Hepatitis C infection is universal and the most common indication of liver transplantation in the United States. The period of less effective interferon therapy with intolerable side effects has gone. Now we have step...Hepatitis C infection is universal and the most common indication of liver transplantation in the United States. The period of less effective interferon therapy with intolerable side effects has gone. Now we have stepped into the era of direct acting anti-viral agents(DAAs) against hepatitis C virus. Treatment of hepatitis C is now extremely effective, tolerable and requires a short duration of intake of oral agents. Less monitoring is required with the current therapy and drug-drug interactions are less than the previous regimen. The current treatment options of chronic hepatitis C with various DAAs are discussed in this article.展开更多
AIM: To analyze the association of HCV-RNA with peripheral blood mononuclear cells (PBMC) and to answer the question whether HCV-RNA positivity in PBMC is due to viral replication. METHODS: HCV-RNA was monitored in se...AIM: To analyze the association of HCV-RNA with peripheral blood mononuclear cells (PBMC) and to answer the question whether HCV-RNA positivity in PBMC is due to viral replication. METHODS: HCV-RNA was monitored in serum and PBMC preparations from 15 patients with chronic HCV infection before, during and after an IFN-alpha therapy using a nested RT/PCR technique. In a second approach, PBMC from healthy donors were incubated in HCV positive plasma. RESULTS: In the IFN-alpha responding patients,HCV-RNA disappeared first from total RNA preparations of PBMC and then from serum. In contrast, in relapsing patients, HCV-RNA reappeared first in serum and then in PBMC. A quantitative analysis of the HCV-RNA concentration in serum was performed before and after transition from detectable to non detectable HCV-RNA in PBMC-RNA and vice versa. When HCV-RNA was detectable in PBMC preparations, the HCV concentration in serum was significantly higher than the serum HCV-RNA concentration when HCV-RNA in PBMC was not detectable. Furthermore, at no time during the observation period was HCV specific RNA observed in PBMC, if HCV-RNA in serum was under the detection limit. Incubation of PBMC from healthy donors with several dilutions of HCV positive plasma for two hours showed a concentration dependent PCR positivity for HCV-RNA in reisolated PBMC. CONCLUSION: The detectability of HCV-RNA in total RNA from PBMC seems to depend on the HCV concentration in serum. Contamination or passive adsorption by circulating virus could be the reason for detection of HCV-RNA in PBMC preparations of chronically infected patients.展开更多
The United States Food and Drug Administration recently warned that the direct acting antiviral(DAA) combination hepatitis C virus(HCV) treatment of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin(PODr +...The United States Food and Drug Administration recently warned that the direct acting antiviral(DAA) combination hepatitis C virus(HCV) treatment of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin(PODr + R) can cause severe liver injury in patients with advanced liver disease. Drug induced liver injury was observed in a small number of patients with decompensated cirrhosis treated with other DAAs, but has not been reported in patients with compensated cirrhosis. We report a case of a 74-year-old woman with chronic HCV and Child-Pugh class A cirrhosis(compensated cirrhosis) treated with PODr + R. The patient presented on day 14 of PODr + R therapy with jaundice and new-onset ascites. Her total bilirubin level increased to 23 mg/dL and international normalized ratio rose to 1.65, while aminotransferase levels remained relatively stable. Hepatitis C treatment was discontinued on day 24 and she gradually recovered. Follow-up testing showed that she achieved a sustained virologic response. In conclusion, hepatic decompensation developed within two weeks of starting treatment withPODr + R in a patient with Child-Pugh class A cirrhosis and was characterized by jaundice and ascites with stable aminotransferase levels. Careful monitoring is warranted in patients with HCV-related cirrhosis treated with PODr + R.展开更多
Aim:Patients with chronic hepatitis C virus(HCV)infection who develop hepatocellular carcinoma(HCC)soon after treatment with direct antiviral agents(DAA)may have been harboring hitherto hidden tumors.If this were true...Aim:Patients with chronic hepatitis C virus(HCV)infection who develop hepatocellular carcinoma(HCC)soon after treatment with direct antiviral agents(DAA)may have been harboring hitherto hidden tumors.If this were true,they should have a lower sustained viral response(SVR)rate,since active HCC hampers DAA efficacy.We aimed to verify this hypothesis.Methods:We included all patients who attended an HCV clinic,provided that they:(1)had no previous history of HCC;(2)had received at least one DAA dose;and(3)had been followed-up clinically and ultrasonographically for at least six months after concluding DAA.Results:The study population included n=789 patients(55%males,median age 62 years).A median of 9.3 months(8.8-11.9)after concluding DAA,n=19(2.4%)patients were discovered to harbor HCC.In comparison to all others,patients with HCC were more commonly male(84%vs.54%,P=0.009),obese(47%vs.17%,P=0.002),and cirrhotic(95%vs.35%,P<0.001)and had less commonly achieved an SVR(68%vs.98%,P<0.001).Moreover,they had a trend for being less commonly treatment na?ve(58%vs.67%,P=0.051).Based on multivariate analysis, ;the independent predictors of HCC were male sex(P=0.031),cirrhosis(P=0.004),obesity(P=0.006),and failure to achieve an SVR(P<0.001).Conclusion:Lack of achieving SVR is a strong independent predictor of development of HCC early after treatment of hepatitis C with DAA.Treatment failure should further alert clinicians to the possibility of this dreadful complication.展开更多
文摘Hepatitis C infection is universal and the most common indication of liver transplantation in the United States. The period of less effective interferon therapy with intolerable side effects has gone. Now we have stepped into the era of direct acting anti-viral agents(DAAs) against hepatitis C virus. Treatment of hepatitis C is now extremely effective, tolerable and requires a short duration of intake of oral agents. Less monitoring is required with the current therapy and drug-drug interactions are less than the previous regimen. The current treatment options of chronic hepatitis C with various DAAs are discussed in this article.
