Stage Of Liver Cirrhosis Research Articles

Search for Effective Serum Tumor Markers for Early Diagnosis of Hepatocellular Carcinoma Associated with Hepatitis C

The aim of the study was to identify the most effective serum tumor markers for early diagnosis of hepatocellular carcinoma based on the combination of diagnostic characteristics and correlations.Materials and Methods.There were observed 55 patients with chronic hepatitis C in the stage of liver cirrhosis with a verified diagnosis of hepatocellular carcinoma. The control group consisted of 55 patients with chronic hepatitis C at the stage of liver cirrhosis without hepatocellular carcinoma, comparable to the experimental group in terms of basic clinical profile. The following tumor markers were estimated in both groups: alpha-fetoprotein (AFP), alpha-fetoprotein-L3 (AFP-L3), annexin A2 (ANXA2), heparin-binding growth factor Midkine (MDK), glypican-3 (GPC3), des-gamma-carboxyprothrombin (DCP, PIVKA-II), dickkopf-related protein 1 (DKK-1), osteopontin (OPN), and Golgi protein 73 (GP73). There were also evaluated such indices as diagnostic sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio of a positive test, the possible correlation between alpha-fetoprotein and other tumor markers. The area under the ROC curve (AUC) was calculated at the 95% confidence interval.Results.The greatest sensitivity was revealed when using heparin-binding growth factor, annexin A2, osteopontin. Alpha-fetoprotein, alpha-fetoprotein-L3, glypican-3, des-gamma-carboxyprothrombin, dickkopf-related protein 1 had the best specificity. AUC>0.75 was found in annexin A2, heparin-binding growth factor, glypican-3, des-gamma-carboxyprothrombin, osteopontin, Golgi protein 73. The likelihood ratio of a positive test result was the highest for glypican-3. A significant correlation was found between alpha-fetoprotein and alpha-fetoprotein-L3, annexin A2, des-gamma-carboxyprothrombin.Conclusion.According to the aggregate indicators of diagnostic efficiency, heparin-binding growth factor, glypican-3, and osteopontin are the most promising tumor markers of those studied. When they are used, integral AUC values are above the average, the level of these tumor markers in the blood of patients with hepatocellular cancer does not correlate with alpha-fetoprotein. They are applicable for diagnosing liver cancer in AFP-negative patients. The combined use of AFP + GPC3, AFP + OPN has already shown their advantages. However, the efficacy of the combination of AFP + MDK, GPC3 + OPN has not been determined yet; therefore, significance of the combined use of these tumor markers in the diagnosis of liver cancer should be investigated in the near future.

Diverse Functions of γδ T Cells in the Progression of Hepatitis B Virus and Hepatitis C Virus Infection.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are primary risk factors for a wide spectrum of liver diseases that severely affect human health. The liver is an immunological organ that has an abundance of immune cells. Thus, various innate or adaptive immune cells are involved in the progression of HBV or HCV infection. Among those cells, a unique kind of immune cell, the γδ T cell, contributes to promoting or inhibiting the progression of liver diseases. To reveal the diverse roles of γδ T cells in HBV or HCV infection, the properties and functions of these cells in human and mouse models are analyzed. Here, we briefly describe the characteristics and functions of γδ T cells subsets in liver diseases. Then, we fully discuss the diverse roles of γδ T cells in the progression of HBV or HCV infection, including stages of acute infection, chronic infection, liver cirrhosis, and hepatocellular carcinoma. Finally, the functions and existing problems of γδ T cells in HBV or HCV infection are summarized. A better understanding of the function of γδ T cells during the progression of HBV and HCV infection will be helpful for the treatment of virus infection.

Serum Concentration of Fluoride in Patients with Alcoholic Liver Cirrhosis from the Lublin Region in Eastern Poland.

In view of previous reports, it is important to determine the relationship between liver function and the level of fluoride in the serum. The aim of this study was to investigate serum concentrations of fluoride in 72 patients with alcoholic liver cirrhosis, living in the region of Lublin (Eastern Poland) divided based on the severity of disease according to the Child-Turcotte-Pugh criteria. Higher plasma fluoride concentrations were associated with changes in liver related parameters. In all groups of analyzed patients with different stages of alcoholic liver cirrhosis, elevated levels of plasma fluoride and increased activities of both alanine aminotransferase (ALT) and total bilirubin concentration were shown.

