Kind Of Liver Disease Research Articles

Prediction of liver diseases with Random Forest classifier with principal component feature extraction

Liver disease is one of the most major illnesses that has a negative influence on the normal, healthy stature of a human being. This is because many different factors may lead to liver disease. The liver is the organ that is most often afflicted by liver disease even though it is the largest organ found inside the body. A few examples of the various subtypes of liver illness include fatty liver disease, cirrhosis, hepatitis, chronic liver disease, liver cancer, liver tumors, and other kinds of liver disease. This study creates machine learning algorithms to enhance the prediction of liver disease using various data balancing techniques, such as the Synthetic Minority Oversampling Technique (SMOTE) with Edited Nearest Neighbourhood (ENN). The traits that were derived from SMOTE-ENN balanced features are then normalised using the principal component analysis (PCA) method. In addition, approaches like as correlation and skewness are used to clean the dataset and minimize the number of features. Finally, the prediction operation is carried out by a Random Forest classifier with PCA extracted and SEMOTE-ENN balanced features. The simulations conducted liver-disease dataset show that the proposed method results in improved performance over existing methods.

Hepatitis B Screening Program for patients attending out-patient department (OPD) at Sir Salimullah Medical College Mitford Hospital, Dhaka – An Observational Study

Background: Hepatitis B (HBV) is a major cause of chronic hepatitis, cirrhosis of liver and hepatocellular carcinoma in Bangladesh. It is also the most common cause of death from liver disease in the country. The prevalence of hepatitis B is 5-6% in the general population. So the present status of the virus is considered as an important public health concern of Bangladesh. Objectives: To investigate hepatitis B prevalence among the persons attending the OPD and to increase awareness about hepatitis B. Materials and methods: A cross-sectional observational study was carried out the at the Department of Hepatology, Sir Salimullah Medical College Mitford Hospital, Dhaka on March 17&18, 2022 at Special Treatment Campaign on the occasion of celebration of the birth anniversary of the Father of Nation, Bangabandhu Sheikh Mujibur Rahman. A total of 190 people of both sexes from 18 years to 50 years of age group were enrolled in the study. These people were unaware of whether they were carrying hepatitis B virus or also was not aware of whether they are suffering from any kind of liver disease. Informed consent was taken and a pre-designed structured questionnaire was used. Screening was done by HBsAg detection using rapid diagnostic kit. Result: The mean age of respondents was 35.95±6.42 years with a male to female ratio of 0.83. Most of the respondents were married (72.63%) and Muslim (87.37%). Among them 47.36% of the respondents were service holders. Only 17.89% had a previous history of some types of hepatitis. 25.26% of respondents had history of different types of surgical procedure. 8 (4.2%) participants were found positive for HBsAg on the screening test in our study. Conclusion: This study shows 4.2 % of participants were screening positive among the respondents. This correlate with the intermediate prevalence of hepatitis B in Bangladesh as stated in World Health Organization data. Screening program increases knowledge and awareness among the population and thereby increase treatment seeking, which ultimately reduce incidence of disease and complications as well as death. Sir Salimullah Med Coll J 2023; 31: 3-8

Integrating metabolomics and network pharmacology to reveal the mechanisms of Delphinium brunonianum extract against nonalcoholic steatohepatitis

