Programmed death 1, ligand 1 and 2 correlated genes and their association with mutation, immune infiltration and clinical outcomes of hepatocellular carcinoma.

BACKGROUND: The exact regulation network of programmed death 1 (PD-1), programmed death ligand 1 (PD-L1), and programmed death ligand 2 (PD-L2) signaling in immune escape is largely unknown. We aimed to describe the gene expression profiles related to PD-1 as well as its ligands PD-L1 and PD-L2, thus deciphering their possible biological processes in hepatocellular carcinoma (HCC). AIM: To find the possible mechanism of function of PD-1, PD-L1, and PD-L2 in HCC. METHODS: Based on the expression data of HCC from The Cancer Genome Atlas, the PD-1/PD-L1/PD-L2 related genes were screened by weighted correlation network analysis method and the biological processes of certain genes were enriched. Relation of PD1/PD-L1/PD-L2 with immune infiltration and checkpoints was investigated by co-expression analysis. The roles of PD-1/PD-L1/PD-L2 in determination of clinical outcome were also analyzed. RESULTS: Mutations of calcium voltage-gated channel subunit alpha1 E, catenin beta 1, ryanodine receptor 2, tumor suppressor protein p53, and Titin altered PD-1/PD-L1/PD-L2 expression profiles in HCC. PD-1, PD-L1, and PD-L2 related genes were mainly enriched in biological procedures of T cell activation, cell adhesion, and other important lymphocyte effects. In addition, PD-1/PD-L1/PD-L2 was related with immune infiltration of CD8 T cells, cytotoxic lymphocytes, fibroblasts, and myeloid dendritic cells. Immune checkpoints of CTLA4, CD27, CD80, CD86, and CD28 were significantly related to the PD-1/PD-L1/PD-L2 axis. Clinically, PD-1 and PD-L2 expression was correlated with recurrence (P = 0.005 for both), but there was no significant correlation between their expression and HCC patient survival. CONCLUSION: Mutations of key genes influence PD-1, PD-L1, and PD-L2 expression. PD-1, PD-L1, and PD-L2 related genes participate in T cell activation, cell adhesion, and other important lymphocyte effects. The finding that PD-1/PD-L1/PD-L2 is related to immune infiltration and other immune checkpoints would expand our understanding of promising anti-PD-1 immunotherapy.

Undifferentiated embryonal sarcoma of the liver: Clinical characteristics and outcomes.

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare liver malignancy originating from primary mesenchymal tissue. The clinical manifestations, laboratory tests, and imaging examinations of the disease lack specificity and the preoperative misdiagnosis rate is high. The overall prognosis is poor and survival rate is low. AIM: To investigate the diagnosis, treatment, and prognosis of UESL. METHODS: We performed a retrospective, single-center cohort study in Shengjing Hospital of China Medical University, which is a central hospital in northeast China. From 2005 to 2017, we recruited 14 patients with pathologically confirmed UESL. We analyzed the clinical manifestations, laboratory tests, imaging examinations, pathological examinations, therapy, and prognosis of these patients. RESULTS: There were nine males and five females aged 2-60 years old included in the study. The major initial symptoms were abdominal pain (71.43%) and fever (57.14%). Preoperative laboratory tests revealed that seven patients had increased leukocyte levels, four showed a decrease in hemoglobin levels, seven patients had increased glutamyl transpeptidase levels, nine had increased lactate dehydrogenase levels, and three showed an increase in carbohydrate antigen 199. There was no difference in the rate of misdiagnosis in preoperative imaging examinations of UESL between adults and children (6/6 vs 5/8, P = 0.091). The survival rate after complete resection was 6/10, while that after incomplete resection was 0/4 (P = 0.040), suggesting that complete resection is important to improve survival rate. In total, five out of the eight children achieved survival. During the follow-up, the maximum survival time was shown to be 11 years and minimum survival time was 6 mo. Six adult patients relapsed late after surgery and all of them died. CONCLUSION: Preoperative imaging examination for UESL has a high misdiagnosis rate. Multidisciplinary collaboration can improve the diagnostic accuracy of UESL. Complete surgical resection is the first choice for treatment of UESL.

Declining diagnostic accuracy of non-invasive fibrosis tests is associated with elevated alanine aminotransferase in chronic hepatitis B.

