BACKGROUND Post-hepatectomy liver failure(PHLF)is a common consequence of radical partial hepatectomy in hepatocellular carcinoma(HCC).AIMS To investigate the relationship between preoperative antiviral therapy and PH...BACKGROUND Post-hepatectomy liver failure(PHLF)is a common consequence of radical partial hepatectomy in hepatocellular carcinoma(HCC).AIMS To investigate the relationship between preoperative antiviral therapy and PHLF,as well as assess the potential efficacy of hepatitis B virus(HBV)DNA level in predicting PHLF.METHODS A retrospective study was performed involving 1301 HCC patients with HBV who underwent radical hepatectomy.Receiver operating characteristic(ROC)analysis was used to assess the capacity of HBV DNA to predict PHLF and establish the optimal cutoff value for subsequent analyses.Logistic regression analyses were performed to assess the independent risk factors of PHLF.The increase in the area under the ROC curve,categorical net reclassification improvement(NRI),and integrated discrimination improvement(IDI)were used to quantify the efficacy of HBV DNA level for predicting PHLF.The P<0.05 was considered statistically significant.RESULTS Logistic regression analyses showed that preoperative antiviral therapy was independently associated with a reduced risk of PHLF(P<0.05).HBV DNA level with an optimal cutoff value of 269 IU/mL(P<0.001)was an independent risk factor of PHLF.All the reference models by adding the variable of HBV DNA level had an improvement in area under the curve,categorical NRI,and IDI,particularly for the fibrosis-4 model,with values of 0.729(95%CI:0.705-0.754),1.382(95%CI:1.341-1.423),and 0.112(95%CI:0.110-0.114),respectively.All the above findings were statistically significant.CONCLUSION In summary,preoperative antiviral treatment can reduce the incidence of PHLF,whereas an increased preoperative HBV DNA level has a correlative relationship with an increased susceptibility to PHLF.展开更多
AIM:To evaluate the efficacy and safety of tenofovir disoproxil fumarate(TDF) for chronic hepatitis B(CHB) patients after multiple failures.METHODS:A total of 29 CHB patients who had a suboptimal response or developed...AIM:To evaluate the efficacy and safety of tenofovir disoproxil fumarate(TDF) for chronic hepatitis B(CHB) patients after multiple failures.METHODS:A total of 29 CHB patients who had a suboptimal response or developed resistance to two or more previous nucleoside/nucleotide analogue(NA) treatments were included.Study subjects were treated with TDF alone(n = 13) or in combination with lamivudine(LAM,n = 12) or entecavir(ETV,n = 4) for ≥ 6 mo.Complete virologic response(CVR) was defined as an achievement of serum hepatitis B virus(HBV) DNA level ≤ 60 IU/mL by real-time polymerase chain reaction method during treatment.Safety assessment was based on serum creatinine and phosphorus level.Eleven patients had histories of LAM and adefovir dipivoxil(ADV) treatment and 18 patients were exposed to LAM,ADV,and ETV.Twenty-seven patients(93.1%) were hepatitis B e antigen(HBeAg) positive and the mean value of the baseline serum HBV DNA level was 5.5 log IU/mL ± 1.7 log IU/mL.The median treatment duration was 16 mo(range 7 to 29 mo).RESULTS:All the patients had been treated with LAM and developed genotypic and phenotypic resistance to it.Resistance to ADV was present in 7 patients and 10 subjects had a resistance to ETV.One patient had a resistance to both ADV and ETV.The cumulative probabilities of CVR at 12 and 24 mo of TDF containing treatment regimen calculated by the Kaplan Meier method were 86.2% and 96.6%,respectively.Although one patient failed to achieve CVR,serum HBV DNA level decreased by 3.9 log IU/mL from the baseline and the last serum HBV DNA level during treatment was 85 IU/mL,achieving near CVR.No patients in this study showed viral breakthrough or primary non-response during the follow-up period.The cumulative probability of HBeAg clearance in the 27 HBeAg positive patients was 7.4%,12%,and 27% at 6,12,and 18 mo of treatment,respectively.Treatment efficacy of TDF containing regimen was not statistically different according to the presence of specific HBV mutations.History of prior exposure to specific antiviral agents did not make a difference to treatment outcome.Treatment efficacy of TDF was not affected by combination therapy with LAM or ETV.No patient developed renal toxicity and no cases of hypophosphatemia associated with TDF therapy were observed.There were no other adverse events related to TDF therapy observed in the study subjects.CONCLUSION:TDF can be an effective and safe rescue therapy in CHB patients after multiple NA therapy failures.展开更多
