Outcome of Hepatitis C Virus-Infected Kidney Transplant Candidates Who Remain on the Waiting List

The management of patients awaiting transplantation is a growing concern. This retrospective cohort study examined outcomes of hepatitis C virus (HCV)-infected kidney candidates who remain waitlisted. Records from 315 HCV+ kidney candidates evaluated between 1992 and 2002, were reviewed. A total of 300 (95.1%) patients were receiving renal replacement therapy at evaluation, median duration 48.2 + 4.3 months. The diabetes prevalence was 42.9% in HCV+ candidates, compared to 35.9% among 602 currently listed HCV- patients (p = 0.023). Liver disease, defined by abnormal hepatic biochemistry or histology, was observed in 59% patients. Median post-evaluation follow-up was 1440 +/- 75 days; 138 candidates were transplanted. Kaplan-Meier survival was higher among transplanted than non-transplanted patients (p = 0.003). Of 177 patients not transplanted, 76 were delisted, mostly due to death (45%) and non-compliance (28%), infrequently because of liver disease (8.8%). A Cox regression model was fit to examine risk factors for waitlist death; only diabetes was associated (HR: 2.17, 95% CI: 1.1-4.1, p = 0.02), while liver disease was not. This study demonstrates that, in waitlisted HCV+ kidney patients, diabetes occurs with increased prevalence and is a major mortality determinant. Diabetic HCV+ kidney candidates are therefore a patient subgroup that requires frequent and careful reevaluation to ensure ongoing transplantability.     

Prevalence of Occult Hepatitis B and Hepatitis C Virus Infections in Turkish Hemodialysis Patients

Background and Objective. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are important causes of morbidity and mortality in maintenance hemodialysis patients. Although their exact prevalence is not known, HBV and HCV viral infections and occult viral hepatitis are frequent in these patients. This study aimed to determine the prevalence of occult HBV and HCV infections in maintenance hemodialysis patients. Materials and Methods. One hundred and eighty-eight end-stage renal disease patients on maintenance hemodialysis (100 male, mean age 49±29 [16–80] years, and mean duration of hemodialysis 98±66 [12–228] months) were enrolled in this study. Serological markers for HBV and HCV were determined with immunoenzymatic assay (ELISA) by using commercial diagnostic kits (Access and BioRad, Beckman-Coulter). HCV-RNA (Cobas Amplicor HCV kit) and HBV-DNA (Artus GmbH HBV kit) were determined quantitatively by polymerase chain reaction. Results. Among the patients screened, 25 (13.3%) had HBV infection alone and 38 (20.2%) had HCV infection alone, while seven (3.7%) had dual infection of both viruses. Serological markers for occult hepatitis B and occult hepatitis C were positive in five (2.7%) and nine (4.8%) of the patients, respectively. Isolated anti-HBc was positive in 12 (6.4%) of all patients, three (7.9%) of the patients with anti-HCV and two (40%) of the patients with occult hepatitis B. Isolated anti-HBc positivity was more frequent in patients with occult hepatitis B than in those without (40% [2/5] vs. 5.5% [10/183], p=0.002). None of the patients with HCV had occult hepatitis B. Conclusions. Both occult and non-occult forms of HCV infection are more prevalent than HBV infection in hemodialysis patients. Especially the patients with isolated anti-HBc positivity should be tested for probable occult hepatitis B infection.     

Emerging Issues in Hepatitis C Virus-Positive Liver and Kidney Transplant Recipients

Hepatitis C virus (HCV) infection is a major health care issue in liver and kidney transplantation. Besides negatively affecting both patient and graft survival, HCV is associated with a heightened risk for new onset diabetes mellitus (NODM). The mechanisms underlying the diabetogenicity of HCV are complex but are likely to involve insulin resistance caused by inhibitory actions of the virus on insulin regulatory pathways in the liver. The resultant glucose dysregulation is an important determinant of increased morbidity and mortality in liver and kidney recipients. This review highlights the concerns for outcomes in HCV-positive liver and kidney transplant patients with particular focus on the interrelationship between hepatitis C and diabetes. Data about the potential role of calcineurin inhibitors, corticosteroids and mycophenolate mofetil in HCV infection and HCV-associated NODM will also be discussed.     

