Reactivation of hepatitis B virus infection in patients with hemolymphoproliferative diseases, and its prevention

Reactivation of hepatitis B virus(HBV)replication is characterized by increased HBV-DNA serum values of about 1 log or by HBV DNA turning positive if previously undetectable in serum,possibly associated with liver damage and seldom life-threatening.Due to HBV reactivation,hepatitis B surface antigen(HBsAg)-negative/anti-HBc-positive subjects may revert to HBsAg-positive.In patients with hemo-lymphoproliferative disease,the frequency of HBV reactivation depends on the type of lymphoproliferative disorder,the individual's HBV serological status and the potency and duration of immunosuppression.In particular,it occurs in 10%-50%of the HBsAg-positive and in 2%-25%of the HBsAg-negative/anti-HBc-positive,the highest incidences being registered in patients receiving rituximab-based therapy.HBV reactivation can be prevented by accurate screening of patients at risk and by a pharmacological prophylaxis with anti-HBV nucleo(t)sides starting 2-3 wk before the beginning of immunosuppressive treatment and covering the entire period of administration of immunosuppressive drugs and a long subsequent period,the duration of which depends substantially on the degree of immunodepression achieved.Patients with significant HBV replication before immunosuppressive therapy should receive anti-HBV nucleo(t)sides as a long-term(may be life-long)treatment.This review article is mainly directed to doctors engaged every day in the treatment of patients with onco-lymphoproliferative diseases,so that they can broaden their knowledge on HBV infection and on its reactivation induced by the drugs with high immunosuppressive potential that they use in the care of their patients.

Gene therapy and liver diseases

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Risk of hepatitis B virus reactivation in patients with autoimmune diseases undergoing non-tumor necrosis factor-targeted biologics

Hepatitis B virus reactivation(HBVr)can occur in patients treated with immunosuppressive medications.Risk stratification for HBVr based on hepatitis B virus(HBV)serology and viral load is an important strategy to determine appropriate HBV monitoring and antiviral prophylaxis use.Recent advances in the understanding of pathophysiology of autoimmune diseases have led the development of cytokine-targeted therapies.Tumor necrosis factor(TNF)-αinhibitors have been widely used for patients with inflammatory bowel disease,psoriasis,and rheumatic diseases.Further,the clinical benefits of interleukin(IL)-12/23,IL-17,or Janus kinases inhibitors have been demonstrated in these patients.It is well known that TNF-αinhibitor use can lead to HBVr,however,the risk of HBVr in patients undergoing non-TNF-targeted biologics have not been fully understood.In this review,we discuss the risk of HBVr in patients treated with non-TNF-targeted biologics,and immunological mechanisms of these medications causing HBVr.

Testosterone therapy reduces hepatic steatosis in men with type 2 diabetes and low serum testosterone concentrations

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in people with diabetes with no available treatment.AIM To explore the effect of testosterone treatment on liver.Testosterone therapy improves insulin resistance and reduces total body fat,but its impact on the liver remains poorly studied.METHODS This secondary analysis of a 40 wk,randomised,double-blinded,placebocontrolled trial of intramuscular testosterone undecanoate in men with type 2 diabetes and lowered serum testosterone concentrations evaluated the change in hepatic steatosis as measured by liver fat fraction on magnetic resonance imaging(MRI).RESULTS Of 88 patients enrolled in the index study,39 had liver MRIs of whom 20 received testosterone therapy and 19 received placebo.All patients had>5%hepatic steatosis at baseline and 38 of 39 patients met diagnostic criteria for NAFLD.Median liver fat at baseline was 15.0%(IQR 11.5%-21.1%)in the testosterone and 18.4%(15.0%-28.9%)in the placebo group.Median ALT was 34units/L(26-38)in the testosterone and 32units/L(25-52)in the placebo group.At week 40,patients receiving testosterone had a median reduction in absolute liver fat of 3.5%(IQR 2.9%-6.4%)compared with an increase of 1.2%in the placebo arm(between-group difference 4.7%P<0.001).After controlling for baseline liver fat,testosterone therapy was associated with a relative reduction in liver fat of 38.3%(95%confidence interval 25.4%-49.0%,P<0.001).CONCLUSION Testosterone therapy was associated with a reduction in hepatic steatosis in men with diabetes and low serum testosterone.Future randomised studies of testosterone therapy in men with NAFLD focusing on liver-related endpoints are therefore justified.