The hepatitis C virus has a high mutation capacity that leads to the emergence of resistance-associated substitutions(RAS).However,the consequence of resistance selection during new direct-acting antiviral drug(DAA)tr...The hepatitis C virus has a high mutation capacity that leads to the emergence of resistance-associated substitutions(RAS).However,the consequence of resistance selection during new direct-acting antiviral drug(DAA)treatment is not necessarily the therapeutic failure.In fact,DAA treatment has shown a high rate(>95%)of sustained virological response even when high baseline RAS prevalence has been reported.In the context of RAS emergence and high rates of sustained viral response,the clinical relevance of variants harboring RAS is still controversial.Therefore,in order to summarize the data available in international guidelines,we have reviewed the clinical utility of testing RAS in the era of new pangenotypic DAA drugs.展开更多
The specific induction of hepatic differentiation presents a significant challenge in developing alternative liver cell sources and viable strategies for clinical therapy of acute liver failure (ALF). The past decade ...The specific induction of hepatic differentiation presents a significant challenge in developing alternative liver cell sources and viable strategies for clinical therapy of acute liver failure (ALF). The past decade has witnessed the blossom of microRNAs in regenerative medicine. Herein, microRNA 122-functionalized tetrahedral framework nucleic acid (FNA-miR-122) has emerged as an unprecedented and potential platform for directing the hepatic differentiation of adipose-derived mesenchymal stem cells (ADMSCs), which offers a straightforward and cost-effective method for generating functional hepatocyte-like cells (FNA-miR-122-iHep). Additionally, we have successfully established a liver organoid synthesis strategy by optimizing the co-culture of FNA-miR-122-iHep with endothelial cells (HUVECs), resulting in functional Hep:HUE-liver spheroids. Transcriptome analysis not only uncovered the potential molecular mechanisms through which miR-122 influences hepatic differentiation in ADMSCs, but also clarified that Hep:HUE-liver spheroids could further facilitate hepatocyte maturation and improved tissue-specific functions, which may provide new hints to be used to develop a hepatic organoid platform. Notably, compared to transplanted ADMSCs and Hep-liver spheroid, respectively, both FNA-miR-122-iHep-based single cell therapy and Hep:HUE-liver spheroid-based therapy showed high efficacy in treating ALF in vivo. Collectively, this research establishes a robust system using microRNA to induce ADMSCs into functional hepatocyte-like cells and to generate hepatic organoids in vitro, promising a highly efficient therapeutic approach for ALF.展开更多
AIM:To study the clinical efficacy of traditional Chinese medicine(TCM)intervention"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK...AIM:To study the clinical efficacy of traditional Chinese medicine(TCM)intervention"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK")for treating liver failure due to chronic hepatitis B.METHODS:We designed the study as a randomized controlled clinical trial.Registration number of Chinese Clinical Trial Registry is Chi CTR-TRC-12002961.A total of 144 patients with liver failure due to infection with chronic hepatitis B virus were enrolled in this randomized controlled clinical study.Participants were randomly assigned to the following three groups:(1)a modern medicine control group(MMC group,36patients);(2)a"tonifying qi and detoxification"("TQD")group(72 patients);and(3)a"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK")group(36patients).Patients in the MMC group received general internal medicine treatment;patients in the"TQD"group were given a TCM formula"tonifying qi and detoxification"and general internal medicine treatment;patients in the"TTK"group were given a TCM formula of"TTK"and general internal medicine treatment.All participants were treated for 8 wk and then followed at 48 wk following their final treatment.The primaryefficacy end point was the patient fatality rate in each group.Measurements of various virological and biochemical indicators served as secondary endpoints.The one-way analysis of variance and the t-test were used to compare patient outcomes in the different treatment groups.RESULTS:At the 48-wk post-treatment