Utilization of HCV viremic donors in kidney transplantation: a chance or a threat?

Kidney transplantation is the treatment of choice in end-stage renal disease. The main issue which does not allow to utilize it fully is the number of organs available for transplant. Introduction of highly effective oral direct-acting antivirals (DAAs) to the treatment of chronic hepatitis C virus infection (HCV) enabled transplantation of HCV viremic organs to naive recipients. Despite an increasing number of reports on the satisfying effects of using HCV viremic organs, including kidneys, they are more often rejected than those from HCV negative donors. The main reason is the presence of HCV viremia and not the quality of the organ. The current state of knowledge points to the fact that a kidney transplant from an HCV nucleic acid testing positive (NAT+) donor to naive recipients is an effective and safe solution to the problem of the insufficient number of organs available for transplantation. It does not, however, allow to draw conclusions as to the long-term consequence of such an approach. This review analyzes the possibilities and limitations of the usage of HCV NAT + donor organs. Abbreviations: DAA: direct-acting antivirals; HCV: hepatitis C virus; NAT: nucleic acid testing; OPTN: Organ Procurement and Transplantation Network; KDIGO: Kidney Disease: Improving Global Outcomes; Ab: antigen; eGFR: estimated glomerular filtration rate; D: donor; R: recipient; CMV: cytomegalovirus; HBV: hepatitis B virus; UNOS: United Network for Organ Sharing; PHS: Public Health Service; EBR/GZR: elbasvir/grazoprevir; SVR: sustained virologic response; RAS: resistance-associated substitutions; SOF: soforbuvir; GLE/PIB: glecaprevir/pibrentasvir; ACR: acute cellular rejection; AR: acute rejection; DSA: donor-specific antibodies; KTR: kidney transplant recipients; AASLD: American Association for the Study of Liver Disease; IDSA: Infectious Diseases Society of America; PPI: proton pump inhibitors; CKD: chronic kidney disease; GN: glomerulonephritis; KAS: The Kidney Allocation system.

Changing epidemiology, implications, and recommendations for hepatitis C in women of childbearing age and during pregnancy.

Despite the remarkable advances in HCV treatment brought about by the advent of direct-acting antivirals, HCV remains a global public health concern. One particular concern relates to the rising prevalence of HCV in women of childbearing age. Active HCV during pregnancy is associated with cholestasis of pregnancy as well as the risk of mother-to-child transmission. Guidelines are increasingly recommending universal screening during pregnancy, while the treatment of HCV during pregnancy is an area of ongoing research.

Transplantation of Kidneys From Hepatitis C Virus-Infected Donors to Hepatitis C Virus-Negative Recipients: One-Year Kidney Allograft Outcomes.

RATIONALE & OBJECTIVE: Transplant centers in the United States are increasingly willing to transplant kidneys from hepatitis C virus (HCV)-infected (HCV+) donors into HCV- recipients. We studied the association between donor HCV infection status and kidney allograft function and posttransplantation allograft biopsy findings. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: We examined 65 HCV- recipients who received a kidney from a HCV+ donor and 59 HCV- recipients who received a kidney from a HCV- donor during 2018 at a single transplant center. EXPOSURE: Predictor(s) of donor infection with HCV. OUTCOMES: Kidney allograft function and allograft biopsy findings during the first year following transplantation. ANALYTICAL APPROACH: We compared estimated glomerular filtration rate (eGFR), findings on for-cause and surveillance protocol biopsies, development of de novo donor-specific antibodies (DSAs), and patient and allograft outcomes during the first year following transplantation between recipients of HCV+ and HCV- kidneys. We used linear regression to estimate the independent association between allograft function and HCV viremic status of the kidney donor. RESULTS: The mean age of recipients was 52 ± 11 (SD) years, 43% were female, 19% and 80% of recipients were White and Black, respectively. Baseline characteristics were similar between the HCV+ and HCV- groups. There were no statistically significant differences between the HCV+ and HCV- groups in delayed graft function rates (12% vs 8%, respectively); eGFRs at 3, 6, 9, and 12 months post-transplantation; proportions of patients with cellular rejection (6% vs 7%, respectively); and proportions with antibody-mediated rejection (7% vs 10%, respectively) or de novo DSAs (31% vs 20%, respectively). HCV viremic status was not associated with eGFR at 3, 6, 9, or 12 months. LIMITATIONS: Generalizability from a single-center study and small sample size was limited. CONCLUSIONS: Recipients of kidneys from donors infected with HCV had similar kidney allograft function and probability of rejection in the first year after transplantation compared to those who received kidneys from donors without HCV infection.