Hepatic encephalopathy as a complication of liver disease

INTRODUCTIONHepatic encephalopathy ( HE) is a frequent complication of chronic liver disease .It is defined as a characteristic functional and reversible alteration of the mental state ,due to impaired liver function and / or increased portosystemic shunting .

Pathogenesis and treatment of hepatitis C virus-related liver diseases

BACKGROUND: Few comprehensive reviews on the pa- thogenesis of hepatitis C virus (HCV)-related liver diseases have been presented to the present. This article was to re- view the pathogenesis and treatment of HCV-related liver diseases. DATA SOURCES: Data presented here are mostly taken from Japanese studies. RESULTS: HCV infection is characterized by persistent in- flammation of the liver and frequent development of hepa- tocellular carcinoma (HCC) in most cases. These charac- teristic evidences could be explained by immunological al- terations and oxidative stress in the hepatocyte caused by HCV infection. Interferon (IFN) treatment is carried out, at present, not only for the elimination of infected HCV for the treatment of chronic liver diseases, but also for both the prevention of HCC and the treatment of advanced HCC with chemotherapy. The treatment for oxidative stress is al- so important for non-responders to IFN. CONCLUSION: It is important to understand the pathoge- nesis of HCV-related liver diseases for a successful treat- ment.

Impact of modern antiviral therapy of chronic hepatitis B and C on clinical outcomes of liver disease

Chronic infections with the hepatitis B and C viruses have significant worldwide health and economic impacts.Previous treatments for hepatitis C such as interferon and ribavirin therapy were ineffective and poorly tolerated by patients.The introduction of directly acting curative antiviral therapy for hepatitis C and the wider use of nucleos(t)ide analogues for suppression of chronic Hepatitis B infection have resulted in many positive developments.Decreasing the prevalence of hepatitis B and C have concurrently reduced transmission rates and hence,the number of new infections.Antiviral treatments have decreased the rates of liver decompensation and as a result,lowered hospitalisation and mortality rates for both chronic hepatitis B and C infection.The quality of life of chronically infected patients has also been improved significantly by modern treatment.Antiviral therapy has stopped the progression of liver disease to cirrhosis in certain patient cohorts and prevented ongoing hepatocellular damage in patients with existing cirrhosis.Longer term benefits of antiviral therapy include a reduced risk of developing hepatocellular carcinoma and decreased number of patients requiring liver transplantation.This review article assesses the literature and summarises the impact of modern antiviral therapy of chronic hepatitis B and C on clinical outcomes from liver disease.

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.

Molecular biology and the diagnosis and treatment of liver diseases

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Hepatogenous diabetes: Is it a neglected condition in chronic liver disease?

Diabetes mellitus(DM) that occurs because of chronic liver disease(CLD) is known as hepatogenous diabetes(HD). Although the association of diabetes and liver cirrhosis was described forty years ago, it was scarcely studied for long time. Patients suffering from this condition have low frequency of risk factors of type 2 DM. Its incidence is higher in CLD of viral, alcoholic and cryptogenic etiology. Its pathophysiology relates to liver damage, pancreatic dysfunction, interactions between hepatitis C virus(HCV) and glucose metabolism mechanisms and genetic susceptibility. It associates with increased rate of liver complications and hepatocellular carcinoma, and decreased 5-year survival rate. It reduces sustained virological response in HCV infected patients. In spite of these evidences, the American Diabetes Association does not recognize HD. In addition, the impact of glucose control on clinical outcomes of patients has not been evaluated. Treatment of diabetes may be difficult due to liver insufficiency and hepatotoxicity of antidiabetic drugs. Notwithstanding, no therapeutic guidelines have been implemented up to date. In this editorial, authors discuss the reasons why they think that HD may be a neglected pathological condition and call attention to the necessity for more clinical research on different fields of this disease.