Translation of IRF-1 Restricts Hepatic Interleukin-7 Production to Types I and II Interferons: Implications for Hepatic Immunity.

Interleukin-7 (IL-7) is an important cytokine with pivotal pro-survival functions in the adaptive immune system. However, the role of IL-7 in innate immunity is not fully understood. In the present study, the impact of hepatic IL-7 on innate immune cells was assessed by functional experiments as well as in patients with different stages of liver cirrhosis or acute-on-chronic liver failure (ACLF). Human hepatocytes and liver sinusoidal endothelial cells secreted IL-7 in response to stimulation with interferons (IFNs) of type I and II, yet not type III. De novo translation of interferon-response factor-1 (IRF-1) restricted IL-7 production to stimulation with type I and II IFNs. LPS-primed human macrophages were identified as innate immune target cells responding to IL-7 signaling by inactivation of Glycogen synthase kinase-3 (GSK3). IL-7-mediated GSK3 inactivation augmented LPS-induced secretion of pro-inflammatory cytokines and blunted LPS tolerance of macrophages. The IFN-IRF-1-IL-7 axis was present in liver cirrhosis patients. However, liver cirrhosis patients with or without ACLF had significantly lower concentrations of IL-7 in serum compared to healthy controls, which might contribute to LPS-tolerance in these patients. In conclusion, we propose the presence of an inflammatory cascade where IFNs of type I/II induce hepatocellular IL-7 in an IRF-1-restriced way. Beyond its role in adaptive immune responses, IL-7 appears to augment the response of macrophages to LPS and to ameliorate LPS tolerance, which may improve innate immune responses against invading pathogens.

HEMOSTATIC POTENTIAL ASSESSMENT OF PATIENTS WITH LIVER CIRRHOSIS AND ATRIAL FIBRILLATION BY LOW-FREQUENCY PIEZOELECTRIC THROMBOELASTOGRAPHY

The aim: Our aim was to assess the hemostatic potential of patients with liver cirrhosis and atrial fibrillation by LPTEG global coagulation assay, to investigate changes in LPTEG parameters according to the stage of liver cirrhosis and compare results with liver cirrhosis group. Materials and methods: We performed a prospective cross-sectional study including 70 patients with liver cirrhosis and atrial fibrillation, 36 patients with liver cirrhosis and 20 healthy individuals. LPTEG parameters were measured using ARP-01M "Mednord" in order to assess coagulation abnormalities. Results: t1 and Intensity of contact coagulation didn't differ (p>0,05), Constant of thrombin activity was increased (47.53±0.8vs.34.51±1.88, p<0.001), t3 was reduced (5,0±0.1vs.6.7±0.36 p<0.001), Intensity of coagulation drive was increased (52.8±1.8vs.38.55±1.54, p = 0.001), Intensity of clot polymerization was increased (19.66±0.28vs.16.29±0.28,p<0.001), time t5 was reduced (32.94±0.36 vs. 36.8±1.30, p<0.01), Maximum amplitude was increased (655.7±9.19 vs. 547±19.38, p<0.001), Intensity of total coagulation was increased (19.41±0.34vs.15,09±0.56, p<0.001), Intensity of clot retraction and lysis was increased (4.1±0.07vs.3±0.15, p<0.001) and Coefficient of total anticoagulant activity was increased (2.81±0.05 vs. 2.48 ± 0.06, p<0.001) compared to liver cirrhosis. Conclusions: In patients with liver cirrhosis and atrial fibrillation the hemostatic potential is significantly shifted towards hypercoagulation with a gradual worsening of coagulation disorders, starting from the compensated stage of liver cirrhosis.