AIM: To explore the effect of alanine aminotransferase (ALT) on the performance of non-invasive fibrosis tests in chronic hepatitis B (CHB) patients. METHODS: A total of 599 treatment-naive and biopsy-proven CHB patients were included in the study. The cohort was divided into the following three groups: Normal ALT (ALT ≤ 40), slightly elevated ALT (40 < ALT ≤ 80) and elevated ALT (ALT > 80). The diagnostic performance of five common non-invasive fibrosis tests for liver fibrosis (stages S2-4), including the aspartate aminotransferase (AST)-to-platelet (PLT) ratio index (APRI), fibrosis index based on 4 factors (FIB-4), King's score, Forns index and gamma-glutamyl transpeptidase (GGT)-to-PLT ratio (GPR), were evaluated for each group. RESULTS: Higher ALT levels were associated with higher non-invasive fibrosis test scores. Patients with the same fibrosis stage but higher ALT levels showed higher non-invasive test scores. The areas under the receiver operating characteristics curves (AUROCs) of the non-invasive tests for prediction of ≥ S2 were higher for patients with ALT ≤ 40 U/L (range 0.705-0.755) and 40 < ALT ≤ 80 U/L (range 0.726-0.79) than for patients with ALT > 80 U/L (range 0.604-0.701). The AUROCs for predicting ≥ S3 and S4 were higher in patients with ALT ≤ 40 U/L (range 0.736-0.814 for ≥ S3, 0.79-0.833 for S4) than in patients with 40 < ALT ≤ 80 U/L (range 0.732-0.754 for ≥ S3, range 0.626-0.723 for S4) and ALT > 80 U/L (range 0.7-0.784 for ≥ S3, range 0.662-0.719 for S4). The diagnostic accuracy of the non-invasive tests decreased in a stepwise manner with the increase in ALT. CONCLUSION: ALT has a significant effect on the diagnostic performance of non-invasive fibrosis tests. The ALT level should be considered before performing these non-invasive tests.

Hepatitis B virus serosurvey and awareness of mother-to-child transmission among pregnant women in Shenyang, China: An observational study.

Preventing hepatitis B virus (HBV) mother-to-child transmission (MTCT) is the key to controlling the prevalence of chronic HBV infection. Adequate awareness of hepatitis B in hepatitis B s antigen (HBsAg) positive pregnant women may be helpful to reduce HBV MTCT.The aim of this study was to explore HBV seroprevalence among pregnant women and investigate the level of hepatitis B awareness among HBsAg positive pregnant women.HBV serum biomarkers were tested among pregnant women visiting Shengjing Hospital of China Medical University. HBsAg-positive pregnant women received a HBV DNA test and completed a questionnaire. The different HBV DNA loads were interpreted as follows: 20 to  < 2 × 10 IU/mL was low viral load, 2 × 10 to  < 2 × 10 IU/mL was intermediate viral load and ≥2 × 10 IU/mL was high viral load. The pregnant women with high viral load were treated with telbivudine (LdT). HBV DNA at different times was tested. The rate of HBV MTCT was confirmed at 28 weeks postpartum.HBsAg prevalence among pregnant women was 3.1% (441/14314). There was significant difference in comparing HBsAg prevalence in different age groups (χ = 13.86, P < .01). Among 441 HBsAg-positive pregnant women, 151 (34.2%) were hepatitis B e antigen (HBeAg) positive and 112 (25.4%) had high viral load. After 4 weeks of treatment, the average HBV DNA load of 66 cases with high viral load was (5.0 ±â€Š0.8) log10 IU/mL. The average HBV DNA load at 4 weeks postpartum rebounded to (7.9 ±â€Š1.0) log10 IU/mL, which was not significantly different from that at baseline (t = 1.23, P = .22). At 28 weeks postpartum, the rate of HBV MTCT in the treatment group was significantly lower than that in the observation group (0% vs 12.2%; P = .02). Only 23.4% of pregnant women knew their HBV status before gestation and 17.7% of pregnant women knew the HBV status before delivery. However, only 21.3% of pregnant women realized to need antiviral treatment to prevent MTCT.The pregnant women in Shenyang had a low HBsAg prevalence. Antiviral treatment for pregnant women with high viral load can effectively reduce the rate of HBV MTCT. HBV screening and education among HBsAg-positive pregnant women should be strengthened.

Daclatasvir plus asunaprevir in treatment-naïve patients with hepatitis C virus genotype 1b infection.