Pathophysiology, epidemiology, classification and treatment options for polycystic liver diseases

Polycystic liver diseases(PLD)represent a group of genetic disorders in which cysts occur in the liver(autosomal dominant polycystic liver disease)or in combination with cysts in the kidneys(autosomal dominant polycystic kidney disease).Regardless of the genetic mutations,the natural history of these disorders is alike.The natural history of PLD is characterized by a continuous increase in the volume and the number of cysts.Both genders are affected;however,women have a higher prevalence.Most patients with PLD are asymptomatic and can be managed conservatively.Severe symptoms can affect 20%of patients who develop massive hepatomegaly with compression of the surrounding organs.Rrarely,patients with PLD suffer from acutecomplications caused by the torsion of hepatic cysts,intraluminal cystic hemorrhage and infections.The most common methods for the diagnosis of PLD are cross sectional imaging studies.Abdominal ultrasound and computerized tomography are the two most frequently used investigations.Magnetic resonance imaging is more sensitive and specific,and it is a valuable test for patients with intravenous contrast allergies or renal dysfunction.Different treatment modalities are available to physicians caring for these patients.Medical treatment has been ineffective.Percutaneous sclerotherapy,transarterial embolization,cyst fenestration,hepatic resection and liver transplantation are indicated to specific groups of patients and have to be tailored according to the extent of disease.This review outlines the current knowledge of the pathophysiology,clinical course,diagnosis and treatment strategies of PLD.

Hepatitis C: From inflammatory pathogenesis to antiinflammatory/hepatoprotective therapy

Hepatitis C virus(HCV) infection commonly causes progressive liver diseases that deteriorate from chronic inflammation to fibrosis, cirrhosis and even to hepatocellular carcinoma. A long-term, persistent and uncontrolled inflammatory response is a hallmark of these diseases and further leads to hepatic injury and more severe disease progression. The levels of inflammatory cytokines and chemokines change with the states of infection and treatment, and therefore, they may serve as candidate biomarkers for disease progression and therapeutic effects. The mechanisms of HCV-induced inflammation involve classic pathogen pattern recognition, inflammasome activation, intrahepatic inflammatory cascade response, and oxidative and endoplasmic reticulum stress. Direct-acting antivirals(DAAs) are the first-choice therapy for effectively eliminating HCV, but DAAs alone are not sufficient to block the uncontrolled inflammation and severe liver injury in HCV-infected individuals. Some patients who achieve a sustained virologic response after DAA therapy are still at a long-term risk for progression to liver cirrhosis and hepatocellular carcinoma. Therefore, coupling with antiinflammatory/hepatoprotective agents with anti-HCV effects is a promising therapeutic regimen for these patients during or after treatment with DAAs. In this review, we discuss the relationship between inflammatory mediators and HCV infection, summarize the mechanismsof HCV-induced inflammation, and describe the potential roles of anti-inflammatory/hepatoprotective drugs with anti-HCV activity in the treatment of advanced HCV infection.

Reversible lesions in the brain parenchyma in Wilson's disease confirmed by magnetic resonance imaging:earlier administration of chelating therapy can reduce the damage to the brain

The aim of this study was to evaluate the resolution of brain lesions in patients with Wilson’s disease during the long-term chelating therapy using magnetic resonance imaging and a possible signiifcance of the time latency between the initial symptoms of the disease and the introduction of this therapy. Initial magnetic resonance examination was performed in 37 patients with proven neurological form of Wilson’s disease with cerebellar, parkinsonian and dystonic presentation. Magnetic resonance reexamination was done 5.7 ± 1.3 years later in 14 patients. Patients were divided into： group A, where chelating therapy was initiated 〈 24 months from the ifrst symp-toms and group B, where the therapy started≥ 24 months after the initial symptoms. Symmetry of the lesions was seen in 100% of patients. There was a signiifcant difference between groups A and B regarding complete resolution of brain stem and putaminal lesions （P= 0.005 andP=0.024, respectively）. If the correct diagnosis and adequate treatment are not established less than 24 months after onset of the symptoms, irreversible lesions in the brain parenchyma could be ex-pected. Signal abnormalities on magnetic resonance imaging might therefore, at least in the early stages, represent reversible myelinolisis or cytotoxic edema associated with copper toxicity.