Prognostic value of computed tomographic perfusion in the diagnosis of liver fibrosis and cirrhosis. Pilot study

Relevance: Most diffuse liver diseases lead to fibrosis over time with the risk of cirrhosis. With progressive fibrosis and cirrhosis of the liver both physical properties of the hepatic parenchyma and its hemodynamics change. The only reliable method for determining the stage of the disease is puncture biopsy and subsequent histological examination, but this method is invasive and associated with complications. Currently, the determination of the severity of cirrhosis is based on clinical data (the Child-Pugh scale) and elastography is considered to be the main non-invasive instrumental method. It lets reliably differentiate the initial fibrosis and cirrhosis of the liver, while the F2 and F3 stages according to the conventional METAVIR scale remain a "gray zone", as well as the differentiation of degrees of the severity of cirrhosis. In addition elastography has a number of limitations. The main ones of which are operator dependence, apparatus dependence and the inability to determine functional changes in the liver. With the use of perfusion computed tomography (CT perfusion) it is possible to assess the functionality of the liver by quantifying changes in hemodynamics. The method applied measures the characteristics of blood flow in the tissue at a given scanning level by computed-tomographic data on the dynamics of the distribution of the contrast agent in the area of interest is collected, besides the type of liver perfusion is determined. This parameter is needed to assess the dynamics of treatment against the background of drug therapy.Objective: To identify statistically significant parameters of CT perfusion to determine the severity of hemodynamic disturbances in patients with various stages of liver fibrosis and cirrhosis and to compare the values of parameters of liver CT perfusion with fibrosis according to the METAVIR conditional scale determined using elastography.Materials and methods: 18 patients were included in this parallel pilot study. On the basis of clinical and laboratory data and the results of elastography, 10 of them were diagnosed with fibrosis and cirrhosis. The stages of fibrosis F1, F2 were determined in 3 patients; stages F3, F4 – in 7. In the group of patients with F3, F4, according to the METAVIR conditional scale, subgroups were distinguished depending on the severity of cirrhosis: compensated – 3 patients, subcompensated – 2, decompensated – 2. The control group consisted of 8 patients with organ diseases abdominal cavity not associated with liver damage. All patients underwent CT perfusion of the liver on a Philips iCT 256 using the following scan parameters: 80 KVp, 120 mAc, total scan time 56 s, and slice thickness 5.0 mm. Intravenously, bolus was administered to all patients with 50 ml of ioversol 350 mg/ml, the rate of administration was 3.8–4.0 ml/s, the time from the moment of administration of the contrast medium to the start of scanning was 6 s. After receiving a series of images, the data was processed on a Philips workstation. Quantitative analysis was carried out according to the following indicators: TTP (time to peak, s), BV (blood volume, ml/100 g), AP (arterial perfusion, ml/min/100 ml), PP (portal perfusion, ml/min/100 ml), TP (total perfusion, ml/min/100 ml) and HPI (hepatic perfusion index, %).Results: In the control group of 8 patients, the perfusion values were: TTP 37.4±5.2 s, BV 16.1±5.0 ml/100 g, AP 25.0±7.5 ml/min/100 ml, PP 44.5±14.5 ml/min/100 ml, TP 70.1±14.9 ml/min/100 ml, HPI 70.1±14.9%. In 3 patients with F1, F2, according to the METAVIR conditional scale, the following statistically significant values (p&lt;0.039) of perfusion indices were determined: BV 27.2±8.6 ml/100 g, AP 20.0±3.8 ml/min/100 ml; with compensated liver cirrhosis (n=3): TTP 46.2±1.7 s, BV 12.4±1.9 ml/100 g, AP 10.7±2.8 ml/min/100 ml, PP 37.3±5.2 ml/min/100 ml, TP 48.1±3.5 ml/min/100 ml, HPI 22.4±5.5%; subcompensated (n=2): TTP 43.0±3.2 s, BV 8.9±2.6 ml/100 g, AP 12.8±3.0 ml/min/100 ml, PP 27.7±9.0 ml/min/100 ml, TP 40.5±7.3 ml/min/100 ml; decompensated (n=2): BV 30.5±1.8 ml/100 g, PP 8.5±1.5 ml/min/100 ml, HPI 81.3±1.8%.Conclusion: The preliminary results obtained confirm that CT perfusion can be used to predict and assess the severity of hemodynamic disturbances in patients with varying degrees of severity of cirrhosis and supplements clinical, laboratory and elastography data.

