Expanding the liver donor pool worldwide with hepatitis C infected livers, is it the time?

Liver transplantation(LT)provides a life-saving option for cirrhotic patients with complications and hepatocellular carcinoma.Despite the increasing number of liver transplants performed each year,the number of LT candidates on the waitlist remains unchanged due to an imbalance between donor organ supply and the demand which increases the waitlist time and mortality.Living donor liver transplant had a great role in increasing the donor pool and shortened waitlist time for LT candidates.Nevertheless,further strategies can be implemented to increase the pool of potential donors in deceased donor LT,such as reducing the rate of organ discards.Utilizing hepatitis C virus(HCV)seropositive liver grafts is one of the expanded donor organ criteria.A yearly increase of hundreds of transplants is anticipated as a result of maximizing the utilization of HCV-positive organs for HCV-negative recipients.Direct-acting antiviral therapy's efficacy has revolutionized the treatment of HCV infection and the use of HCV-seropositive donors in transplantation.The American Society of Transplantation advises against performing transplants from HCV-infected liver donors(D+)into HCV-negative recipient(R-)unless under Institutional Review Board-approved study rules and with full informed consent of the knowledge gaps associated with such transplants.Proper selection of patients to be transplanted with HCV-infected grafts and confirming their access to direct-acting antivirals if needed is im-portant.National and international consensuses are needed to regulate this process to ensure the maximum benefit and the least adverse events.

Current testing strategies for hepatitis C virus infection in blood donors and the way forward

Screening tests for blood donations are based upon sensitivity, cost-effectiveness and their suitability for high-throughput testing. Enzyme immunoassay (EIAs) for hepatitis C virus (HCV) antibodies were the initial screening tests introduced. The ”first generation“ antibody EIAs detected seroconversion after unduly long infectious window period. Improved HCV antibody assays still had an infectious window period around 66 d. HCV core antigen EIAs shortened the window period considerably, but high costs did not lead to widespread acceptance. A fourth-generation HCV antigen and antibody assay (combination EIA) is more convenient as two infectious markers of HCV are detected in the same assay. Molecular testing for HCV-RNA utilizing nucleic acid amplification technology (NAT) is the most sensitive assay and shortens the window period to only 4 d. Implementation of NAT in many developed countries around the world has resulted in dramatic reductions in transfusion transmissible HCV and relative risk is now < 1 per million donations. However, HCV serology still continues to be retained as some donations are serology positive but NAT negative. In resource constrained countries HCV screening is highly variable, depending upon infrastructure, trained manpower and financial resource. Rapid tests which do not require instrumentation and are simple to perform are used in many small and remotely located blood centres. The sensitivity as compared to EIAs is less and wherever feasible HCV antibody EIAs are most frequently used screening assays. Efforts have been made to implement combined antigen-antibody assays and even NAT in some of these countries.

An autoregressive integrated moving average model for short-term prediction of hepatitis C virus seropositivity among male volunteer blood donors in Karachi,Pakistan

AIM： To identify the stochastic autoregressive integrated moving average （ARIMA） model for short term forecasting of hepatitis C virus （HCV） seropositivity among volunteer blood donors in Karachi, Pakistan.METHODS： Ninety-six months （1998-2005） data on HCV seropositive cases （1000-1 x month1） among male volunteer blood donors tested at four major blood banks in Karachi, Pakistan were subjected to ARIMA modeling. Subsequently, a fitted ARIMA model was used to forecast HCV seropositive donors for 91-96 mo to contrast with observed series of the same months. To assess the forecast accuracy, the mean absolute error rate （%） between the observed and predicted HCV seroprevalence was calculated. Finally, a fitted ARIMA model was used for short-term forecasts beyond the observed series.RESULTS： The goodness-of-fit test of the optimum ARIMA （2,1,7） model showed non-significant autocorrelations in the residuals of the model. The forecasts by ARIMA for 91-96 mo closely followed the pattern of observed series for the same months, with mean monthly absolute forecast errors （%） over 6 mo of 6.5%. The short-term forecasts beyond the observed series adequately captured the pattern in the data and showed increasing tendency of HCV seropositivity with a mean ± SD HCV seroprevalence （1000^-1× month^-1） of 24.3 ±1.4 over the forecast interval.CONCLUSION： To curtail HCV spread, public health authorities need to educate communities and health care providers about HCV transmission routes based on known HCV epidemiology in Pakistan and its neighboring countries. Future research may focus on factors associated with hyperendemic levels of HCV infection.

