Application of Kushenin on Patients with Chronic Hepatitis C after Renal Transplantation

Objective： To evaluate the efficacy of kushenin in treating patients with chronic hepatitis C after renal transplantation. Methods： Fifty-five patients were randomly assigned by lottery to the treatment group （29 cases） and control group （26 cases）. The same immunosuppression therapy was given to all patients in both groups. Patients in the treatment group were treated with kushenin 0.6 g once a day, while those in the control group were treated with conventional liver protective agents such as vitamins. The treatment duration of both groups was 3 months. The incidences of serious hepatitis and acute rejection reaction, serum biochemistry parameters including indicators of liver and kidney functions, hepatic fibrosis index, and serum HCV-RNA were compared between the two groups. Results： （1） The incidence of serious hepatitis in the treatment group and the control group was 3.45% （1/29 cases） and 11.54% （3/26 cases）, respectively, which was insignificantly different between the two groups （P=0.335）. （2） The incidence of acute rejection in the treatment group was 6.90% （2/29 cases） and that in the control group was 7.69% （2/26 cases）, showing insignificant difference （P=0.335）. （3） The differences in serum alanine aminotransferase （ALT）, direct bilirubin （DBIL）, hyaluronic acid （HA）, propeptide collagen type Ⅲ （PC Ⅲ）, laminin （LN）, collagen type Ⅳ（Col Ⅳ） levels between the two groups were insignificant before transplantation （P〉0.05）, while the above-mentioned parameters in the treatment group were significantly lower than those in the control group after transplantation （P〈0.05）. The difference in serum creatinine （SCr） and endogenous creatinine clearance rate （CCr） between the two groups was insignificant before and after transplantation （P〉0.05）. （4） The negative conversion rate of HCV-RNA in the treatment group was 31.03% （9/29 cases）, significantly higher than the value of 11.54% （3/26 cases） in the control group after transplantation （P〈0.05）. （5） The levels of serum ALT and DBIL in patients with HCV-RNA converted to negative were significantly lower than those with still-positive HCV-RNA （P〈0.05）. Conclusions： Kushenin has a certain effect on inhibiting the proliferation of HCV, protecting liver cells, and anti-liver fibrosis. On the other hand, it has no obvious influence on renal allograft function. Thus, the drug is clinically safe and effective for use in treating patients with chronic hepatitis C after renal transplantation.

Hepatitis C and renal transplantation in era of new antiviral agents

Data from World Health Organization estimates that the hepatitis C virus(HCV) prevalence is 3% and approxi-mately 71 million persons are infected worldwide. HCV infection is particularly frequent among patients affected by renal diseases and among those in dialysis treatment. In addition to produce a higher rate of any cause of death, HCV in renal patients and in renal transplanted patients produce a deterioration of liver disease and is a recognized cause of transplant glomerulopathy, new onset diabetes mellitus and lymphoproliferative disorders. Treatment of HCV infection with interferon alpha and/or ribavirin had a poor efficacy. The treatment was toxic, expensive and with limited efficacy. In the post-transplant period was also cause of severe humoral rejection. In this review we have highlighted the new direct antiviral agents that have revolutionized the treatment of HCV both in the general population and in the renal patients. Patients on dialysis or with low glomerular filtration rate were particularly resistant to the old therapies, while the direct antiviral agents allowed achieving a sustained viral response in 90%- 100% of patients with a short period of treatment. This fact to date allows HCV patients to enter the waiting list for transplantation easier than before. These new agents may be also used in renal transplant patients HCV -positive without relevant clinical risks and achieving a sustained viral response in almost all patients. New drug appears in the pipeline with increased profile of efficacy and safety. These drugs are now the object of several phases Ⅱ, Ⅲ clinical trials.