Hepatitis C Virus Treatment in Children: A Challenge for Hepatitis C Virus Elimination.

Hepatitis C is a global public health threat. The introduction of direct-acting antivirals (DAAs) brings the prospect of curing the 71 million people living with the disease, dramatically changing the landscape of hepatitis C. The World Health Organization developed a roadmap for the elimination and cure of hepatitis C by 2030 with a clear goal with measurable targets. However, there is a lack of a well-defined strategy to tackle the hepatitis C virus (HCV) problem in children and adolescents vis-à-vis the adult population. Hepatitis C in children and adolescents can be addressed as part of a national policy for elimination in the whole population, namely macroelimination, or could be fragmented into a microelimination approach targeting the high-risk population groups. Children born to HCV-infected mothers, adolescents who are injecting drugs, migrants, and those suffering from inherited blood diseases are important target populations. After the U.S. Food and Drug Administration approval for the use of DAAs in children aged 3 years and above, evidence from clinical trials and real-world experience was accumulated using brand and generic medicines, with sustained virological response rates exceeding 95%. The evidence created should guide policies on the management of hepatitis C in children and adolescents. There are many challenges in managing HCV in this left-behind marginalized population. The lack of awareness and epidemiological data, consent age, prohibitive prices of medicines, and absence of policies on access to diagnostics, treatment, and linkage to care are among the many barriers to service delivery that should be addressed to achieve the elimination goal by 2030.

OPTN/SRTR 2018 Annual Data Report: Hepatitis C.

Direct acting antivirals (DAAs) have fundamentally changed the treatment of hepatitis C virus (HCV) infection and reduced the discard rate of HCV-infected organs by offering a treatment option with a high likelihood of cure posttransplant. This has spurred increased interest in transplanting organs from HCV-positive donors into recipients both with and without HCV. In this chapter, we examine data from 2007 to 2018 to determine trends in HCV (+) donor transplants across various organ types. Since 2015, willingness to accept HCV (+) organs increased for candidates waitlisted for kidney, lung, heart, and pancreas transplant, but decreased for those listed for intestine transplant. For candidates listed for liver transplant, willingness to accept HCV (+) organs decreased from 2007 to 2017, but began increasing in 2017. Willingness to accept was not concentrated in a single US geographic area, and there was substantial variation among transplant programs and donation service areas. Numbers of anti-HCV (+) donor kidney, heart, lung, and liver transplants have increased considerably in the past few years. Short-term allograft survival for kidney and liver transplant recipients of anti-HCV (+) organs appears to be comparable to that for recipients of anti-HCV (-) organs in an unadjusted analysis. However, an unadjusted analysis indicates that long-term allograft survival may be worse. Kidney transplant between HCV-infected donors and uninfected recipients with posttransplant DAA treatment is an emerging area. Short-term data are promising, with similar 1-year allograft survival compared with HCV-uninfected donor to HCV-uninfected recipient kidney transplants in unadjusted analyses. However, long-term data are lacking and close monitoring in the future is warranted.

Scaling up prevention and treatment towards the elimination of hepatitis C: a global mathematical model.

