Early Stages Of Liver Fibrosis Research Articles

Identification of Early Stage Liver Fibrosis by Modifications in the Interstitial Space Diffusive Microenvironment Using Fluorescent Single-Walled Carbon Nanotubes.

During liver fibrosis, recurrent hepatic injuries lead to the accumulation of collagen and other extracellular matrix components in the interstitial space, ultimately disrupting liver functions. Early stages of liver fibrosis may be reversible, but opportunities for diagnosis at these stages are currently limited. Here, we show that the alterations of the interstitial space associated with fibrosis can be probed by tracking individual fluorescent single-walled carbon nanotubes (SWCNTs) diffusing in that space. In a mouse model of early liver fibrosis, we find that nanotubes generally explore elongated areas, whose lengths decrease as the disease progresses, even in regions where histopathological examination does not reveal fibrosis yet. Furthermore, this decrease in nanotube mobility is a purely geometrical effect as the instantaneous nanotube diffusivity stays unmodified. This work establishes the promise of SWCNTs both for diagnosing liver fibrosis at an early stage and for more in-depth studies of the biophysical effects of the disease.

Sex Drives Functional Changes in the Progression and Regression of Liver Fibrosis.

Liver fibrosis is a common and reversible feature of liver damage associated with many chronic liver diseases, and its onset is influenced by sex. In this study, we investigated the mechanisms of liver fibrosis and regeneration, focusing on understanding the mechanistic gaps between females and males. We injected increasing doses of carbon tetrachloride into female and male mice and maintained them for a washout period of eight weeks to allow for liver regeneration. We found that male mice were more prone to developing severe liver fibrosis as a consequence of early chronic liver damage, supported by the recruitment of a large number of Ly6Chigh MoMφs and neutrophils. Although prolonged liver damage exacerbated the fibrosis in mice of both sexes, activated HSCs and Ly6Chigh MoMφs were more numerous and active in the livers of female mice than those of male mice. After eight weeks of washout, only fibrotic females reported no activated HSCs, and a phenotype switching of Ly6Chigh MoMφs to anti-fibrogenic Ly6Clow MoMφs. The early stages of liver fibrosis mostly affected males rather than females, while long-term chronic liver damage was not influenced by sex, at least for liver fibrosis. Liver repair and regeneration were more efficient in females than in males.

Biased Quantification of Rat Liver Fibrosis-Meta-Analysis with Practical Recommendations and Clinical Implications.

For liver fibrosis assessment, the liver biopsy is usually stained with Masson's trichrome (MT) or picrosirius red (PSR) to quantify liver connective tissue (LCT) for fibrosis scoring. However, several concerns of such semiquantitative assessments have been raised, and when searching for data on the amount of LCT in healthy rats, the results vastly differ. Regarding the ongoing reproducibility crisis in science, it is necessary to inspect the results and methods, and to design an unbiased and reproducible method of LCT assessment. We searched the Medline database using search terms related to liver fibrosis, LCT and collagen, rat strains, and staining methods. Our search identified 74 eligible rat groups in 57 studies. We found up to 170-fold differences in the amount of LCT among healthy Wistar and Sprague-Dawley rats, with significant differences even within individual studies. Biased sampling and quantification probably caused the observed differences. In addition, we also found incorrect handling of liver fibrosis scoring. Assessment of LCT using stereological sampling methods (such as systematic uniform sampling) would provide us with unbiased data. Such data could eventually be used not only for the objective assessment of liver fibrosis but also for validation of noninvasive methods of the assessment of early stages of liver fibrosis.

Comparison of the optimized direct spectrophotometric serum prolidase enzyme activity assay method with the currently used spectrophotometric assay methods and liver fibrosis indexes to distinguish the early stages of liver fibrosis in patients with chronic hepatitis B infection.