Ethnopharmacological relevanceHerba Delphinii Brunoniani, a Tibetan Material Medica, derived from the aerial parts of Delphinium brunonianum Royle, possesses efficacy of cooling blood to remove apthogentic heat, and dispelling wind to arrest itching, and has been used for the treatment for liver disease according to Tibetan Medicine Theories in Shel Gong Shel Phreng. However, the mechanisms of action remain unclear. Aim of the studyThis work aimed to investigate the efficacy mechanism of Delphinium brunonianum extract (DBE) on nonalcoholic steatohepatitis (NASH), a kind of liver disease by integrating serum metabolomics and network pharmacology analysis. Materials and methodsIn this study, NASH model mice were established by a high-fat diet. The indexes of lipid accumulation, insulin resistance, and inflammatory reaction were used to evaluate the efficacy of DBE. A combination of UHPLC-QTOF-MS based metabolomics and network pharmacology was established to illustrate the serum biomarkers of NASH mice and to demonstrate the anti-NASH mechanisms of DBE. Serum metabolomics demonstrated potential metabolites and the corresponding metabolic pathways in the efficacy of DBE. Network pharmacology screened the targets of DBE against NASH. Finally, the mechanisms of DBE against NASH were verified by in-vivo pharmacology. ResultsMetabolomics revealed that DBE significantly regulated the abnormal levels of twenty-two metabolites, which involved the biosynthesis of unsaturated fatty acids and steroid hormone, linoleic acid metabolism, arachidonic acid metabolism, and alpha-Linolenic acid metabolism pathways. Network pharmacology showed that DBE exhibited anti-NASH effects through regulating the targets of PTGS2, PLA2, ALOX5, ALOX15, FASN, and CYP450. Finally, united pharmacological verification result, we found that the mechanisms of DBE against NASH may be related to the regulation of the unsaturated fatty acids biosynthesis and the arachidonic acid metabolism pathway. ConclusionsIntegrating serum metabolomic and network analysis, we found that DBE might inhibit the pathological process of NASH by regulating the relative targets and the metabolic pathways, which may be a potential mechanism for the anti-NASH efficacy of DBE. This integrated strategy also provided a rational way for revealing the pharmacodynamic mechanisms of multi-components, multi-targets, and multi-pathways in Traditional Chinese Medicine (TCM).

Metabolomic profiling and discrimination of autoimmune hepatitis, primary biliary cholangitis, and overlap syndrome

<p indent="0mm">Autoimmune liver disease (AILD) is a kind of liver disease caused by immune dysfunction, including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and overlap syndrome (OS). In AILD patients, the immune system attacks the liver, and elevated autoantibodies can be found in serum. AIH and PBC are two kinds of AILD with high incidence, and their pathogenesis is different. AIH is characterized by interfacial hepatitis caused by the autoimmune system attacking hepatocytes. The clinical features of PBC are non-suppurative, destructive cholestasis resulting from immune damage affecting the interlobular bile ducts. Due to the complex and promiscuous pathogenesis of autoimmune diseases and the low specificity of clinical features, challenges remain in the clinical diagnosis of AILD. Liver biopsy results are necessary for the accurate diagnosis of AILD, but biopsy is not conducive to the prognosis of patients, and the pathological changes of patients may be non-specific. Therefore, the need of finding serological metabolites with low high specificity and invasive features becomes urgent. Metabolomics has unique advantages in reflecting the overall pathophysiological changes of the body by analyzing the metabolites. Untargeted metabolomics has been widely used in the study of liver-related diseases and has good application value for clinical diagnosis. In this study, we attempted to characterize the metabolic signatures of autoimmune liver diseases by serum metabolomics. A mass spectrometry-based untargeted metabolomics study was performed on the serum of AIH (<italic>n</italic>=42), PBC (<italic>n</italic>=103), and AIH-PBC OS (<italic>n</italic>=57) patients. The differentiable metabolites for PBC and AIH samples were obtained by principal component analysis and orthogonal partial least-squares-discriminant analysis, which consisted of the metabolomic signatures. Among the metabolomic signatures, the fingerprint metabolites were further extracted by clustering analysis using the values of area under the curve (AUC) of each differentiable metabolite, binary logistic regression model, and variable importance projection scores. 101 signature metabolites from all metabolite variables were identified, and 29 fingerprint metabolites were further screened out and enriched in bile, phospholipids, and amino acids metabolisms pathway, with most classification ability to distinguish PBC and AIH. The eigenmetabolite compressed from the fingerprint metabolites visualized the significant difference between PBC and AIH (<italic>P</italic>&lt;0.0001) and achieved a good potential for classification (AUC=0.797). Based on fingerprint metabolites, AIH and PBC samples could be separated into three zones, the “pure zone” of PBC, the “pure zone” of AIH, and the mixture zone of PBC and AIH. We put OS samples into the model and found that samples showed different distribution characteristics in three zones, indicating that OS patients according to the current diagnostic criteria have different metabolic characteristics and etiological tendencies, requiring a more accurate diagnosis. This study revealed a metabolic outlook for AIH, PBC, and their overlap syndrome, and the diagnostic model based on fingerprint metabolites with the potential ability to facilitate precise diagnosis and management of patients with autoimmune liver diseases.