time point,the patient fatality rates in the MMC,"TQD",and"TTK"groups were 51.61%,35.38%,and 16.67%,respectively,and the differences between groups were statistically significant(P<0.05).However,there were no significant differences in the levels of hepatitis B virus DNA or prothrombin activity among the three groups(P>0.05).Patients in the"TTK"group had significantly higher levels of serum total bilirubin compared to MMC subjects(339.40μmol/L±270.09μmol/L vs 176.13μmol/L±185.70μmol/L,P=0.014).Serum albumin levels were significantly increased in both the"TQD"group and"TTK"group as compared with the MMC group(31.30 g/L±4.77g/L,30.72 g/L±2.89 g/L vs 28.57 g/L±4.56 g/L,P<0.05).There were no significant differences in levels of alanine transaminase among the three groups(P>0.05).Safety data showed that there was one case of stomachache in the"TQD"group and one case of gastrointestinal side effect in the"TTK"group.CONCLUSION:Treatment with"TTK"improved the survival rates of patients with liver failure due to chronic hepatitis B.Additionally,liver tissue was regenerated and liver function was restored.展开更多
AIMTo describe factors associated with treatment failure and frequency of resistance-associated substitutions （RAS）.METHODSHuman immunodefciency virus （HIV）/hepatitis C virus （HCV） coinfected patients starting a...AIMTo describe factors associated with treatment failure and frequency of resistance-associated substitutions （RAS）.METHODSHuman immunodefciency virus （HIV）/hepatitis C virus （HCV） coinfected patients starting a first direct-acting antiviral （DAA） regimen before February 2016 and included in the French ANRS CO13 HEPAVIH cohort were eligible. Failure was defned as： （1） non-response [HCV-RNA remained detectable during treatment, at end of treatment （EOT）]; and （2） relapse （HCV-RNA suppressed at EOT but detectable thereafter）. Sequencing analysis was performed to describe prevalence of drug class-specifc RAS. Factors associated with failure were determined using logistic regression models.RESULTSAmong 559 patients, 77% had suppressed plasmaHIV-RNA 〈 50 copies/mL at DAA treatment initiation41% were cirrhotic, and 68% were HCV treatmentexperienced. Virological treatment failures occurred in22 patients and were mainly relapses （17, 77%） thenundefined failures （3, 14%） and non-responses （29%）. Mean treatment duration was 16 wk overall. Posttreatment NS3, NS5A or NS5B RAS were detected in10/14 patients with samples available for sequencinganalysis. After adjustment for age, sex, ribavirin useHCV genotype and treatment duration, low platelecount was the only factor signifcantly associated with ahigher risk of failure （OR： 6.5; 95%CI： 1.8-22.6）. CONCLUSIONOnly 3.9% HIV-HCV coinfected patients failed DAAregimens and RAS were found in 70% of those failingLow platelet count was independently associated withvirological failure.展开更多
Alcoholic hepatitis(AH)is an acute hepatic inflammation associated with significant morbidity and mortality.Current evidence suggests that the pathogenesis is the end result of the complex interplay between ethanol me...Alcoholic hepatitis(AH)is an acute hepatic inflammation associated with significant morbidity and mortality.Current evidence suggests that the pathogenesis is the end result of the complex interplay between ethanol metabolism,inflammation and innate immunity.Several clinical scoring systems have been derived to predict the clinical outcomes of patients with AH;such as Child-Turcotte-Pugh score,the Maddrey discriminant function,the Lille Model,the model for end stage liver disease scores,and the Glasgow alcoholic hepatitis score.At present,Corticosteroids or pentoxifylline are the current pharmacologic treatment options;though the outcomes from the therapies are poor.Liver trans-plantation as the treatment of alcoholic hepatitis remains controversial,and in an era of organ shortage current guidelines do not recommend transplantation as the treatment option.Because of the limitations in the therapeutic options,it is no doubt that there is a critical need for the newer and more effective pharmacological agents to treat AH.展开更多