The aim of this study was to optimize the currently used direct spectrophotometric serum prolidase enzyme activity (SPEA) assay method and compare its diagnostic accuracy with current precipitation and direct spectrophotometric assay methods, AST-to-ALT ratio, age platelet index, AST-to-platelet ratio index, cirrhosis discriminate score, Doha score, FIB-4, FibroQ, fibrosis index, Goteborg University Cirrhosis Index , King's score, and Pohl score for distinguishing Ishak F0 from F1-F3 in patients with chronic hepatitis B (CHB) infection. Liver biopsy results from 112 patients were included in this study. The SPEA values were 529(292-794) U/L, 671(486-927) U/L, and 1077(867-1399) U/L with the precipitation, current, and optimized direct spectrophotometric assay methods, respectively. According to multivariate logistic regression analysis optimized direct spectrophotometric SPEA was the only statistically significant parameter to predict the early stages of liver fibrosis. Optimized direct spectrophotometric SPEA assay method could be used to distinguish early stages of liver fibrosis in patients with CHB infection instead of the currentlyused spectrophotometric SPEA assay methods and other evaluated liver fibrosis indexes.

A novel alternative strategy for monitoring and insight into liver fibrosis progression: The combination of surface-enhanced Raman spectroscopy (SERS) and gut microbiota

Nowadays, the studies on the interaction and relationship between the intestinal microorganisms and liver diseases are increasing. However, it is still a huge challenge for the in-depth investigation and dynamic monitoring of such a complex network. Herein, a significant discovery was made. A strong association between gut microbial structural and functional genomics and SERS spectra of hepatocytes were revealed. Based on the study of gut microbes and SERS spectra, complementary information could be provided for the mechanism analysis of related diseases. Liver fibrosis, a chronic liver disease that lack specific cure was thus comprehensive studied. Liver targeting gold nanoparticle dimers were prepared as the SERS tags, and abundant SERS peak signals were acquired. Meanwhile, the gut microbiomes were also comparative studied. The changes of carbohydrates and lipids in liver cells were observed at the early stages of liver fibrosis, and TLR4 (toll-like receptors 4) was activated to elicit immune responses. Then again, oxidative stress, endotoxin and serum inflammatory factors were the major observations at the late stages. The SERS signals and the microbiome analysis were well confirmed and complemented each other, which suggested that the detection strategy could be another valuable method for the “gut-liver axis” study.

Early Treatment of Hepatitis C Virus Improves Health Outcomes and Yields Cost-Savings: A Modeling Study in Argentina

OBJECTIVE: Most untreated hepatitis C virus (HCV) patients develop chronic infection and severe complications, including death. Direct-acting antivirals in early stages of liver fibrosis reduce complications and healthcare costs. However, therapy is often delayed, and patients in early stages have limited access to effective treatments. We assessed the clinical and economic effect of treating chronic HCV at early versus late stages of disease in Argentina. 
 
 METHODS: A Markov model of the natural HCV history was used to forecast lifetime liver-related and economic outcomes from social security sector perspective. Healthcare use and transition probabilities were drawn from literature. Demographic characteristics of the patients and treatment attributes were based on data from registrational trials of glecaprevir/pibrentasvir. 
 
 RESULTS: Lower rates of all hepatic complications and liver-related mortality were predicted when treatment was initiated in mild versus advanced disease. Sustained virologic response rates were similar among all stages. Higher quality-adjusted life years (QALYs) were predicted when treatment was initiated in mild (F0-F1) versus moderate (F2-F3) or advanced (F4) liver disease (11.5, 9.9, and 7.5 QALYs, respectively). Delaying treatment increased long-term total lifetime costs (F4: AR$ 1 437 816; F2-F3: AR$ 967 673; F0-F1: AR$ 954 018; 37.10 AR$=1 USD, Nov 2018 exchange rate) and provided fewer QALYs. 
 
 CONCLUSIONS: Our study show early treatment was a dominant strategy compared with treatment in advanced stages of liver disease. These results may help health policy makers take actions to reduce health and economic burden of HCV in Argentina.