Hepatocellular carcinoma in nonalcoholic fatty liver disease: A growing challenge.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide, and its prevalence increases continuously. As it predisposes to hepatocellular carcinoma both in the presence and in the absence of cirrhosis, it is not surprising that the incidence of NAFLD-related hepatocellular carcinoma would also rise. Some of the mechanisms involved in hepatocarcinogenesis are particular to individuals with fatty liver, and they help explain why liver cancer develops even in patients without cirrhosis. Genetic and immune-mediated mechanisms seem to play an important role in the development of hepatocellular carcinoma in this population. Currently, it is consensual that patients with NAFLD-related cirrhosis should be surveilled with ultrasonography every 6 mo (with or without alpha-fetoprotein), but it is known that they are less likely to follow this recommendation than individuals with other kinds of liver disease. Moreover, the performance of the methods of surveillance are lower in NAFLD than they are in other liver diseases. Furthermore, it is not clear which subgroups of patients without cirrhosis should undergo surveillance. Understanding the mechanisms of hepatocarcinogenesis in NAFLD could hopefully lead to the identification of biomarkers to be used in the surveillance for liver cancer in these individuals. By improving surveillance, tumors could be detected in earlier stages, amenable to curative treatments.

Comparative analysis of the expression profiles of genes related to the Gadd45α signaling pathway in four kinds of liver diseases.

Gadd45α (growth arrest and DNA damage inducible alpha) is a member of a group of genes whose transcript levels are increased following stressful conditions that lead to growth arrest and treatment with agents that lead to DNA damage. Gadd45α is upregulated in liver cirrhosis (LC), hepatic cancer (HC), acute liver failure (AHF) and non-alcoholic fatty liver disease(NAFLD). Here, we investigated the essential differences in the Gadd45α signaling pathway in these diseases at the transcriptional level. The results showed that 44, 46, 71 and 27 genes significant changes in these diseases, and the H-cluster showed that the expression of the Gadd45α signaling-related genes was significantly different in the four liver diseases. DAVID functional analysis showed that the Gadd45α signaling pathway-related genes were mainly involved in cell adhesion and migration, cell proliferation, apoptosis, stress and inflammatory responses, etc. Ingenuity pathway analysis (IPA) software was used to predict the functions of the Gadd45α signaling-related genes, and the results indicated that there were significant changes in cell differentiation, DNA damage repair, autophagy, apoptosis and necrosis. Gadd45α signaling pathway is involved in four kinds of liver disease and regulates a variety of activities via P38 MAPK, NF-κB, mTOR/STAT3, P21, PCNA, PI3K/Akt and other signaling pathways. Modulation of Gadd45α may be exploited to prevent the progression of liver disease, and to identify specific treatments for different stages of liver disease. In summary, the Gadd45α signaling pathway is involved in four kinds of liver disease and regulates a variety of physiological activities through various signaling pathways.

Effect of Sichuan Pickle Lactobacillus on Preventing Non‐Alcoholic Fatty Liver by Regulating Intestinal Function in Mice