Natural history of chronic hepatitis C in patients on hemodialysis: Case control study with 4-23 years of follow-up

AIM:Hepatitis C virus(HCV)infection is very common among end-stage kidney disease patients on hemodialysis,but its natural history is not known. METHODS:In this study,189 dialysis patients(case) positive for HCV antibodies who were followed up for more than 4 years were compared with twice as many sex/age matched controls with chronic hepatitis C who were diagnosed in the same month as the case and followed up for comparable periods.The longest follow-up was 23 years in dialysis cases. The disease activities were graded into'asymptomatic'if ALT was less than 40(35 in cases)IU/L,'low activities'if ALT was 40(35)-79 IU/L,and'high activities'if ALT was above 80 IU/L during the last or latest 4 year period. RESULTS:All 25 dialysis cases who were followed up for more than 15 years were asymptomatic and 15 of them were negative for HCV RNA.Of the 50 controls followed up for more than 15 years,34 had high activities,and none deared HCV RNA.There were 60 controls who were asymptomatic, but they were all positive for HCV RNA,while 22.3% of asymptomatic dialysis cases were RNA negative.No dialysis patients with chronic hepatitis C progressed to cirrhosis, whereas the disease progressed to cirrhosis in more than one quarter of the controls.These differences were highly significant(P<0.0001). CONCLUSION:Chronic hepatitic C among hemodialysis patients is mild in disease activity,and is not progressive, perhaps due to immunological abnormalities in these patients. Hepatic C virus is frequently cleared in asymptomatic dialysis patients during a long course.A possible mechanism for viral clearance is viral particle destruction on the surface of the dialyzer membrane.

Efficacy and tolerability of low-dose interferon-α in hemodialysis patients with chronic hepatitis C virus infection

AIM: To evaluate the efficacy and tolerability of low-dose standard or pegylated interferon (PEG-IFN) in hepatitis C virus (HCV)-positive hemodialysis patients.

Interferon-free regimens in patients with hepatitis C infection and renal dysfunction or kidney transplantation

Treatment of patients with chronic kidney disease(CKD) and chronic hepatitis C(CHC) differs from that used in the general CHC population mostly when glomerular filtration rate(GFR) is below 30 m L/min, as sofosbuvir, the backbone of several current regimens, is officially contraindicated. Given that ribavirin free regimens are preferable in CKD, elbasvir/grazoprevir is offered in CHC patients with genotype 1 or 4 and ombitasvir/paritaprevir and dasabuvir in genotype 1b for 12 wk. Although regimens containing peginterferon with or without ribavirin are officially recommended for patients with CKD and genotype 2, 3, 5, 6, such regimens are rarely used because of their low efficacy and the poor safety and tolerance profile. In this setting, especially in the presence of advanced liver disease, sofosbuvirbased regimens are often used, despite sofosbuvir contraindication. It seems to have good overall safety with only 6% or 3.4% of CKD patients to discontinue therapy or develop serious adverse events without drug discontinuation. In addition, sustained virological response(SVR) rates with sofosbuvir based regimens in CKD patients appear to be comparable with SVR rates in patients with normal renal function. Treatment recommendations for kidney transplant recipients are the same with those for patients with CHC, taking into consideration potential drug-drug interactions and baseline GFR before treatment initiation. This review summarizes recent data on the current managementof CHC in CKD patients highlighting their strengths and weaknesses and determining their usefulness in clinical practice.

Anti-hepatitis C virus therapy in chronic kidney disease patients improves long-term renal and patient survivals

BACKGROUND Hepatitis C virus (HCV) infection is a documented risk factor for chronic kidney disease (CKD) and progression to end-stage renal disease (ESRD). However, to date there are no reports on the long-term hard endpoints (ESRD and death) of anti-HCV therapy [interferon-based therapy (IBT) or new direct-acting antivirals] in CKD patients. Direct-acting antivirals are not available in Taiwan’s singlepayer national health insurance database currently released for research. Therefore, we hypothesized that a retrospective analysis of the long-term outcomes of IBT in CKD patients will serve as a proxy for direct-acting antivirals to increase our understanding of progression to ESRD following HCV infection. AIM To evaluate the long-term outcomes (ESRD and death) of anti-HCV therapy, especially IBT, in HCV-infected patients with stage 1-5 CKD. METHODS We analyzed 93894 Taiwan Residents adults diagnosed with CKD and without HBV infection. Of these, 4.9% were infected with HCV. Of the 4582 HCV-infected CKD patients, 482 (10.5%) received IBT (treated cohort). They were matched 1:4 with 1928 untreated HCV-infected CKD patients (untreated cohort) by propensity scores and year, which further matched 1:2 by propensity scores with 3856 CKD patients without HCV infection (uninfected cohort). All participants were followed until the occurrence of ESRD, death, or the end of 2012. The association between HCV infection, IBT use, and risks of ESRD and death was analyzed using competing risk analysis. RESULTS Taking the uninfected cohort as a reference, the adjusted hazard ratios for ESRD, after adjusting for competing mortality, were 0.34 (0.14-0.84, P = 0.019) and 1.28 (1.03-1.60, P = 0.029) in the treated and untreated cohorts, respectively. The treated cohort had a 29%(0.54-0.92, P = 0.011) decrease in mortality compared to the untreated cohort, in which the mortality was 31%(1.18-1.45, P < 0.001) higher than in the uninfected cohort. The reduced risks of ESRD (0.14, 0.03–0.58, P = 0.007) and death (0.57, 0.41-0.79, P = 0.001) were greatest in HCV-infected CKD patients who received at least 4 mo of IBT, which accounted for 74% of the treated cohort.CONCLUSION Adequate anti-HCV therapy in CKD patients improves long-term renal and patient survival.