BACKGROUND: The revolution in hepatitis C virus (HCV) treatment through the development of direct-acting antivirals (DAAs) has generated international interest in the global elimination of the disease as a public health threat. In 2017, this led WHO to establish elimination targets for 2030. We evaluated the impact of public health interventions on the global HCV epidemic and investigated whether WHO's elimination targets could be met. METHODS: We developed a dynamic transmission model of the global HCV epidemic, calibrated to 190 countries, which incorporates data on demography, people who inject drugs (PWID), current coverage of treatment and prevention programmes, natural history of the disease, HCV prevalence, and HCV-attributable mortality. We estimated the worldwide impact of scaling up interventions that reduce risk of transmission, improve access to treatment, and increase screening for HCV infection by considering six scenarios: no change made to existing levels of diagnosis or treatment; sequentially adding the following interventions: blood safety and infection control, PWID harm reduction, offering of DAAs at diagnosis, and outreach screening to increase the number diagnosed; and a scenario in which DAAs are not introduced (ie, treatment is only with pegylated interferon and oral ribavirin) to investigate the effect of DAA use. We explored the effect of varying the coverage or impact of these interventions in sensitivity analyses and also assessed the impact on the global epidemic of removing certain key countries from the package of interventions. FINDINGS: By 2030, interventions that reduce risk of transmission in the non-PWID population by 80% and increase coverage of harm reduction services to 40% of PWID could avert 14·1 million (95% credible interval 13·0-15·2) new infections. Offering DAAs at time of diagnosis in all countries could prevent 640 000 deaths (620 000-670 000) from cirrhosis and liver cancer. A comprehensive package of prevention, screening, and treatment interventions could avert 15·1 million (13·8-16·1) new infections and 1·5 million (1·4-1·6) cirrhosis and liver cancer deaths, corresponding to an 81% (78-82) reduction in incidence and a 61% (60-62) reduction in mortality compared with 2015 baseline. This reaches the WHO HCV incidence reduction target of 80% but is just short of the mortality reduction target of 65%, which could be reached by 2032. Reducing global burden depends upon success of prevention interventions, implemention of outreach screening, and progress made in key high-burden countries including China, India, and Pakistan. INTERPRETATION: Further improvements in blood safety and infection control, expansion or creation of PWID harm reduction services, and extensive screening for HCV with concomitant treatment for all are necessary to reduce the burden of HCV. These findings should inform the ongoing global action to eliminate the HCV epidemic. FUNDING: Wellcome Trust.

Viral hepatitis in patients on hemodialysis.

Hepatitis B and hepatitis C (HCV) prevalence are higher in people on hemodialysis (HD) than the general population. Through implementation of prevention interventions including vaccines, serologic screening, and post-exposure management, transmissions linked to HD have decreased dramatically. In this manuscript, we review epidemiology of viral hepatitis, summarize current screening and vaccine recommendations, and appraise the available data about efforts to decrease incidence within HD facilities, including isolation of people with viral hepatitis within HD units. Also included is a discussion of the highly effective all-oral HCV treatment options and treatment for HCV in people awaiting kidney transplant.

Hepatitis C Virus Infection in Pregnancy: An Update.

Parenteral transmission is the major route of hepatitis C virus transmission in adults; however, vertical transmission is most common in children. There are several factors that have been shown to be associated with vertical transmission of hepatitis C virus, including hepatitis C virus RNA, human immunodeficiency virus coinfection, and peripheral blood mononuclear cell infection. As there is no effective vaccine to prevent hepatitis C virus infection, and there are no human data describing the safety of the new direct acting antiviral agents in pregnancy, the only preventive strategy for vertical transmission is to treat the hepatitis C virus infection before becoming pregnant. Direct acting antiviral agents are interferon-free, and many are also ribavirin-free. Based on animal studies, sofosbuvir plus ledipasvir may be the best safety profile during pregnancy for now; however, it is too early to recommend treating hepatitis C virus-infected pregnant women with these direct acting antiviral agents currently.

Eliminating Hepatitis C Virus Among Human Immunodeficiency Virus-Infected Men Who Have Sex With Men in Berlin: A Modeling Analysis.

BACKGROUND: Despite high hepatitis C virus (HCV) treatment rates, HCV incidence among human immunodeficiency virus (HIV)-infected men who have sex with men (HIV-infected MSM) in Germany rose before HCV direct-acting antivirals (DAAs). We model what intervention can achieve the World Health Organization (WHO) elimination target of an 80% reduction in HCV incidence by 2030 among HIV-infected MSM in Berlin. METHODS: An HCV transmission model among HIV-diagnosed MSM was calibrated to Berlin (rising HCV incidence and high rates of HCV testing and treatment). We modeled the HCV incidence among HIV-diagnosed MSM in Berlin until 2030 (relative to 2015 WHO baseline) under scenarios of DAA scale-up with or without behavior change (among HIV-diagnosed MSM and/or all MSM). RESULTS: Continuing current treatment rates will marginally reduce the HCV incidence among HIV-diagnosed MSM in Berlin by 2030. Scaling up DAA treatment rates, beginning in 2018, to 100% of newly diagnosed HCV infections within 3 months of diagnosis and 25% each year of previously diagnosed and untreated HCV infections could reduce the HCV incidence by 61% (95% confidence interval, 55.4%-66.7%) by 2030. The WHO target would likely be achieved by combining DAA scale-up with a 40% reduction in HCV transmission among HIV-diagnosed MSM and a 20% reduction among HIV-undiagnosed or HIV-uninfected MSM. DISCUSSION: HCV elimination among HIV-infected MSM in Berlin likely requires combining DAA scale-up with moderately effective behavioral interventions to reduce risk among all MSM.