Hepatitis C Infection and Related Factors in Hemodialysis Patients in China: Systematic Review and Meta-Analysis

Background and Aims. To provide a comprehensive and reliable tabulation of available data on the epidemiological characteristics and risk factors for hepatitis C virus (HCV) infection in maintenance hemodialysis (HD) patients in China, and to help inform prevention programs and guide future research. Methods. A systematic review was constructed based on the computerized literature database by two reviewers independently. Ninety-five percent confidence intervals (CI) of infection rates were calculated using the approximate normal distribution model. Odds ratios and 95% CI were calculated by fixed or random effects models. Results. Forty-three studies met our inclusion criteria. The pooled prevalence of HCV infection among HD patients in China was 41.1% (95% CI 39.5–42.6%). No significant difference was found in HCV infection rates between male and female HD patients (OR = 0.75, 95% CI 0.52–1.07, p = 0.11). HD patients with blood transfusion were 5.65 times more likely to be infected with HCV than HD patients without blood transfusion. A longer duration of HD was associated with increased HCV prevalence. Co-infection with hepatitis B virus did not increase the probability of HCV infection among HD patients (OR = 1.19, 95% CI 0.34–3.20, p = 0.73). Conclusions. Viral hepatitis is still one of the main complications in HD patients, with hepatitis C being the most common one. The key to reducing the incidence of viral hepatitis in HD patients is to control contagion and reduce the frequency of blood transfusion and cross-infection.     

维持性血液透析病人庚型、丙型和乙型肝炎病毒感染的研究

目的 :评价维持性血液透析 (HD)病人庚型、丙型和乙型肝炎病毒感染状况和危险因子。方法 :应用第二代ELISA方法对 10 5例本院HD病人进行HGV、HCV和HBV检则 ,并与透析时间、输血次数等关系进行对比分析。结果 :10 5例HD病人肝炎感染率分别为 :HGV 14.3%、HCV 5 1.4%、HBV 2 2 .9% ,均明显高于对照组 (P <0 .0 5～ <0 .0 1)。其中HCV感染率与透析时间、输血次数相关程度密切 (P <0 .0 0 1) ,且输血次数相对危险性 (OR =2 .735 1)大于透析年度 (OR =2 .0 315 )。结论 :透析环境是HD病人感染HGV、HCV和HBV的危险因子 ,其中HCV感染率随透析年度增加呈增高趋势 ,可能是通过共用透析机和重复透析器传播。输血仍是感染HCV另一重要危险因子 ,且比透析年度危险性更大     

Hemodialysis Reduces the Viral Load in Uremic Patients with Chronic Hepatitis B Infection

Background and aims. The effect of hemodialysis (HD) to change the viral load of hepatitis B virus (HBV) in uremic patients with chronic HBV infection has never been studied. In this study, we investigated the HBV viral loads and their changes between the HD procedure in the uremic patients. Patients and methods. A total of 38 chronic HBV-infected uremic patients were enrolled, but eight cases were excluded due to HCV co-infection and under anti-viral therapy. To evaluate the HBV DNA levels and their changes through the course of HD, we quantified serial serum samples from each patient immediately before HD, at the end of HD, and 48 hours later—immediately before the next HD. Results. Most of our HBV-infected uremic patients had a relatively lower HBV viral load; 80% cases with HBV DNA %4 Log₁₀copies/mL, in comparison with the Taiwan epidemiologic study for community base HBV carriers. There was no significant difference of HBV DNA level between HBeAg-positive and -negative patients, but a significant higher DNA level in the high ALT group (p = 0.029) and liver cirrhosis patients (p = 0.002). The mean HBV DNA levels, before and after HD, respectively, in our 30 patients were 3.823 ± 1.130 Log₁₀copies/mL and 3.686 ± 1.114 Log₁₀copies/mL. It was a significant decrease on HBV DNA level in chronic HBV-infected patients through HD procedure (p = 0.004). The mean HBV DNA level of two days after HD was 3.702 ± 1.094 Log₁₀copies/mL, which was not significantly different from the HBV DNA level before (p = 0.076) or after (p = 0.267) HD; however, the mean reduction of HBV DNA by a single HD was 0.11 ± 0.38 Log₁₀copies/mL. Patients with low viral load also had a significant high platelet count (p = 0.03), high serum albumin (p = 0.016), and low AST level (p = 0.002). Conclusions. Most uremic patients with chronic HBV infection under regular HD in Taiwan had a relatively lower viral load, of which the major mechanism could be due to the elimination of serum HBV viral load by the HD procedure.     