Management of patients with hepatitis C infection and renal disease

Hepatitis C virus(HCV) infection in patients with end-stage renal disease(ESRD) is associated with more rapid liver disease progression and reduced renal graft and patients' survival following kidney transplantation. Evaluations and management of HCV in patients with renal disease are challenging. The pharmacokinetics of interferons(IFN), ribavirin(RBV) and some direct acting antiviral(DAA), such as sofosbuvir, are altered in patients with ESRD. With dose adjustment and careful monitoring, treatment of HCV in patients with ESRD can be associated with sustained virological response(SVR) rates nearly comparable to that of patients with normal renal function. DAA-based regimens, especially the IFNfree and RBV-free regimens, are theoretically preferred for patients with ESRD and KT in order to increase SVR rates and to reduce treatment side effects. However, based on the data for pharmacokinetics, dosing safety and efficacy of DAA for patients with severe renal impairment are lacking. This review will be focused on the evaluations, available pharmacologic data, and management of HCV in patients with severe renal impairment, patients who underwent KT, and those who suffered from HCV-related renal disease, according to the available treatment options, including DAA.

Efficacy and safety of treatment of hepatitis C virus infection in renal transplant recipients

AIM: To assess the efficacy and safety of combinedpegylated interferon and ribavirin therapy in hepatitis C virus (HCV) infection in renal transplant recipients. METHODS: This is a retrospective chart review of post renal transplant patients who were positive for anti-HCV and HCV-RNA, and who have received treatment with combination of pegylated interferon and ribavirin between October 2003 and December 2008. Only patients with stable graft function and absence of evidence of cirrhosis and who received the therapy for continuous 48 wk were included. Nineteen patients (13 male and 6 female) were identified and included. The patient's complete blood count, liver and kidney prof ile, and cal- culated glomerular f iltration rate (GFR) were monitored every 6-8 wk while on treatment. HCV-RNA was tested at 12 wk for early virological response, at 48 wk for end of treatment response (ETR), and then retested at 24, and 48 wk after completion of therapy for sustained virological response (SVR). Liver biopsies were obtained before treatment from all patients and graft kidney biopsies were performed as required. RESULTS: Of the entire cohort, 9 patients (47.4%) showed an ETR and 8 had SVR (42.1%). Of the 8 patients with abnormal alanine aminotransferase (ALT) levels at baseline, 78.9% had their ALT normalized (including the virological non responders). ALT was normal in all responders at the end of therapy and at 24 wk post therapy (100%). Only one patient (5.3%) developed an increase in creatinine and decline in GFR from baseline towards the end of treatment. This patient's kidney biopsy revealed borderline rejection. There was no impact on response by HCV-genotype, initial HCV RNA load, age or sex of the patient or duration post transplant before commencement of therapy. All patients tolerated treatment in the same way as non-transplant with no unusual or increased occurrence of side effects. CONCLUSION: The combination of pegylated interferon and ribavirin is effective in suppressing HCV-RNA,with a low risk of graft rejection or failure in HCV infected renal transplant recipients.