Epidemiological features of chronic hepatitis C infection caused by remunerated blood donors:A nearly 27-year period survey

AIM To understand the prevalence of hepatitis C virus(HCV) infection in blood donors over a nearly 27-year interval and to explore the factors that affect the outcome of HCV infection.METHODS A retrospective and cross-sectional study was conducted.The participants,mostly plasma donors,were selected from three administrative villages in the Jiangsu province in Eastern China.A questionnaire was administered among the villagers who had a history of blood donation from the late 1980 s to the early 1990 s.All participants underwent physical examination,liver B-ultrasonography,and liver stiffness measurement.In addition,10 m L of blood was collected from each participant to measure simple liver function parameters(albumin,alanine aminotransferase,aspirate aminotransferase),blood factors(platelet),and for hepatitis B surface antigen,anti HCV,and antihuman immunodeficiency virus detection.HCV RNA detection,HCV genotyping,and other tests were carried out in anti HCV-positive patients.RESULTS After a median of 27 years(25-31 years) from the last blood donation to the time of survey,a total of 1694 participants were investigated,and the anti HCVpositive individuals were categorized into three groups:blood donors(n = 12,3.3%),plasma donors(n = 534,68.5%),and mixed donors(n = 324,58.8%).A total of 592(68.05%) patients had detectable HCV RNA,and 91.9% had genotype 1 b.A total of 161(27.2%,161/592) patients with chronic HCV were considered to have cirrhosis with a liver stiffness measurement level higher than 12 k Pa.Multiple logistic(binary) regression analysis results showed that platelet and Ig G levels were associated with cirrhosis.CONCLUSION The nearly 27-year interval investigation revealed that chronic hepatitis C infection is a very serious public health problem in Eastern China.Plasma donation and subsequent return of blood cells to the donor are the main causes of hepatitis C infection.The main HCV genotype is 1 b.Nearly 28% of cases progressed to cirrhosis.Age,especially over 60 years,and regular drinking habits were risk factors associated with cirrhosis.

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.

TT virus and hepatitis G virus infections in Korean blood donors and patients with chronic liver disease

AIM:To determine the prevalences of TTV and HGV infections among blood donors and patients with chronic liver disease in Korea,to investigate the association of TTV and HGV infections with blood transfusion,and to assess the correlation between TTV and HGV viremia and hepatic damage. METHODS:A total of 391 serum samples were examined in this study.Samples were obtained from healthy blood donors(n=110),hepatitis B surface antigen(HBsAg)-positive donors(n=112),anti-hepatitis C virus(anti-HCV)-positive donors(n=69),patients with type B chronic liver disease (n=81),and patients with type C chronic liver disease(n=19). Trv DNA was detected using the hemi-nested PCR.HGV RNA was tested using RT-PCR.A history of blood transfusion and serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were also determined. RESULTS:TTV DNA was detected in 8.2%of healthy blood donors,16.1%of HBsAg-positive donors,20.3%of anti- HCV-positive donors,21.0%of patients with type B chronic liver disease,and 21.1%of patients with type C chronic liver disease.HGV RNA was detected in 1.8%of healthy blood donors,1.8%of HBsAg-positive donors,17.4%of anti-HCV-positive donors,13.6%of patients with type B chronic liver disease,and 10.5%of patients with type C chronic liver disease.The prevalence of TTV and HGV infections in HBV- or HCV-positive donors and patients was significantly higher than in healthy blood donors(P<0.05), except for the detection rate of HGV in HBsAg-positive donors which was the same as for healthy donors.There was a history of transfusion in 66.7%of TTV DNA-positive patients and 76.9%of HGV RNA-positive patients(P<0.05).No significant increase in serum ALT and AST was detected in the TTV or HGV-positive donors and patients. CONCLUSION:TTV and HGV infections are more frequently found in donors and patients infected with HBV or HCV than in healthy blood donors.However,there is no significant association between TTV or HGV infections and liver injury.