Comparison of Intramuscular and Intradermal Applications of Hepatitis B Vaccine in Hemodialysis Patients

This study compared the application of intramuscular recombinant hepatitis B vaccine in hemodialysis patients with the application of accelerated intradermal recombinant hepatitis B vaccine, which can be applied with one-tenth of the standard dose. Sixty seronegative patients for hepatitis B were randomly separated into two groups. Twenty μg of the recombinant hepatitis B vaccine was intramuscularly applied at 0-, 1-, 2-, and 6-month intervals to the first group (32 cases). One more dose was applied at month 12 to those whose anti-HBs titers remained below 100 mIU/mL at month 7. The same vaccine was intradermally applied at 2μg dose six times with one-month intervals to the second group (28 cases). Vaccine applications were continued in those whose anti-HBs titers remained below 100 mIU/mL at month 7 until antibody titers reached above this value or until the dose number became 12. Measurements of antibody titers were repeated at month 13 in both groups. As a result, in the vaccination of hemodialysis patients against hepatitis B, the accelerated ID application of hepatitis B vaccine with a dose reduced to one-tenth is more cost-effective than the standard dose vaccination schedules. Especially for hemodialysis patients, the time has come for routine application of ID hepatitis B vaccine as an alternative vaccination method.     

Effect of Hepatitis C Virus on Hemoglobin and Hematocrit Levels in Saudi Hemodialysis Patients

Background. Hepatitis C virus infection is common among patients undergoing hemodialysis, and HD patients are at high risk for infection with such virus. Recently, some studies and case reports indicated attenuated anemia in HD patients with HCV infection, and they previously considered this to be related to increased erythropoietin production after hepatic stimulation by chronic infection with hepatitis virus. Aim. The aim of our study is to investigate whether HCV-positive HD patients have higher hemoglobin (Hb) and hematocrit (HCT) values compared to HCV-negative patients. Methods. We retrospectively studied 83 chronic HD patients from Prince Salman Center for Kidney Disease, and monthly samples were collected between July 2007 and July 2008. The HCV status was determined by anti-HCV antibodies and confirmed with RNA polymerase chain reaction (PCR). Those with a history of blood transfusion or massive blood loss during the last six months were excluded from the study. Results. Thirty-three percent of our patients tested positive for anti-HCV antibody (51.8% were male). The mean age for HCV-positive group was 54.92 ± 15.61 years, while it was 51.01 ± 14.81 years for the HCV-negative group (p = 0.27). Mean Hb in the HCV-positive group was 11.18 ± 1.41gm/dL compared to 10.87 ± 1.29 gm/dL for the HCV-negative group (p = 0.05). Mean HTC values for the HCV-positive group was 34.4 ± 3.9, compared to 32.41 ± 3.41 for the HCV-negative group 12 months after starting hemodialysis. Eighty-one patients (27 HCV-positive and 54 HCV-negative) received erythropoietin (EPO) therapy. Seventy-two patients (25 HCV-positive and 47 HCV-negative) received IV iron (p = 0.28). Mean erythropoietin dose was (114.83 ± 84.92 IU/kg/week) for HCV-positive compared to (122.2 ± 91.46 IU/kg/week) for HCV-negative group (p = 0.74). Liver function tests were normal except for higher bilirubin level in the HCV-positive group, 7.74 ± 4.03 Umol/L compared to 5.47 ± 3.71 Umol/L in the HCV-negative group (p = 0.01). Conclusion. Our study showed that ESRD patients on HD with HCV infection have higher Hb and HCT levels compared with HCV-negative patients.     