Opportunities for treatment of the hepatitis C virus-infected patient with chronic kidney disease

The prevalence of hepatitis C virus(HCV) infection amongst patients with chronic kidney disease(CKD) and end-stage renal disease exceeds that of the general population. In addition to predisposing to the development of cirrhosis and hepatocellular carcinoma, infection with HCV has been associated with extra-hepatic complications including CKD, proteinuria, glomerulonephritis, cryoglobulinemia, increased cardiovascular risk, insulin resistance, and lymphoma. With these associated morbidities, infection with HCV is not unexpectedly accompanied by an increase in mortality in the general population as well as in patients with kidney disease. Advances in the understanding of the HCV genome have resulted in the development of direct-acting antiviral agents that can achieve much higher sustained virologic response rates than previous interferon-based protocols. The direct acting antivirals have either primarily hepatic or renal metabolism and excretion pathways. This information is particularly relevant when considering treatment in patients with reduced kidney function. In this context, some of these agents are not recommended for use in patients with a glomerular filtration rate < 30 m L/min per 1.73 m^2. There are now Food and Drug Administration approved direct acting antiviral agents for the treatment of patients with kidney disease and reduced function. These agents have been demonstrated to be effective with sustained viral response rates comparable to the general population with good safety profiles. A disease that was only recently considered to be very challenging to treat in patients with kidney dysfunction is now curable with these medications.

Kidney transplantation from donors with hepatitis C infection

The increasing demand for organ donors to supply the increasing number of patients on kidney waiting lists has led to most transplant centers developing protocols that allow safe utilization from donors with special clinical situations which previously were regarded as contraindications. Deceased donors with previous hepatitis C infection may represent a safe resource to expand the donor pool. When allocated to serology-matched recipients, kidney transplantation from donors with hepatitis C may result in an excellent short-term outcome and a significant reduction of time on the waiting list. Special care must be dedicated to the pre-transplant evaluation of potential candidates, particularly with regard to liver functionality and evidence of liver histological damage, such as cirrhosis, that could be a contraindication to transplantation. Pre-transplant antiviral therapy could be useful to reduce the viral load and to improve the long-term results, which may be affected by the progression of liver disease in the recipients. An accurate selection of both donor and recipient is mandatory to achieve a satisfactory long-term outcome.

Management of hepatitis C infection before and after liver transplantation

Chronic hepatitis C(CHC) is the most common indication for liver transplantation(LT). Aggressive treatment of hepatitis C virus(HCV) infection before cirrhosis development or decompensation may reduce LT need and risk of HCV recurrence post-LT. Factors associated with increased HCV risk or severity of recurrence include older age, immunosuppression, HCV genotype 1 and high viral load at LT. HCV recurrence post-LT leads to accelerated liver disease and cirrhosis development with reduced graft and patient survival. Currently, interferon(IFN)-based regimens can be used in dualagent regimens with ribavirin, in triple-agent antiviral strategies with direct-acting antivirals(e.g., protease inhibitors telaprevir or boceprevir), or before transplant in compensated patients to reduce HCV viral load to prevent or reduce the risk of post-LT recurrence and complications; they cannot be used in patients with decompensated cirrhosis. IFN-based regimens are used in less than half of HCV-infected patients waiting for LT due to extremely low efficacy and poor tolerability. However, antiviral therapy is indicated after LT in patients with histologically confirmed CHC despite tolerability issues. Improvements in side effect management have increased survival in patients achieving therapeutic targets. HCV treatment pre- and post-LT results in significant health care costs especially when lack of efficacy leads to disease worsening, although studies have shown sofosbuvir treatment before LT vs conventional post-LT dual antiviral is cost effective. The suboptimal efficacy and tolerability of IFN-based therapies, plus the significant economic burden, means the need for effective and well tolerated IFN-free antiHCV therapy for pre- and post-LT remains high.