AIM: To assess daclatasvir plus asunaprevir (DUAL) in treatment-naïve patients from mainland China, Russia and South Korea with hepatitis C virus (HCV) genotype 1b infection. METHODS: Patients were randomly assigned (3:1) to receive 24 wk of treatment with DUAL (daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily) beginning on day 1 of the treatment period (immediate treatment arm) or following 12 wk of matching placebo (placebo-deferred treatment arm). The primary endpoint was a comparison of sustained virologic response at posttreatment week 12 (SVR12) compared with the historical SVR rate for peg-interferon plus ribavirin (70%) among patients in the immediate treatment arm. The first 12 wk of the study were blinded. Safety was assessed in DUAL-treated patients compared with placebo patients during the first 12 wk (double-blind phase), and during 24 wk of DUAL in both arms combined. RESULTS: In total, 207 patients were randomly assigned to immediate (n = 155) or placebo-deferred (n = 52) treatment. Most patients were Asian (86%), female (59%) and aged < 65 years (90%). Among them, 13% had cirrhosis, 32% had IL28B non-CC genotypes and 53% had baseline HCV RNA levels of ≥ 6 million IU/mL. Among patients in the immediate treatment arm, SVR12 was achieved by 92% (95% confidence interval: 87.2-96.0), which was significantly higher than the historical comparator rate (70%). SVR12 was largely unaffected by cirrhosis (89%), age ≥ 65 years (92%), male sex (90%), baseline HCV RNA ≥ 6 million (89%) or IL28B non-CC genotypes (96%), although SVR12 was higher among patients without (96%) than among those with (53%) baseline NS5A resistance-associated polymorphisms (at L31 or Y93H). During the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving DUAL. During 24 wk of DUAL therapy (combined arms), the most common adverse events (≥ 10%) were elevated alanine aminotransferase and upper respiratory tract infection; emergent grade 3-4 laboratory abnormalities were infrequently observed, and all grade 3-4 aminotransferase abnormalities (alanine aminotransferase, n = 9; aspartate transaminase, n = 6) reversed within 8-11 d. Two patients discontinued DUAL treatment; one due to aminotransferase elevations, nausea, and jaundice and the other due to a fatal adverse event unrelated to treatment. There were no treatment-related deaths. CONCLUSION: DUAL was well-tolerated during this phase 3 study, and SVR12 with DUAL treatment (92%) exceeded the historical SVR rate for peg-interferon plus ribavirin of 70%.

Mesenchymal stem cells rescue acute hepatic failure by polarizing M2 macrophages.

AIM: To investigate whether M1 or M2 polarization contributes to the therapeutic effects of mesenchymal stem cells (MSCs) in acute hepatic failure (AHF). METHODS: MSCs were transfused into rats with AHF induced by D-galactosamine (DGalN). The therapeutic effects of MSCs were evaluated based on survival rate and hepatocyte proliferation and apoptosis. Hepatocyte regeneration capacity was evaluated by the expression of the hepatic progenitor surface marker epithelial cell adhesion molecule (EpCAM). Macrophage polarization was analyzed by M1 markers [CD68, tumor necrosis factor alpha (TNF-α), interferon-γ (IFN-γ), inducible nitric oxide synthase (INOS)] and M2 markers [CD163, interleukin (IL)-4, IL-10, arginase-1 (Arg-1)] in the survival and death groups after MSC transplantation. RESULTS: The survival rate in the MSC-treated group was increased compared with the DPBS-treated control group (37.5% vs 10%). MSC treatment protected rats with AHF by reducing apoptotic hepatocytes and promoting hepatocyte regeneration. Immunohistochemical analysis showed that MSC treatment significantly increased the expression of EpCAM compared with the control groups (P < 0.001). Expression of EpCAM in the survival group was significantly up-regulated compared with the death group after MSC transplantation (P = 0.003). Transplantation of MSCs significantly improved the expression of CD163 and increased the gene expression of IL-10 and Arg-1 in the survival group. IL-4 concentrations were significantly increased compared to the death group after MSC transplantation (88.51 ± 24.51 pg/mL vs 34.61 ± 6.6 pg/mL, P < 0.001). In contrast, macrophages showed strong expression of CD68, TNF-α, and INOS in the death group. The concentration of IFN-γ was significantly increased compared to the survival group after MSC transplantation (542.11 ± 51.59 pg/mL vs 104.07 ± 42.80 pg/mL, P < 0.001). CONCLUSION: M2 polarization contributes to the therapeutic effects of MSCs in AHF by altering levels of anti-inflammatory and pro-inflammatory factors.