Optimal management for alcoholic liver disease: Conventional medications, natural therapy or combination?

Alcohol consumption is the principal factor in thepathogenesis of chronic liver diseases.Alcoholic liver disease(ALD)is defined by histological lesions on the liver that can range from simple hepatic steatosis to more advanced stages such as alcoholic steatohepatitis,cirrhosis,hepatocellular carcinoma and liver failure.As one of the oldest forms of liver injury known to humans,ALD is still a leading cause of liver-related morbidity and mortality and the burden is exerting on medical systems with hospitalization and management costs rising constantly worldwide.Although the biological mechanisms,including increasing of acetaldehyde,oxidative stress with induction of cytochrome p4502E1,inflammatory cytokine release,abnormal lipid metabolism and induction of hepatocyte apoptosis,by which chronic alcohol consumption triggers serious complex progression of ALD is well established,there is no universally accepted therapy to prevent or reverse.In this article,we have briefly reviewed the pathogenesis of ALD and the molecular targets for development of novel therapies.This review is focused on current therapeutic strategies for ALD,including lifestyle modification with nutrition supplements,available pharmacological drugs and new agents that are under development,liver transplantation,application of complementary medicines,and their combination.The relevant molecular mechanisms of each conventional medication and natural agent have been reviewed according to current available knowledge in the literature.We also summarized efficacy vs safety on conventional and herbal medicines which are specifically used for the prevention and treatment of ALD.Through a system review,this article highlighted that the combination of pharmaceutical drugs with naturally occurring agents may offer an optimal management for ALD and its complications.It is worthwhile to conduct large-scale,multiple centre clinical trials to further prove the safety and benefits for the integrative therapy on ALD.

A small molecule fibrokinase inhibitor in a model of fibropolycystic hepatorenal disease

AIM To evaluate the novel platelet-derived growth factor receptor and vascular endothelial growth factor receptor dual kinase inhibitor ANG3070 in a polycystic kidney disease-congenital hepatic fibrosis model.METHODS At 6 wk of age, PCK rats were randomized to vehicle or ANG3070 for 4 wk. At 10 wk, 24 h urine and left kidneys were collected and rats were continued on treatment for 4 wk. At 14 wk, 24 h urine was collected, rats were sacrificed, and liver and right kidneys were collected for histological evaluation. For Western blot studies, PCK rats were treated with vehicle or ANG3070 for 7 d and sacrificed approximately 30 min after the last treatments.RESULTS Compared to the wild-type cohort, the PCK kidney(Vehicle cohort) exhibited a marked increase in kidney and liver mass, hepato-renal cystic volume, hepato-renal fibrosis and hepato-renal injury biomarkers. Intervention with ANG3070 in PCK rats decreased kidney weight, reduced renal cystic volume and reduced total kidney hydroxyproline, indicating significantly reduced rental interstitial fibrosis compared to the PCK-Vehicle cohort. ANG3070 treatment also mitigated several markers of kidney injury, including urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, cystatin C and interleukin-18 levels. In addition, this treatment attenuated key indices of renal dysfunction, including proteinuria, albuminuria and serum blood urea nitrogen and creatinine, and significantly improved renal function compared to the PCK-Vehicle cohort. ANG3070 treatment also significantly decreased liver enlargement, hepatic lesions, and liver fibrosis, and mitigated liver dysfunction compared to the PCK-Vehicle cohort.CONCLUSION These results suggest that ANG3070 has the potential to slow disease, and may serve as a bridge toward hepato-renal transplantation in patients with fibropolycystic disease.

