' ''steatohepatitis,'' ''nonalcoholic fatty liver disease (NAFLD),'' ''nonalcoholic steatohepatitis (NASH),'' "alcoholic steatohepatitis (ASH)," ''type 2 diabetes (T2DM),'' "cryptogenic cirrhosis," "drug-induced liver injury (DILI)," "immune checkpoint inhibitor therapy," and "COVID-19 and liver" were used. Nonalcoholic fatty liver disease has become the most common chronic liver disease in the United States. NASH is the progressive form of nonalcoholic fatty liver disease. The hallmarks of steatohepatitis are steatosis, ballooned hepatocytes, and lobular inflammation. NASH and alcoholic steatohepatitis share similar histologic features, but some subtle differences may help their distinction. NASH is commonly seen in patients with metabolic dysfunction but can also be caused by other etiologies. Examples are medications including newly developed immune checkpoint inhibitors and viral infections such as coronavirus disease 2019 (COVID-19). NASH is also a common cause of cryptogenic cirrhosis but can be reversed. The results from recent clinical trials for NASH treatment are promising in reducing the severity of steatosis, ballooning, and fibrosis.

Metabolic-associated fatty liver disease-related liver cirrhosis and cryptogenic liver cirrhosis

Metabolic-associated fatty liver disease (MAFLD) is currently the most common chronic liver disease in the world, which may eventually progress to cirrhosis, hepatocellular carcinoma and liver failure. Fatty liver disease was once considered to be the most common cause of cryptogenic cirrhosis. Recently, a new definition of MAFLD suggests that MAFLD-related liver cirrhosis is no longer a kind of cryptogenic cirrhosis, and it belong to two different concepts and may have different liver and extrahepatic adverse outcomes. In this paper, the definition, epidemiology, diagnosis, treatment and other aspects of MALFD-related liver cirrhosis and cryptogenic liver cirrhosis are described in order to facilitate clinical practice, improve the efficiency of clinical research, and benefit clinicians and patients.

Opportunistic Screening for Nonalcoholic Fatty Liver Disease (NAFLD) in Ghana: A Prospective Study

Abstract Objectives Non-alcoholic fatty liver disease (NAFLD) is a leading cause of cryptogenic cirrhosis and liver transplant in the United States. It is associated with increased length of stay and poor surgical outcomes. NAFLD affects approximately 30% of American adults, and even more Africans. However reported rates of NAFLD in African countries vary widely, where recent studies have shown that up to 50–87% Africans are could be living with NAFLD. The objective of this study was to estimate the prevalence of NAFLD in Ghana and to assess whether NAFLD is associated with increased length of stay and surgical complications. Methods A prospective study on 96 surgical patients aged 18 and older, without a history of alcohol abuse or liver disease, who presented at Eastern Reginal Hospital in Ghana for elective general and gynecological procedures between September and December 2018. A single, expert radiologist screened all patients for NAFLD using an abdominal ultrasound machine. NAFLD was diagnosed in conjunction with the American Association for the study of liver disease guidelines, assessing for increased hepatic echogenicity compared to the spleen and kidneys. Patients were followed up for 30 days and information was collected on length of stay and surgical site occurrences (SSO). Univariate analysis and multivariable logistic regression were performed using SAS 9.4. Results Of 97 patients, mean age 46 ± 14 years, mean BMI 26.9 ± 7.7, and 40 (42%) Male, the mean length of stay was 2.7 days ± 2.7 days. Eighteen (19%) patients had a length of stay ≥ 5 days and 9 (9%) developed a SSO. Ultrasonography revealed that 54 (56%) of patients had NAFLD, of which 15 (28%) patients had moderate disease (25–50% of liver), and 39 (72%) had mild (5–25%) disease. Diabetes, hypertension, obesity, and BMI were not associated with NAFLD. NAFLD and sex were independent predictors of an increased length of stay ≥ 5 days, where patients with NAFLD were 5x as likely to have an extended length of stay, but not SSO compared to those without NAFLD (OR: 4.8 95% CI 1.1–18.5). Conclusions Ghana has almost twice the prevalence of NAFLD compared to the United States, suggesting that NAFLD is very common in Africa. It is associated with delayed surgical recovery leading to more than twice the average length of stay. Funding Sources None.