NAFLD is a kind of liver disease with great harm. It is caused by excessive nutrition that leads to excessive weight gain and overweight. The incidence of NAFLD in obese people is much higher than that in normal weight people. Therefore, weight loss is the first choice for most NAFLD patients. Traditional Sichuan pickle is a kind of food made from pickled vegetables with a certain concentration of salt water, which is mainly fermented by lactic acid, acetic acid and alcohol. Lactic acid bacteria play a key role in its fermentation process. In this study, the NAFLD (nonalcoholic fatty liver disease) model of C57BL/6N mice was established by high‐fat diet, and the effect and mechanism of a Lactobacillus isolated from Sichuan pickle on the prevention of NAFLD by regulating the intestinal function of mice were observed. In this study, 16S rDNA technology was used for microbial identification. After establishing the NAFLD model, the serum, liver, epididymis, small intestine and feces of mice were detected by biochemical and molecular biological methods. The identification results showed that the target strain was a Lactobacillus plantarum strain, named as LactoLactobacillus plantarum CQPC11 (LP‐CQPC11). The in vivo results showed that LP‐CQPC11 could effectively reduce the body weight, liver weight and liver index of NAFLD mice. The results of serum test showed that LP‐CQPC11 could reduce the levels of ALT, AST, AKP, TC, TG, LDL‐C and increase the levels of HDL‐C in the serum of NAFLD mice (model group); meanwhile, LP‐CQPC11 could also reduce the cytokine levels of IL‐1β, IL‐4, IL‐6, IL‐10, TNF‐α and INF‐γ in the serum. The pathological results also showed that LP‐CQPC11 could improve the pathological changes of liver, epididymis and small intestine caused by NAFLD, and protect the body tissues. Further qPCR and Western blot results showed that LP‐CQPC11 could up regulate the mRNA and protein expression of LPL, PPAR‐α, CYP7A1, CPT1 and down regulate the expression of PPAR‐γ, C/EBP‐α in the liver of NAFLD mice; in addition, LP‐CQPC11 could also up regulate the expression of occludin, ZO‐1 and down regulate the expression of CD36, TNF‐α in the small intestine of NAFLD mice. The results showed that LP‐CQPC11 could reduce the level of Firmicutes and improve the level of Bacteroides and Akkermansia in the feces of NAFLD mice. At the same time, LP‐CQPC11 could also reduce the proportion of Firmicutes/Bacteroides and regulate the intestinal microecology. It can be seen that LP‐CQPC11 can improve the intestinal environment of NAFLD mice, so as to prevent NAFLD, and the effect is positively correlated with its dose.Support or Funding InformationThis work was supported by Research Project of Chongqing University of Education (KY2015TBZC) and Science and Technology Research Project of Chongqing Education Commission (KJZD‐K201901601), China.

Meta-analysis of the association between MBOAT7 rs641738, TM6SF2 rs58542926 and nonalcoholic fatty liver disease susceptibility

Nonalcoholic fatty liver disease (NAFLD) is a kind of liver disease caused by factors other than excessive alcohol use. It is the leading cause of liver injury in developed countries. The membrane-bound O-acyltransferase 7 (MBOAT7) and transmembrane 6 superfamily member 2 (TM6SF2) are associated with lipid metabolism. Studies found a mutation on MBOAT7, rs641738 and another on TM6SF2, rs58542926 were associated with liver diseases, including NAFLD. However, the results were inconclusive and inconsistent. In the present meta-analysis, the databases Pubmed, Embase, Chinese National Knowledge Infrastructure, and Chinse Biomedical Literature Database were searched for related studies. The deadline of publications was July 10th, 2018. The data from included studies were extracted by 2 independent investigators. STATA 12.0 software was used in the present meta-analysis. A total of 9 papers with 20 studies, including 5415 cases and 17896 controls were identified for the meta-analysis. The results indicated lower risks of NAFLD for CC genotype of TM6SF2 rs58542926 in homozygous, heterozygous, dominant and recessive models (CC vs. TT: OR = 0.33; CC vs. CT: OR = 0.58; CC vs. CT + TT: OR = 0.64; CC + CT vs. TT: OR = 0.32). These decreased risks of NAFLD also existed in Asians in all genetic models except allelic model, and in Caucasians in the heterozygous model (CC vs. CT, OR = 0.52) and the dominant model (CC + CT vs. TT, OR = 0.50). No association existed between MBOAT7 rs641738 and NAFLD risks in all genetic models (CC vs. TT: OR = 0.91; CC vs. CT: OR = 0.96; CC vs. CT + TT: OR = 0.95; CC + CT vs. TT: OR = 0.91; C vs. T: OR = 0.99). CC genotype of TM6SF2 rs58542926 was associated with a significantly lower risk of NAFLD, while MBOAT7 rs641738 was not related to NAFLD risks.

