Lionel Rostaing

Lionel Rostaing is a nephrologist and kidney-transplant specialist based in Toulouse whose name recurs at the points where hepatitis C becomes a problem of both clinical management and institutional judgment. He is identified as a co-editor of the volume, a contributor to its chapter on hepatitis C after kidney transplantation, and the professor responsible for the Department of Nephrology, Dialysis, and Organ Transplantation Unit at CHU Rangueil and Toulouse University Hospital. His published role in the book is therefore not confined to one disease or one procedure: it follows hepatitis C through diagnosis, dialysis, transplantation, immunosuppression, antiviral therapy, graft injury, and organ allocation.

Identity and Professional Setting

Lionel Rostaing appears in the volume as a Toulouse-based physician working at the intersection of nephrology, dialysis, organ transplantation, and virology. The institutional affiliations associated with his work include the Department of Nephrology, Dialysis, and Organ Transplantation at CHU Rangueil, Toulouse University Hospital, and INSERM U563, IFR 30. This setting places him within a clinical and research network concerned not only with renal replacement but also with the systemic consequences of chronic hepatitis C in patients whose kidney function has already failed.

His editorial position reinforces that breadth. He is listed among the volume's co-editors alongside Beatriz Domínguez-Gil, Josep M. Campistol, and Michel Jadoul, while Jose M. Morales is named volume editor. Rostaing is also associated with the chapter on hepatitis C and renal disease, where the subject is treated through epidemiology, diagnosis, pathogenesis, and therapy rather than as an isolated hepatic infection. The volume thus presents him as one of the figures helping to construct its central clinical vocabulary: active viremia, liver staging, sustained virological response, allograft dysfunction, and the hazards of immunosuppression.

Work on Hepatitis C and Renal Disease

Rostaing is credited as a co-author of the chapter “Hepatitis C and Renal Disease: Epidemiology, Diagnosis, Pathogenesis and Therapy,” with Jose M. Morales and N. Kamar. That chapter's scope is significant because it joins the population-level spread of infection to the mechanisms by which hepatitis C affects the kidney and to the therapeutic decisions that follow. In this framework, dialysis is not merely a waiting room for transplantation: it is a site of infection surveillance, mortality risk, liver-disease assessment, and possible antiviral intervention.

The evidence summarized in the volume shows why such a framework is necessary. Hepatitis C-related liver disease is often asymptomatic in long-term dialysis patients, while fatigue, cognitive impairment, and other symptoms are difficult to interpret because they are common in dialysis regardless of serologic status. Biochemical signals may nevertheless appear, including elevated transaminases and gamma-glutamyl transpeptidase, an association with alkaline phosphatase activity in a United States cohort of 13,664 dialysis patients, and higher intact parathormone levels among infected patients. Cirrhosis remains relatively infrequent in dialysis patients in the Western world, reported at approximately 1.5–2 percent in some international registries, but the infection still carries a measurable survival penalty.

The chapter's mortality evidence gives that penalty a precise shape. A meta-analysis of seven observational studies involving 11,589 long-term dialysis patients found an independent relative risk for mortality of 1.34 among those with anti-HCV antibodies. Liver-related mortality was still more pronounced, with an unadjusted relative risk of 5.89 compared with anti-HCV-negative dialysis patients. A large Australia and New Zealand study of 23,046 patients found an adjusted hazard ratio of 1.25 for all-cause mortality over ten years and an adjusted hazard ratio of 5.79 for hepatic failure, although hepatic failure remained an infrequent cause of death. Comparable associations were reported in a Japanese cohort of 76,201 patients, an Australia and New Zealand cohort of 21,487 patients, and the Dialysis Outcomes and Practice Patterns Study.

Rostaing's clinical field also encompasses the less visible burden of infection. Among 165 regular dialysis patients studied with the SF-36 questionnaire, 83 were anti-HCV positive, and anti-HCV positivity was independently associated with a lower mental component summary score, while no significant association was found with the physical component summary score. The volume connects this result to depression, fatigue, cognitive impairment, and the anxiety produced by a diagnosis with long-term implications. Hepatitis C in this account is therefore both a biological process and a condition managed through labels, surveillance, waiting lists, and decisions about treatment eligibility.

Kidney Transplantation and Treatment After Transplantation

Rostaing is the lead author of “Treatment of Hepatitis C Virus Infection after Kidney Transplantation,” written with Hugo Weclawiak, Jacques Izopet, and Nassim Kamar. The chapter's decisive argument is that hepatitis C should, when possible, be eradicated before kidney transplantation rather than treated afterward. Powerful immunosuppression can sharply increase viral replication and permit severe liver injury, including cirrhosis and fibrosing cholestatic hepatitis. Yet the principal post-transplant antiviral option discussed in the chapter, alpha-interferon, carries a direct threat to the renal allograft.

The early experience with standard alpha-interferon was poor. In small series from the early 1990s, doses of 3–10 million units were administered three times weekly. Aminotransferase levels improved in only about half of patients, virological response during treatment reached only about 25 percent, sustained virological response was very low, and adverse effects caused many patients to discontinue therapy. Acute renal failure occurred in connection with acute rejection episodes and led to some graft losses; later observations indicated that many of these rejection episodes were humoral in type.