Patients with non-viral liver disease have a greater tumor burden and less curative treatment options when diagnosed with hepatocellular carcinoma

AIM To assess the impact of underlying liver disease etiology on the presenting features and outcomes in a large cohort of patients with hepatocellular carcinoma(HCC). METHODS A prospective database of all patients with HCC was established from 1998 to March 2012. One thousand and seventy-eight patients were categorized into three groups, based on the etiology of their liver disease: hepatitis B virus(HBV), hepatitis C virus(HCV) and non-viral liver disease(NVLD). Overall survival was determined by Kaplan Meier analysis to time of death or last follow-up.RESULTS HCC patients with HCV(85%) were more likely to be diagnosed as part of a surveillance program, compared to HBV or NVLD(both 71%)(P < 0.001). Patients with NVLD were more likely to receive best supportive care(29%) compared to those with HBV(21%) or HCV(20%)(P < 0.02). Twelve percent of NVLD and 13% of HBV patients underwent liver transplantation compared to 21% of HCV patients(P = 0.001). Median survival from presentation was lowest in NVLD(1.7 years) when compared to HBV(2.8 years) and HCV(2.6 years)(P < 0.05). In multivariate analysis, independent predictors of survival included Child Turcotte Pugh score, size of dominant lesion, absence of vascular invasion, and management with surgical resection or liver transplantation. Patient age and the etiology of the underlying liver disease were not independent predictors of survival CONCLUSION Patients with NVLD and HCC were less likely to be enrolled in a HCC surveillance program and are less likely to have curative therapies such as liver resection and transplantation after diagnosis with HCC, when compared to patients with Hepatitis B and Hepatitis C.

Factors influencing the failure of interferon-free therapy for chronic hepatitis C:Data from the Polish EpiTer-2 cohort study

BACKGROUND The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C,making it highly effective and safe for patients.However,few researchers have analyzed the factors causing therapy failure in some patients.AIM To analyze factors influencing the failure of direct antiviral drugs in the large,multicenter EpiTer-2 cohort in a real-world setting.METHODS The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020.Data collected from the online EpiTer-2 database included the following:hepatitis C virus(HCV)genotype,stage of fibrosis,hematology and liver function parameters,Child-Turcotte-Pugh and Model for End-stage Liver Disease scores,prior antiviral therapy,concomitant diseases,and drugs used in relation to hepatitis B virus(HBV)and/or human immunodeficiency virus(HIV)coinfections.Adverse events observed during the treatment and follow-up period were reported.Both standard and machine learning methods were used for statistical analysis.RESULTS During analysis,12614 patients with chronic hepatitis C were registered,of which 11938(mean age:52 years)had available sustained virologic response(SVR)data[11629(97%)achieved SVR and 309(3%)did not].Most patients(78.1%)were infected with HCV genotype 1b.Liver cirrhosis was diagnosed in 2974 patients,while advanced fibrosis(F3)was diagnosed in 1717 patients.We included patients with features of hepatic failure at baseline[ascites in 142(1.2%)and encephalopathy in 68(0.6%)patients].The most important host factors negatively influencing treatment efficacy were liver cirrhosis,clinical and laboratory features of liver failure,history of hepatocellular carcinoma,and higher body mass index.Among viral factors,genotype 3 and viral load also exerted an influence on treatment efficacy.Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex,which was not confirmed by the multivariate analysis using the machine learning algorithm(random forest).Coinfection with HBV(including patients with on-treatment reactivation of HBV infection)or HIV,extrahepatic manifestations,and renal failure did not significantly affect the treatment efficacy.CONCLUSION In patients with advanced liver disease,individualized therapy(testing for resistance-associated variants and response-guided treatment)should be considered to maximize the chance of achieving SVR.