Herbal Medicine in the Treatment of Non-Alcoholic Fatty Liver Diseases-Efficacy, Action Mechanism, and Clinical Application.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease with high prevalence in the developed countries. NAFLD has been considered as one of the leading causes of cryptogenic cirrhosis and chronic liver disease. The individuals with obesity, insulin resistance and diabetes mellitus, hyperlipidaemia, and hypertension cardiovascular disease have a high risk to develop NAFLD. The related critical pathological events are associated with the development of NAFLD including insulin resistance, lipid metabolism dysfunction, oxidative stress, inflammation, apoptosis, and fibrosis. The development of NAFLD range from simple steatosis to non-alcoholic steatohepatitis (NASH). Hepatic steatosis is characterized by fat accumulation, which represents the early stage of NAFLD. Then, inflammation triggered by steatosis drives early NAFLD progression into NASH. Therefore, the amelioration of steatosis and inflammation is essential for NAFLD therapy. The herbal medicine have taken great effects on the improvement of steatosis and inflammation for treating NAFLD. It has been found out that these effects involved the multiple mechanisms underlying lipid metabolism and inflammation. In this review, we pay particular attention on herbal medicine treatment and make summary about the research of herbal medicine, including herb formula, herb extract and naturals compound on NAFLD. We make details about their protective effects, the mechanism of action involved in the amelioration steatosis and inflammation for NAFLD therapy as well as the clinical application.

Cryptogenic cirrhosis: Old and new perspectives in the era of molecular and genomic medicine

Cryptogenic cirrhosis (CC) is defined as cirrhosis of unknown etiology despite extensive clinical, laboratory and pathologic work-up, and constitutes approximately 5-10% of all cirrhosis cases. Histologic examination can provide important clues and help identify the potential etiology of CC. Most CC cases can still be classified into four histologic patterns: hepatitic, steatotic, biliary, and patternless (bland). The use of genetic testing has significantly improved diagnostic ability and treatment, especially in pediatric patients with acute and chronic liver diseases. More recently, whole exome sequencing has been used for identifying genetic alterations that lead to a diagnosis in adults with liver disease of unknown etiology. Recent advances in genomic analysis has allowed the unraveling of the underlying etiology in a subset of CC cases, and also helped identify new disorders. Providing a diagnosis for these patients has several important implications for treatment, possible genetic counseling, and transplant eligibility. However, detailed clinical and histologic characterization of the patients still remains an important part of the CC work-up, since clinicopathologic and genomic correlation is crucial in making a diagnosis, or in some cases, discovery of a new entity. This article summarizes the main histologic findings that can be observed in CC cases, potential causes of CC, and recent advances in the field.

Position statement on the diagnosis and management of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a major national and international health burden. It is one of the most common liver diseases worldwide and the most common cause of abnormal liver enzymes in many developed countries. Non-alcoholic fatty liver disease is also known as an important cause of cryptogenic cirrhosis and second leading cause for liver transplantation. It is commonly associated with metabolic syndrome. Non-alcoholic steatohepatitis (NASH) is the progressive phenotype of NAFLD. In spite of promising performance of non-invasive tools, liver biopsy remains the gold standard test for NASH diagnosis. Over decades, many drugs have been investigated in phase 2 and 3; however, no approved therapy to date. Despite the alarming global rates of NAFLD, there are no local community-based studies on the prevalence of NAFLD or local practice guidelines on its management; this expert review aims to fill this gap.

Seropositive Form of Occult Hepatitis B Virus Infection in Iranian Patients with Cryptogenic Liver Cirrhosis

Background: The causes of cryptogenic cirrhosis, as one of the most important unresolved issues in the management of liver failure, remains unknown. Hepatitis B virus (HBV) infection with a high impact in Iranian liver graft recipients may have a key role in introducing and developing cryptogenic cirrhosis, especially in the occult form. Therefore, the prevalence of occult HBV infection was evaluated in liver transplant recipients with cryptogenic cirrhosis. Methods: In this cross-sectional study, a total of 127 liver transplant recipients with cryptogenic cirrhosis were recruited. The serum samples of patients were evaluated for immunological HBV infective markers, using enzyme-linked immune sorbent assay (ELISA) methods. Moreover, immunohistochemistry (IHC) was used for detection of HBsAg in liver tissue sections. Collected serums and liver tissue samples were also examined for HBV genomic DNA, using a qualitative polymerase chain reaction (PCR) technique. Results: HBsAg was not found in any studied liver tissue or serum samples. However, HBV genomic DNA was found in the liver tissue and serum samples of 35.4% and 36.2% of the liver transplant patients with cryptogenic cirrhosis, respectively. Occult HBV infection was found in 35.4% of the patients with cryptogenic cirrhosis. Seropositive and seronegative types of occult HBV infection were found in 82.2% and 17.8% of the patients, respectively. Conclusions: Findings of the high prevalence of molecular and immunological markers of HBV infection, especially occult ones, in liver transplanted patients with cryptogenic cirrhosis was re-enforced. These results indicate the important role of occult HBV infection in the pathogenesis of cryptogenic cirrhosis, which needs to be evaluated in the future through comprehensive studies.