Morphologic changes in hepatitis virus-related liver cirrhosis: Relationship to hemodynamics of portal vein on dynamic contrast-enhanced CT

IntroductionThe morphologic changes in the compensated stage of liver cirrhosis (cLC) are not diffuse atrophic changes. With cLC lobar or segmental changes combined with atrophy of the right lobe and medial segment together with hypertrophy of the caudate lobe and lateral segment are commonly seen. The purpose of this study was to evaluate the morphologic changes in hepatitis virus-related liver cirrhosis in relationship to haemodynamics of the portal vein on dynamic contrast-enhanced computed tomography (DCE-CT) MethodsThis study included 72 patients, 46 with hepatitis virus-related cirrhosis and 26 with a normally functioning liver, who underwent DCE-CT. In cirrhosis patients, the morphologic change index (MCI) of the liver was calculated and categorised into two groups, high-MCI (MCI ≥ 0.4) (n = 21) and low-MCI (MCI < 0.4) (n = 25). Cross-sectional areas of the main, right and left portal veins and the intra-portal distribution from splenic venous flow were evaluated for their relationships with the MCI and compared among three groups (normal-control, low MCI and high MCI). ResultsThere was a significant difference in the cross-sectional area of the left portal vein between the high-MCI group and the low-MCI group (p = 0.013) and the control group (p = 0.008). A significant correlation was identified between the cross-sectional area of the left portal vein and the MCI (r = 0.508, p < 0.001). ConclusionCross-sectional area of the left portal vein may be a factor related to morphologic changes in hepatitis virus-related liver cirrhosis and could be a possible index of the left portal venous flow volume. Implications for practiceThis study may be useful for predicting the degree of hepatic morphologic changes and the condition of cirrhosis in association with regional hepatic morphologic changes.

Analysis of novel serum markers of fibrosis and angiogenesis in patients with alcoholic liver cirrhosis.

Alcohol consumption causes acute and chronic liver injury. The clinical forms of alcohol liver disease (ALD) include steatosis, hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) associated with liver cirrhosis. The aim of the study was to determine the levels of novel markers of fibrogenesis and angiogenesis in patients with alcoholic liver cirrhosis. Serum levels of angiopoietin-like peptide 4 (ANGPTL-4), asialoglycoprotein receptor 1 (ASGP-R1), and S100 calcium-binding protein A8 (S100A8) were assessed. Levels of hyaluronic acid (Hyal) and collagen IV (Coll IV) werealso determined at various stages of alcoholic liver cirrhosis. The study group consisted of 72 patients with alcoholic liver cirrhosis, while the control group included 22 healthy subjects without a history of alcohol abuse. The degree of liver cirrhosis was evaluated according to the Pugh-Child criteria (Pugh-Child score). Based on thse scores, patients were assigned to one of three groups: Pugh-Child (P-Ch) A - 21 with stage A, P-Ch B - 23 with stage B and P-Ch C - 28 with stage C liver cirrhosis. Serum levels of markers were determined using ELISA. The study findings demonstrated higher levels of ANGPTL-4, ASGP-R1, S100A, hyaluronic acid and serum collagen IV in the group of patients with alcoholic liver cirrhosis, compared to the control group. Furthermore, their levels increased with the progression of alcoholic liver cirrhosis. The biomarkers analysed in the study may be useful for diagnosis and prognosis in patients with alcoholic liver cirrhosis.

The Mutational and Transcriptional Landscapes of Hepatocarcinogenesis in a Rat Model.

SummaryHepatocellular carcinoma (HCC) initiation is characterized by stepwise accumulation of molecular alterations, during which the early events are largely unknown. Here, we presented a comprehensive genomic and transcriptomic landscape at stages of hepatitis, cirrhosis, and HCC by using a diethylnitrosamine-induced rat HCC model. We observed the early occurrence of gene instability and aberrant cancer associated signaling pathways in liver hepatitis. We further characterized the progressive molecular changes during hepatocarcinogenesis, wherein the intense rivalry between tumor-suppressive and oncogenic strengths occurred in cirrhosis stage. Despite the significant pathological difference, mutation signatures and expression landscape are highly similar between hepatitis and cirrhosis stages. Furthermore, we identified PI3K-Akt signaling pathway as a key pathway in the process of hepatocarcinogenesis through integrative analysis, and PIK3CD is a potential biomarker indicating HCC recurrence. The dynamic immune response during hepatocarcinogenesis, such as continuous decline of monocytes, suggests an immunological intervention strategy beyond chemoprevention for liver cancer.