Impact of sustained virologic response on chronic kidney disease progression in hepatitis C

AIM To determine how sustained virological response at 12 wk(SVR12) with direct acting antivirals(DAAs) for the treatment of hepatitis C virus(HCV) infection affects chronic kidney disease(CKD) progression. METHODS A retrospective analysis was performed in patients aged ≥ 18 years treated for HCV with DAAs at the VA Greater Los Angeles Healthcare System from 2014-2016. The treatment group was compared to patients with HCV from 2011-2013 who did not undergo HCV treatment, prior to the introduction of DAAs; the control group was matched to the study group in terms of age, gender, and ethnicity. Analysis of variance and co-variance was performed to compare means between SVR12 subgroups adjusting for co-variates.RESULTS Five hundred and twenty-three patients were evaluated. When comparing the rate of change in estimated glomerular filtration rate(e GFR) one-year after HCV treatment to one-year before treatment, patients who achieved SVR12 had a decline in GFR of 3.1 m L/min ± 0.75 m L/min per 1.73 m^2 compared to a decline in e GFR of 11.0 m L/min ± 2.81 m L/min per 1.73 m^2 in patients who did not achieve SVR12(P = 0.002). There were no significant clinical differences between patients who achieved SVR12 compared to those who did not in terms of cirrhosis, treatment course, treatment experience, CKD stage prior to treatment, diuretic use or other co-morbidities. The decline in e GFR in those with untreated HCV over 2 years was 2.8 m L/min ± 1.0 m L/min per 1.73 m^2, which was not significantly different from the e GFR decline noted in HCV-treated patients who achieved SVR12(P = 0.43).CONCLUSION Patients who achieve SVR12 have a lesser decline in renal function, but viral eradication in itself may not be associated improvement in renal disease progression.

Advances in hepatitis C therapy: What is the current state-what come's next?

Chronic hepatitis C virus(HCV) infection affects 80-160 million people worldwide and is one of the leading causes of chronic liver disease.It is only a few years ago that standard treatment regimes were based on pegylated interferon alpha and ribavirin.However,treatment of HCV has undergone a revolutionary change in recent years.The admission of the nucleotide polymerase inhibitor Sofosbuvir enabled an interferon-free regimen with direct antiviral agents(DAA).Meanwhile seven DAAs are available and can be applied in several combinations for 8 to 24 wk depending on HCV genotype and patient characteristics such as cirrhosis and chronic renal failure.High rates of sustained virological response(SVR) rates can be achieved with these novel drugs.Even in difficult to treat populations such as patients with liver cirrhosis,HCV-human immunodeficiency virus co-infections,after liver transplantion,or with chronic kidney disease comparable high rates of SVR can be achieved.The anticipated 2nd generation DAAs are strikingly effective in patients so far classified as difficult to treat including decompensated liver cirrhosis or posttransplant patients.These 2nd generations DAAs will have higher resistance barriers,higher antiviral effects and a pan-genotypic spectrum.This review highlights the current state of the art of antiviral treatment in hepatitis Cand gives an outlook for upcoming therapies.

Hepatitis C in non-hepatic solid organ transplant candidatesand recipients:A new horizon

Hepatitis C virus(HCV) infection is estimated to affect 130-150 million people globally which corresponds to2%-3% of the total world population. It remains the leading indication for liver transplant worldwide and has been demonstrated to negatively impact both patient and graft survival following non-hepatic organ transplantation. In the era of interferon-based therapy, although treatment and cure of HCV prior to nonhepatic transplant improved survival, tolerability and low cure rates substantially limited therapy. Interferon(IFN)-based therapy following non-hepatic solid organ transplant, due to the risk of allograft rejection, is generally contraindicated. Rapid advances in IFN-free therapy with direct acting antivirals(DAAs) in the last few years have completely changed the paradigm of hepatitis C therapy. Compared to IFN-based regimens, DAAs have less frequent and less severe adverse effects, shorter durations of therapy, and higher cure rates that are minimally impacted by historically negative predictors of response such as cirrhosis, ethnicity, and post-transplant state. Recent studies have shown that liver transplant(LT) recipients can be safely and effectively treated with DAA combination therapies; although data are limited, many of the principles of therapy in LT may be extrapolated to non-hepatic solid organ transplant recipients. Here we review the data on DAA combination therapies in transplantation, discuss the advantages and disadvantages of pre- vs post-transplant HCV therapy and future directions.