STUDY THE ANTIFIBROUS EFFICACY OF PLANT PROANTHOCYANIDIN IN RATS WITH CHRONIC HELIOTRINE LIVER DAMAGE

Under experimental conditions, the effect of plant proanthocyanidin – yantacin isolated from a camel thorn plant (Alhagi pseudalhagi) – Yantacin, when administered orally at a dose of 100 mg / kg, on possible changes in the early stages of liver fibrosis that occurred against the background of chronic heliotrine hepatitis was studied. The studies were conducted on male rats with a body weight of 100 ±10 g. The effect of yantacin on the general and biochemical parameters of the blood, as well as the amount of NO – nitrates (in connection with lipoproteins), proteins in the blood against the background of heliotrine liver damage was studied. At the same time, yantacin demonstrated a significant protective effect compared to the control group on the detected fibrosis, according to which certain indicators, against the background of chronic toxic liver damage. In this regard, a more extensive in-depth study of the effect of the studied substance plant proanthocyanidin on normal and impaired liver activity is carried out.

STUDY THE EFFECT OF YANTACIN ON SOME INDICATORS OF CELLULAR RENEWAL AND ON THE LEVEL OF PROTEIN EXPRESSION ON RAT HEPATOCYTES IN CHRONIC HELIOTRINE LIVER DAMAGE

The effect of plant proanthocyanidin – yantacin isolated from the camel thorn plant (Alhagi pseudalhagi) – Yantacin, when administered orally at a dose of 100 mg / kg, on possible changes in the early stages of liver fibrosis that occurred against the background of chronic heliotrine hepatitis in experimental conditions was studied. The studies were conducted on male rats with a body weight of 100 ±10 g. The effect of yantacin on the general and biochemical parameters of blood, as well as on p53, PCNA of liver tissue, mitotic and apoptotic index against the background of heliotrine liver damage was studied. As a result of the conducted studies, yantacin demonstrated a significant protective effect compared with the control group on the detected fibrosis, according to which certain indicators, against the background of chronic toxic liver damage. In this regard, a more extensive in-depth study of the protective and restorative effects of the studied plant proanthosianide substance on chronic changes in the liver, serious structural and functional disorders is being carried out.

Liver injury in Wilson's disease: An immunohistochemical study

PurposeWilson's disease (WD) is an inherited disorder involving copper accumulation in the liver and brain. An important mechanism responsible for hepatocyte injury in WD is mitochondria destruction, although damage may also be caused by oxidative stress and lipid peroxidation. Patients/methodsThe study included 54 treated patients with WD without liver cirrhosis and 10 healthy controls. All patients had liver biopsy and immunohistochemical analysis of liver samples was performed using targeted staining for markers of mitochondrial injury (thioredoxin-2 [TRX2], cytochrome c oxidases subunit 2 [COX2], and cytochrome c oxidases complex IV subunit 4 isoform 1 [COX4-1]), of oxidative stress (peroxiredoxin-1 [PRDX1] and 8-hydroxyguanosine [8-OHdG]), and of lipid peroxidation (4-hydroxynonenal [4-HNE]). ResultsExpression, measured as mean strengths of intensity (SI) of immunohistochemical reactions per 5 fields of view, was significantly lower in patients with WD compared to controls for COX2 (2.9 vs 8.3), 8-OHdG (0.05 vs 3.8), TRX2 (4.9 vs 10.1), and PRDX1 (4.6 vs 10.1) (all P ​< ​10−5). COX4-1 expression was undetected in patients with WD but detected in control specimens (8.1) (P ​< ​10−5). 4-HNE was overexpressed in patients with WD compared to controls (10.1 vs 9.1; P ​< ​0.07). ConclusionsNegligible COX4-1 and low COX2 expression in liver specimens may serve as markers of inner mitochondrial membrane injury in treated patients with WD and early stages of liver fibrosis.

Inflammation and Cancer: From the Development of Personalized Indicators to Novel Therapeutic Strategies.