Telbivudine therapy for chronic hepatitis B: A journey to identify super-responders and to optimize treatment using the roadmap model.

Hepatitis B virus (HBV) infection is one of the most serious health problems worldwide with a high risk for cirrhosis and liver cancer. Several antiviral agents have been approved for the treatment of chronic hepatitis B, leading to a rapid reduction in HBV DNA and normalization of serum alanine aminotransferase levels. Telbivudine, a potent inhibitor of HBV replication, has been shown to be well tolerated. Because of the emergence of drug resistance, optimization strategies for telbivudine therapy have been shown to improve patient responses. Optimal baseline characteristics in so-called super-responders have been used to predict the virological response. Baseline HBV DNA levels < 9 log10 copies/mL (2 × 108 IU/mL) or alanine aminotransferase levels of more than or equal to twofold the upper limit of normal in HBeAg-positive patients and HBV DNA < 7 log10 copies/mL (2 × 106 IU/mL) in HBeAg-negative patients were strong predictors for virological response. In addition, the roadmap model, based on early virological response at week 24 of therapy, is considered as a powerful tool to identify patients at risk of treatment failure (HBV DNA ≥ 300 copies/mL, i.e. 60 IU/mL) and to reduce the risk of antiviral resistance. When considering pre-treatment characteristics and on-treatment responses, telbivudine may provide physicians with a wide choice of options to effectively treat patients with chronic hepatitis B, especially those with or at risk of renal impairment, or women of childbearing age.

Treating chronic hepatitis B virus: Chinese physicians' awareness of the 2010 guidelines.

AIM: To investigate Chinese physicians' awareness of the 2010 guidelines on the treatment of chronic hepatitis B virus (HBV) infection. METHODS: This was a quantitative survey that investigated the characteristics and practices of physicians who were treating patients with hepatitis B, the profile of their patients and physician practices regarding the diagnosis and treatment of HBV at the time of the survey. Participants were randomly selected from available databases of Chinese physicians and requested to complete either an online or paper-based survey. Data from the survey responses were analysed. For data validation and interpretation, qualitative indepth interviews were conducted with 39 of the respondents. RESULTS: Five-hundred completed surveys, from 663 physicians were available for analysis. A mean of 175 chronic hepatitis B (CHB) patients was seen by each physician every month, of whom 85 (49%) were treated in line with therapeutic indications stated in the 2010 guidelines. A total of 444 (89%) physicians often (> 60% of the time) adhered to the guidelines. Most physicians used antiviral medications as recommended. For patients with compensated and decompensated cirrhosis, 342 (68%) and 336 (67%) of physicians, respectively, often followed the recommendation to use potent nucleos(t)ide analogues with a high genetic barrier to resistance, using the appropriate treatment more than 60% of the time. Physicians from infectious disease or liver disease departments were better informed than those from gastrointestinal or other departments. CONCLUSION: The majority of Chinese physicians often adhere to Chinese 2010 CHB guidelines and are well-informed about the use of antiviral medications for hepatitis B.

Will Sofosbuvir/Ledipasvir (Harvoni) Be Cost-Effective and Affordable for Chinese Patients Infected with Hepatitis C Virus? An Economic Analysis Using Real-World Data.

BACKGROUND: Little is known on the cost-effectiveness of novel regimens for hepatitis C virus (HCV) compared with standard-of-care with pegylated interferon (pegIFN) and ribavirin (RBV) therapy in developing countries. We evaluated cost-effectiveness of sofosbuvir/ledipasvir for 12 weeks compared with a 48-week pegIFN-RBV regimen in Chinese patients with genotype 1b HCV infection by economic regions. METHODS: A decision analytic Markov model was developed to estimate quality-adjusted-life-years, lifetime cost of HCV infection and incremental cost-effectiveness ratios (ICERs). SVR rates and direct medical costs were obtained from real-world data. Parameter uncertainty was assessed by one-way and probabilistic sensitivity analyses. Threshold analysis was conducted to estimate the price which can make the regimen cost-effective and affordable. RESULTS: Sofosbuvir/ledipasvir was cost-effective in treatment-experienced patients with an ICER of US$21,612. It varied by economic regions. The probability of cost-effectiveness was 18% and 47% for treatment-naive and experienced patients, and it ranged from 15% in treatment-naïve patients in Central-China to 64% in treatment-experienced patients in Eastern-China. The price of 12-week sofosbuvir/ledipasvir treatment needs to be reduced by at least 81% to US$18,185 to make the regimen cost-effective in all patients at WTP of one time GDP per capita. The price has to be US$105 to make the regimen affordable in average patients in China. CONCLUSION: Sofosbuvir/ledipasvir regimen is not cost-effective in most Chinese patients with genotype 1b HCV infection. The results vary by economic regions. Drug price of sofosbuvir/ledipasvir needs to be substantially reduced when entering the market in China to ensure the widest accessibility.