直接抗病毒药物治疗肾移植供者来源性HCV感染的疗效分析

目的评估直接抗病毒药物(direct antiviral drugs,DAAs)治疗接受丙型肝炎病毒(hepatitis C virus,HCV)阳性供肾的HCV阴性肾移植受者的安全性及有效性。方法共纳入2018-2023年期间华中科技大学同济医学院附属同济医院器官移植研究所12例患者,其中10例于移植当天立即启动预防性应用DAAs方案,2例于移植后出现肝功能异常及检测出HCV RNA(+)后再予以抗病毒治疗。所有患者均应用12周索非布韦(sofosbuvir,SOF)/维帕他韦(velpatasvir,VEL)口服抗病毒药,并定期复查转氨酶、血肌酐、eGFR、药物浓度及病毒载量等来评估DAAs的疗效和安全性。结果10例预防性用药患者在完成SOF/VEL方案后出现1例治疗失败,检测其基因亚型为3b,其余9例均于停药后12周获得持续性病毒学应答(sustained virological response,SVR12)。初治失败患者在连续两次更换抗病毒方案后最终通过联合利巴韦林(ribavirin,RIB)的方案也实现了SVR12。2例治疗性患者术后1个月时检测到肝功能异常及较高水平病毒载量,立即启动DAAs治疗,在接受治疗后转氨酶水平均能迅速恢复正常并实现SVR12。初治失败患者在使用含利巴韦林抗病毒方案时出现了持续性胆红素升高,所有患者随访期间血肌酐、药物浓度水平均维持稳定。结论HCV阴性受者接受HCV阳性供肾在肾移植术后预防性或治疗性使用DAAs是安全有效的,针对HCV 3b亚型的泛基因型抗病毒方案可能出现治疗失败,初治失败后可选择含利巴韦林的联合抗病毒方案。

Hepatocellular carcinoma in patients with chronic kidney disease

AIM: To investigate outcomes of hepatocellular carcinomas (HCCs) in patients with chronic kidney disease (CKD). METHODS: Four hundred and forty patients referred between 2000 and 2002 for management of HCCs were categorized according to their CKD stage, i.e. , estimated glomerular filtration rate (eGFR) > 90 (stage 1), 60-90 (stage 2), 30-60 (stage 3), 15-30 (stage 4), and < 15 (stage 5) mL/min per 1.73 m 2 , respectively. Demographic, clinical and laboratory data were collected and mortality rates and cause of mortality were analyzed. The mortality data were examined with Kaplan-meier method and the significance was tested using a log-rank test. An initial univariate Cox regression analysis was performed to compare the frequency of possible risk factors associated with mortality. To control for possible confounding factors, a multivariate Cox regression analysis (stepwise backward approach) was performed to analyze those factors that were significant in univariate models (P < 0.05) and met the assumptions of a proportional hazard model. RESULTS: Most HCC patients with CKD were elderly, with mean age of diagnosis of 60.6 ± 11.9 years, and mostly male (74.8%). Hepatitis B, C and B and C coinfection virus were positive in 61.6%, 45.7% and 14.1% of the patients, respectively. It was found that patients with stages 4 and 5 CKD were not only older (P = 0.001), but also had higher hepatitis C virus carrier rate (P = 0.001), lower serum albumin level (P = 0.001), lower platelet count (P = 0.037), longer prothrombin time (P = 0.001) as well as higher proportions of advanced cirrhosis (P = 0.002) and HCCs (P = 0.001) than patients with stages 1 and 2 CKD. At the end of analysis, 162 (36.9%) patients had died. Kaplan-Meier analysis revealed that patients with stages 4 and 5 CKD suffered lower cumulative survival than stages 1 and 2 CKD (log-rank test, χ 2 = 11.764, P = 0.003). In a multivariate Cox-regression model, it was confirmed that CKD stage [odds ratio (OR) = 1.988, 95%CI: 1.012-3.906, P = 0.046)], liver cirrhosis stage (OR = 3.571, 95%CI: 1.590-8.000,P = 0.002) and serum albumin level (OR = 0.657, 95%CI: 0.491-0.878, P = 0.005) were significant predictors for mortality in this population. CONCLUSION: HCC patients with stages 4 and 5 CKD had inferior survival than stages 1 and 2 CKD. This warrants further studies.