More than five years ago,the treatment of hepatitis C virus infection was revolutionized with the introduction of all-oral direct-acting antiviral(DAA)drugs.They proved highly efficient in curing patients with chronic...More than five years ago,the treatment of hepatitis C virus infection was revolutionized with the introduction of all-oral direct-acting antiviral(DAA)drugs.They proved highly efficient in curing patients with chronic hepatitis C(CHC),including patients with cirrhosis.The new DAA treatments were alleged to induce significant improvements in clinical outcome and prognosis,but the exact cause of the expected benefit was unclear.Further,little was known about how the underlying liver disease would be affected during and after viral clearance.In this review,we describe and discuss the liver-related effects of the new treatments in regards to both pathophysiological aspects,such as macrophage activation,and the time-dependent effects of therapy,with specific emphasis on inflammation,structural liver changes,and liver function,as these factors are all related to morbidity and mortality in CHC patients.It seems clear that antiviral therapy,especially the achievement of a sustained virologic response has several beneficial effects on liver-related parameters in CHC patients with advanced liver fibrosis or cirrhosis.There seems to be a timedependent effect of DAA therapy with viral clearance and the resolution of liver inflammation followed by more discrete changes in structural liver lesions.These improvements lead to favorable effects on liver function,followed by an improvement in cognitive dysfunction and portal hypertension.Overall,the data provide knowledge on the several beneficial effects of DAA therapy on liverrelated parameters in CHC patients suggesting short-and long-term improvements in the underlying disease with the promise of an improved longterm prognosis.展开更多
Objective To assess the effectiveness of artificial liver support system (ALSS) treatment in patients with hepatic failure. Methods 235 cases of hepatic failure were treated with ALSS in our hospital. All data were ...Objective To assess the effectiveness of artificial liver support system (ALSS) treatment in patients with hepatic failure. Methods 235 cases of hepatic failure were treated with ALSS in our hospital. All data were analyzed by SPSS. The effectiveness of ALSS treatment was compared according to different stages (i.e., early, middle and end stages). Results 108 patients survived after therapy of ALSS. After each ALSS treatment, the liver function of these patients was greatly improved, the serum endotoxin and HBV-DNA concentrations were significantly decreased, and the serum concentration of aromatic amino acids (AAA) such as methionine decreased while the ratio of branched chain amino acids and aromatic amino acids (BCAA/AAA ratio) increased; patients treated with ALSS in the early or middle stages of disease had much higher survival rates than patients in the end stage of disease.Conclusion ALSS is a reliable therapy for advanced liver diseases and treatment at early or middle stages is appropriate.展开更多
基金Supported by Science and Technology Innovation 2030-Major Project,No.2021ZD0140406 and No.2021ZD0140401.
文摘BACKGROUND Post-hepatectomy liver failure(PHLF)is a common consequence of radical partial hepatectomy in hepatocellular carcinoma(HCC).AIMS To investigate the relationship between preoperative antiviral therapy and PHLF,as well as assess the potential efficacy of hepatitis B virus(HBV)DNA level in predicting PHLF.METHODS A retrospective study was performed involving 1301 HCC patients with HBV who underwent radical hepatectomy.Receiver operating characteristic(ROC)analysis was used to assess the capacity of HBV DNA to predict PHLF and establish the optimal cutoff value for subsequent analyses.Logistic regression analyses were performed to assess the independent risk factors of PHLF.The increase in the area under the ROC curve,categorical net reclassification improvement(NRI),and integrated discrimination improvement(IDI)were used to quantify the efficacy of HBV DNA level for predicting PHLF.The P<0.05 was considered statistically significant.RESULTS Logistic regression analyses showed that preoperative antiviral therapy was independently associated with a reduced risk of PHLF(P<0.05).HBV DNA level with an optimal cutoff value of 269 IU/mL(P<0.001)was an independent risk factor of PHLF.All the reference models by adding the variable of HBV DNA level had an improvement in area under the curve,categorical NRI,and IDI,particularly for the fibrosis-4 model,with values of 0.729(95%CI:0.705-0.754),1.382(95%CI:1.341-1.423),and 0.112(95%CI:0.110-0.114),respectively.All the above findings were statistically significant.CONCLUSION In summary,preoperative antiviral treatment can reduce the incidence of PHLF,whereas an increased preoperative HBV DNA level has a correlative relationship with an increased susceptibility to PHLF.