Occult hepatitis B virus co-infection in human immunodeficiency virus-positive patients: A review of prevalence, diagnosis and clinical significance

The prevalence of human immunodeficiency virus(HIV) and hepatitis B virus(HBV) co-infection is high as they share similar mechanisms of transmission. The development and widespread use of highly sensitive tests for HBV diagnosis has demonstrated that a significant proportion of apparently healthy individuals with evidence of exposure to HBV continue to carry fully functional HBV DNA in their hepatocytes, a situation that predisposes them to the development of progressive liver disease and hepatocellular carcinoma. The presence of co-infections frequently influences the natural evolution of each of the participating infections present by either facilitating their virulence or competing for resources. Furthermore, the drugs used to treat these infections may also contribute to changes in the natural course of these infections, making the analysis of the impact of co-infection more difficult. The majority of studies has examined the impact of HIV on overt chronic hepatitis B, finding that co-infection carries an increased risk of progressive liver disease and the development of hepatocellular carcinoma. Although the effect of HIV on the natural history of occult hepatitis B infection(OBI) has not been fully assessed, all available data suggest a persisting risk of repeated flares of hepatitis and progressive liver disease. We describe studies regarding the diagnosis, prevalence and clinical significance of OBI in HIVpositive patients in this short review. Discrepancies in worldwide prevalence show the urgent need for the standardization of diagnostic criteria, as established by the Taormina statements. Ideally, standardized protocols for testing should be employed to enable the comparison of data from different groups. Additional studies are needed to define the differences in risk for OBI without HIV and in HIV-HBV co-infected patients with or without overt disease.

Modelling the prevalence of hepatitis C virus amongst blood donors in Libya:An investigation of providing a preventive strategy

AIM: To determine hepatitis C virus(HCV) seroprevalence among the Libyan population using blood donors and applying the autoregressive integrated moving average(ARIMA) model to predict future trends and formulate plans to minimize the burden of HCV infection.METHODS: HCV positive cases were collected from 1008214 healthy blood donors over a 6-year period from 2008 to 2013. Data were used to construct the ARIMA model to forecast HCV seroprevalence among blood donors. The validity of the model was assessed using the mean absolute percentage error between the observed and fitted seroprevalence. The fitted ARIMA model was used to forecast the incidence of HCV beyond the observed period for the year 2014 and further to 2055.RESULTS: The overall prevalence of HCV among blood donors was 1.8%, varying over the study period from 1.7% to 2.5%, though no significant variation was found within each calendar year. The ARIMA model showed a non-significant auto-correlation of the residuals, and the prevalence was steady within the last 3 years as expressed by the goodness-of-fit test. The forecast incidence showed an increase in HCV seropositivity in 2014, ranging from 500 to 700 per 10000 population, with an overall prevalence of 2.3%-2.7%. This may be extended to 2055 with minimal periodical variation within each 6-year period.CONCLUSION: The applied model was found to be valuable in evaluating the seroprevalence of HCV among blood donors, and highlighted the growing burden of such infection on the Libyan health care system. The model may help in formulating national policies to prevent increases in HCV infection and plan future strategies that target the consequences of the infection.