The ILTS Consensus Conference on NAFLD/NASH and Liver Transplantation: Setting the Stage.

The ILTS Consensus Conference on NAFLD/NASH and Liver Transplantation: Setting the Stage.

Hepatic AMP Kinase as a Potential Target for Treating Nonalcoholic Fatty Liver Disease: Evidence from Studies of Natural Products.

Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is the leading cause of cryptogenic cirrhosis and has consistently been implicated in related metabolic disorders, such as dyslipidemia and type 2 diabetes (T2D). However, the pathogenesis of NAFLD remains to be elucidated, and no established therapeutic regimens for treating NAFLD exist. Adenosine monophosphate (AMP)-activated protein kinase (AMPK), the main cellular energy sensor, has been implicated as a key regulator of hepatic lipid and glucose metabolism. Recently, emerging evidence indicates that many plant-derived natural products are capable of ameliorating NAFLD by targeting AMPK. The published literature in PubMed relating to this topic was searched through June 2016. Significant advances have been made with respect to understanding the protective effects of plant-derived natural products against NAFLD. A variety of natural products, including alkaloids (berberine, demethyleneberberine, nicotine, caffeine, etc.), polyphenols (resveratrol, puerarin, curcumin, caffeic acid, etc.) and other compounds (β- caryophyllene, gastrodin, compound K, betulinic acid, etc.), have demonstrated promising results in preclinical studies. Mechanistic studies of these compounds have focused on their activation of AMPK and its downstream effectors involved in lipid metabolism. The findings of this review confirm that plant-derived natural products capable of activating the AMPK signaling pathway are potential therapeutic agents for NAFLD.

Vitamin D Supplementation and Non-Alcoholic Fatty Liver Disease: Present and Future.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic hepatic disease throughout the Western world and is recognized as the main cause of cryptogenic cirrhosis; however, the identification of an effective therapy for NAFLD is still a major challenge. Vitamin D deficiency is a wide-spread condition which reaches epidemic proportions in industrialized countries, mainly in relation to current lifestyle and limited dietary sources. Epidemiological studies point towards an association between hypovitaminosis D and the presence of NAFLD and steatohepatitis (NASH), independently of confounders such as obesity and insulin resistance. Furthermore, several pieces of experimental data have shown the anti-fibrotic, anti-inflammatory and insulin-sensitizing properties exerted by vitamin D on hepatic cells. However, results from trials evaluating the effects of oral vitamin D supplementation on liver damage in NAFLD and NASH are controversial. The aim of this review is to give an overview of the evidence currently available from clinical trials and to discuss possible shortcomings and new strategies to be considered in future investigations.

Severe reduction of blood lysosomal acid lipase activity in cryptogenic cirrhosis: A nationwide multicentre cohort study