MiR-876 Inhibits EMT and Liver Fibrosis via POSTN to Suppress Metastasis in Hepatocellular Carcinoma.

Background The asymptomatic onset, frequent recurrence, and poor prognosis of hepatocellular carcinoma (HCC) prompted us to identify new therapeutic targets or predictive markers of HCC diagnosis or prognosis. Methods In this study, bioinformatics analysis was used to screen for target miRNAs from the open-access TCGA database. Transwell assays, Western blotting, and qRT-PCR analyses were used to detect cellular functions and gene expression in HCC cells and samples. A nude mouse tumorigenesis model was established to facilitate the observation of HCC progression. Other assays included luciferase reporter assays, IHC, and survival analysis. Results We found that the identified miR-876 from TCGA was expressed at low levels in HCC cell lines and that low miR-876 expression was corrected with liver cirrhosis, tumor thrombus, and TNM stage. Further research revealed that miR-876 regulated cell invasion, EMT, and collagen expression by targeting POSTN expression. miR-876 and POSTN were inversely correlated in HCC samples and associated with EMT status and liver fibrosis in clinical HCC tissues. miR-876 inhibited the liver cancer progression in in vivo animal assays. Finally, both miR-876 and POSTN were risk factors for HCC survival, and HCC patients with combined low miR-876 and high POSTN expression had worse prognosis. Conclusions miR-876 inhibited HCC EMT and fibrosis by targeting POSTN, thus affecting HCC progression and prognosis. miR-876 and POSTN may be useful therapeutic targets or prognostic markers of HCC.

A novel method for accurate extraction of liver capsule and auxiliary diagnosis of liver cirrhosis based on high-frequency ultrasound images

Liver cirrhosis is a common chronic progressive disease with a high mortality rate. The early diagnosis and treatment of liver cirrhosis is an important research subject in the medical field. In this paper, a novel method is proposed for the accurate extraction of the liver capsule and auxiliary diagnosis of cirrhosis based on high frequency ultrasound images. First, a self-developed method is used to extract the predictive capsule of ultrasound images, which involves the detection of liver ascites with sliding windows, image enhancement with multiscale detail and fuzzy set, structure segmentation with morphological processing, and predictive capsule detection with traversal search method. Thereafter, the real capsule is obtained by the gray difference method according to different gray values between the liver capsule region of the original ultrasound images and the set threshold. Finally, according to the analysis of smoothness, as well as the continuity and fluctuation of predictive and real capsule, four novel features called NoL, VoS, CV, and NoF are proposed for the computer auxiliary diagnosis model. This model is designed on the basis of support vector machine and k-means clustering and can classify normal liver and three liver cirrhosis stages. The experimental results reveal that the accuracy of the liver capsule extraction using this model is 95.13% and final classification accuracy of four stages can reach 92.54%, 88.46%, 89.23% and 94.55%, respectively. The results also indicate that the method proposed in this paper can achieve the classification of liver cirrhosis stages much more accurately and efficiently compared with previously utilized methods.

Water-Soluble Pristine C60 Fullerene Inhibits Liver Alterations Associated with Hepatocellular Carcinoma in Rat

Excessive production of reactive oxygen species is the main cause of hepatocellular carcinoma (HCC) initiation and progression. Water-soluble pristine C60 fullerene is a powerful and non-toxic antioxidant, therefore, its effect under rat HCC model and its possible mechanisms were aimed to be discovered. Studies on HepG2 cells (human HCC) demonstrated C60 fullerene ability to inhibit cell growth (IC50 = 108.2 μmol), to induce apoptosis, to downregulate glucose-6-phosphate dehydrogenase, to upregulate vimentin and p53 expression and to alter HepG2 redox state. If applied to animals experienced HCC in dose of 0.25 mg/kg per day starting at liver cirrhosis stage, C60 fullerene improved post-treatment survival similar to reference 5-fluorouracil (31 and 30 compared to 17 weeks) and inhibited metastasis unlike the latter. Furthermore, C60 fullerene substantially attenuated liver injury and fibrosis, decreased liver enzymes, and normalized bilirubin and redox markers (elevated by 1.7–7.7 times under HCC). Thus, C60 fullerene ability to inhibit HepG2 cell growth and HCC development and metastasis and to improve animal survival was concluded. C60 fullerene cytostatic action might be realized through apoptosis induction and glucose-6-phosphate dehydrogenase downregulation in addition to its antioxidant activity.

Atresia de vías biliares extrahepaticas en pediatria y citomegalovirus como causante

La atresia de vías biliares es una alteración con gran importancia clínica, más frecuente en la primera infancia, secaracteriza por la obliteración proliferativa de los conductos biliares que progresa a fibrosis hepática, cirrosis einsuficiencia hepática en etapa terminal.El objetivo es presentar un caso clínico inusual y conocer la forma de actuar ante un caso similar. Se trata depaciente femenino de 4 meses de edad, con piel y mucosas ictéricas – verdosas, con hígado palpable debajodel reborde costal derecho, bazo palpable debajo del reborde costal izquierdo. Serología para Citomegaloviruspositivo. La ecografía abdominal reporto: Atresia de vías biliares.Se indicó una portoenterostomia de Kasai, sin embargo por la edad de la paciente, el procedimiento quirúrgicono se realizó.La atresia de vías biliares es una patología poco frecuente, su etiología es desconocida, pero es importante saberreconocerla durante los primeros 2 meses de vida, para evitar complicaciones.

Features of the State of Internal Organs and the Structure of Comorbidity in Deceased Persons With Alcoholic Liver Cirrhosis, Non-alcoholic Fatty Liver Disease at the Cirrhosis Stage and Alcoholic Liver Cirrhosis Associated With Insulin Resistance and Obesity

Features of the State of Internal Organs and the Structure of Comorbidity in Deceased Persons With Alcoholic Liver Cirrhosis, Non-alcoholic Fatty Liver Disease at the Cirrhosis Stage and Alcoholic Liver Cirrhosis Associated With Insulin Resistance and Obesity

Changes in indicators of fibrosis in patients with alcoholic liver cirrhosis associated with non-alcoholic fatty liver disease depending on the stage of cirrhosis

Objective was to study changes in liver parenchyma fibrosis in patients with alcoholic liver cirrhosis associated with non-alcoholic fatty liver disease depending on decompensation using shear wave elastography and FIB-4 index.Material and methods. The study included 204 patients. Among them, 78 patients (Group I) had alcoholic liver cirrhosis (ALC) and 126 patients (Group II) had a combination of ALC with non-alcoholic fatty liver disease (NAFLD). Patients were subgrouped according to compensation classes by the Child-Pugh score (A, B, C). The degree of liver parenchyma fibrosis was assessed by calculating the FIB-4 (FibroIndex-4) and the liver parenchyma elasticity (kPa) determined by the shear wave elastography method.Results. Values of liver parenchyma elasticity in patients of group II of classes A, B, and C were higher compared to group I same classes (P &lt; 0.05). FIB-4 indicators in patients of group II were higher than classes A, B, and C compared to group I (P &lt; 0.05). In patients with ALC in combination with NAFLD, direct correlations were established between the value of Child-Pugh score and the elasticity of the liver parenchyma, the value of the MELD index and the elasticity of the liver parenchyma, the value of Child-Pugh score and FIB-4 index, the value of MELD index and FIB-4 index, FIB-4 index and liver parenchyma elasticity.Conclusions. In patients with ALC according to elastography and FIB-4 index, fibrosis indicators increase depending on the stage of decompensation. According to elastography and FIB-4 index in patients with ALC, fibrosis indicators were higher in combination with NAFLD at all stages of liver cirrhosis. The magnitude of fibrosis in patients with ALC in combination with NAFLD according to elastography and the FIB-4 index correlates with the severity of liver cirrhosis by Child-Pugh and MELD prognostic index. The combination of shear wave elastography and FIB-4 index are important diagnostic indicators for assessing the degree of fibrosis in the liver.