Colorectal (CRC) and hepatocellular carcinoma (HCC) are associated with chronic inflammation, which plays a role in tumor development and malignant progression. An unmet medical need in these settings is the availability of sensitive and specific noninvasive biomarkers. Their use will allow surveillance of high-risk populations, early detection, and monitoring of disease progression. Moreover, the characterization of specific fingerprints of patients with nonalcoholic fatty liver disease (NAFLD) without or with nonalcoholic steatohepatitis (NASH) at the early stages of liver fibrosis is necessary. Some lines of evidence show the contribution of platelets to intestinal and liver inflammation. Thus, low-dose Aspirin, an antiplatelet agent, reduces CRC and liver cancer incidence and mortality. Aspirin also produces antifibrotic effects in NAFLD. Activated platelets can trigger chronic inflammation and tissue fibrosis via the release of soluble mediators, such as thromboxane (TX) A2 and tumor growth factor (TGF)-β, and vesicles containing genetic material (including microRNA). These platelet-derived products contribute to cyclooxygenase (COX)-2 expression and prostaglandin (PG)E2 biosynthesis by tumor microenvironment cells, such as immune and endothelial cells and fibroblasts, alongside cancer cells. Enhanced COX-2-dependent PGE2 plays a crucial role in chronic inflammation and promotes tumor progression, angiogenesis, and metastasis. Antiplatelet agents can indirectly prevent the induction of COX-2 in target cells by inhibiting platelet activation. Differently, selective COX-2 inhibitors (coxibs) block the activity of COX-2 expressed in the tumor microenvironment and cancer cells. However, coxib chemopreventive effects are hampered by the interference with cardiovascular homeostasis via the coincident inhibition of vascular COX-2-dependent prostacyclin biosynthesis, resulting in enhanced risk of atherothrombosis. A strategy to improve anti-inflammatory agents’ use in cancer prevention could be to develop tissue-specific drug delivery systems. Platelet ability to interact with tumor cells and transfer their molecular cargo can be employed to design platelet-mediated drug delivery systems to enhance the efficacy and reduce toxicity associated with anti-inflammatory agents in these settings. Another peculiarity of platelets is their capability to uptake proteins and transcripts from the circulation. Thus, cancer patient platelets show specific proteomic and transcriptomic expression profiles that could be used as biomarkers for early cancer detection and disease monitoring.

Correlation of Antithrombin Functional Status and Levels with Liver Fibrosis in Patients with Hepatitis C.

Abnormal levels of coagulation factors and their inhibitors have shown association with liver diseases. The objective of this study was to determine the qualitative and quantitive status of antithrombin (AT) in patients with chronic liver disease associated hepatitis C infection and their correlation with severity of liver fibrosis. In this study, 75 (43 male and 32 female) known patients with chronic liver disease associated hepatitis C infection were enrolled. AT activity and quantitative immunoassays were carried out using Stachrom AT reagent kit (Diagnostica Stago, France) and Liatest AT reagent (Diagnostica Stago, France), respectively. Hepatic biopsies were obtained and graded for liver fibrosis from all study participants. Of the 75 patients, 45 had normal AT while 30 showed lower activity of AT. Similarly, the quantitative assay showed reduced levels of AT in 30 patients and normal levels in 45 patients. In the early stages of liver fibrosis, AT activity and antigenic levels were found to be normal or minimally affected. While advanced stages of the disease showed markedly reduced levels of AT and activity. Hence, it can be concluded that the degree of fibrosis affects the status of AT.

Diagnostic and prognostic potential of kallistatin in assessment of liver parenchyma changes in patients with non-alcoholic fatty liver disease and hypertension kallistatin in patients with NAFLD and hypertension