One Case of Diabetes Nephropathy Stage V, Combined Valvular Disease, Total Heart Failure with Diabetes Foot Gangrene

The patient was found to have 4+urine sugar by physical examination 14 years ago and was treated with oral hypoglycemic drugs. Insulin was injected intramuscularly nine years ago. Two and a half years ago, it was found that the color of the thumb, index and middle toe of the left foot became black. He went to a third-class hospital in Beijing and was diagnosed as “diabetes foot”. He was treated with “balloon dilation of lower limb blood vessels of diabetes foot”. Half a year ago, the third toe on the right side was broken and treated in the hospital again. “Popliteal artery stent implantation” was given for the diagnosis of “double kidney insufficiency, diabetes foot, left heart failure, combined heart valve disease”, “Hemofiltration therapy” and anti-inflammatory, amino acid supplementation, kidney function protection, anticoagulation, anemia correction and other treatments. Later, he went to our hospital and was diagnosed by the TCM diagnosis: category of consumptive disease, toe or finger gangrene (syndrome/pattern of qi and yin deficiency). Western medicine diagnosed: stage V of diabetes nephropathy, type II diabetes foot gangrene, combined with heart valve disease, hypoalbuminemia, double kidney cyst, moderate anemia, pleural effusion, hyperkalemia, pulmonary infection, and total heart failure. The patient was treated by the Qi-acupuncture therapy of TCM in combination with Chinese and Western medicine Medical treatment made the patient significantly better and discharged.

血府逐瘀汤治疗冠心病研究进展

冠心病是临床常见的心血管疾病之一,其发病率和病死率呈上升趋势,严重危害居民健康,加重国家经济负担。血府逐瘀汤有活血化瘀、理气止痛的功效,主治胸中血瘀证。临床上根据其功效常用于治疗血瘀证冠心病,并取得良好疗效。此文旨在对血府逐瘀汤治疗冠心病的临床运用、作用机制及研究进展展开探讨,为深入挖掘血府逐瘀汤临床及实验研究提供新思路。

半量索磷布韦联合全量达卡他韦治疗终末期肾病合并慢性丙型肝炎患者疗效和耐受性评价

目的评估索磷布韦联合达卡他韦治疗终末期肾病合并慢性丙型肝炎(CHC)患者的疗效和耐受性。方法2020年5月~2022年5月我院诊治的接受维持性血液透析治疗的终末期肾病合并CHC患者42例,均接受索磷布韦联合达卡他韦治疗12 w。采用Simmonds基因分型法进行HCV基因型鉴定,定期评估快速病毒学应答(RVR)、治疗结束病毒学应答(ETVR)、停药6个月持续病毒学应答(SVR6)和停药12个月持续病毒学应答(SVR12)。结果本组终末期肾病合并1b、2a、2b和3型HCV感染患者分别为22例、9例、6例和5例;除基因3型感染者SVR6和SVR12为80.0%外,其他各型HCV感染者RVR、ETVR和SVR均为100.0%(P>0.05);在随访12 m,42例患者血清ALT为23(20,38)U/L,AST为21(17,35)U/L,显著低于基线水平【分别为61(42,92)U/L和59(45,83)U/L,P<0.05】,而外周血血小板计数为155(130,194)×10^(9)/L,估算的肾小球滤过率(eGFR)为14.9(12.5,17.3)ml/min×1.73 m^(2),均显著高于基线水平【分别为122(98,141)×10^(9)/L和9.3(8.0,11.5)ml/min×1.73m^(2),P<0.05】;在治疗前后,所有患者血清肌酐(sCr)和尿素(BUN)水平无显著性变化(P>0.05);在直接抗病毒药物(DAAs)治疗过程中,出现8种共55例次不良事件,如恶心、疲劳、瘙痒、食欲减退、高钾血症、低血糖、高血压和关节疼痛等,总体耐受性良好,无因不良事件导致治疗非计划终止。结论应用索非布韦联合达卡他韦治疗终末期肾病合并CHC患者疗效可靠,副作用较小,值得扩大临床研究。