Hepatitis C virus among blood donors and general population in Middle East and North Africa:Meta-analyses and meta-regressions

BACKGROUND Despite the Middle East and North Africa(MENA)Region reported to have the highest prevalence of hepatitis C virus(HCV)globally,HCV infection levels in the majority of MENA countries remain inadequately characterized.Blood donor data have been previously used as a proxy to assess levels and trends of HCV in the general population,however,it is unclear how comparable these populations are in MENA and whether blood donors provide an appropriate proxy.AIM To delineate HCV epidemiology among blood donors and the general population in the MENA.METHODS The data source was the systematically gathered MENA HCV Epidemiology Synthesis Project Database.Random-effects meta-analyses and meta-regressions were conducted.For comparison,analyses were conducted for Europe,utilizing the Hepatitis C Prevalence Database of the European Centre for Disease Prevention and Control.RESULTS One thousand two hundred and thirteen HCV antibody prevalence measures and 84 viremic rate measures were analyzed for MENA.Three hundred and seventyseven antibody prevalence measures were analyzed for Europe.In MENA,pooled mean prevalence was 1.58%[95%confidence interval(CI):1.48%–1.69%]among blood donors and 4.49%(95%CI:4.10%–4.90%)in the general population.In Europe,pooled prevalence was 0.11%(95%CI:0.10%–0.13%)among blood donors and 1.59%(95%CI:1.25%–1.97%)in the general population.Prevalence in the general population was 1.72-fold(95%CI:1.50–1.97)higher than that in blood donors in MENA,but it was 15.10-fold(95%CI:11.48–19.86)higher in Europe.Prevalence was declining at a rate of 4%per year in both MENA and Europe[adjusted risk ratio:0.96(95%CI:0.95–0.97)in MENA and 0.96(95%CI:0.92–0.99)in Europe].Pooled mean viremic rate in MENA was 76.29%(95%CI:67.64%–84.02%)among blood donors and 65.73%(95%CI:61.03%–70.29%)in the general population.CONCLUSION Blood donor data provide a useful proxy for HCV infection in the wider population in MENA,but not Europe,and could improve HCV burden estimations and assess progress toward HCV elimination by 2030.

Living donor liver transplantation to patients with hepatitis C virus cirrhosis

Living donor liver transplantation （LDLT） is an alternative therapeutic option for patients with end-stage hepatitis C virus （HCV） cirrhosis because of the cadaveric organ shortage. HCV infection is now a leading indication for LDLT among adults worldwide, and there is a worse prognosis with HCV recurrence. The antivirus strategy after transplantation, however, is currently under debate. Recent updates on the clinical and therapeutic aspects of living donor liver transplantation for HCV are discussed in the present review.

Bacterial infections post-living-donor liver transplantation in Egyptian hepatitis C virus-cirrhotic patients: A singlecenter study

AIM To determine risk factors, causative organisms and antimicrobial resistance of bacterial infections following living-donor liver transplantation(LDLT) in cirrhotic patients.METHODS This prospective study included 45 patients with hepatitis C virus-related end-stage liver disease who underwent LDLT at Ain Shams Center for Organ Transplant, Cairo, Egypt from January 2014 to November 2015. Patients were followed-up for the first 3 mo after LDLT for detection of bacterial infections. All patients were examined for the possible risk factors suggestive of acquiring infection pre-, intra-and post-operatively. Positive cultures based on clinical suspicion and patterns of antimicrobial resistance were identified. RESULTS Thirty-three patients(73.3%) suffered from bacterial infections; 21 of them had a single infection episode, and 12 had repeated infection episodes. Bile was the most common site for both single and repeated episodes of infection(28.6% and 27.8%, respectively). The most common isolated organisms were gramnegative bacteria. Acinetobacter baumannii was the most common organism isolated from both single and repeated infection episodes(19% and 33.3%, respectively), followed by Escherichia coli for repeated infections(11.1%), and Pseudomonas aeruginosa for single infections(19%). Levofloxacin showed high sensitivity against repeated infection episodes(P = 0.03). Klebsiella, Acinetobacter and Pseudomonas were multi-drug resistant(MDR). Pre-transplant hepatocellular carcinoma(HCC) and duration of drain insertion(in days) were independent risk factors for the occurrence of repeated infection episodes(P = 0.024).CONCLUSION MDR gram-negative bacterial infections are common post-LDLT. Pre-transplant HCC and duration of drain insertion were independent risk factors for the occurrence of repeated infection episodes.