Background and aimsBlood lysosomal acid lipase (LAL) is reduced in non-alcoholic steatohepatitis, which is the major cause of cryptogenic cirrhosis (CC); few data on LAL activity in CC do exist. We investigated LAL activity in a cohort of patients with liver cirrhosis. MethodsThis is a multicentre cohort study including 274 patients with liver cirrhosis of different aetiology from 19 centres of Internal Medicine, Gastroenterology and Hepatology distributed throughout Italy. Blood LAL activity (nmol/spot/h) was measured with dried blood spot extracts using Lalistat 2. ResultsOverall, 133 patients had CC, and 141 patients had cirrhosis by other causes (61 viral, 53 alcoholic, 20 alcoholic + viral, 7 autoimmune). Mean age was 64.2 ± 13.4 years, and 28.5% were women. Patients with CC were older compared to other aetiology-cirrhosis, with a lower Child-Turcotte-Pugh (CTP, p=0.003) and MELD (p=0.009) score, and a higher prevalence of cardio-metabolic risk factors and previous ischemic events. In the whole cohort, median LAL activity value was 0.58 nmol/spot/h, 0.49 and 0.65 in the groups of CC and known-aetiology cirrhosis, respectively (p=0.002). The difference remained significant after adjustment for white blood cells count (p=0.001). Multivariable linear regression analysis showed that CC (vs. known aetiology, Beta = −0.144, p=0.018), platelet count (Beta = 0.398, p < 0.001) and CTP score (Beta = −0.133, p=0.022) were associated with log-LAL activity. Similar results were found using MELD as covariate. ConclusionsWe found a marked reduction of LAL activity in patients with cryptogenic cirrhosis compared to the other known aetiologies. A prospective study will clarify the role of LAL in chronic liver diseases.

Prevalence of Type 2 Diabetes Mellitus and Dyslipidemia in Patients with Cryptogenic Cirrhosis: a Hospital-Based Study

Background: Liver cirrhosis is the end stage of liver disease that is caused by various etiologies. Type 2 diabetes mellitus (T2DM), dyslipidemia and obesity are the most common situations that are seen together with non-alcoholic steatohepatitis (NASH), which is frequently asymptomatic and can silently lead to cirrhosis. There are some studies suggesting that NASH might be one of the underlying causes of cryptogenic cirrhosis (CC). Materials and Methods: Two hundred twenty six cirrhotic patients registered in transplantation unit of Namazi Hospital of Shiraz University of Medical Sciences from January 2006 to the last day of June 2014 were selected in two groups of CC and non-CC patients. Age, sex, weight, child class of cirrhosis and presence of T2DM, dyslipidemia and lipid profile were extracted from their records. Results: There was significant difference between prevalence of T2DM and FBS levels among CC and non-CC subjects (P &lt;0.01). Prevalence of T2DM in CC group (38.9%) was more than two times higher than non-CC group (18.6%). On the contrary, the differences between prevalence of dyslipidemia and its laboratory characteristics such as total cholesterol, TG, HDL and LDL were insignificant among both groups (P &gt;0.05). Conclusion: Results showed a higher prevalence of T2DM in subjects with CC but there are some doubts about T2DM being one of the risk factors of CC. Dyslipidemia and its components including TG, LDL, HDL and total cholesterol were not significantly different in CC and non-CC subjects.[GMJ. 2015;4(3):112-16]

Role of adipokines in the pathogenesis of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome. The increased prevalence of obesity, diabetes, hypertension, hypertriglyceridaemia and hypercholesterolemia are considered to be the potential causative factors for NAFLD. NAFLD is emerging as a major clinical problem worldwide. Recently much attention has been focused in India as the prevalence of obesity and diabetes is rising. NAFLD is responsible for unexplained raise in transaminases, and an important cause of cryptogenic cirrhosis and cryptogenic hepatocellular carcinoma in India. NAFLD is a spectrum of disease ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), potentially leading to fibrosis and cirrhosis. Studies have suggested that the adipokines are involved in the pathogenesis of NAFLD and its progression to NASH, through their metabolic and pro- or anti-inflammatory activity. Adipokines in particular tumor necrosis factor-α and interleukin-6 are believed to mediate the shift in pathology from steatosis to steatohepatitis. In addition, other adipokines such as adiponectin, leptin and resistin also play a crucial role in the development and progression of NAFLD through their metabolic and pro-or anti-inflammatory activity. This suggests that imbalance between pro-inflammatory and anti-inflammatory cytokines may have a role in the development of liver damage in NAFLD. Understanding the relationship between adipokines and NAFLD may play an important role in the early identification/diagnosis, treatment and also help in preventing disease progression.