A meta-analysis of twelve clinical trials involving 102 unique renal-transplant patients estimated a sustained virological response of 18 percent and a dropout rate of 35 percent for alpha-interferon-based therapy. Graft dysfunction was the most frequent adverse effect requiring treatment interruption, accounting for 28 cases, or 71.7 percent of such interruptions. The analysis also found a significant inverse association between reference year and dropout rate, but its overall conclusion remained that alpha-interferon-based therapy had poor tolerance and safety after renal transplantation. On that basis, alpha-interferon or pegylated alpha-interferon alone was not recommended for HCV-positive kidney-transplant recipients.

The chapter distinguishes this post-transplant risk from the more encouraging results of treatment during dialysis. A meta-analysis of ten studies involving 151 unique dialysis patients, 97.4 percent of whom were receiving long-term hemodialysis, estimated a sustained virological response of 56 percent and a dropout rate of 25 percent for alpha-interferon plus ribavirin. Anemia caused 26 percent of treatment interruptions and heart failure caused 9 percent. These findings supported the volume's practical preference for attempting eradication before transplantation, when the transplanted kidney is not yet exposed to interferon-associated rejection.

Post-Transplant Complications and Targeted Intervention

Rostaing's treatment framework leaves room for carefully selected post-transplant intervention when the disease is rapidly destructive. Alpha-interferon plus ribavirin may be considered for patients who develop rapidly progressive cirrhosis or fibrosing cholestatic hepatitis after transplantation, and it may also be attempted in selected cases of de novo cryoglobulinemic glomerulonephritis within the allograft. The recommendation is deliberately narrow: the potential benefit must be weighed against the possibility of damaging or losing the graft.

The same balance governs the discussion of cryoglobulinemia-associated membranoproliferative glomerulonephritis. In a series of seven kidney-transplant patients, five of whom were HCV positive, patients developed type III cryoglobulinemia-associated membranoproliferative glomerulonephritis, impaired renal function, and, in five cases, de novo nephrotic syndrome. Five patients had severe hypertension, one had nephritic syndrome, and one had increased serum creatinine. Weekly rituximab was administered at 375 mg/m2 for two, three, or four weeks according to the case. Renal parameters improved dramatically: nephrotic syndrome entered sustained remission in three patients, disappeared in one patient with nephritic syndrome, and improved in two others; cryoglobulins cleared sustainably in six. Severe infectious complications nevertheless occurred in two cases, preserving the treatment's character as a high-stakes rescue rather than a routine substitute for viral eradication.

The chapter's summary therefore gives priority to pre-transplant clearance. Antiviral therapy is considered reasonable after transplantation when severe liver fibrosis or fibrosing cholestatic hepatitis develops, while rituximab may be attempted for cryoglobulinemia-associated membranoproliferative glomerulonephritis with heavy proteinuria. But because interferon can jeopardize kidney allograft function, the safer strategic moment for eliminating HCV is generally before kidney transplantation, during dialysis, when treatment can achieve results comparable to those in the general population.

Allocation, Waiting, and Clinical Judgment

Rostaing's work also enters the institutional question of who may receive a transplant and which organs should be used. The volume describes the shortage that makes this question unavoidable: at the end of 2009, 63,000 patients were on organ waiting lists in the European Union while only 28,000 transplant procedures were performed that year; in the United States, almost 111,000 people were registered in May 2011, against approximately 28,000 procedures annually. Within that scarcity, kidneys from hepatitis C virus-positive donors remain controversial because the infection can be transmitted through transplantation and because centers differ widely in whether they accept such organs.

The evidence does not support treating every HCV-infected end-stage renal disease patient as disqualified from transplantation. Transplant recipients with HCV have inferior long-term survival compared with uninfected recipients, and a meta-analysis of eight clinical trials involving 6,365 patients estimated a relative risk for mortality of 1.79, partly explained by increased liver-related death. Yet transplantation still provides a survival advantage over remaining on dialysis. Studies reported lower mortality among anti-HCV-positive patients who received a kidney, including a relative risk of death of 0.31 during the seven- to forty-eight-month post-transplant period in one comparison. In another analysis of 175 HCV-infected listed candidates, the hazard ratio for death was 2.51 during the first six months after transplantation but fell to 0.32 during months seven through eighty-four. The clinical conclusion is that transplantation remains the preferred renal replacement therapy when advanced liver injury is absent.

This logic supports the possibility of transplanting kidneys from HCV-positive donors into HCV-positive recipients. The United States registry found that such recipients waited 310 fewer days than the average patient at their center and 395 fewer days than comparable patients who waited for an HCV-negative kidney. Receiving an HCV-positive kidney was independently associated with better survival than remaining on the waiting list, with an adjusted hazard ratio of 0.76. A Spanish experience involving 162 HCV-positive recipients of HCV-positive kidneys and 306 HCV-positive recipients of HCV-negative kidneys found no difference in patient survival over a mean follow-up of 74.5 months; deaths related to liver disease were scarce in both groups, three versus two.

The Spanish data also show why allocation cannot be reduced to donor serology alone. Graft survival was lower among recipients of HCV-positive kidneys, but this was attributed to older donor and recipient age and to a more frequent pretransplant viremic state. