Hepatitis C virus (HCV), a non-cytopathic positive-stranded RNA virus, is one of the most common causes of chronic liver diseases such as chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Upon HCV infection, the majority of patients fail to clear the virus and progress to chronic hepatitis C. Chemokines are small chemotactic cytokines that direct the recruitment of immune cells and coordinate immune responses upon viral infection. Chemokine production during acute HCV infection contributes to the recruitment of immune cells with antiviral effector functions and subsequent viral clearance. In chronic HCV infection, however, continuous production of chemokines due to persistent viral replication might result in incessant recruitment of inflammatory cells to the liver, giving rise to persistence of chronic inflammation and liver injury. In this review, we will summarize the roles of chemokines in acute and chronic settings of HCV infection and the clinical relevance of chemokines in the treatment of hepatitis C.
Antiviral Agents/therapeutic use ; Chemokines/*metabolism ; Hepatitis C/drug therapy/*immunology/*metabolism ; Hepatitis C, Chronic/drug therapy/*immunology/*metabolism ; Humans

BACKGROUNDTo study the significance of the expression of HCV core protein in PBMC of patients with chronic hepatitis C and to evaluate the relationship between HCV core protein expression and clinical states.

METHODSIdentification of HCV protein antigen (Ag) in PBMC of 66 hepatitis C patients by immunohistochemical method and clinical status of the patients with HCV protein positive expression were investigated. In 27 out off 66 patients the HCV RNA and HCV Ag in PBMC were detected with RT-PCR and immunohistochemical method.

RESULTSThe HCV Ag (core+NS3) was identified in PBMC in 51 out of 66 patients (77.27%). It was also demonstrated that HCV core protein in nucleus showed strong expression and NS3 protein in cytoplasm showed weak expression. The expression of core protein in nucleus of PBMC were 35.29% in advanced chronic hepatitis patients, which was significantly higher than that from moderate cases (5.88%).

CONCLUSIONSThis study suggested that the expression of PMBC-HCV core protein may be related to the clinical state of the patients. The nuclear expression of HCV core protein in PBMC of patients with hepatitis C may be related to the persistence and activity of the chronic hepatitis C virus and play an important role in the pathogenesis of cirrhrosis and hepatocellular carcinoma.

Hepatitis C Antigens ; blood ; Hepatitis C, Chronic ; virology ; Humans ; Immunohistochemistry ; Leukocytes, Mononuclear ; metabolism ; RNA, Viral ; blood ; Viral Core Proteins ; blood

Animals ; Carcinoma, Hepatocellular ; genetics ; virology ; Hepatitis B, Chronic ; complications ; Hepatitis C, Chronic ; complications ; Humans ; Liver Neoplasms ; genetics ; virology ; Neoplasm Recurrence, Local ; genetics ; Point Mutation ; Telomerase ; metabolism

BACKGROUND: Transforming growth factor beta-1 (TGF beta 1) has been suggested to play a role in the development, growth or progression of hepatocellular carcinoma (HCC). Genotype and serum titer of HCV also affect the occurrence of HCC in chronic hepatitis C. In this study, we were to evaluate the effects of genotype or serum titer of HCV on the expression of TGF beta 1. We also intended to examine the correlation between the up-regulation of TGF beta 1 and the association with HCC in patients with chronic hepatitis C. METHODS: We studied 19 patients with chronic hepatitis C and 18 with HCC associated with HCV infection. HCV genotype was determined by line probe reverse hybridization assay and the amount of HCV-RNA was quantitated by branched DNA signal amplification assay. Serum TGF beta 1 level was measured by enzyme linked immunosorbent assay. RESULTS: HCV genotypes of patients with HCC were similar to those without it. Serum HCV-RNA titer was higher in genotype 1b than in non-1b (p < 0.05). Serum TGF beta 1 levels were higher in HCC than in chronic hepatitis (p < 0.05). However, there was no significant difference in the serum TGF beta 1 level between genotype 1b and non-1b. Also, it was not correlated with the serum HCV-RNA titer or alanine aminotransferase levels. CONCLUSION: TGF beta 1 seems to be overexpressed in HCC compared to that of chronic hepatitis C: it was not affected by serum ALT levels, genotype or serum HCV titer. It is suggested that TGF beta 1 may be associated with the malignant transformation of hepatocyte or the progression of HCV-associated HCC.
Adult ; Aged ; Alanine Transaminase/blood ; Carcinoma, Hepatocellular/virology ; Carcinoma, Hepatocellular/metabolism* ; Female ; Genotype ; Hepatitis C, Chronic/virology ; Hepatitis C, Chronic/metabolism* ; Hepatitis C-Like Viruses/genetics ; Hepatitis C-Like Viruses/classification ; Human ; Liver Neoplasms/virology ; Liver Neoplasms/metabolism* ; Male ; Middle Age ; RNA, Viral/blood ; Transforming Growth Factor beta/blood*

Animals ; Fatty Liver ; complications ; genetics ; metabolism ; virology ; Hepatitis B virus ; genetics ; isolation & purification ; physiology ; Hepatitis C, Chronic ; complications ; genetics ; metabolism ; virology ; Humans

Objective: To investigate the efficacy of chitinase-3-like protein 1 (CHI3L1) and Golgi protein 73 (GP73) in the diagnosis of cirrhosis and the dynamic changes of CHI3L1 and GP73 after HCV clearance in patients with chronic hepatitis C (CHC) treated with direct-acting antiviral drugs (DAAs). The comparison of continuous variables of normal distribution were statistically analyzed by ANOVA and t-test. The comparison of continuous variables of non-normal distribution were statistically analyzed by rank sum test. The categorical variables were statistically analyzed by Fisher's exact test and χ(2) test. Correlation analysis was performed using Spearman correlation analysis. Methods: Data of 105 patients with CHC diagnosed from January 2017 to December 2019 were collected. The receiver operating characteristic curve (ROC curve) was plotted to study the efficacy of serum CHI3L1 and GP73 for the diagnosis of cirrhosis. Friedman test was used to compare CHI3L1 and GP73 change characteristics. Results: The areas under the ROC curve for CHI3L1 and GP73 in the diagnosis of cirrhosis at baseline were 0.939 and 0.839, respectively. Serum levels of CHI3L1 and GP73 in the DAAs group decreased significantly at the end of treatment compared with baseline [123.79 (60.25, 178.80) ng/ml vs. 118.20 (47.68, 151.36) ng/ml, P = 0.001; 105.73 (85.05, 130.69) ng/ml vs. 95.52 (69.52, 118.97) ng/ml, P = 0.001]. Serum CHI3L1 and GP73 in the pegylated interferon combined with ribavirin (PR) group were significantly lower at the end of 24 weeks of treatment than the baseline [89.15 (39.15, 149.74) ng/ml vs. 69.98 (20.52, 71.96) ng/ml, P < 0.05; 85.07 (60.07, 121) ng/ml vs. 54.17 (29.17, 78.65) ng/ml, P < 0.05]. Conclusion: CHI3L1 and GP73 are sensitive serological markers that can be used to monitor the fibrosis prognosis in CHC patients during treatment and after obtaining a sustained virological response. Serum CHI3L1 and GP73 levels in the DAAs group decreased earlier than those in the PR group, and the serum CHI3L1 levels in the untreated group increased compared with the baseline at about two years of follow-up.
Humans ; Hepatitis C, Chronic/drug therapy* ; Antiviral Agents/therapeutic use* ; Membrane Proteins/metabolism* ; Liver Cirrhosis/diagnosis* ; Fibrosis ; Biomarkers

Adult ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; Humans ; Male ; Middle Aged ; Platelet-Derived Growth Factor ; metabolism ; Proto-Oncogene Proteins c-sis ; Young Adult

OBJECTIVEThe aim of this study was to explore the diagnostic value of liver stiffness measurement combined with serum high-sensitivity C-reactive protein detection in HBV-related cirrhosis patients complicated with primary liver cancer.

METHODSA total of 156 previously untreated chronic hepatitis B-related cirrhosis patients and 50 healthy subjects were included in this study. The 156 patients were divided into two groups: those with primary liver cancer (67 cases) and without liver cancer (89 cases). The 50 healthy subjects were considered as normal control group. Liver stiffness measurement (LSM) was conducted and serum high-sensitivity C-reactive protein (CRP) level was assayed in all the 156 patients and 50 normal individuals, and their measurement values were statistically compared and analyzed.

RESULTSThe LSM value was (39.72±29.05) kPa in the liver cancer patients, significantly higher than the (27.81±18.46) kPa in the cirrhosis alone patients and (4.25±0.74) kPa in the healthy controls (P<0.01 for both). Serum hs-CRP levels in the liver cancer patients was 5.81mg/L, significantly higher than 1.78 mg/L in the cirrhosis alone patients and 0.38mg/L in healthy controls, (P<0.01 for both). The higher the grade of LSM values was, the positive rate of CRP was higher in the cirrhosis patients complicated with primary liver cancer. In patients with LSM values ≥27.6 kPa, the serum CRP positive rate was 64.2% in patients with primary liver cancer, significantly higher than the 38.0% in patients with cirrhosis alone (P<0.01). In the 67 HBV-related cirrhosis patients complicated primary liver cancer, the LSM value and serum hs-CRP level in AFP-positive patients were (48.95±28.59) kPa and 4.91 mg/L, respectively, higher than those in the AFP-negative patients (28.64±26.83) kPa and 4.16 mg/L, but with a non-significant difference (P>0.05).

CONCLUSIONLiver stiffness measurement combined with serum high-sensitivity C-reactive protein detection may have potential diagnostic implications as a marker of primary liver cancer occurrence in patients with HBV-related cirrhosis.

Biomarkers ; C-Reactive Protein ; metabolism ; Elasticity Imaging Techniques ; Fibrosis ; Hepatitis B, Chronic ; complications ; metabolism ; Humans ; Liver Cirrhosis ; etiology ; metabolism ; virology ; Liver Neoplasms

OBJECTIVETo investigate the possible relationship between polymorphism of codon25 in signal peptide region of transforming growth factor beta 1 (TGFb1) and hepatitis C virus (HCV) infection susceptibility.

METHODSGenotypes of TGFb1 of 191 subjects (85 HCV infected patients and 106 healthy controls) were studied. Genotypes of TGFb1 codon25 were determined by amplification refractory mutation system (ARMS).

RESULTSDifferences of codon25 polymorphism were not found between HCV infected patients and the controls (P more than 0.05), which showed a similar pattern between the chronic hepatitis C group and HCV-associated liver cirrhosis group (P more than 0.05). There were no differences of genotype distribution of codon25 between ALT normal and ALT elevated patients (P more than 0.05), but G allele frequency was higher in ALT elevated group (P=0.040). There were great differences between the distribution of genotypes (P=0.005) and allele frequency (P=0.000) of the HCV RNA positive and the negative groups in that the HCV RNA positive group differed greatly from the negative group.

CONCLUSIONPolymorphism of TGFb1 codon25 may influence the grade of liver inflammatory activity. High G allele frequency of codon25 may be associated with viremia in patients with chronic HCV infection. It seems that polymorphism of codon25 in the signal peptide region of TGFb1 may contribute to the outcome of HCV infected patients.

Adult ; Blood Donors ; Case-Control Studies ; Female ; Genotype ; Hepatitis C, Chronic ; genetics ; metabolism ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Transforming Growth Factor beta1 ; genetics ; metabolism

OBJECTIVETo study the potential role of mast cells and the related molecular mechanism in chronic hepatitis (CH) using a rat model system.

METHODSThirty Wistar rats (15 males, 15 females; weight range: 230-290 g) were randomly divided into the normal contrast (NC) group and experimental CH group. The CH group received subcutaneous injection of CCl4 and a diet high in cholesterol and alcohol content and low in protein and choline content. Throughout the 4-week modeling period, aseptic blood samples were taken to test plasma tryptase (TS) and hyaluronic acid (HA) levels. The rats were euthanized to assess the changes in liver mast cells by histology and morphology analyses and the changes in liver expression of c-kit and stem cell factor (SCF) proteins by immunohistochemistry and mRNAs by RT-PCR.

RESULTSCompared to the NC group, the CH group had higher plasma and liver concentration of HA (78.09 +/- 38.55 vs. 145.14 +/- 52.54 ng/ml, 51.58 +/- 20.45 vs. 106.59 +/- 43.15 ng/100 mg; t = 2.457 and 2.825 respectively, both P less than 0.05) and TS (0.416 +/- 0.143 vs 0.753 +/- 0.210 mg/ml; t = 4.165, P less than 0.05). The CH group also showed fatty degeneration and fibrosis with many degranulating and degranulated mast cells filled with purple granula located around the liver blood vessels and in fiber-intervals. The CH livers also showed a significantly higher number of mast cells (2.167 +/- 0.924 vs. NC: 10.92 +/- 1.575; t = 7.633, P less than 0.05) and stronger intensity of c-kit staining (2.783 +/- 0.577 vs. 12.86 +/- 3.126; t = 9.511, P less than 0.05) and SCF staining (3.383 +/- 1.583 vs. 15.58 +/- 6.431; t = 9.625, P less than 0.05). The expressions of c-kit and SCF were positively correlated with HA level (r = 0.478 and 0.556 respectively, both P less than 0.05). The c-kit and SCF mRNA expression levels were also significantly higher in the CH liver tissues.

CONCLUSIONMast cell degranulation and histamine release is significantly increased under conditions of chronic hepatitis, and the related mechanism may involve up-regulation of the membrane receptor c-kit and its ligand SCF.

Animals ; Cell Degranulation ; Disease Models, Animal ; Female ; Hepatitis, Chronic ; metabolism ; pathology ; Hepatocytes ; metabolism ; Liver ; metabolism ; Liver Cirrhosis ; metabolism ; pathology ; Male ; Mast Cells ; metabolism ; physiology ; Proto-Oncogene Proteins c-kit ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar ; Stem Cell Factor ; metabolism