Abstract Background and aim Non-alcoholic fatty liver disease (NAFLD) is closely linked to hypertension (HT). An important issue remains the search for non-invasive tests to NAFLD detection in the early stages of liver fibrosis. The objective of the study was to evaluate the diagnostic and prognostic value of kallistatin in assessing the liver fibrosis progression in NAFLD and HT patients. Patients and methods One hundred fifteen patients with NAFLD with and without HT were examined, the control group consisted of 20 relatively healthy volunteers. Plasma kallistatin level measurement, ultrasound steatometry and elastography were performed in all patients. Results Kallistatin level was 65.03 ng mL−1 (95% CI 61.38; 68.68), 83.42 ng mL−1 (95% CI 81.89; 84.94) and 111.70 ng mL−1 (95% CI 106.14; 113.22) in patients with NAFLD and HT, isolated NAFLD and control group, respectively. There were significant differences in the liver parenchyma condition between groups. Kallistatin levels strongly inversely correlated with the attenuation coefficient and the mean liver stiffness in NAFLD and HT (rs = −0.70) and in the isolated NAFLD patients (rs = −0.56; rs = −0.68, respectively). Kallistatin level was 71.82 ng mL−1 (95% CI 70.16; 79.51) and 58.62 ng mL−1 (95% CI 55.81; 64.45) in patients with HT stage I and HT stage II, respectively (P &lt; 0.001). Conclusions Concomitant HT in NAFLD patients is associated with greater severity of fatty and fibrotic liver changes. The course of NAFLD is accompanied by decrease in kallistatin level. Increased degree of liver steatosis and fibrosis, inflammation activity, increased BMI and increased stage of HT lead to inhibition of kallistatin activity. Kallistatin may be considered as a biomarker for progression assessment of NAFLD with or without HT.

NMDA receptor expression during cell transformation process at early stages of liver cancer in rodent models.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, which is not sensitive to radiotherapy and chemotherapy and very often experiences postoperative relapse. In this regard, effective screening of liver cancer is considered as the most important and urgent task. The aim of our study was to determine whether N-methyl-D-aspartate receptor (NMDAR) and, in particular, its subunits, can serve as biomarkers to distinguish the precancerous liver at early stages of liver fibrosis. We assessed the development of HCC after 10, 15, and 22 wk using a HCC rat model. The expression of NMDAR subunits was monitored at different stages of HCC by means of immunohistochemistry combined with epifluorescence microscopy imaging, Western blotting, and direct bisulfite sequencing. NMDAR subunits were not found in healthy liver tissues. In contrast, NMDAR subunits, in particular NR1 and NR2B, appeared at the stage of severe liver fibrosis (precancerous liver disease) in rats and were expressed during the development of HCC in rats and mice. Using the direct bisulfite sequencing, we detected that increased expression of NMDAR directly correlated with the demethylation of CpG islands in the promoter region of genes encoding receptor subunits. The obtained results confirmed that NMDAR subunits can serve as new biomarkers of precancerous liver disease, severe fibrosis, and its progression towards HCC.NEW & NOTEWORTHY We have shown NMDAR expression in cell transformation process at early stages of cancer, specifically HCC. The aim of our study was to define the disease stages from precancerous liver disease towards liver cancer progression when NMDAR subunits were expressed/detected. A fibrosis/HCC rat model, immunohistochemistry combined with epifluorescence microscopy imaging, Western blotting was used. The dynamics of appearance of NMDAR subunits, their expression and methylation status during the development of HCC were shown and discussed.

Latency-associated Peptide Degradation Fragments Produced in Stellate Cells and Phagocytosed by Macrophages in Bile Duct-ligated Mouse Liver.

Transforming growth factor-β (TGF-β) activation is involved in various pathogeneses, such as fibrosis and malignancy. We previously showed that TGF-β was activated by serine protease plasma kallikrein-dependent digestion of latency-associated peptides (LAPs) and developed a method to detect LAP degradation products (LAP-DPs) in the liver and blood using specific monoclonal antibodies. Clinical studies have revealed that blood LAP-DPs are formed in the early stages of liver fibrosis. This study aimed to identify the cell source of LAP-DP formation during liver fibrosis. The N-terminals of LAP-DPs ending at residue Arg58 (R58) were stained in liver sections of a bile duct-ligated liver fibrosis model at 3 and 13 days. R58 LAP-DPs were detected in quiescent hepatic stellate cells at day 3 and in macrophages on day 13 after ligation of the bile duct. We then performed a detailed analysis of the axial localization of R58 signals in a single macrophage, visualized the cell membrane with the anti-CLEC4F antibody, and found R58 LAP-DPs surrounded by the membrane in phagocytosed debris that appeared to be dead cells. These findings suggest that in the early stages of liver fibrosis, TGF-β is activated on the membrane of stellate cells, and then the cells are phagocytosed after cell death.

