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High-dose interferon-α2b induction therapy in combination with ribavirin for treatment of chronic hepatitis C in patients with non-response or relapse after interferon-a monotherapy

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World Journal of Gastroenterology 2005年第34期11卷 5342-5346页

作者： Holger G. Hass Christian Kreysel Johannes Fischinger Josef Menzel Stephan Kaiser Department of Gastroenterology and Hepatology University of Tuebingen Germany Department of Gastroenterology Klinikum Krefeld Germany Department of Gastroenterology and Hepatology University of Saarland Germany Department of Gastroenterology and Hepatology University of Muenster Germany

AIM： To evaluate the daily high-dose induction therapy with interferon-α2b （IFN-α2b） in combination with ribavirin for the treatment of patients who failed with interferon monotherapy and had a relapse, based on the assumption that the viral burden would decline faster, thus increasing the likelihood of higher response rates in this difficult-totreat patient group. METHODS： Seventy patients were enrolled in this study. Treatment was started with 10 NU IFN-α2b daily for 3 wk, followed by IFN-α2b 5 NU/TIW in combination with ribavirin （1 000-1 200 mg/d） for 21 wk. In case of a negative HCV RNA PCR, treatment was continued until wk 48 （IFN-α2b 3MU/TIW＋1000-1200 mg ribavirin/daily）. RESULTS： The dose of IFN-α2b or ribavirin was reduced in 16% of patients because of hematologic side effects, and treatment was discontinued in 7% of patients. An early viral response （EVR） was achieved in 60% of patients. Fifty percent of all patients achieved an end-oftreatment response （EOT） and d0% obtained a sustained viral response （SVR）. Patients with no response had a significantly lower response rate than those with a former relapse （SVR 30% vs 53%; P=0.049）. Furthermore, lower response rates were observed in patients infected with genotype la/b than in patients with non-1-genotype （SVR 28% vs7d%; P=0.001）. As a significant predictive factor for a sustained response, a rapid initial decline of HCV RNA could be identified. No patient achieving a negative HCV-RNA PCR at wk 18 or later eventually eliminated the virus. CONCLUSION： Daily high-dose induction therapy with interferon-α2b is well tolerated and effective for the treatment of non-responders and relapsers, when interferon monotherapy fails. A fast decline of viral load during the first 12 wk is strongly associated with a sustained viral response.

关键词： Chronic hepatitis C High-dose interferon-α induction therapy Ribavirin nonresponder Relapse

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Resistance mechanisms in melanoma to immuneoncologic therapy with checkpoint inhibitors

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Cancer Drug Resistance 2019年第3期2卷 744-761页

作者： Sarah E.Fenton Jeffrey A.Sosman Sunandana Chandra Division of Hematology Oncology Northwestern UniversityChicagoIL 60611USA.

Checkpoint inhibitors act by blocking physiologic mechanisms coopted by tumor cells to evade immune surveillance,restoring the immune system’s ability to identify and kill malignant *** therapies have dramatically improved outcomes in multiple tumor types with durable responses in many patients,leading to FDA approval first in advanced melanoma,then in many other ***,as experience with checkpoint inhibitors has grown,populations of patients who are primary nonresponders or develop secondary resistance have been the majority of cases,even in *** of resistance include those inherent to the tumor microenvironment,the tumor cells themselves,and the function of the patient’s native immune *** review will discuss resistance to checkpoint inhibitors in melanoma as well as possible methods to restore sensitivity.

关键词： Melanoma checkpoint inhibitor resistance nonresponder secondary resistance

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Field epidemiological and experimental study on relationship between genetic factor and nonresponse or hyporesponse to hepatitis B vaccine

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Chinese Medical Journal 2000年第6期113卷 67-70页

作者：刘蓬勃徐慧文王学良李辉庄贵华乌正赉张孔来 Department of Epidemiology Fourth Military Medical University Xi' an 710032 China Department of Epidemiology Xi' An Medical University Xi' an 710061 China Department of Epidemiology Institute of Basic Medical Sciences CAMS and PUMC Beijing 100005 China

Objective To evaluate the role of genetic factor in the development of nonresponder or hyporesponder to hepatitis B vaccine in Chinese people from field epidemiology and experimental study Methods Six hundred and thirty four susceptible healthy students were vaccinated with three doses of plasma derived hepatitis B vaccine Twenty nine non or hypo responders (subjects) and 30 hyperresponders (controls) as well as their 80 and 79 first degree relatives were determined and recruited in the study The first degree relatives of subjects and controls were then immunized with hepatitis B vaccine and followed up On the basis of the above results, alleles of HLA A,B,C,DR and DQ locus were further detected in the two groups Results The non and hypo response rate in immunized students was 4 6% (29/634) After administered with hepatitis B vaccine, the first degree relatives of the subjects displayed a 17 9% frequency of nonresponsiveness, higher than in the controls The phenotype frequency of HLA DR7 and B54 was 52 2% and 21 7% in subjects, 9 1% and 0 0% higher than in controls, respectively The extended haplotype B54 DR7 was more frequent in the former (17 0%) than in the latter (0 0%) ( P <0 01) Conclusion These results demonstrated that the genetic factor was likely associated with the non and hypo response to hepatitis B vaccine in Chinese people

关键词： hepatitis B vaccine human leucocyte antigen nonresponder

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