Prevalence and current therapy in chronic liver disorders.

Herbal medicine plays an important role in health, particularly in remote parts of developing areas with few health facilities. According to WHO estimates, about three-quarters of the world's population currently use herbs or traditional medicines to treat various ailments, including liver diseases. Several studies have found that the use of medicinal plants was effective in the treatment of infectious and non-infectious diseases. Hepatitis and liver cirrhosis associated with many clinical manifestations can be treated with allopathic medicines, but reports of a number of side effects including immunosuppression, bone marrow suppression, and renal complications have motivated researchers to explore more natural herbal medicines with low or no side effects and with high efficacy in treating hepatic diseases. Databases including PubMed, Medline, and Google Scholar were searched for findings on the hepatoprotective effects of plants. Various medicinal plants are used for the treatment of liver disorders. The range of alternative therapies is huge, and they are used worldwide, either as part of primary health care or in combination with conventional medicine. Hepatoprotective plants contain a variety of chemical constituents including flavonoids, alkaloids, glycosides, carotenoids, coumarins, phenols, essential oil, organic acids, monoterpenes, xanthenes, lignans, and lipids. This review shows that numerous plants are found to contain hepatoprotective compounds. However, further studies are needed to determine their association with existing regimes of antiviral medicines and to develop evidence-based alternative medicine to cure different kinds of liver disease in humans.

On a Multi‐Scale and Multi‐Phase Model of Paracetamol‐induced Hepatotoxicity for Human Liver

AbstractMore than 650 Million people worldwide suffer from a certain kind of liver disease. One of the most common disease is the non‐alcoholic fatty liver disease (NAFLD) which affects about 20‐30 % of the population in industrial countries. During a NAFLD fat is stored in liver cells causing tissue growth which impacts blood perfusion inside the liver. The liver is responsible for detoxification of drugs and toxins, e.g. the pain killer Paracetamol. However high dosages of toxic metabolites can harm the liver. The detoxification is perfusion‐dependent, due to the substances transported by the blood flow. To understand and predict the processes during a liver disease, we have developed a computational model using a multi‐scale and multi‐phase function‐perfusion approach basend on the Theory of Porous Media (TPM).

Portal hypertensive colopathy in Egyptian cirrhotic patients: an endoscopic study

BackgroundHepatitis C virus (HCV) infection is a major health problem in Egypt. It is often complicated by liver cirrhosis and portal hypertension, resulting in gastroesophageal varices, gastropathy, and colopathy. However, there is still lack of data with respect to the prevalence and clinical relevance of colopathy in this kind of liver disease. The aim of this study was to determine the prevalence of colopathic lesions in HCV-related cirrhotic patients, and to study their associations with the severity of liver disease and manifestations of portal hypertensionPatients and methodsThis cross-sectional study included 60 patients with liver cirrhosis who were submitted to thorough clinical, laboratory, and ultrasonographic examinations. In addition, both upper and lower gastrointestinal endoscopy were performed to detect portal hypertensive complications including colopathic lesions. According to their severity, colopathic lesions were graded into three grades. Patients with higher colopathic grading (grade 2 and 3) were compared with the remaining participants with respect to the severity of the liver disease and other manifestations of portal hypertension.ResultsThe prevalence of colopathy in cirrhotic patients with underlying HCV etiology was 91%. Patients with higher grades of colopathy were characterized by more severe liver disease. Moreover, they had increased frequency of both esophageal and gastric varices, and prior sclerotherapy or band ligation, as well as more collaterals and gastropathy, and higher grades of esophageal varices.ConclusionColopathic lesions are frequent in patients with HCV-induced cirrhosis. Getting endoscopic treatment for varices is a risk factor for developing higher grades of colopathy. The latter could be considered as a marker of a worse prognosis in patients with HCV cirrhosis.

