scholarly journals Chronic Liver Diseases: From Development to Novel Pharmacological Therapies

2021 ◽  
Author(s):  
Maria Borrello ◽  
Derek Mann
Keyword(s):  
Liver Cirrhosis ◽  
Liver Diseases ◽  
Tissue Injury ◽  
Experimental Models ◽  
Chronic Liver ◽  
Molecular Regulation ◽  
Main Process ◽  
Critical Factors ◽  
Chronic Liver Diseases ◽  
Therapeutic Approaches

Chronic liver diseases comprises a broad spectrum of burdensome diseases that still lack effective pharmacological therapies. Our research group focuses on Fibrosis which is a major precursor of liver cirrhosis. Fibrosis consists in a progressive disturbance of liver sinusoidal architecture characterised by connective tissue deposition as a reparative response to tissue injury. Multifactorial events and several types of cells, participate in fibrosis initiation and progression and the process still needs to be completely understood. The development of experimental models of liver fibrosis alongside the identification of critical factors progressing fibrosis to cirrhosis will facilitate the development of more effective therapeutic approaches for such condition. This review provides an overlook of the main process leading to hepatic fibrosis and therapeutic approaches that have emerged from a deep knowledge of the molecular regulation of fibrogenesis in the liver.

scholarly journals The Role of the Gut Microbiome in Liver Cirrhosis Treatment

2020 ◽  
Vol 22 (1) ◽  
pp. 199
Author(s):  
Na Young Lee ◽  
Ki Tae Suk
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Liver Diseases ◽  
Sclerosing Cholangitis ◽  
Chronic Liver ◽  
Chronic Liver Diseases

Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, diseases such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis and Wilson’s disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease of other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver fibrosis.

scholarly journals Noninvasive, Accurate Diagnosis of Chronic Liver Diseases Using Whole-Transcriptome Profiling of Platelets

2020 ◽  
Author(s):  
Huikun Wu ◽  
Gang Chen ◽  
Tianyuan Zhang ◽  
Mingzhong Xiao ◽  
Ye Xia ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Liver Diseases ◽  
Chronic Liver ◽  
Support Vector ◽  
Rna Seq ◽  
Chronic Liver Diseases

Abstract Background: Hepatocellular carcinoma (HCC) is the most serious tumor in the world. It generally undergoes a series of processes from HBV infection, chronic hepatitis, cirrhosis, and HCC from early to late stages. Patients could benefit from early detection of chronic liver diseases (CLD). Tumor-Educated Platelets play an important role in tumor progression, which maybe a potential biomarker for CLD early diagnosis. Here, we developed a noninvasive liquid biopsy technique using platelet RNA for the early screening of patients with liver diseases. Methods: This study included a total of 163 individuals, including 50 healthy individuals, 39 chronic hepatitis B (CHB) patients, 40 liver cirrhosis (LC) and 34 patients with HCC. Blood was collected before initiation of treatment. Platelet RNA-Seq combined with Support Vector Machine (SVM), was used for the first time to distinguish the different stages of CLD in Asian patients.Results: Developed diagnostic model could distinguished with 92.4% accuracy between 34 HCC and 50 healthy, 89.92% accuracy between 34 patients HCC and 129 non-cancer individuals, and 83.67% between 50 healthy and 113 CLD. Across four different individual types, the accuracy of distinction (healthy/chronic hepatitis B/liver cirrhosis/hepatocellular carcinoma) was 65.31%. This model was internally validated, resulting in optimism-corrected AUC's of 86.8%.Conclusions: Our data indicate that the developed platelet RNA-Seq is a valuable platform for the diagnosis of CLD, providing an effective solution for its diagnosis.

scholarly journals Urisodeoxycholic Acid in Treatment of Liver Cirrhosis

2021 ◽  
Vol 9 (9) ◽  
pp. 1869-1873
Author(s):  
Sangale Mukta
Keyword(s):  
Liver Cirrhosis ◽  
Bile Acid ◽  
Primary Biliary Cirrhosis ◽  
Ursodeoxycholic Acid ◽  
Primary Sclerosing Cholangitis ◽  
Liver Diseases ◽  
Sclerosing Cholangitis ◽  
Chronic Liver ◽  
Biliary Cirrhosis ◽  
Chronic Liver Diseases