Prevalence of occult hepatitis B virus infection

Occult hepatitis B virus(HBV) infection(OBI) is characterized by the persistence of HBV DNA in the liver tissue in individuals negative for the HBV surface antigen.The prevalence of OBI is quite variable depending on the level of endemic disease in different parts of the world,the different assays utilized in the studies,and the different populations studied.Many studies have been carried out on OBI prevalence in different areas of the world and categories of individuals.The studies show that OBI prevalence seems to be higher among subjects at high risk for HBV infection and with liver disease than among individuals at low risk of infection and without liver disease.

2018-2022年我国18家省级血液中心献血者HCV检测结果分析

目的分析我国省级血液中心服务区域献血人群丙型肝炎病毒(hepatitis C virus,HCV)检测数据。方法对我国东中西部不同地区的18家省级血液中心,2018—2022年初次献血和重复献血者抗-HCV和HCV RNA检测数据收集整理,分析献血者中抗-HCV ELISA和抗-HCV ELISA阴性中HCV RNA检测不合格率与年度、血液中心以及初次献血和重复献血者之间的关系。结果2018年—2022年HCV总不合格率从24.61/万逐年减少至15.17/万(χ^(2)=717.71,P<0.01),西部地区为25.72/万最高,东部11.96/万最低(χ^(2)=2382.54,P<0.01);初次献血者抗-HCV ELISA不合格率(30.50/万)比重复献血者(7.42/万)高(χ^(2)=9694.63,P<0.01);各血液中心抗-HCV ELISA阴性中HCV-RNA单独不合格率范围为0~7.54/万。结论我国18家血液中心服务区域献血者的HCV检测不合格率呈逐年降低趋势;HCV检测不合格率存在明显的地域分布差异;与初次献血者相比,重复献血者为HCV检测不合格低危人群;HCV-RNA检测在血液安全方面发挥重要作用。

Occult hepatitis B virus infection in Egypt

The emerging evidence of the potentially clinical importance of occult hepatitis B virus(HBV) infection(OBI) increases the interest in this topic. OBI may impact in several clinical contexts, which include the possible transmission of the infection, the contribution to liver disease progression, the development of hepatocellular carcinoma, and the risk of reactivation. There are several articles that have published on OBI in Egyptian populations. A review of MEDLINE database was undertaken for relevant articles to clarify the epidemiology of OBI in Egypt. HBV genotype D is the only detectable genotype among Egyptian OBI patients. Higher rates of OBI reported among Egyptian chronic HCV, hemodialysis, children with malignant disorders, and cryptogenic liver disease patients. There is an evidence of OBI reactivation after treatment with chemotherapy. The available data suggested that screening for OBI must be a routine practice in these groups of patients. Further studies needed for better understand of the epidemiology of OBI among Egyptian young generations after the era of hepatitis B vaccination.

Epidemiology of hepatitis C virus in Iran

In Iran,the prevalence of hepatitis C virus(HCV) infection is relatively low according to the populationbased epidemiological studies. However,the epidemiology of HCV is changing and the rate of HCV infection is increasing due to the growth in the number of injecting drug users in the society. In addition,a shift has occurred in the distribution pattern of HCV genotypes among HCV-infected patients in Iran. Genotype 1a is the most prevalent genotype in Iran,but in recent years,an increase in the frequency of 3a and a decrease in 1a and 1b have been reported. These variations in the epidemiology of HCV reflect differences in the routes of transmission,status of public health,lifestyles,and risk factors in different groups and geographic regions of Iran. Health policy makers should consider these differences to establish better strategies for control and prevention of HCV infection. Therefore,this review was conducted to present a clear view regarding the current epidemiology of HCV infection in Iran.