High-throughput chinmedomics strategy for discovering the quality-markers and potential targets for Yinchenhao decoction

BackgroundYinchenhao decoction (YCHD) has been widely applied in the clinic for various kinds of liver disease, especially for the therapy of dampness-heat jaundice syndrome (DHJS). Some studies have investigated the pharmacological activity and compositions of YCHD. However, its Q-markers and the action targets are still unrevealed. PurposeThis work aims to clarify the therapeutic effect of YCHD against DHJS and discover the quality-markers (Q-markers) of YCHD based on the high-throughput chinmedomics strategy and then predict the potential targets and action mechanism of YCHD against DHJS. MethodsUltra-high performance liquid chromatography/mass spectrometry (UPLC-MS) combined with pattern recognition method was utilized to analyze serum samples and urine samples. Multivariate data analysis and network pharmacology technology were used to identify the effective components and biomarkers associated with therapeutic effects. ResultsWith the high sensitivity UPLC-MS technology, a total of 69 compounds from YCHD were identified and 41 of them were absorbed in blood. Besides, 34 urine biomarkers from DHJS were identified. Of note, we utilized chinmedomics technology on the correlation analysis of urine biomarkers and absorbed components to determine 9 core-compounds as the Q-markers responsible for the efficacy of YCHD. Finally, a total of 12 potential targets were discovered. ConclusionThis work provides a powerful method for clarifying the efficacy of TCM and discovering the effective ingredients as Q-markers.

English

Liver cirrhosis (LC) is a kind of liver disease which is pathologically characterized by abnormality and necrosis of hepatic cells, proliferation of fibrous tissue, nodular regeneration and pseudolobule formation. To explore the mechanism of LC occurrence at the level of mRNA, Rat Genome 230 2.0 Array was used to detect gene expression profiles of rat fibrotic livers in 3, 6 and 9 weeks after CCl4 treatment in this study. It was found that a total of 305 genes including 153 up-regulated, 150 down-regulated and 2 up/down-regulated genes, were related to LC occurrence. Then, k-means clustering was employed to classify above 305 genes into 5 clusters based on gene expression similarity, and EASE analysis further indicated that the above genes were mainly associated with metabolic process, stress reaction, cell growth and apoptosis/death. Thereafter, ingenuity pathway analysis (IPA) software was used to analyze potential effects of the above-mentioned 305 genes, and the results suggested that lipid metabolism and cell growth were inhibited while cell apoptosis/death was activated, but immune/inflammatory response was first activated and then inhibited. Furthermore, IPA also predicted that several signal pathways “ERK/MAPK Signaling”, “p38 MAPK”, “Endothelin-1 Signaling”, “Growth Hormone Signaling”, “LPS/IL-1-mediated inhibition of RXR function” and “IL-6 Signaling” were involved in regulating the occurrence of liver cirrhosis. It was concluded that 305 genes and 3 kinds of physiological activities were closely related to LC occurrence. Key words: Liver cirrhosis, gene expression profile, systems biology analysis, physiological activity.

Multiplex Reverse Transcriptase-PCR for Simultaneous Detection of Hepatitis B, C, and E Virus

The hepatitis B virus (HBV), HCV, and HEV may occur as singly or concurrently in patients of different kind of liver disease. The rapid, reliable, and cost-effective screening of these pathogens is required for the large epidemiological studies. Therefore, a study has been planned to develop a multiplex Reverse Transcriptase-PCR assay which can be used for the screening of maximum number of pathogens at a time. To develop multiplex Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) assay for simultaneous detection of HBV, HCV, and HEV; the serum samples of 54 patients who were positive either singly or in co-infection with for HBV, HCV, and HEV serologically were screened by uniplex PCR/RT-PCR followed by multiplex RT-PCR for HBV, HCV, and HEV using specific primers. These primers can detect most genotypes of these viruses. Multiplex RT-PCR was done in one tube for the identification of viral DNA/RNA using a mixture of three pairs of specific primers for hepatitis B, C, and E viruses. Representative positive samples of these viruses by uniplex/multiplex RT-PCR were also confirmed by sequencing followed by alignment with reference strains sequence. The specificity of multiplex PCR was 100% with high sensitivity 89%, 87%, and 74% for HBV, HCV, and HEV respectively. The sensitivity and specificity of RT-multiplex PCR demonstrated a good correlation with that of uniplex PCR. The study suggests that multiplex RT-PCR can serve as a simple and reliable assay for rapid, sensitive, and cost-effective method for simultaneous detection of super-infections with HEV particularly in Asian countries as a cause of decompensation of chronic liver disease.