Severe Hepatitis C Infection in a Renal Transplant Recipient Following Hepatitis C Genotype Mismatch Transplant

We report a case of a 32-year-old female with histologically and clinically inactive chronic hepatic C infection, who received a cadaveric renal transplant from a hepatitis C-positive donor with a different genotype. The genotype mismatch (genotype 1 to genotype 2) and change to tacrolimus-based immunosuppression resulted in severe hepatitis C infection characterized by a 10-fold increase in transaminase levels and grade 3 inflammation histologically. Our report highlights the risk of genotype-mismatch transplants in solid organ transplantation.     

251例血液透析患者HBsAg与抗-HCV检测结果分析

目的分析血液透析患者乙型肝炎表面抗原（HBsAg）与丙型肝炎抗体（抗-HCV）检测结果,旨在寻求血透患者感染的依据,减少医源性感染。方法应用酶联免疫吸附法（EuSA）检测2006年12月份在我院进行血液透析的251例患者HBsAg与抗-HCV,并对透析1年以上的149例患者的肝炎标志物阳性率与透析年限、输血史、手术史的相关性进行分析。结果透析1年以上的149例患者中,HBsAg阳性者19例,阳性率为12．8％;抗-HCV阳性者29例,阳性率19．5％。HB—sAg、抗-HCV同时为阳性者仅1例（0．4％）。抗-HCV阳性率随透析年限、输血次数、手术次数增加而增高（P〈0．05）,多因素非条件多元Logistic回归分析提示,透析年限是抗-HCV阳性率最有统计学意义的因素（OR〉I）;而HBsAg阳性率与透析年限、输血、手术、性别的相关性均无明显统计学意义（P〉0．05）。结论透析年限、输血、手术与抗-HCV阳性率具有显著相关性,随着透析年限的增加抗-HCV阳性率上升,而与HBsAg阳性率无明显相关性。     

Influenza Virus Infection in Adult Solid Organ Transplant Recipients

BACKGROUND: Solid organ transplant (SOT) recipients have been reported to be more susceptible to influenza virus. However, little is known about the clinical epidemiology and the implications of influenza viral infection among SOT recipients. METHODS: Cohort study of influenza viral infection in SOT recipients at the University of Pittsburgh Medical Center. RESULTS: Between November 1990 and April 2000, 30 cases of influenza were diagnosed in SOT recipients at our center, including influenza A (n = 22) and influenza B (n = 8). These included recipients of lung (n = 19), liver (n = 5) and kidney (n = 6) transplants. The incidence of influenza viral infection was 41.8 cases/1,000 person years (PYs), 2.8 cases/1000 PYs and 4.3 cases/ 1,000 PYs among lung, liver and renal transplant patients, respectively (p <0.0001). Symptoms were reported in all patients and included malaise, myalgia/ arthralgia, fever, cough, and shortness of breath. Secondary bacterial pneumonia occurred in five patients (17%). Other complications were seen in three SOT recipients (2 liver and 1 kidney) and included: myocarditis, myositis, and bronchiolitis obliterans. Biopsy of the transplanted organ was performed in 21 SOT recipients (18 lung, 1 liver and 2 kidney) at the time of influenza viral infection. Overall, 62% (13/21) showed variable degrees of acute allograft rejection, and included 61% (11/18) of lung, and 100% (2/2) of kidney transplant recipients. CONCLUSIONS: Influenza infection is associated with significant morbidity in different groups of SOT recipients. Studies are needed to determine if yearly chemoprophylaxis with antiviral drugs might benefit this patient population.     