Role of Serum Adiponectin, IL-6 and Hs CRP in Nonalcoholic Fatty Liver Egyptian Patients

Scientific Background: Non alcoholic fatty liver (NAFLD) is accumulation of fat in the liver cells of peoples who drink little or no alcohol causing mild steatosis with mostly no signs, symptoms or complication but this may progress to steatohepatitis (NASH) and may liver cirrhosis then failure. NAFLD is recognized as the most common type of chronic liver disease in Western countries and the leading cause of cryptogenic cirrhosis. Insulin resistance (IR) is a key factor in the pathogenesis of NAFLD, the latter being considered as the hepatic component of IR or metabolic syndrome (MetS). Although the pathogenesis of NAFLD is not fully elucidated, a complex interaction between adipokines and cytokines produced by adipocytes and/or inflammatory cells infiltrating adipose tissue appears to play a crucial role in MetS and NAFLD and its progress. A number of factors are linked with NAFLD such as obesity, type 2 diabetis mellitus (T2DM), hyperlipidemia, gastric Original Research Article International Journal of Biochemistry Research & Review, 4(6): 493-504, 2014 494 bypass, and its progress to NASH correlate with certain cytokines secreted like adiponectin, interlukin-6 (IL-6), and Creactive protein CRP. Adiponectin is a novel adipocyte-specific protein, which, it has been suggested, plays a role in the development of insulin resistance and atherosclerosis. The role of (IL-6) in liver pathology is very complex, and its participation in the development of NAFLD remains unclear. IL-6 is a key element in the acute phase response, mediating the synthesis of several acute phase proteins (such as CRP and serum amyloid A). Thus, we cannot exclude the possibility that IL-6 might also play an indirect deleterious role in NAFLD pathogenesis. In diet-induced obese mice, treatment with IL-6 antibodies improved sensitivity to insulin. Objective: This study aim is to evaluate the level of adiponectin, IL-6 and CRP in Egyptian patients with NAFLD. Methods: This study was conducted on 2 groups 104 NAFLD as diagnosed by ultrasound examination and 21 healthy participants as control group. All the subjects were subjected to an abdominal ultrasonography, liver enzymes ALT & AST, lipid profile (triglycerides, HDL, LDL, cholesterol, CRP, IL-6 & Adiponectin). Results: Plasma adiponectin levels were significantly lower in NAFLD patients than control gp (3.05±2.65μg/ml vs 10.52±3.35 (μg/ml). IL-6 level was higher in NAFLD than control gp but not significant (114.24±22.32pg/ml vs 104.9±19.98pg/ml). CRP was significantly higher in NAFLD than control gp (17.86±11.59mg/L vs 5.4±3.81mg/L). Adiponectin ROC curve showed an AUROC curve in NAFLD gp (0.918 p=0.0001). IL-6 ROC curve showed an AUROC curve in NAFLD gp (0.703 p=0.0003). CRP ROC curve showed an AUROC curve in NAFLD gp (0.853 p=0.0001). Conclusion: Patients with NAFLD have lower adiponectin levels and higher IL-6 and CRP levels compared with their control group.

HFE Gene Mutations in Cryptogenic Cirrhosis Patients

Dear Editor, In Western countries, HFE-linked hereditary hemochromatosis (HH) is considered to be the most common cause of iron overload. The HFE gene, first identified in 1996, is located on the short arm of chromosome 6. The majority of patients with phenotypic HH are homozygous for the C282Y mutation, a major mutation of the HFE gene, whereas compound heterozygosity (C282Y/H63D) is found in patients with a milder iron loading phenotype [1]. Because hepatic iron overload promotes liver fibrogenesis in HH, it is crucial to know whether the presence of any HFE gene mutations might accelerate liver damage. In a study by Jowkar et al. [2] published in the November issue of Hepatitis Monthly, the C282Y mutation was not detected in cryptogenic cirrhosis patients as well as healthy individuals; however, 22% of the patients and 28% of the healthy individuals were found to be heterozygous for the H63D mutation. Therefore, they concluded that HH is not the major cause of cryptogenic cirrhosis in the Iranian population. Although this study adds to the general knowledge on the molecular genetics of HH in the different regions of Iran, the findings of this study should be debated. We, as well as other researchers, have studied the frequency of HFE gene mutation among Iranian patients with chronic hepatitis and healthy individuals [3][4][5]. In the aforementioned studies, it was found that the allele frequency of the C282Y mutation was between 0% and 0.1%, whereas the allele frequency of the H63D mutation varied between 8.6 and 12.5% in healthy individuals. It is also noteworthy to mention that cryptogenic cirrhosis is a diagnosis of exclusion. Therefore, it is assumed that several of the patients in these studies are in fact alcoholic hepatitis or nonalcoholic steatohepatitis (NASH) patients. The patients' reluctance to admit to alcohol consumption along with the absence of advanced molecular techniques result in a higher number of false positive cases of cryptogenic cirrhosis in Iran. It is also not quite plausible to conclude that "HH is not a major cause of cryptogenic cirrhosis in the Iranian population" as Jowkar et al. have indicated in their study [2]. Perhaps, the authors meant to say that the development of cirrhosis in these patients cannot be attributed to HFE mutations. In the absence of any positive laboratory index of iron overload, there would be no evidence to correlate merely HFE mutations with hepatic cirrhosis even if these patients harbored HFE mutations. Taken together, our understanding of the role of HFE mutations in liver fibrogenesis in the context of viral hepatitis, alcoholic hepatitis, or other unknown accelerating factors is very premature, and further research and broader translational studies are required to unravel the underlying mechanisms.

