AIM To assess daclatasvir plus asunaprevir(d UAL) in treatment-na?ve patients from China's Mainland, Russia and South Korea with hepatitis C virus(HCV) genotype 1 b infection. METHODS Patients were randomly assign...AIM To assess daclatasvir plus asunaprevir(d UAL) in treatment-na?ve patients from China's Mainland, Russia and South Korea with hepatitis C virus(HCV) genotype 1 b infection. METHODS Patients were randomly assigned(3:1) to receive 24 wk of treatment with d UAL(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(placebodeferred 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 d UAL-treated patients compared with placebo patients during the first 12 wk(doubleblind phase), and during 24 wk of d UAL 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 IL28 B non-CC genotypes and 53% had baseline HCV RNA levels of ≥ 6 million IU/m L. 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 IL28 B non-CC genotypes(96%), although SVR12 was higher among patients without(96%) than among those with(53%) baseline NS5 A resistanceassociated polymorphisms(at L31 or Y93 H). during the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving d UAL. during 24 wk of d UAL 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 d UAL 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 d UAL was well-tolerated during this phase 3 study, and SVR12 with d UAL treatment(92%) exceeded thehistorical SVR rate for peg-interferon plus ribavirin of 70%.展开更多
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 disea...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.展开更多
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 a...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 in-depth 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.展开更多
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-galact...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(DGal N). 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(Ep CAM). 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 Ep CAM compared with the control groups(P < 0.001). Expression of Ep CAM 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/m L vs 34.61 ± 6.6 pg/m L,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/m L vs 104.07 ± 42.80 pg/m L,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.展开更多
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 ...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/PDL1/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, PDL1, 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.展开更多
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 ...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 noninvasive test scores. The areas under the receiver operating characteristics curves(AUROCs) of the noninvasive 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 noninvasive tests.展开更多
文摘AIM To assess daclatasvir plus asunaprevir(d UAL) in treatment-na?ve patients from China's Mainland, Russia and South Korea with hepatitis C virus(HCV) genotype 1 b infection. METHODS Patients were randomly assigned(3:1) to receive 24 wk of treatment with d UAL(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(placebodeferred 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 d UAL-treated patients compared with placebo patients during the first 12 wk(doubleblind phase), and during 24 wk of d UAL 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 IL28 B non-CC genotypes and 53% had baseline HCV RNA levels of ≥ 6 million IU/m L. 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 IL28 B non-CC genotypes(96%), although SVR12 was higher among patients without(96%) than among those with(53%) baseline NS5 A resistanceassociated polymorphisms(at L31 or Y93 H). during the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving d UAL. during 24 wk of d UAL 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 d UAL 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 d UAL was well-tolerated during this phase 3 study, and SVR12 with d UAL treatment(92%) exceeded thehistorical SVR rate for peg-interferon plus ribavirin of 70%.
基金The National Science and Technology Major Project,No.2017ZX10201201 and No.2017ZX10202202Liaoning Provincial Natural Science Foundation,No.20180550096。
文摘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.
文摘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 in-depth 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.
基金Supported by Liaoning Provincial Science and Technology Key Project for Translational Medicine,No.2014225020Outstanding Scientific Fund of Shengjing Hospital,No.201102Liaoning Provincial Science and Technology Key Project for Translational Medicine,No.2016509
文摘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(DGal N). 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(Ep CAM). 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 Ep CAM compared with the control groups(P < 0.001). Expression of Ep CAM 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/m L vs 34.61 ± 6.6 pg/m L,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/m L vs 104.07 ± 42.80 pg/m L,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.
基金National Science and Technology Major Project,No. 2017ZX10201201 and No. 2017ZX10202202Liaoning Province Natural Science Foundation,No. 20180550096。
文摘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/PDL1/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, PDL1, 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.
基金Supported by the Liaoning Provincial Science and Technology Key Project for Translational Medicine,No.2014225020Outstanding Scientific Fund of Shengjing Hospital,No.201102+1 种基金Liaoning Provincial Science and Technology Key Project for Translational Medicine,No.2016509National Science and Technology Major Project,Nos.2017ZX10201201,2017ZX10202202,2017ZX10202203
文摘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 noninvasive test scores. The areas under the receiver operating characteristics curves(AUROCs) of the noninvasive 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 noninvasive tests.