Current impact of viral hepatitis on liver cancer development: The challenge remains.

Chronic infections due to hepatitis B and hepatitis C viruses are responsible for most cases of hepatocellular carcinoma (HCC) worldwide, and this association is likely to remain during the next decade. Moreover, viral hepatitis-related HCC imposes an important burden on public health in terms of disability-adjusted life years. In order to reduce such a burden, some major challenges must be faced. Universal vaccination against hepatitis B virus, especially in the neonatal period, is probably the most relevant primary preventive measure against the development of HCC. Moreover, considering the large adult population already infected with hepatitis B and C viruses, it is also imperative to identify these individuals to ensure their access to treatment. Both hepatitis B and C currently have highly effective therapies, which are able to diminish the risk of development of liver cancer. Finally, it is essential for individuals at high-risk of HCC to be included in surveillance programs, so that tumors are detected at an early stage. Patients with hepatitis B or C and advanced liver fibrosis or cirrhosis benefit from being followed in a surveillance program. As hepatitis B virus is oncogenic and capable of leading to liver cancer even in individuals with early stages of liver fibrosis, other high-risk groups of patients with hepatitis B are also candidates for surveillance. Considerable effort is required concerning these strategies in order to decrease the incidence and the mortality of viral hepatitis-related HCC.

Use of Texture Analysis on Noncontrast MRI in Classification of Early Stage of Liver Fibrosis.

Purpose. To compare the diagnostic value of texture analysis- (TA-) derived parameters from out-of-phase T1W, in-phase T1W, and T2W images in the classification of the early stage of liver fibrosis. Methods. Patients clinically diagnosed with hepatitis B infection, who underwent liver biopsy and noncontrast MRI scans, were enrolled. TA parameters were extracted from out-of-phase T1-weighted (T1W), in-phase T1W, and T2-weighted (T2W) images and calculated using Artificial Intelligent Kit (AK). Features were extracted including first-order, shape, gray-level cooccurrence matrix, gray-level run-length matrix, neighboring gray one tone difference matrix, and gray-level differential matrix. After statistical analyses, final diagnostic models were constructed. Receiver operating curves (ROCs) and areas under the ROC (AUCs) were used to assess the diagnostic value of each final model and 100-time repeated cross-validation was applied to assess the stability of the logistic regression models. Results. A total of 57 patients were enrolled in this study, with 27 in the fibrosis stage < 2 and 30 in stages ≥ 2. Overall, 851 features were extracted per ROI. Eight features with high correlation were selected by the maximum relevance method in each sequence, and all had a good diagnostic performance. ROC analysis of the final models showed that all sequences had a preferable performance with AUCs of 0.87, 0.90, and 0.96 in T2W and in-phase and out-of-phase T1W, respectively. Cross-validation results reported the following values of mean accuracy, specificity, and sensitivity: 0.98 each for out-of-phase T1W; 0.90, 0.89, and 0.90 for in-phase T1W; and 0.86, 0.88, 0.84 for T2W in the training set, and 0.76, 0.81, and 0.72 for out-of-phase T1W; 0.74, 0.72, and 0.75 for in-phase T1W; and 0.63, 0.64, and 0.63 for T2W for the test group, respectively. Conclusion. Noncontrast MRI scans with texture analysis are viable for classifying the early stages of liver fibrosis, exhibiting excellent diagnostic performance.