文摘AIM:To evaluate the efficacy and safety of tenofovir disoproxil fumarate(TDF) for chronic hepatitis B(CHB) patients after multiple failures.METHODS:A total of 29 CHB patients who had a suboptimal response or developed resistance to two or more previous nucleoside/nucleotide analogue(NA) treatments were included.Study subjects were treated with TDF alone(n = 13) or in combination with lamivudine(LAM,n = 12) or entecavir(ETV,n = 4) for ≥ 6 mo.Complete virologic response(CVR) was defined as an achievement of serum hepatitis B virus(HBV) DNA level ≤ 60 IU/mL by real-time polymerase chain reaction method during treatment.Safety assessment was based on serum creatinine and phosphorus level.Eleven patients had histories of LAM and adefovir dipivoxil(ADV) treatment and 18 patients were exposed to LAM,ADV,and ETV.Twenty-seven patients(93.1%) were hepatitis B e antigen(HBeAg) positive and the mean value of the baseline serum HBV DNA level was 5.5 log IU/mL ± 1.7 log IU/mL.The median treatment duration was 16 mo(range 7 to 29 mo).RESULTS:All the patients had been treated with LAM and developed genotypic and phenotypic resistance to it.Resistance to ADV was present in 7 patients and 10 subjects had a resistance to ETV.One patient had a resistance to both ADV and ETV.The cumulative probabilities of CVR at 12 and 24 mo of TDF containing treatment regimen calculated by the Kaplan Meier method were 86.2% and 96.6%,respectively.Although one patient failed to achieve CVR,serum HBV DNA level decreased by 3.9 log IU/mL from the baseline and the last serum HBV DNA level during treatment was 85 IU/mL,achieving near CVR.No patients in this study showed viral breakthrough or primary non-response during the follow-up period.The cumulative probability of HBeAg clearance in the 27 HBeAg positive patients was 7.4%,12%,and 27% at 6,12,and 18 mo of treatment,respectively.Treatment efficacy of TDF containing regimen was not statistically different according to the presence of specific HBV mutations.History of prior exposure to specific antiviral agents did not make a difference to treatment outcome.Treatment efficacy of TDF was not affected by combination therapy with LAM or ETV.No patient developed renal toxicity and no cases of hypophosphatemia associated with TDF therapy were observed.There were no other adverse events related to TDF therapy observed in the study subjects.CONCLUSION:TDF can be an effective and safe rescue therapy in CHB patients after multiple NA therapy failures.
文摘The hepatitis C virus has a high mutation capacity that leads to the emergence of resistance-associated substitutions(RAS).However,the consequence of resistance selection during new direct-acting antiviral drug(DAA)treatment is not necessarily the therapeutic failure.In fact,DAA treatment has shown a high rate(>95%)of sustained virological response even when high baseline RAS prevalence has been reported.In the context of RAS emergence and high rates of sustained viral response,the clinical relevance of variants harboring RAS is still controversial.Therefore,in order to summarize the data available in international guidelines,we have reviewed the clinical utility of testing RAS in the era of new pangenotypic DAA drugs.
基金National Key Research and Development Program of China(2019YFA0111300)Thousand Talents Plan,the Guangdong Provincial Pearl River Talents Program(2019QN01Y131)Medical Science and Technology Research Fund of Guangdong Province(A2022112).
文摘The specific induction of hepatic differentiation presents a significant challenge in developing alternative liver cell sources and viable strategies for clinical therapy of acute liver failure (ALF). The past decade has witnessed the blossom of microRNAs in regenerative medicine. Herein, microRNA 122-functionalized tetrahedral framework nucleic acid (FNA-miR-122) has emerged as an unprecedented and potential platform for directing the hepatic differentiation of adipose-derived mesenchymal stem cells (ADMSCs), which offers a straightforward and cost-effective method for generating functional hepatocyte-like cells (FNA-miR-122-iHep). Additionally, we have successfully established a liver organoid synthesis strategy by optimizing the co-culture of FNA-miR-122-iHep with endothelial cells (HUVECs), resulting in functional Hep:HUE-liver spheroids. Transcriptome analysis not only uncovered the potential molecular mechanisms through which miR-122 influences hepatic differentiation in ADMSCs, but also clarified that Hep:HUE-liver spheroids could further facilitate hepatocyte maturation and improved tissue-specific functions, which may provide new hints to be used to develop a hepatic organoid platform. Notably, compared to transplanted ADMSCs and Hep-liver spheroid, respectively, both FNA-miR-122-iHep-based single cell therapy and Hep:HUE-liver spheroid-based therapy showed high efficacy in treating ALF in vivo. Collectively, this research establishes a robust system using microRNA to induce ADMSCs into functional hepatocyte-like cells and to generate hepatic organoids in vitro, promising a highly efficient therapeutic approach for ALF.