Refined method for estimating medical expenditures for liver disease using the patient survey and claim data in Japan.

This study was performed to develop a estimation method for medical expenditures based on detailed data for the various kinds of liver disease. Using claim data from the Survey of National Medical Care Insurance Services and the Patient Survey in Japan, we estimated the medical expenditures for various liver diseases using a refined method, in which the amount of expenditure by age and sex was multiplied by the respective numbers of patients. According to our estimates, the total medical expenditures per year for all liver diseases in Japan was 680 billion yen. The breakdown included: viral hepatitis (256 billion yen); malignant neoplasms of the liver and intrahepatic bile ducts (170 billion yen); cirrhosis of the liver (97 billion yen); other liver diseases (63 billion yen); chronic hepatitis (61 billion yen); and alcoholic hepatitis (33 billion yen). These are the first published estimates, not only for the total medical expenditure for all liver diseases, but also for individual categories. The method we employed in this study can readily be applied to estimate medical costs for other diseases.

Role of NADPH Oxidases in Liver Fibrosis

Hepatic fibrosis is the common pathophysiologic process resulting from chronic liver injury, characterized by the accumulation of an excessive extracellular matrix. Multiple lines of evidence indicate that oxidative stress plays a pivotal role in the pathogenesis of liver fibrosis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is a multicomponent enzyme complex that generates reactive oxygen species (ROS) in response to a wide range of stimuli. In addition to phagocytic NOX2, there are six nonphagocytic NOX proteins. In the liver, NOX is functionally expressed both in the phagocytic form and in the nonphagocytic form. NOX-derived ROS contributes to various kinds of liver disease caused by alcohol, hepatitis C virus, and toxic bile acids. Recent evidence indicates that both phagocytic NOX2 and nonphagocytic NOX isoforms, including NOX1 and NOX4, mediate distinct profibrogenic actions in hepatic stellate cells, the main fibrogenic cell type in the liver. The critical role of NOX in hepatic fibrogenesis provides a rationale to assess pharmacological NOX inhibitors that treat hepatic fibrosis in patients with chronic liver disease. Although there is compelling evidence indicating a crucial role for NOX-mediated ROS generation in hepatic fibrogenesis, little is known about the expression, subcellular localization, regulation, and redox signaling of NOX isoforms in specific cell types in the liver. Moreover, the exact mechanism of NOX-mediated fibrogenic signaling is still largely unknown. A better understanding through further research about NOX-mediated fibrogenic signaling may enable the development of novel anti-fibrotic therapy using NOX inhibition strategy. Antio

GROWTH ENHANCEMENT OF SCHIZOSACCHAROMYCES CERVEVISIAE WITH HEARBS EXTRACTS TO PREPARE A POTENT KAMBUCHA (TEA) FORMULA THAT CORRECTED LIVER PATIENT DISEASES OF MALE &amp; FEMALE HUMANS STUDY IN THERAPEUTIC NUTRITION.