维持性血液透析患者感染丙型病毒性肝炎150个月随访研究

目的:评价血液透析患者感染丙型肝炎病毒(HCV)的阳转率和危险因素。方法:随访1998年6月～2010年6月在本院透析的血透患者,共纳入2 465例血透患者,采用ELISA法每隔6月在同一实验室检测抗-HCV。结果:1998年6月的抗HCV阳性率为54.7%,每隔半年的阳性率分别为54.7%,53.8%,52.6%,53.0%,51.2%,45.9%,45.5%,48.2%,35.6%,33.7%,33.7%,31.7%,30.4%,28.4%,27.2%,24.5%,20.8%,19.4%,16.6%,14.4%,15.3%,15.2%,12.5%,11.9%和10.0%。在1～150个月随访期间,总计238例患者阳转,随访1～12月者阳转率为4.5%,13～24月者为6.9%,25～48月者为11.9%,49～60月者28.1%,61～72月者35.1%,73～84月者38.6%,85～96月者阳转率46.9%,97～108月者56.3%,109～126月者63.6%,随访至139～150月时,阳转率已高达75%。结论:提示透析环境对HCV传播有影响,可能一方面通过共用透析机,一方面是由于未隔离阳性患者;严格的消毒隔离措施对降低HCV感染和阳转有重要作用。     

血液透析患者丙型肝炎病毒医院感染的危险因素及预防

目的:分析维持性血液透析病人院内感染丙型肝炎病毒的危险因素,探讨其预防措施。方法:选择我院肾内科2005年～2009年行规律性血液透析的患者212例,观察丙型肝炎病毒(HCV)感染情况并分析其与透析时间、输血、透析器复用的关系,设立非透析患者对照组。结果:透析组HCV感染率(22.17%)明显高于对照组(7.04%),透析龄越长、输血次数越多和复用透析器时,HCV感染的风险越高。规范透析操作及推广使用一次性耗材后,新发HCV感染显著下降。结论:血液透析患者是HCV感染的高危人群,透析时间、输血及透析器复用是血液透析患者感染HCV的高危因素,专机专用,减少输血次数,加强透析治疗环节交叉感染的质量控制,可减少HCV感染。     

Characterization of Hepatitis B Virus Surface Antigen and Polymerase Mutations in Liver Transplant Recipients Pre- and Post-Transplant

We evaluated serum samples from 18 chronic hepatitis B virus (HBV) patients who underwent liver transplantation for the presence of HBV polymerase and S gene mutations and HBV genotype using a new commercially available sequencing assay. All three patients with hepatitis B immune globulin (HBIG) treatment failure followed by nucleoside analogue treatment failure were infected with HBV genotype C; a pre-existing HBV S antigen (HBsAg) mutation (sD144A) was identified in one patient pretransplant, while sG145R mutations emerged in the other two patients post-transplant. These HBsAg mutations persisted for the duration of the study (5-6 years), despite the absence of HBIG administration for a 4-5-year period. Significant viral polymerase mutations (rtL180M and rtM204I/V) also emerged in all of these patients following treatment with lamivudine and/or famciclovir. Four of six patients with HBIG breakthrough without nucleoside analogue treatment failure yielded potentially significant HBsAg mutations post transplant. These data do not support previous reports highlighting the disappearance of HBsAg mutants in liver transplant recipients after discontinuation of HBIG. Determination of HBV genotype, as well as identification of HBV polymerase and S gene mutations in liver transplant candidates may be warranted to optimize HBV management strategies post transplant.     

Low Dose Intradermal Vaccination Is Superior to High Dose Intramuscular Vaccination for Hepatitis B in Unresponsive Hemodialysis Patients

After two intramuscular (IM) vaccination protocols (40 μg at 0, 1, 2, and 6 months), patients who were unresponsive to hepatitis B vaccination were collected from three HD centers. The aim of this study was to compare the effectiveness of intradermal (ID) and repeated IM vaccination protocols. Thirty-three of 639 HD patients were found to be unresponsive. Patients were randomly assigned into two groups: one to receive 80 μg ID and the other 160 μg IM vaccination protocol. Both ID (p?=?0.000) and IM (p?=?0.03) groups disclosed statistically significant seroconversion rates six months after the last vaccination dose. The seroconversion rate was 94.1% in the ID and 50% in the IM groups—showing a significant improvement in the ID group (p?=?0.011). A low-dose ID is superior to standard IM vaccination protocol and also more cost-effective in unresponsive HD patients.