Seroprevalence and genotyping of hepatitis B,hepatitis C and HIV among healthy population and Turkish soldiers in Northern Cyprus

AIM： To compare the prevalence of hepatitis viral markers among soldiers from Turkey, blood donors from Northern Cyprus, and soldiers from Northern Cyprus. METHODS： Hepatitis B surface antigen （HBsAg）, anti-HCV and anti-human immunodeficiency virus （HIV） seroprevalence, HBV DNA, HCV RNA and HCV genotyping among soldiers from Turkey （group Ⅰ ）, civil blood donors from Northern Cyprus （group Ⅱ ）, and soldier candidates from Northern Cyprus （group Ⅲ） were studied and compared to one another. In total, 17 545 cases （13 546 males and 3999 females with a mean age of 34.5 ± 10.3 year, group Ⅰ = 11234, group Ⅱ = 5057, and group Ⅲ = 1254） were included into the study. RESULTS： Among all cases, HBsAg positivity rates were 2.46%, anti-HCV was 0.46% and anti-HIV was 0.00%. HBV DNA was 2.25%, HCV RNA was 0.33% in all groups. HBsAg positivity rates were 2.16% in group Ⅰ, 3.00% in group Ⅱ and 2.71% in group Ⅲ. There was a significant difference between group Ⅰ and group Ⅱ （χ^2= 6.11, P = 0.047 〈 0.05）. Anti-HCV positivity rates were 0.45% in group Ⅰ, 0.45% in group Ⅱ, and 0.56% in group Ⅲ. Genotypes of HCV were 1b and 1a in group Ⅰ, 1b, 1a and 2 in group Ⅱ, and tb, 1a in group Ⅲ. HBsAg carrier rates were 2.20% in females and 2.53% in males. Anti-HCV prevalence was 0.38% in females and 0.48% in males. HBsAg positivity rates were 2.53% in individuals younger than 50, and 1.47% in older than 50. There was a significant difference between the two groups （χ^2 =23.48, P = 0.001） CONCLUSION： Prevalences of HBsAg, HCV and HIV infections in Northern Cyprus population are similar to those of Turkey.

Recurrent hepatitis C after liver transplant

End stage liver disease from hepatitis C is the most common indication for liver transplantation in many parts of the world accounting for up to 40% of liver transplants. Antiviral therapy either before or after liver transplantation is challenging due to side effects and lower efficacy in patients with cirrhosis and liver transplant recipients, as well as from drug interactions with immunosuppressants. Factors that may affect recurrent hepatitis C include donor age, immunosuppression, IL28 B genotype, cytomegalovirus infection, and metabolic syndrome. Older donor age has persistently been shown to have the greatest impact on recurrent hepatitis C. After liver transplantation, distinguishing recurrent hepatitis C from acute cellular rejection may be difficult, although the development of molecular markers may help in making the correct diagnosis. The advent of interferon free regimens with direct acting antiviral agents that include NS3/4A protease inhibitors, NS5 B polymerase inhibitors and NS5 A inhibitors holds great promise in improving outcomes for liver transplant candidates and recipients.

High frequencies of HGV and TTV infections in blood donors in Hangzhou

AIM: To determine the frequencies of HGV and TTV infections in blood donors in Hangzhou. METHODS: RT-nested PCR for HGV RNA detection and semi-nested PCR for TTV DNA detection in the sera from 203 blood donors, and nucleotide sequence analysis were performed. RESULTS: Thirty-two (15.8%) and 30 (14.8%) of the 203 serum samples were positive for HGV RNA and TTV DNA, respectively. And 5 (2.5%) of the 203 serum samples were detectable for both HGV RNA and TTV DNA. Homology of the nucleotide sequences of HGV RT-nested PCR products and TTV semi-nested PCR products from 3 serum samples compared with the reported HGV and TTV sequences was 89.36%, 87.94%, 88.65% and 63.51%, 65.77% and 67.12%, respectively. CONCLUSION: The infection rates of HGV and/or TTV in blood donors are relatively high, and to establish HGV and TTV examinations to screen blood donors is needed for transfusion security. The genomic heterogeneity of TTV or HGV is present in the isolates from different areas.