基金Supported by National Science and Technology Key Projects on"Major Infectious Diseases such as HIV/AIDS,Viral Hepatitis Prevention and Treatment",No.2008ZX10005-007Research Projects of Key Disease of National Traditional Chinese Medicine(Hepatopathy)Clinical Research Center(Hubei Province),No.JDZX2012054+3 种基金National Natural Science Foundation of China,No.81373513,No.90709041,No.30672590,No.30271562,No.30371787,No.81102531 and No.81274147Key Projects of Natural Science Foundation of Hubei Province,No.2011CDB463Specialized Research Fund for the Doctoral Programs in Institution of Higher Education,No.20124230110001Key Subjects of Department of Science and Technology of Wuhan City,No.201260523199
文摘AIM:To study the clinical efficacy of traditional Chinese medicine(TCM)intervention"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK")for treating liver failure due to chronic hepatitis B.METHODS:We designed the study as a randomized controlled clinical trial.Registration number of Chinese Clinical Trial Registry is Chi CTR-TRC-12002961.A total of 144 patients with liver failure due to infection with chronic hepatitis B virus were enrolled in this randomized controlled clinical study.Participants were randomly assigned to the following three groups:(1)a modern medicine control group(MMC group,36patients);(2)a"tonifying qi and detoxification"("TQD")group(72 patients);and(3)a"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK")group(36patients).Patients in the MMC group received general internal medicine treatment;patients in the"TQD"group were given a TCM formula"tonifying qi and detoxification"and general internal medicine treatment;patients in the"TTK"group were given a TCM formula of"TTK"and general internal medicine treatment.All participants were treated for 8 wk and then followed at 48 wk following their final treatment.The primaryefficacy end point was the patient fatality rate in each group.Measurements of various virological and biochemical indicators served as secondary endpoints.The one-way analysis of variance and the t-test were used to compare patient outcomes in the different treatment groups.RESULTS:At the 48-wk post-treatment time point,the patient fatality rates in the MMC,"TQD",and"TTK"groups were 51.61%,35.38%,and 16.67%,respectively,and the differences between groups were statistically significant(P<0.05).However,there were no significant differences in the levels of hepatitis B virus DNA or prothrombin activity among the three groups(P>0.05).Patients in the"TTK"group had significantly higher levels of serum total bilirubin compared to MMC subjects(339.40μmol/L±270.09μmol/L vs 176.13μmol/L±185.70μmol/L,P=0.014).Serum albumin levels were significantly increased in both the"TQD"group and"TTK"group as compared with the MMC group(31.30 g/L±4.77g/L,30.72 g/L±2.89 g/L vs 28.57 g/L±4.56 g/L,P<0.05).There were no significant differences in levels of alanine transaminase among the three groups(P>0.05).Safety data showed that there was one case of stomachache in the"TQD"group and one case of gastrointestinal side effect in the"TTK"group.CONCLUSION:Treatment with"TTK"improved the survival rates of patients with liver failure due to chronic hepatitis B.Additionally,liver tissue was regenerated and liver function was restored.