Mutations in different regions of the genome of hepatitis C virus genotype 1b and association with response to interferon therapy.

The aim of this study was to investigate the association of mutations in the E2/NS1 [hypervariable regions 1 and 2 (HVR1 and HVR2)] and NS5A regions of the hepatitis C virus (HCV) genome and the effectiveness of interferon (IFN) therapy, and assess whether the degree of heterogeneity of HCV quasispecies predicts response to IFN treatment. Fourteen patients infected with HCV genotype 1b (HCV-1b) who were treated with pegylated IFN-α-2a and ribavirin for 24 weeks, were studied. E2/NS1 and NS5A gene segments were amplified by reverse-transcription polymerase chain reaction. HCV quasispecies heterogeneity in the E2/NS1 region was determined by cloning and sequencing. Mutations in the NS5A region were detected by direct sequencing. The heterogeneity of HCV quasispecies in the HVR1 was significantly greater in the non-responder group than in the responder group, but was not significant for HVR2 or NS5A. The correlation between mutations in IFN sensitivity-determining region (ISDR, NS5A2209-2248) and IFN sensitivity could not be supported. The degree of quasispecies heterogeneity in HVR1, but not in HVR2 and NS5A, may be predictive of response to IFN therapy. An ISDR may not apply to patients infected with HCV-1b.

[Quantitative analysis of HBV cccDNA from liver biopsy specimens in HBV carriers: correlation with serological makers and sera HBV DNA].

OBJECTIVE: To investigate the correlation of sera HBV DNA and serological makers with hepatic tissue HBVcccDNA in chronic HBV carriers. METHODS: Real time fluorescence quantitative polymerase chain reaction (RT-PCR) were used to detect HBV covalently closed circular DNA (cccDNA) and total intrahepatic HBV DNA from 30 needle-biopsy specimens as well as HBV DNA in sera in chronic HBV carriers. Quantification of the HBsAg, HBeAg in sera were quantified using Chemiluminescence immunoassay. RESULTS: HBVcccDNA can be detected in chronic HBV carriers, which rang from 3.15 x 10(3) copies/mg to 1.06 x 10(7) copies/mg. There was a positive correlation between the cccDNA and HBVtDNA (r = 0.375, P < 0.05), but there was no correlation between the cccDNA and sera HBV DNA (P = 0.174). There was a positive correlation between cccDNA and sera HBsAg quantification (r = 0.562, P < 0.001) but no correlation with sera HBeAg qantification (r = 0.152, P > 0.05). CONCLUSION: HBV cccDNA can be replicated stably in hepatic tissue in all chronic HBV carriers. HBV DNA in sera can not be indicated hepatic tissue cccDNA level. While HBsAg quantification in sera can be used as a marker of cccDNA quantification in hepatic tissue to some extent.

Genotyping the hepatitis B virus with a fragment of the HBV DNA polymerase gene in Shenyang, China.

The hepatitis B virus (HBV) has been classified into eight genotypes (A-H) based on intergenotypic divergence of at least 8% in the complete nucleotide sequence or more than 4% in the S gene. To facilitate the investigation of the relationship between the efficacy of drug treatment and the mutation with specific genotype of HBV, we have established a new genotyping strategy based on a fragment of the HBV DNA polymerase gene. Pairwise sequence and phylogenetic analyses were performed using CLUSTAL V (DNASTAR) on the eight (A-H) standard full-length nucleotide sequences of HBV DNA from GenBank (NCBI) and the corresponding semi-nested PCR products from the HBV DNA polymerase gene. The differences in the semi-nested PCR fragments of the polymerase genes among genotypes A through F were greater than 4%, which is consistent with the intergenotypic divergence of at least 4% in HBV DNA S gene sequences. Genotyping using the semi-nested PCR products of the DNA polymerase genes revealed that only genotypes B, C, and D were present in the 50 cases, from Shenyang, China, with a distribution of 11 cases (22%), 25 cases (50%), and 14 cases (28%) respectively. These results demonstrate that our new genotyping method utilizing a fragment of the HBV DNA polymerase gene is valid and can be employed as a general genotyping strategy in areas with prevalent HBV genotypes A through F. In Shenyang, China, genotypes C, B, and D were identified with this new genotyping method, and genotype C was demonstrated to be the dominant genotype.