Ефективність адеметіоніну при лікуванні пацієнтів з неалкогольною жировою хворобою печінки

Nonalcoholic fatty liver disease is the most common liver disease in the world, showing a variety of histopathological findings ranging from simple steatosis to nonalcoholic steatohepatitis and cirrhosis. Patients with nonalcoholic fatty liver disease have the potential to develop fibrosis and cirrhosis leading to portal hypertension, liver decompensation, and even hepatocellular carcinoma. Nonalcoholic fatty liver disease can be differentiated from simple steatosis by liver biopsy and is diagnosed when all of the following three criteria are met: macrovesicular fatty change of hepatocytes, inflammatory cell infiltration, and ballooning degeneration of hepatocytes. Lipid accumulation in hepatocytes can lead to inflammation within them. Accordingly, significant fibrosis can cause cirrhosis over a period of 10-20 years, but the pathophysiology is not well understood yet. However, liver biopsy is invasive, has drawbacks such as sampling error and cost, and it is not applicable for all patients. Also, there was a greater interest in science and practical medicine in the use of non-invasive methods for diagnosing the stages of nonalcoholic fatty liver disease. Primed on clinical and scientific data, non-invasive markers of liver fibrosis have to be highly sensitive and specific in identifying the early stages of liver fibrosis. The purpose of the work was to determine the effect of S-adenosylmethionine (ademetionine) on the stage of liver fibrosis, the level of pentraxin-3, C-reactive protein and metabolic parameters in patients with comorbide course of non-alcoholic fatty liver disease and arterial hypertension. Results and discussion. On the 61st day from the start of ademetionine use, there was a tendency to a decrease in the number of patients with comorbid course of non-alcoholic fatty liver disease and arterial hypertension in the stage of liver fibrosis F1 and F2 and an increase in the F0 stage. In addition, a significant decrease in the indicators of systemic inflammation (pentraxin-3, C-reactive protein) was achieved (p &lt;0.05). The patients with comorbid course of non-alcoholic fatty liver disease and arterial hypertension also had a statistically significant (p &lt;0.05) positive dynamics of hepatocyte cytolysis indicators was achieved in comparison with those before treatment and with the control group (p &lt;0.05), as well as the lipid profile (p &lt;0.05). Conclusion. The study showed that using ademetionine in patients with comorbid course of non-alcoholic fatty liver disease and arterial hypertension promoted regression of the stage of liver fibrosis, a significant decrease in the level of pentraxin-3, C-reactive protein, and an improvement in metabolic parameters. Appointment of ademetionine is an expedient method of treating patients with comorbid course of non-alcoholic fatty liver disease and arterial hypertension as a pathogenetic medicine with a pronounced antifibrotic, anti-inflammatory and cytoprotective effect

Hepatic manifestations of cystic fibrosis.

Liver disease in cystic fibrosis (CF) usually develops before puberty, is often asymptomatic and slowly progressive. Multilobular cirrhosis develops in approximately 5-10% of patients by the age of 18, and is a significant contributor to the morbidity and mortality. No therapy, including ursodeoxycholic acid and cystic fibrosis transmembrane conductance regulator correctors or potentiators, has proven effective to prevent or halt the progression of liver disease towards cirrhosis and portal hypertension. This review provides the current knowledge in the epidemiology of CF liver disease and development of noninvasive tools to assess liver disease severity and progression overtime in order to optimize clinical management and therapeutic options. Liver disease not only develops during childhood but also later in the lifetime of patients with CF; the incidence of cirrhosis with portal hypertension increases progressively reaching 10% by age 30. Several noninvasive tools to measure liver stiffness as an indirect measure of fibrosis are being investigated, and show promising results for the assessment of early stages of liver fibrosis and disease progression. Identifying noninvasive biomarkers is fundamental to improving early diagnosis, monitoring disease evolution and measuring treatment effects. A prerequisite is the use of consistent definitions for CF- liver disease (LD) in clinical trials.