Effectiveness comparison of indocyanine green retention test with the cirrhotic severity scoring in evaluating the pathological severity of liver cirrhosis in patients with hepatocellular carcinoma and Child-Pugh grade A liver function

BackgroundEvaluating cirrhotic severity is essential for individualizing surgical modalities for patients with hepatocellular carcinoma (HCC). Our previous study proposed a non-invasive method named cirrhotic severity scoring (CSS) to stage liver cirrhosis. Indocyanine green retention rate at 15 min (ICG-R15) has been widely used for the preoperative evaluation of hepatic functional reserve; however, whether ICG-R15 is well correlated with cirrhotic severity, and especially whether comparable with CSS in predicting cirrhotic severity in HCC patients with Child-Pugh grade A liver function remains unknown.MethodsOverall, 510 HCC patients with Child-Pugh grade A liver function undergoing hepatectomy between January 2011 and December 2014 were retrospectively studied. Cirrhotic severity was pathologically assessed using the Laennec staging system. The correlations between ICG-R15, CSS, and cirrhotic severity were analyzed. Furthermore, the performance of ICG-R15 and CSS in predicting posthepatectomy liver failure (PHLF) and 90-day mortality was compared.ResultsPatients with no, mild, moderate, and severe cirrhosis accounted for 15.9%, 29.2%, 35.9%, and 19.0%, respectively, in the entire cohort. ICG-R15 was found to be less than 10% in 100%, 93.3%, 86.3%, and 70.1% of the patients with no, mild, moderate, and severe cirrhosis, respectively. There was only a weak correlation between ICG-R15 and the pathological severity of liver cirrhosis (r = 0.325; P < 0.001). However, CSS showed a strong correlation with the pathological severity of liver cirrhosis (r = 0.788; P < 0.001). For those with ICG-R15 in the normal range, the accuracy of CSS in diagnosing no/mild, moderate, and severe cirrhosis was 89.1%, 72.8%, and 72.1%, respectively. In addition, CSS was superior to ICG-R15 in predicting PHLF and 90-day mortality.ConclusionsCSS was more useful than ICG-R15 in the preoperative assessment of cirrhotic severity in HCC patients with Child-Pugh grade A liver function. More studies are needed to further validate CSS in patients with different Child-Pugh grades.

Prognostic value of programmed cell death ligand 1 (PD-L1) for hepatocellular carcinoma: a meta-analysis.

The prognostic role of programmed death ligand-1 (PD-L1) expression in hepatocellular carcinoma (HCC) has been widely studied but the results are controversial. In this comprehensive meta-analysis, we elucidated the clinical value of PD-L1 in HCC. Relevant studies were systematically searched in the Cochrane Library, EMBASE, and PubMed until June 27, 2019. Eligible studies were validated for the prognostic effect of PD-L1 on the overall survival (OS), disease-free survival (DFS), and relapse-free survival (RFS) in HCC using a hazard ratio (HR) and its 95% confidence interval (95% CI). Twenty-three studies with 3529 patients were involved in this meta-analysis. The pooled results revealed that high membrane-bound PD-L1 (mPD-L1) expression was associated with poor OS (HR: 1.42; 95% CI: 1.12–1.80; P = 0.004) and had no significant correlation with RFS (HR: 1.14; 95% CI: 0.85–1.54; P = 0.39), and DFS (HR: 1.36; 95% CI: 0.81–2.28; P = 0.25). The results also indicated that high soluble PD-L1 (sPD-L1) levels were associated with worse OS (HR: 2.93; 95% CI: 2.20–3.91; P < 0.00001). In addition, high mPD-L1 expression was associated with high alpha-fetoprotein levels (AFP; OR = 1.46; 95% CI: 1.16–1.84; P = 0.001), hepatitis (OR = 0.72; 95% CI: 0.54–0.98; P = 0.03), poor tumor differentiation (OR = 0.68; 95% CI: 0.55–0.84; P = 0.03), and tumor-infiltrating lymphocytes (OR = 3.39; 95% CI: 1.06–10.91; P = 0.04). The mPD-L1 expression had no significant correlation with age, number of tumors, gender, tumor size, liver cirrhosis, vascular invasion, tumor encapsulation, or TNM stage. The study revealed that high mPD-L1 expression in the tumor tissue and high sPD-L1 levels were associated with shorter OS in HCC. Moreover, overexpression of mPD-L1 was significantly associated with poor tumor differentiation, hepatitis, AFP elevation, and tumor-infiltrating lymphocytes.

Prognosis value of liver stiffness measurements by 2D-SWE in primary HBV-positive hepatocellular carcinoma following radiofrequency ablation.