To enhance the growth of Schizosaccharomyces cervevisiae the principal microorganism Kambucha a total number of 14 herbs were used with the black tea .Herbs with vary thick growths (3herb) were excluded and the remained herbs (Ammi visnage, Cassia Occidentalis,, Cichorium Inty bus, Erythraea Centaurium, Hibiscus sabdoriffa sabdariffa, Hordeum vulgare, Matricaria chamomilla, Rheum Rhoponticum , salvia officinalis , thymus vulgaris, Rosmarinus officinalis ) were used to purpose 6 groups of herb blends .such blends on (with a control with only tea )were is used, and only 3 of them were selected based on the most proper growth of Kambucha pellicle. The liquid (tea) of these three groups were mixed at the ratio (1:1:1 v/v/v) and the final liquid (called also Kambucha tea) was given to liver patients (1cup) with a cup of warm water and one tablespoon of bee honey for 3 months & on this steps (1,2&3 times a day in the 1st,2nd and 3rd month respectively) Liver out patients of present study (males & Females) were 10-63 years old and the trial was with participation of a doctor (consultant of liver and immunity).Food habits revealed good practices such as like fresh vegetables & fruits and preferring boiling for cooking; or and other not correct as 31.9% of females and 9.0% of females drink only 500 ml of liquid per day .Out patients had also other disease ( besides liver disease) such as hypertension, diabetes ,gout ,gravel, anemia osteoporosis , renal failure , and others. They suffer of different kinds of liver disease (fatty liver fibrosis, liver cancer, HAV, HBV, MCV, HBV+HCV and hypertrophy +spleenomegaly);also parasitic infection, nasal hemorrhage ,ascites ,trema and dizziness were found .Suggested treatment of present work corrected the level of GPT,GOT,ALB ,BIL ,ALK.P & T. prot. to nearly the normal level ,indicating the value of this remedy.

Nonalcoholic steatosis and steatohepatitis IV. Nonalcoholic fatty liver disease abnormalities in macrophage function and cytokines.

Macrophage products, such as cytokines, prostanoids, nitric oxide, and reactive oxygen intermediates, influence the function and viability of macrophages and neighboring cells. Given that the liver has one of the largest resident macrophage populations in the body, it is not surprising that hepatic macrophages [i.e., Kupffer cells (KC)] are involved in the pathogenesis of many kinds of liver disease. This review summarizes the abnormalities that have been demonstrated in bone marrow, peritoneal and hepatic macrophage of leptin-resistant (fa/fa) rats and leptin-deficient (ob/ob) mice, two animal models for nonalcoholic fatty liver disease (NAFLD). Evidence supports the concept that altered KC function influences the viability of other cells, such as lymphocytes and hepatocytes, in fatty livers, thereby contributing to the pathogenesis of NAFLD in animals with reduced leptin activity. Further work is needed to determine whether KC dysfunction is a component of more generalized mechanisms that lead to NAFLD.

Drug-Induced Hepatic Disorders

Drug-induced liver injury has been associated with more than 800 different drugs, leading to hospital admission in 1 of 600 to 3500 admissions. This amounts to 2 to 3% of all hospitalisations due to adverse drug reactions, or about 3% of all jaundiced patients. The prognosis of clinically overt drug hepatotoxicity is relatively serious. The clinical picture is essentially nonspecific, with a highly variable latency period from days to years. Drug hepatotoxicity can mimic almost any kind of liver disease. A thorough drug history, a low threshold of suspicion and the exclusion of other causes of liver disease are important for the detection of drug-induced liver disorders. Treatment consists of discontinuation of suspected drug(s), acetylcysteine in the course of paracetamol (acetaminophen) toxicity, and liver transplantation in selected cases of fulminant liver failure. Guidelines regarding the use of selected drugs such as methotrexate and halothane should be followed. Potentially hepatotoxic drugs should be used cautiously in alcoholic patients with or without liver involvement. Patients with uncompensated liver disease should receive a reduced dose of drugs adjusted to the degree of liver function impairment. The general public should be warned against abuse of hepatotoxic drugs such as paracetamol and anabolic steroids.

METAL ANALYSIS BY PIXE IN THE LIVER TISSUE FROM PATIENTS WITH LIVER DISEASES

We used the particle induced X-ray emission (PIXE) spectrometry to perform elemental analysis of liver biopsy materials from patients with three different kinds of liver diseases; acute hepatitis, chronic hepatitis and liver cirrhosis. We compared the Cu/Fe and Zn/Fe concentration ratios in these different liver diseases. There was no significant difference in the ratios because of the kind of liver disease. However, we found a positive correlation between the Cu/Fe concentration ratio and both serum GOT (glutamate oxalacetic transaminase) and GPT (glutamate pyruvate transaminase) levels in 14 patients with liver diseases.