Abstract: Ursodeoxycholic acid is a dihy- droxy bile acid with a rapidly expanding spectrum of usage in acute and chronic liver diseases. The various mechanisms of action of this hydrophilic bile acid include direct cytoprotection, detergent action on dysfunctional microtubules, immunomodulation and induction of hypercholer- esis. Its efficacy in primary biliary cirrhosis and primary sclerosing cholangitis as an adjunct to medical therapy has been well established.Ursodeoxycholic acid prolongs survival in primary biliary cirrhosis and it improves biochemical parameters of cholestasis in various other cholestatic disorders including primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, cystic fibrosis and total parenteral nutritioninduced cholestasis. However, a positive effect on survival remains to be established in these diseases. Ursodeoxycholic acid is of unproven efficacy in non- cholestatic disorders such as acute rejection after liver transplantation, non-alcoholic steatohepatitis, alcoholic liver disease and chronic viral hepatitis. This review outlines the present knowledge of the Pharmacology of ursodeoxycholic acid, and presents data from clinical trials on its use in chronic liver diseases. Keywords: Liver cirrhosis, Urisodeoxycholic acid

scholarly journals Involvement of the cytotoxic/suppressor T-cell subset in liver tissue injury of patients with acute and chronic liver diseases

1983 ◽  
Vol 85 (3) ◽  
pp. 657-662 ◽  
Author(s):  
G.R. Pape ◽  
E.P. Rieber ◽  
J. Eisenburg ◽  
R. Hoffmann ◽  
C.M. Balch ◽  
...  
Keyword(s):  
T Cell ◽  
Liver Tissue ◽  
Liver Diseases ◽  
Tissue Injury ◽  
Cell Subset ◽  
Chronic Liver ◽  
Chronic Liver Diseases ◽  
Suppressor T Cell ◽  
T Cell Subset

scholarly journals From Liver Cirrhosis to Cancer: The Role of Micro-RNAs in Hepatocarcinogenesis

2021 ◽  
Vol 22 (3) ◽  
pp. 1492
Author(s):  
Raphael Mohr ◽  
Burcin Özdirik ◽  
Joeri Lambrecht ◽  
Münevver Demir ◽  
Johannes Eschrich ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Diseases ◽  
Treatment Options ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Chronic Liver ◽  
Chronic Liver Diseases ◽  
Micro Rnas ◽  
Almost All

In almost all cases, hepatocellular carcinoma (HCC) develops as the endpoint of a sequence that starts with chronic liver injury, progresses to liver cirrhosis, and finally, over years and decades, results in liver cancer. Recently, the role of non-coding RNA such as microRNA (miRNA) has been demonstrated in the context of chronic liver diseases and HCC. Moreover, data from a phase II trial suggested a potential role of microRNAs as therapeutics in hepatitis-C-virus infection, representing a significant risk factor for development of liver cirrhosis and HCC. Despite progress in the clinical management of chronic liver diseases, pharmacological treatment options for patients with liver cirrhosis and/or advanced HCC are still limited. With their potential to regulate whole networks of genes, miRNA might be used as novel therapeutics in these patients but could also serve as biomarkers for improved patient stratification. In this review, we discuss available data on the role of miRNA in the transition from liver cirrhosis to HCC. We highlight opportunities for clinical translation and discuss open issues applicable to future developments.

scholarly journals Alcohol drinking and risks of liver cancer and non-neoplastic chronic liver diseases in China: a 10-year prospective study of 0.5 million adults

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Pek Kei Im ◽  
Iona Y. Millwood ◽  
Christiana Kartsonaki ◽  
Yu Guo ◽  
Yiping Chen ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Alcohol Consumption ◽  
Liver Cancer ◽  
Liver Diseases ◽  
Alcohol Intake ◽  
Chronic Liver ◽  
Drinking Patterns ◽  
Chronic Liver Diseases ◽  
Alcoholic Fatty Liver