BackgroundLiver fibrosis is closely associated with the occurrence of hepatocellular carcinoma (HCC), which can be evaluated by liver stiffness measurements (LSM). The clinical significance of LSMin patient with hepatitis B virus (HBV) related HCC underwent radiofrequency ablation (RFA) was evaluated.MethodsTotal of 273 patients underwent RFA for primary HBV-positive HCC were included. LSM values were measured by using by 2D-shear wave elastography (2D-SWE) prior to RFA. The relationship between pretreatment LSM value and survival outcome was evaluated. The cutoff value for LSM to predict survival outcome was determined by receiver operating characteristic (ROC) curve analysis.ResultsAt the endpoint of this study, 88 (32.2%) and 73 (26.7%) patients out of all 273 patients studied had died and recurrent, respectively. All patients were divided into two groups based on the cutoff value (13.4 kPa) of LSM. Patients with a LSM ≥13.4 kPa had lower mean overall survival (62.5 vs. 48.5 months, P=0.01) and lower recurrent free survival (60.4 vs. 47.3 months, P=0.02) than patients with a LSM <13.4 kPa in univariate analysis and LSM also been evaluated as independent predictive factor for survival outcome for HCC following RFA. Otherwise, LSM also was related to liver cirrhosis and TNM stage (both P<0.05).ConclusionsLSM measured by 2D-SWE can sever as an independent prognostic indictor for patients undergoing RFA for HBV-positive HCC.

In Vitro Systems for Studying Different Genotypes/Sub-Genotypes of Hepatitis B Virus: Strengths and Limitations

Hepatitis B virus (HBV) infects the liver resulting in end stage liver disease, cirrhosis, and hepatocellular carcinoma. Despite an effective vaccine, HBV poses a serious health problem globally, accounting for 257 million chronic carriers. Unique features of HBV, including its narrow virus–host range and its hepatocyte tropism, have led to major challenges in the development of suitable in vivo and in vitro model systems to recapitulate the HBV replication cycle and to test various antiviral strategies. Moreover, HBV is classified into at least nine genotypes and 35 sub-genotypes with distinct geographical distributions and prevalence, which have different natural histories of infection, clinical manifestation, and response to current antiviral agents. Here, we review various in vitro systems used to study the molecular biology of the different (sub)genotypes of HBV and their response to antiviral agents, and we discuss their strengths and limitations. Despite the advances made, no system is ideal for pan-genotypic HBV research or drug development and therefore further improvement is required. It is necessary to establish a centralized repository of HBV-related generated materials, which are readily accessible to HBV researchers, with international collaboration toward advancement and development of in vitro model systems for testing new HBV antivirals to ensure their pan-genotypic and/or customized activity.

TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION IN THE TREATMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA ON ADVANCED LIVER CIRRHOSIS

OBJECTIVE was to evaluate the results of transcatheter arterial chemoembolization (TACE) in the treatment of patients with hepatocellular carcinoma (HCC) on advanced liver cirrhosis (LC) and intermediate stage (B) according to BCLC classification (Barcelona Clinic Liver Cancer classification).METHODS AND MATERIALS. We evaluated results of TACE in 54 patients. Of them, 12 (22 %) had stage A of cirrhosis and 42 (78 %) – stage B of cirrhosis according to the Child-Pugh score. Nine (17 %) patients matched stage A4 and 45 (83 %) – stage В according to BCLC classification. The TACEs was performed according to the conventional practice with using Lipiodol + gelfoam (n=40) and with a drug-eluting beads (n=14) from 1 to 16 (average 6) times. The Doxorubicin was used as a first-line therapy in all cases.RESULTS. After TACE, two patients died of liver failure (3.7 %). According to the m-RECIST, complete response to treatment was observed in 9 (16.5 %), partial response – in 13 (24 %), stabilization – in 19 (35.5 %) and progression – in 13 (24 %) patients. At present, 22 (41 %) patients are alive for 1 to 51 (average 16.2) months. 32 patients (59 %) died between 2 to 62 months: 13 (24 %) – from HCC progression, 19 (35 %) – from liver failure. The 1– 2–3-year survival rate was 75–44–15 %; only one patient survived &gt; 5 years. The median survival rate was (22.0±3.0) months, overall survival rate according to Kaplan – Meier was 26 months.CONCLUSION. TACE is a relatively safe and effective treatment in patients with HCC on advanced LC and intermediate stage (B).