Noninvasive biomarkers predict improvement in liver fibrosis after successful generic DAAs based therapy of chronic hepatitis C in Egypt

BackgroundThe scale of HCV problem in Egypt prioritized the development of a national control strategy that employs the use of locally manufactured generic direct-acting antivirals (DAAs). Achieving sustained virologic response in chronic HCV patients is the key for preventing fibrosis progression and ultimately its resolution. Objective(s)To evaluate impact of generic DAAs on liver fibrosis in chronic HCV patients using some non-invasive biomarkers (NIBMs). MethodsA total of 280 chronic HCV patients (18 treatment experienced and 262 naive) were enrolled and received the standard of care. All patients were clinically evaluated before starting treatment and at 4, 12 and 24 weeks of treatment. ResultsThe sensitivity and the specificity of the tested NIBMs for predicting cirrhosis versus liver ultrasound ranged between 75.0-79.6% and 59.4–67.2% respectively. All NIBMs showed significant linear decline during the treatment and follow up periods among responders but tended to fluctuate in values toward an increase among non-responders. In cox regression analysis, normal baseline ALT, AST, total serum cholesterol, serum albumin, WBCS, prothrombin activity and early stages of liver fibrosis predicted improvement in liver fibrosis by 1.5–2 folds. The mean probability of recovery at 1, 3, 6 months varied between the different scores and ranged from 0.059 to 0.637, 0.125–0.741, 0.538–0.951 respectively. ConclusionThe results provide prognostic data on the improvement in liver fibrosis over the treatment course and follow up periods without the need for a liver biopsy. Early detection and management of HCV infection should be emphasized to maximize the benefits of the treatment.

Content of certain cytokines and chemokines in blood ofpatients with chronic hepatitis B in the early stages of liver fibrosis

Hepatitis B is an infectious viral disease in which damage or destruction of liver tissue occurs, and which can turn into a chronic form. In chronic hepatitis B (CHB), hepatocytes are replaced by connective tissue as they die, resulting in fibrosis, and then cirrhosis of the liver. Early diagnosis of liver fibrosis is an urgent task in the development of CHB. Already at this stage of the disease, the immune system is activated, which plays a leading role in liver damage in CHB. The main regulators of immune processes are cytokines, which mediate intercellular interactions. A separate group of cytokines are chemokines — proteins of cell migration. In CHB, they are responsible for infiltration of liver tissue by activated white blood cells. Cytokines and chemokines are active participants in fibrogenesis, so they can serve as biomarkers for the development of liver fibrosis, including in the early stages. The purpose of this study was to analyze the content of certain cytokines/chemokines in the peripheral blood of patients with CHB in order to search for potential biomarkers of the initial stages of liver fibrosis. The study included 30 patients with a confirmed diagnosis of CHB with stages of liver fibrosis F0-F1 on the Metavir scale, 36 patients with a diagnosis of chronic hepatitis C (F0-F1) and 37 conditionally healthy individuals as a control group. Concentrations of the following cytokines/chemokines were determined: IFNγ, TNFα, CCL2/MCP-1, CCL8/MCP-2, CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-10, CXCL11/I-TAC by multiplex analysis using xMAP technology (Luminex, USA). As a result of the study, it was found that in patients with CHB, the plasma content of cytokine TNFα and chemokines CCL2/MCP-1, CXCL9/MIG and CXCL10/IP-10 was increased, and the chemokine CCL8/MCP-2 was reduced, which indicates the possibility of using these cytokines/chemokines as biomarkers of liver damage in CHB. In the examined group of patients with CHB, there was no dependence of the concentrations of cytokines and chemokines in the blood plasma on the viral load, which may be explained by its low level. For plasma cytokines in patients with CHB, correlations were found between TNFα and CCL2/MCP-1 and CCL8/MCP-2 chemokines , which was not observed in the control group. At the same time, in the control group, a correlation was found between the content of TNFα and the chemokine CXCL9/MIG, which was not detected in the group of patients. For both groups, a correlation was found between the content of CXCL9/MIG and CXCL10/IP-10 chemokines. Based on the study data, an algorithm has been developed that allows us to establish chronic hepatitis B or chronic hepatitis C as the cause of the initial form of fibrosis F0-F1 in terms of the content of cytokines IFNγ, CCL2/MCP-1 and CCL8/MCP-2 in blood plasma with a diagnostic efficiency of 89.4%.