HFE Gene Mutations in Cryptogenic Cirrhosis Patients

Dear Editor, In Western countries, HFE-linked hereditary hemochromatosis (HH) is considered to be the most common cause of iron overload. The HFE gene, first identified in 1996, is located on the short arm of chromosome 6. The majority of patients with phenotypic are homozygous for the C282Y mutation, a major mutation of the HFE gene, whereas compound heterozygosity (C282Y/H63D) is found in patients with a milder iron loading phenotype [1]. Because hepatic iron overload promotes liver fibrogenesis in HH, it is crucial to know whether the presence of any HFE gene mutations might accelerate liver damage. In a study by Jowkar et al. [2] published in the November issue of Hepatitis Monthly, the C282Y mutation was not detected in cryptogenic cirrhosis patients as well as healthy individuals; however, 22% of the patients and 28% of the healthy individuals were found to be heterozygous for the H63D mutation. Therefore, they concluded that is not the major cause of cryptogenic cirrhosis in the Iranian population. Although this study adds to the general knowledge on the molecular genetics of in the different regions of Iran, the findings of this study should be debated. We, as well as other researchers, have studied the frequency of HFE gene mutation among Iranian patients with chronic hepatitis and healthy individuals [3][4][5]. In the aforementioned studies, it was found that the allele frequency of the C282Y mutation was between 0% and 0.1%, whereas the allele frequency of the H63D mutation varied between 8.6 and 12.5% in healthy individuals. It is also noteworthy to mention that cryptogenic cirrhosis is a diagnosis of exclusion. Therefore, it is assumed that several of the patients in these studies are in fact alcoholic hepatitis or nonalcoholic steatohepatitis (NASH) patients. The patients' reluctance to admit to alcohol consumption along with the absence of advanced molecular techniques result in a higher number of false positive cases of cryptogenic cirrhosis in Iran. It is also not quite plausible to conclude that HH is not a major cause of cryptogenic cirrhosis in the Iranian population as Jowkar et al. have indicated in their study [2]. Perhaps, the authors meant to say that the development of cirrhosis in these patients cannot be attributed to HFE mutations. In the absence of any positive laboratory index of iron overload, there would be no evidence to correlate merely HFE mutations with hepatic cirrhosis even if these patients harbored HFE mutations. Taken together, our understanding of the role of HFE mutations in liver fibrogenesis in the context of viral hepatitis, alcoholic hepatitis, or other unknown accelerating factors is very premature, and further research and broader translational studies are required to unravel the underlying mechanisms.

Author’s Reply: HFE Gene Mutations (C282Y and H63D) in a Group of Patients With Cryptogenic Cirrhosis

Dear Editor, I would like to thank Dr Sendi and Mohseni for their interest in our study.In this letter the authors have summarized the contributory effects of hereditary hemochromatosis (HH) in liver diseases in different populations [1]. I completely agree with them concerning the underlying causes of cryptogenic cirrhosis which in countries such as Iran is most commonly nonalcoholic steatohepatitis (NASH). In our study we tried to demonstrate that the epidemiology of the HH and HFE gene mutation in Iran is completely different from that found in the West, and also to emphasize the infrequency of the C282Y mutation in Iran [2]. In recent publications from countries such as India, similar results were found and all the data were in favor of a minor contributory role of HH in the development of cirrhosis in these countries which is different from in the West [3]. Finally I want to emphasize the effect that the presence of the HFE gene mutation has on the fibrogenesis of other liver diseases such as alcoholic or viral hepatitis [4] and this should be investigated in future studies in Iran.