基金Supported by a grant of DFG (SFB 402 Teilprojekt C1 (Mihm))by a grant of Hoffmann La Roche (Grenzach-Wyhden, Germany)Part of the data has been presented as poster at the 1999 EASL-meeting in Neaples
文摘AIM: To analyze the association of HCV-RNA with peripheral blood mononuclear cells (PBMC) and to answer the question whether HCV-RNA positivity in PBMC is due to viral replication. METHODS: HCV-RNA was monitored in serum and PBMC preparations from 15 patients with chronic HCV infection before, during and after an IFN-alpha therapy using a nested RT/PCR technique. In a second approach, PBMC from healthy donors were incubated in HCV positive plasma. RESULTS: In the IFN-alpha responding patients,HCV-RNA disappeared first from total RNA preparations of PBMC and then from serum. In contrast, in relapsing patients, HCV-RNA reappeared first in serum and then in PBMC. A quantitative analysis of the HCV-RNA concentration in serum was performed before and after transition from detectable to non detectable HCV-RNA in PBMC-RNA and vice versa. When HCV-RNA was detectable in PBMC preparations, the HCV concentration in serum was significantly higher than the serum HCV-RNA concentration when HCV-RNA in PBMC was not detectable. Furthermore, at no time during the observation period was HCV specific RNA observed in PBMC, if HCV-RNA in serum was under the detection limit. Incubation of PBMC from healthy donors with several dilutions of HCV positive plasma for two hours showed a concentration dependent PCR positivity for HCV-RNA in reisolated PBMC. CONCLUSION: The detectability of HCV-RNA in total RNA from PBMC seems to depend on the HCV concentration in serum. Contamination or passive adsorption by circulating virus could be the reason for detection of HCV-RNA in PBMC preparations of chronically infected patients.
文摘The United States Food and Drug Administration recently warned that the direct acting antiviral(DAA) combination hepatitis C virus(HCV) treatment of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin(PODr + R) can cause severe liver injury in patients with advanced liver disease. Drug induced liver injury was observed in a small number of patients with decompensated cirrhosis treated with other DAAs, but has not been reported in patients with compensated cirrhosis. We report a case of a 74-year-old woman with chronic HCV and Child-Pugh class A cirrhosis(compensated cirrhosis) treated with PODr + R. The patient presented on day 14 of PODr + R therapy with jaundice and new-onset ascites. Her total bilirubin level increased to 23 mg/dL and international normalized ratio rose to 1.65, while aminotransferase levels remained relatively stable. Hepatitis C treatment was discontinued on day 24 and she gradually recovered. Follow-up testing showed that she achieved a sustained virologic response. In conclusion, hepatic decompensation developed within two weeks of starting treatment withPODr + R in a patient with Child-Pugh class A cirrhosis and was characterized by jaundice and ascites with stable aminotransferase levels. Careful monitoring is warranted in patients with HCV-related cirrhosis treated with PODr + R.
文摘Aim:Patients with chronic hepatitis C virus(HCV)infection who develop hepatocellular carcinoma(HCC)soon after treatment with direct antiviral agents(DAA)may have been harboring hitherto hidden tumors.If this were true,they should have a lower sustained viral response(SVR)rate,since active HCC hampers DAA efficacy.We aimed to verify this hypothesis.Methods:We included all patients who attended an HCV clinic,provided that they:(1)had no previous history of HCC;(2)had received at least one DAA dose;and(3)had been followed-up clinically and ultrasonographically for at least six months after concluding DAA.Results:The study population included n=789 patients(55%males,median age 62 years).A median of 9.3 months(8.8-11.9)after concluding DAA,n=19(2.4%)patients were discovered to harbor HCC.In comparison to all others,patients with HCC were more commonly male(84%vs.54%,P=0.009),obese(47%vs.17%,P=0.002),and cirrhotic(95%vs.35%,P<0.001)and had less commonly achieved an SVR(68%vs.98%,P<0.001).Moreover,they had a trend for being less commonly treatment na?ve(58%vs.67%,P=0.051).Based on multivariate analysis, ;the independent predictors of HCC were male sex(P=0.031),cirrhosis(P=0.004),obesity(P=0.006),and failure to achieve an SVR(P<0.001).Conclusion:Lack of achieving SVR is a strong independent predictor of development of HCC early after treatment of hepatitis C with DAA.Treatment failure should further alert clinicians to the possibility of this dreadful complication.