HCV相关肝硬化患者肝移植术后的抗病毒与免疫调节治疗

HCV相关肝硬化发生肝功能失代偿后的最佳选择可能是肝移植。移植后免疫调节药物尤其是免疫抑制剂的应用可能是加速HCV复发的一个主要因素,如何在减轻移植排斥反应的同时兼顾HCV感染的控制是目前须要探讨的问题。总结了目前HCV相关肝移植术后的抗病毒及免疫调节治疗情况,分析表明,在HCV相关肝硬化肝移植术后进行合理的免疫抑制和抗病毒治疗对于预防HCV复发、延长移植物生存期、改善患者预后具有至关重要的作用,突然改变免疫抑制方案,如快速撤药或改变免疫抑制剂的剂量或类型都有可能导致HCV的复发,类固醇激素缓慢进行性减量和硫唑嘌呤维持治疗也许有益。

肾脏移植后慢性移植物肾病相关基因C-H-ras、TGF-β_1、HSP70和HSP90的表达

目的探讨肾脏移植后慢性移植物肾病（CAN）相关基因C-H-ras、TGF-β1、HSP70及HSP90的表达及其意义。方法实验分为3组：正常对照组10例，为正常肾脏标本；术中穿刺组10例，为肾脏移植术中复流40～60min后的移植肾穿刺标本；CAN组8例，为木后1～7年CAN患者肾组织穿刺标本。采用免疫组织化学及原位杂交法对每例标本行C—H—ras、TGF-β1、HSP70及HSP90蛋白和mRNA表达水平检测。结果术中穿刺组HSP70表达水平最高，CAN组C—H—ras、TGF-β1及HSP90表达水平最高。结论c—H—ras和TGF-β1两种基因的共同高表达与CAN的发生发展关系密切。调控相关基因的表达可能有助于延缓和治疗CAN。

索磷布韦在合并终末期肾病行血液透析的HCV感染者中的应用

对于慢性丙型肝炎合并终末期肾病行血液透析的患者,指南多建议以含蛋白酶抑制剂(PI)的直接抗病毒药物方案进行治疗,但临床中常有透析患者因合并严重肝损伤禁忌使用PI类药物。简述了行透析丙型肝炎患者中未满足的治疗需求,回顾了在此类患者中应用基于索磷布韦(SOF)的无PI抗病毒方案的临床试验及真实世界研究进展,探讨了基于SOF的方案在中国透析患者中的应用价值及有待进一步研究的问题。提示,基于全剂量SOF的方案在透析患者中的疗效、耐受性及安全性良好,为此类患者中合并中、重度肝损伤者提供了更多安全有效的抗病毒治疗选择。

外周血胱抑素C、肾损伤因子-1、中性粒细胞明胶酶相关脂质运载蛋白在慢性乙型肝炎早期肾损伤患者中的诊断价值

目的探究外周血胱抑素C(Cys-C)、肾损伤因子-1(KIM-1)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)在慢性乙型肝炎合并早期肾损伤患者中的诊断价值。方法选取2018年4月至2021年4月于大连市公共卫生临床中心收治的56例慢性乙型肝炎合并早期肾损伤患者作为观察组,并按性别、年龄匹配同期收治的56例未出现肾损伤的慢性乙型肝炎患者作为对照组。比较两组患者的肾小球滤过率(eGFR)、Cys-C、KIM-1、NGAL水平,分析Cys-C、KIM-1、NGAL水平对慢性乙型肝炎合并早期肾损伤患者的检测价值及与eGFR的相关性。结果观察组患者的eGFR低于对照组,Cys-C、KIM-1、NGAL水平高于对照组,差异有统计学意义(P<0.05)。ROC结果显示:血清Cys-C、KIM-1、NGAL水平对慢性乙型肝炎合并早期肾损伤患者诊断价值AUC分别为0.771、0.785、0.766,低于联合检测的0.896(P<0.05)。血清Cys-C、KIM-1、NGAL的cut-off值分别为1.24 mg/L、1.03 mg/L、116.82 ng/ml。Cys-C、KIM-1、NGAL水平与eGFR均呈负相关(P<0.05)。结论血清Cys-C、KIM-1、NGAL水平及三者联合检测均对慢性乙型肝炎合并早期肾损伤患者具有诊断价值,值得临床参考。