In vitro study on hepatitis B virus infecting human choriocarcinoma JEG3 cells and its mechanism.

AIM: To build a hepatitis B virus (HBV)-infected human trophoblast cell model in vitro and determine the mechanism of intrauterine HBV infection. METHODS: Serum from hepatitis B-infected patients containing HBV DNA >10(9) was drawn, subsequently inoculated into human trophoblast cells in vitro (JEG3) and passage-cultured. The supernatants and intracellular HBV viral load of inoculated cells were tested by real-time PCR, and HBV DNA was determined by Southern blot. RESULTS: From inoculation of the 1st passage JEG3 cells, the supernatant viral load of the 1st passage was seen increasing over time, which peaked at 120 h, whereas the HBV viral load was seen decreasing gradually in subsequent passages, and tested negative after the 6th passage. In addition, infected cells of HBV DNA were tested by Southern blot, and showed continual expression in the subsequent cell passages 1-5 while passage 6 was negative. HBsAg was tested as positive from different passages 1-5, and its concentration was also seen decreasing with each subsequent passage cultured until the 6th passage when it tested negative. CONCLUSION: HBV could infect human trophoblast cells (JEG3) in vitro, and it showed continual expression in subsequent cell passages 1-5.

An immunocompetent adult patient with hepatitis and guillain-barré syndrome after cytomegalovirus infection.

OBJECTIVES: It is to describe an immunocompetent adult patient with hepatitis and Guillain-Barré syndrome (GBS) after Cytomegalovirus (CMV) infection. In the initial course of the diagnosis and treatment, CMV infection was ignored. CASE REPORT: A 19-year-old Chinese girl complained of fatigue with pain and numbness of the limbs, with abnormal liver function. She was diagnosed as a case of GBS based on history, clinical findings and auxiliary examinations. On day 13 of admission, her liver function was still abnormal. So CMV was recommended to examine. CMV hepatitis was diagnosed on positive serum anti-CMV IgG and IgM antibodies. The case was improved only with intravenous immunoglobulin therapy, without the use of antiviral therapy. CONCLUSIONS: This case showed an immunocompetent adult patient with hepatitis and GBS induced by CMV. The physicians should take into account multi-system involvement of severe CMV infection.

[Cytokine levels in serum of patients with chronic hepatitis C and its significance].

AIM: To investigate the relationship between the changes of cytokine levels in serum and ALT, HCV genotype, HCV RNA loading and the effectiveness of IFN treatment. The cytokines included IL-2, IFN-γ, IL-5, IL-6, IL-12P70 and IL-12P40. METHODS: Contents of IL-2, IFN-γ, IL-5, IL-6, IL-12P70 and IL-12P40 in serum of 30 patients with chronic hepatitis C and 30 healthy adults were detected. The relationship of cytokine level with ALT level , HCV genotype, HCV RNA load were analyzed . The differences of these cytokine levels in the groups of response and nonresponse to interferon treatment were compared. Serum cytokines were detected by the method of ELISA. HCV genotypes were classified by direct sequencing. HCV RNA loads were determined by fluorescence quantitative PCR. RESULTS: The content of IL-2 was decreased and the contents of IL-5 and I L-12P40 increased in the patients with chronic hepatitis C compared with normal control. The serum level of IL-6 were directly proportional to the serum levels of ALT, while inversely proportional to that of HCV RNA load, and in HCV genotype 1 patients was significantly higher than that in genotype 2 patients, the other cytokine levels had no differences between two genotypes. The sustained response rate of IFN treatment was 46.7%. There were no difference of all cytokines detected between the groups of response and nonresponse before IFN therapy, but the level of IFN-γ were increased after interferon therapy in the response group. CONCLUSION: The imbalance of immune cytokines had correlation with the chronicity if HCV infection and the activity of liver inflammation. There are no correlation between the levels of Th1/Th2 cytokines in the serum before IFN treatment and the outcome of IFN therapy. Increasing IFN-γ in the serum induced by IFN treatment is associated with sustained response.