基金Supported by Inserm-ANRS(French National Institute for Health and Medical Research-ANRS/France REcherche Nord and Sud Sida-hiv Hépatites)
文摘AIMTo describe factors associated with treatment failure and frequency of resistance-associated substitutions （RAS）.METHODSHuman immunodefciency virus （HIV）/hepatitis C virus （HCV） coinfected patients starting a first direct-acting antiviral （DAA） regimen before February 2016 and included in the French ANRS CO13 HEPAVIH cohort were eligible. Failure was defned as： （1） non-response [HCV-RNA remained detectable during treatment, at end of treatment （EOT）]; and （2） relapse （HCV-RNA suppressed at EOT but detectable thereafter）. Sequencing analysis was performed to describe prevalence of drug class-specifc RAS. Factors associated with failure were determined using logistic regression models.RESULTSAmong 559 patients, 77% had suppressed plasmaHIV-RNA 〈 50 copies/mL at DAA treatment initiation41% were cirrhotic, and 68% were HCV treatmentexperienced. Virological treatment failures occurred in22 patients and were mainly relapses （17, 77%） thenundefined failures （3, 14%） and non-responses （29%）. Mean treatment duration was 16 wk overall. Posttreatment NS3, NS5A or NS5B RAS were detected in10/14 patients with samples available for sequencinganalysis. After adjustment for age, sex, ribavirin useHCV genotype and treatment duration, low platelecount was the only factor signifcantly associated with ahigher risk of failure （OR： 6.5; 95%CI： 1.8-22.6）. CONCLUSIONOnly 3.9% HIV-HCV coinfected patients failed DAAregimens and RAS were found in 70% of those failingLow platelet count was independently associated withvirological failure.
基金Supported by K08 AA016570 from the NIH/NIAAA,1I01-CX000361-01 from the Veterans Affairs Research and Admin-istration,Indiana University Research Support Fund GrantW81XWH-12-1-0497 from United States Department of Defense(all to Liangpunsakul S)
文摘Alcoholic hepatitis(AH)is an acute hepatic inflammation associated with significant morbidity and mortality.Current evidence suggests that the pathogenesis is the end result of the complex interplay between ethanol metabolism,inflammation and innate immunity.Several clinical scoring systems have been derived to predict the clinical outcomes of patients with AH;such as Child-Turcotte-Pugh score,the Maddrey discriminant function,the Lille Model,the model for end stage liver disease scores,and the Glasgow alcoholic hepatitis score.At present,Corticosteroids or pentoxifylline are the current pharmacologic treatment options;though the outcomes from the therapies are poor.Liver trans-plantation as the treatment of alcoholic hepatitis remains controversial,and in an era of organ shortage current guidelines do not recommend transplantation as the treatment option.Because of the limitations in the therapeutic options,it is no doubt that there is a critical need for the newer and more effective pharmacological agents to treat AH.
文摘More than five years ago,the treatment of hepatitis C virus infection was revolutionized with the introduction of all-oral direct-acting antiviral(DAA)drugs.They proved highly efficient in curing patients with chronic hepatitis C(CHC),including patients with cirrhosis.The new DAA treatments were alleged to induce significant improvements in clinical outcome and prognosis,but the exact cause of the expected benefit was unclear.Further,little was known about how the underlying liver disease would be affected during and after viral clearance.In this review,we describe and discuss the liver-related effects of the new treatments in regards to both pathophysiological aspects,such as macrophage activation,and the time-dependent effects of therapy,with specific emphasis on inflammation,structural liver changes,and liver function,as these factors are all related to morbidity and mortality in CHC patients.It seems clear that antiviral therapy,especially the achievement of a sustained virologic response has several beneficial effects on liver-related parameters in CHC patients with advanced liver fibrosis or cirrhosis.There seems to be a timedependent effect of DAA therapy with viral clearance and the resolution of liver inflammation followed by more discrete changes in structural liver lesions.These improvements lead to favorable effects on liver function,followed by an improvement in cognitive dysfunction and portal hypertension.Overall,the data provide knowledge on the several beneficial effects of DAA therapy on liverrelated parameters in CHC patients suggesting short-and long-term improvements in the underlying disease with the promise of an improved longterm prognosis.
文摘Objective To assess the effectiveness of artificial liver support system (ALSS) treatment in patients with hepatic failure. Methods 235 cases of hepatic failure were treated with ALSS in our hospital. All data were analyzed by SPSS. The effectiveness of ALSS treatment was compared according to different stages (i.e., early, middle and end stages). Results 108 patients survived after therapy of ALSS. After each ALSS treatment, the liver function of these patients was greatly improved, the serum endotoxin and HBV-DNA concentrations were significantly decreased, and the serum concentration of aromatic amino acids (AAA) such as methionine decreased while the ratio of branched chain amino acids and aromatic amino acids (BCAA/AAA ratio) increased; patients treated with ALSS in the early or middle stages of disease had much higher survival rates than patients in the end stage of disease.Conclusion ALSS is a reliable therapy for advanced liver diseases and treatment at early or middle stages is appropriate.