Improved Graft Survival After Liver Transplantation for Recipients With Hepatitis C Virus in the Direct-Acting Antiviral Era.

Highly effective direct-acting antiviral (DAA) therapy has transformed outcomes of liver transplantation in hepatitis C virus (HCV) patients. We examined longer-term outcomes in HCV-positive recipients in the DAA era and analyzed the Scientific Registry of Transplant Recipients for primary adult, single-organ, nonfulminant liver transplant recipients in the United States from January 1, 2008 to June 30, 2018. Graft loss was compared among HCV-positive liver transplant recipients who received either an HCV-negative or HCV-positive donor (donor [D]-/recipient [R]+; D+/R+) and HCV-negative liver transplant recipients who received a HCV-negative donor (D-/R-). The groups were further divided between the pre-DAA and DAA eras. There were 52,526 patients included: 31,193 were D-/R- patients; 18,746 were D-/R+ patients; and 2587 were D+/R+ patients. The number of D-/R+ transplants decreased from 2010 in 2008 to 1334 in 2017, with this decline particularly noticeable since 2015. D-/R+ patients in the DAA era (n = 7107) were older, had higher rates of hepatocellular carcinoma, and lower Model for End-Stage Liver Disease scores than those in the pre-DAA era. Graft survival improved for all recipients in the DAA era but improved most dramatically in HCV-positive recipients: D-/R+ 1-year survival was 92.4% versus 88.7% and 3-year survival was 83.7% versus 77.7% (DAA versus pre-DAA era, respectively) compared with D-/R- 1-year survival of 92.7% versus 91.0% and 3-year survival of 85.7% versus 84.0% (DAA versus pre-DAA era, respectively). The magnitude of improvement in 3-year graft survival was almost 4-fold greater for D-/R+ patients. The 3-year survival for D+/R+ patients was similar to HCV-negative patients. In conclusion, the number of liver transplants for HCV has decreased by more than one-third over the past decade. Graft survival among HCV-positive recipients has increased disproportionately in the DAA era with HCV-positive recipients now achieving similar outcomes to non-HCV recipients.

Treatment and monitoring of children with chronic hepatitis C in the Pre-DAA era: A European survey of 38 paediatric specialists.

The burden of paediatric Hepatitis C virus (HCV) infection across Europe is unknown, as are current policies regarding monitoring and treatment. This collaborative study aimed to collect aggregate data to characterise the population of ≤18-year-olds with HCV infection in specialist follow up in a 12-month period (2016) across the PENTAHep European consortium, and investigate current policies around monitoring and treatment. A cross-sectional, web-based survey was distributed in April 2017 to 50 paediatricians in 19 European countries, covering patients' profile, and monitoring and treatment practices. Responses were received from 38/50 clinicians collectively caring for 663 children with chronic HCV infection of whom three-quarters were aged ≥6 years and 90% vertically infected. HCV genotype 1 was the most common (n 380; 57.3%), followed by genotype 3, 4 and 2. Seventeen children (3%) with chronic HCV infection were diagnosed with cirrhosis, and six were reported to have received liver transplantation for HCV-related liver disease. The majority (n 425; 64.1%) of the European children with HCV infection remained treatment-naive in 2016. Age affected clinicians' attitudes towards treatment; 94% reported being willing to use direct-acting antivirals, if available, in adolescents (aged ≥11 years), 78% in children aged 6-10 and 42% in those 3-5 years of age (Pearson correlation coefficient -0.98; P 0.0001). This survey provides the largest characterisation of the population of children in clinical follow-up for chronic HCV infection in Europe, alongside important contextual information on their management and treatment. Discussion is needed around strategies and criteria for use of direct-acting antivirals in these children.

HIV co-infection is associated with increased transmission risk in patients with chronic hepatitis C virus.