Abstract Background Alcohol consumption is an important risk factor for hepatic neoplastic and non-neoplastic diseases. Questions remain, however, about the relevance to disease risk of drinking patterns and alcohol tolerability, which differ appreciably between Chinese and Western populations. Methods The prospective China Kadoorie Biobank included 512,715 adults (41% men) aged 30–79 years recruited from ten areas during 2004–2008, recording alcohol intake, drinking patterns, and other characteristics. After median 10 years’ follow-up, 2531 incident liver cancer, 2040 liver cirrhosis, 260 alcoholic liver disease (ALD), and 1262 non-alcoholic fatty liver disease (NAFLD) cases were recorded among 492,643 participants without prior cancer or chronic liver disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HR) relating alcohol intake and drinking patterns to each disease. Results Overall, 33% of men and 2% of women drank alcohol regularly (i.e. at least weekly) at baseline. Among male current regular drinkers, alcohol consumption showed positive dose-response associations with risks of several major chronic liver diseases, with HRs per 280 g/week (i.e. around four drinks/day) higher usual alcohol intake of 1.44 (95% CI 1.23–1.69) for liver cancer (n = 547), 1.83 (1.60–2.09) for liver cirrhosis (n = 388), 2.01 (1.77–2.28) for ALD (n = 200), 1.71 (1.35–2.16) for NAFLD (n = 198), and 1.52 (1.40–1.64) for total liver disease (n = 1775). The association with ALD appeared stronger among men reporting flushing (i.e., with low alcohol tolerance). After adjustment for the total amount of weekly alcohol consumption, daily drinkers had significantly increased risk of ALD (2.15, 1.40–3.31) compared with non-daily drinkers, and drinking without meals was associated with significantly greater risks of liver cancer (1.32, 1.01–1.72), liver cirrhosis (1.37, 1.02–1.85), and ALD (1.60, 1.09–2.33) compared with drinking with meals. Female current regular drinkers had significantly higher risk of ALD, but not other liver diseases, than female abstainers. Conclusions In Chinese men, alcohol intake was associated with significantly increased risks of several major chronic liver diseases, and certain drinking patterns (e.g. drinking daily, drinking without meals) may further exacerbate the disease risks.

scholarly journals The Role of the Gut Microbiome in Liver Fibrosis

2020 ◽  
Author(s):  
Na Young Lee ◽  
Ki Tae Suk
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Liver Diseases ◽  
Sclerosing Cholangitis ◽  
Chronic Liver ◽  
Chronic Liver Diseases

Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, genetic conditions such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis, and Wilson’s disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease from other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver cirrhosis.

scholarly journals A quality of life assessment and the correlation between generic and disease-specific questionnaires scores in outpatients with chronic liver disease-pilot study

2017 ◽  
Vol 55 (3) ◽  
pp. 129-137 ◽  
Author(s):  
Milica Obradovic ◽  
Zoran Gluvic ◽  
Nina Petrovic ◽  
Milan Obradovic ◽  
Ratko Tomasevic ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Chronic Hepatitis ◽  
Liver Disease ◽  
Pilot Study ◽  
Liver Diseases ◽  
Alcoholic Hepatitis ◽  
Chronic Liver ◽  
Control Group ◽  
Chronic Liver Diseases ◽  
Healthy Control

Abstract Introduction. Chronic liver diseases (CLD) are an important cause of morbidity and mortality in general population. The aim of this study was to analyze potential differences between patients with CLD and healthy control group, and to estimate the severity of CLD by using simple questionnaires: general health questionnaire (GHQ-12) and chronic liver disease questionnaire (CLDQ). Methods. A cross-sectional pilot study was performed in Zemun Clinical Hospital during years 2014 and 2015. Sixty participants were divided into 4 groups (15 per group): chronic alcoholic hepatitis, other chronic hepatitis, liver cirrhosis, and healthy control group. Entire study population chose one of four offered answers of structured questionnaires GHQ-12 and CLDQ, based on which mean model of end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) scores were calculated. Results. Mean GHQ12 and CLDQ scores were 10.5 and 5.21 ± 1.11 respectively. Regarding certain CLDQ domain scores, a significant difference between alcoholic and non-alcoholic hepatitis groups in the worry domain was observed. Mean MELD score was 7.42 ± 2.89 and did not differ between chronic hepatitis groups, while mean CTP score was 5.73 ± 0.88. A statistically significant correlation was observed between GHQ12 and CLDQ scores (ρ = -0.404, p < 0.01), but not between subjective and objective scores. Conclusions. Mean GHQ12 and CLDQ scores pointed out to general psychological no-distress condition of the studied participants, as well as scarcely expressed CLD-specific complaints. Mean MELD and CTP scores indicated stable chronic liver diseases, with low three-month mortality rates in the cases of chronic hepatitis, as well as determination to Child A group in the case of liver cirrhosis.

scholarly journals Serum Paraoxonase Activity: A New Additional Test for the Improved Evaluation of Chronic Liver Damage

2002 ◽  
Vol 48 (2) ◽  
pp. 261-268 ◽  
Author(s):  
Natàlia Ferré ◽  
Jordi Camps ◽  
Eduard Prats ◽  
Elisabet Vilella ◽  
Antoni Paul ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Chronic Hepatitis ◽  
Liver Damage ◽  
Liver Diseases ◽  
Chronic Liver ◽  
Pon1 Activity ◽  
Activity Measurement ◽  
Chronic Liver Diseases ◽  
Baseline Serum ◽  
Serum Pon1 Activity