Molecular epidemiological analysis of viral pathogens can identify factors associated with increased transmission risk. We investigated the frequency of genetic clustering in a large data set of NS34A, NS5A, and NS5B viral sequences from patients with chronic hepatitis C virus (HCV). Within a subset of patients with longitudinal samples, Receiver Operator Characteristic (ROC) analysis was applied which identified a threshold of 0.02 substitutions/site as most appropriate for clustering. From the 7457 patients with chronic HCV infection included in this analysis, we inferred 256 clusters comprising 541 patients (7.3%). We found that HCV/HIV co-infection, young age, and high HCV viral load were all associated with increased clustering frequency, an indicator of increased transmission risk. In light of previous work on HCV/HIV co-infection in acute HCV cohorts, our results suggest that patients with HCV/HIV co-infection may disproportionately be the source of new HCV infections and treatment efforts should be geared towards viral elimination in this vulnerable population.

Management of Hepatitis C Infection in children in the era of Direct-acting Antiviral Agents.

Chronic hepatitis C certainly is a global health burden in children as well as in adults. Spontaneous viral clearance can occur in early childhood but is uncommon thereafter. Although the majority of cases are asymptomatic during childhood and young adulthood, without an effective treatment, children who acquire HCV via vertical transmission can develop chronic liver disease and other complications including end-stage liver disease and hepatocellular carcinoma in adulthood. Efforts from worldwide health organizations, the pharmaceutical industry, and clinical and research institutions have resulted in very effective interferon-free therapy with direct-acting antiviral agents (DAAs) for HCV-infected children. In this manuscript, we will briefly review the epidemiology of HCV in children, historic treatment, current published data on DAAs in children and conclude with suggestions for management of the child with HCV in the era of DAAs.

Prevalence of chronic hepatitis C virus infection among childhood cancer survivors in Stockholm, Sweden.

Background: Childhood cancer survivors treated before 1992, when blood donor screening for hepatitis C virus (HCV) infection was introduced, are at risk of transfusion-transmitted HCV infection. A national HCV screening campaign targeting blood transfusion recipients was launched in Sweden in 2007-2010. The aims of this study were to, among adult childhood cancer survivors in Stockholm County, investigate the prevalence of HCV infection, the natural course of infection, treatment outcome and anti-HCV testing frequency before, during and after the screening campaign and finally to actively screen the untested ones. Material and Methods: This was a combined retrospective register based and prospective screening study of adult childhood cancer survivors (n = 686) treated for malignancy in Stockholm before 1992. In the first part, we investigated the prevalence of HCV infection and previous anti-HCV testing, and in the second part, we actively traced and HCV-screened the remaining untested cohort living in Stockholm. Analysis of previous documented anti-HCV tests in medical records, laboratory records, and the national communicable disease registry was performed. In the second part, 231 presumably untested individuals were contacted by mail and offered an anti-HCV test. The natural course of HCV infection and treatment outcome was analyzed for those found to be chronically infected. Results: In total, 235 patients were tested and 11 were HCV-RNA positive. The overall prevalence of chronic HCV infection among the tested childhood cancer survivors was thus 4.7% (95% CI = 2.6-8.2%), which is almost 10 times higher than the national prevalence of 0.5%. Only 12% of the Stockholm cohort were tested during the screening campaign in 2007-2010, while the test uptake using active tracing screening within this study was 40% (p < .001). Conclusion: With today's effective treatment options, active tracing and HCV screening of childhood cancer survivors are recommended.

Change in treatment paradigm in people who previously injected drugs with chronic hepatitis C in the era of direct-acting antiviral therapy.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is highly prevalent among people who inject drugs but is often undiagnosed. The treatment paradigm for HCV patients has been changing since the availability of direct-acting antiviral (DAA) treatment. We aimed to evaluate the change in treatment paradigm of people who previously injected drugs (ex-PWID) in Hong Kong before and after the availability of DAA. METHOD: Consecutive ex-PWID referred from various nongovernmental organizations attended education talks at rehabilitation centers and received point-of-care rapid test for HCV antibody (anti-HCV) at the same session. Subjects tested positive for anti-HCV were invited to undergo further assessment. Afterwards, the patients were referred to the regional hospitals for follow-up and/or treatment. RESULTS: Three hundred sixty-five ex-PWID received HCV rapid test; 268 (73.4%) were found to be anti-HCV positive. Among these 268 HCV-positive ex-PWID, 234 (87.3%) attended the assessment session (mean age 52 years, 90.2% male, 45.5% genotype 1b, 41.1% genotype 6a, and median liver stiffness 5.9 kPa); 187 (69.8%) attended follow-up visits at regional hospitals. Seventy-one patients received antiviral treatment for HCV; 69 first received peginterferon and ribavirin (PegIFN/RBV), whereas 10 patients (eight PegIFN/RBV-treated patients) received DAA treatment. Fifty-two patients achieved sustained virologic response at 12 or 24 weeks. Treatment uptake rates of PegIFN/RBV and DAA treatment in the pre-DAA versus post-DAA era were 22.3% versus 48.5% and 0% versus 15.6%, respectively. CONCLUSIONS: Targeted screening in ex-PWID is effective in identifying patients with HCV infection in the community. To improve treatment uptake, further improvements in the referral system and treatment regimens are needed.

THE GORDON WILSON LECTURE: THE HEPATITIS C VIRUS: FROM HIPPOCRATES TO CURE.

The modern age of viral hepatitis began in the early 1960s with the serendipitous discovery of the Australia antigen, a protein that was later shown to represent the envelope of the hepatitis B virus leading to its designation as the hepatitis B surface antigen. This was the first marker for any hepatitis virus and became not only a diagnostic assay, but also a mandatory blood donor screening test and the basis for the first generation hepatitis B vaccine. Prospective studies of transfusion recipients then showed that hepatitis B virus accounted for only 25% of cases of post-transfusion hepatitis (PTH). Discovery of the hepatitis A virus in 1975 revealed that none of the non-B PTH cases were due to hepatitis A virus infection resulting in the designation of this predominant form of PTH as non-A, non-B hepatitis. Using pedigreed patient samples and the chimp model, it was shown even before the advent of molecular biology that the non-A, non-B agent was small and lipid enveloped suggesting it might be a flavivirus. This was confirmed when the agent was cloned by Houghton and colleagues at the Chiron Corporation in 1987 and renamed the hepatitis C virus (HCV). In 1990 a donor screening assay for HCV was introduced nationwide and by 1997 PTH had virtually disappeared with rates now mathematically estimated to be one case per 2 million transfusions, compared to a 30% incidence before 1970. Clinical and molecular studies of HCV have shown that it results in persistent infection in 75% to 85% of cases due to its high replication rate, its existence as a quasispecies with a high mutation rate and the ability of HCV proteins to blunt and ultimately exhaust the HCV immune response. Although HCV infection is clinically and histologically mild in most patients, it can lead to progressive fibrosis over the course of decades in 30% to 40% and culminate in cirrhosis and end-stage liver disease. HCV can also cause hepatocellular carcinoma, generally on the background of cirrhosis with an incidence of 1% to 3% per year in this setting. After 2 decades of difficult and prolonged treatments with interferon-based regimens that resulted in cure rates of less than 50%, successive generations of HCV specific direct-acting antivirals were introduced that now result in cure rates of 95% to 100% across all genotypes after only 8 to 12 weeks of nontoxic oral therapy. This unprecedented efficacy has led to speculation that HCV infection might be eradicated even in the absence of a vaccine, but there are many impediments to global eradication including ascertainment of silent carriers, access to medication, and high drug cost. Nonetheless, we are in a new era of HCV control and optimism abounds.

New Face of Hepatitis C.

Chronic hepatitis C viral (HCV) infection continues to carry a high burden of disease despite recent and emerging advancements in treatment. The persistently high prevalence of HCV is attributed to the rising opioid epidemic, with a history of injection drug use as the primary risk factor for infection. As a result, the epidemiology of HCV-infected individuals is changing. Previously a disease of "Baby Boomers," males, and non-Hispanic blacks, the new generation of patients with HCV includes younger adults from 20 to 39 years of age, both men and women similarly represented, and non-Hispanic whites. Shifting trends in these demographics may be attributed to the use of injection drugs, which also has suggested impact on fibrosis progression in infected individuals. Awareness of the changing face of HCV is necessary to expand and revise recommendations regarding screening, outreach, and care engagement of infected individuals, in order to best identify patients at-risk for infection.

Cluster of hepatitis C in a family: a twenty-year follow-up.

OBJECTIVE: We described an impressive cluster of hepatitis C in a single family. Of nine members of the family, six - the mother and five daughters - were affected by chronic hepatitis, hepatitis C virus (HCV) genotype 1b, of which two were co-infected with hepatitis B virus (HBV). Sharing a non-disposable injection equipment for intramuscular medical care was the most likely route of contagion. Twenty years after the first observation, we performed a follow up of this family. METHODS: The clinical history was updated, and the members of the family underwent a clinical evaluation, extensive liver laboratory tests, and whole serology for hepatitis C and B. Protein chain reaction for HCV RNA was performed when indicated. The eight spouses of the offspring and their eight children underwent the same evaluation. RESULTS: The main findings of this study are the favourable outcome of the two members of the family mono-infected by HCV, treated with peginterferon and ribavirin (sustained response and free of liver disease), in contrast with the ominous outcome of the two members co-infected with HCV and HBV, who evolved to decompensated cirrhosis, with hepatocellular carcinoma in one case, ultimately leading to death. A further feature is the absence of transmission of HCV to the spouses and to the third generation of children of this family, consistent with the assumption that sexual and vertical transmission is unlikely. CONCLUSIONS: A thorough epidemiological investigation of the two first generations of this family, the study of their spouses and children, and the twenty years of follow up provided a strong presumption that the infection with HCV had occurred within this family through the promiscuous use of the same inadequately sterilized glass syringe for intramuscular therapies, as was a common practice during the fifties and sixties worldwide and still is in some part of the world.

[Tratamiento de infección crónica por virus de hepatitis C en niños, ¿perspectiva hacia la curación o lejos de la meta?]

La infección por el virus de hepatitis C es un problema global de salud pública; en México aproximadamente 2 % de la población se encuentra infectada. En niños, los datos de prevalencia son variables según la edad, pero se estima que 0.1 a 2 % de los niños presenta infección crónica por virus de hepatitis C, cuya principal vía de transmisión es la perinatal. Actualmente existen antivirales de acción directa aprobados en adultos con una tasa de respuesta viral sostenida superior a 95 %; sin embargo, en niños aún son pocos los estudios que confirman su seguridad y efectividad. Aunque todavía estamos lejos de la meta, avanzamos rápidamente hacia un tratamiento óptimo de curación también para pacientes pediátricos.

Infection with hepatitis C virus is a global health problem; in Mexico, approximately 2% of the population is infected. In children, data on prevalence are variable according to the age group, but 0.1-2% of children are estimated to have chronic infection with hepatitis C virus, the main way of transmission of which is perinatal. Currently, there are direct-acting antiviral agents approved in adults that offer a sustained viral response rate higher than 95%; however, in children there are still only few studies confirming their safety and effectiveness. Although we are still far from the goal, we are rapidly advancing towards an optimal curative treatment also for pediatric patients.

Management of HCV-Related Liver Disease in Hemophilia and Thalassemia.

Chronic infection with the hepatitis C virus (HCV) has long been the dominant complication of substitution therapy in patients with inherited blood disorders and the cause of anticipated death due to end-stage liver disease. In hemophilia, transmission of HCV with clotting factors concentrates started to be curbed in the mid-1980s following the adoption of procedures of virus inactivation of concentrates based on heat, whereas in the 1990s treatment of HCV infection with interferon monotherapy was attempted, however, with little success. The advent of combination therapy of interferon with ribavirin led to a substantial improvement of treatment outcome (40% rate of cure), that however was still of limited efficacy in patients with advanced liver disease, those with high load of HCV genotype 1, and patients coinfected with the human immunodeficiency virus. In this latter population, while the course of hepatitis C was accelerated as a consequence of immunodeficiency, the advent of highly active antiretroviral therapy led acquired immunodeficiency syndrome (AIDS) to decline and hepatitis C to progressively emerge as a dominant cause of mortality, in parallel. In patients with thalassemia, transfusion-related transmission of HCV was efficiently interrupted in 1992 with the advent of sensitive screening tests for testing donors for HCV, whereas treatment with interferon and ribavirin of infected thalassemics was constrained by an increased risk of anemia due to the hemolytic properties of ribavirin coupled with interferon-induced bone marrow suppression. The advent of safe and potent regimens based on the oral administration of direct antiviral agents has revolutionized therapy of HCV in patients with congenital blood diseases, providing substantial clinical benefits and making elimination of infection in these populations, possible.