Abstract Background: Paraoxonase 1 (PON1) is an ester hydrolase present in serum and in the liver. The aims of the present study were to investigate the following: (a) the relationship between serum PON1 activity alterations and the degree of liver damage in patients with chronic liver disease; (b) the influence of genetic variability on serum PON1 activity; and (c) the efficacy of serum PON1 activity measurement, alone and in combination with standard liver function tests, in the assessment of liver damage. Methods: We studied 68 patients with liver cirrhosis, 107 patients with chronic hepatitis, and 368 apparently healthy volunteers. Baseline and salt-stimulated PON1 activities were measured by the hydrolysis of paraoxon. PON1 genotyping at positions 55 and 192 was analyzed by PCR and restriction isotyping. Results: Baseline and stimulated PON1 activities were decreased (P &lt;0.001) in chronic hepatitis and in liver cirrhosis. PON1 activity was significantly correlated with serum total proteins, albumin, and bilirubin in patients but not in controls. There were no significant differences with respect to allele and genotype frequencies between patients and controls. The combination of baseline serum PON1 with five standard biochemical tests had a higher classification accuracy (94% of patients; 96% of controls) than the five standard tests alone (75% of patients; 96% of controls). ROC plots demonstrated a high diagnostic accuracy for baseline serum PON1 [area under the curve, 0.89 (95% confidence interval, 0.86–0.93) in chronic hepatitis and 0.96 (95% confidence interval, 0.94–0.99) in cirrhosis]. Baseline PON1 provided the highest ROC area for cirrhosis vs controls. Conclusions: The significant decrease of PON1 activity in chronic liver diseases is related to the degree of hepatic dysfunction and not to allelic or genotypic differences. Addition of serum PON1 activity measurement to the current battery of tests may improve the evaluation of chronic liver diseases.

scholarly journals Clinico-biochemical and morphological mapping in chronic liver diseases in patients of the senior age group

2019 ◽  
Vol 11 (3) ◽  
pp. 49-56
Author(s):  
S. V. Stolov ◽  
T. Yu. Yamshchikova ◽  
T. A. Garan ◽  
T. A. Kochergina ◽  
Z. D. Schwazman ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Liver Cirrhosis ◽  
Chronic Hepatitis ◽  
Liver Disease ◽  
Elderly Patients ◽  
Chronic Liver Disease ◽  
Liver Diseases ◽  
Chronic Liver ◽  
Chronic Liver Diseases ◽  
Histological Activity

Diagnosis of chronic liver diseases in elderly patients has its own features due to polymorbidity, multiple organ failure, being subtle the course of the disease. The purpose of the study was to identify correlations of inflammation biochemical parameters and hepatocellular failure with histology in chronic hepatitis (CH) and liver cirrhosis (LC) in elderly patients. Materials and methods. The study included medical records of patients with chronic liver disease (CLD) who died in the Clinical Hospital for War Veterans of Saint Petersburg between 2009 and 2015 (with the average age of 81 year). The diagnosis of chronic hepatitis (45 cases) and chronic cirrhosis (54 cases) was confirmed by postmortem examination. Morphological changes in the liver were described according to Knodell creteria. The degree of inflammatory activity in the liver was evaluated in points (0.1 to 3.0) depending on the level of AST, ALT, -globulin, alkaline phosphatase, -GTP, bilirubin. For similar scoring severity hepatocellular insufficiency (0.13.0) considered total protein, albumin, prothrombin index, fibrinogen. For cirrhotic patients the Child-Pugh criteria were also used. Results. Chronic liver disease (CLD) hepatitis and cirrhosis of the elderly is detected in 1,5% of cases. In most cases, CLD develop secondary to diseases of the cardiovascular system, and are accompanied by subtle symptoms, which limits their life-time diagnosis. The integral evaluation of the process activity degree according to biochemical indices was significantly higher in the group of chronic hepatitis than in the group of liver cirrhosis. Correlations of the inflammation bichemical parameters (AST and / or ALT, -globulin, alkaline phosphatase, -GTP) having a degree of Knodell Histological Activity Group chronic hepatitis and cirrhosis have not been established. The study established correlation of histological activity with total bilirubin levels in both groups of CLD. Integral assessment of hepatocellular deficiency by biochemical indicators of liver cirrhosis group was higher than in the group of chronic hepatitis.

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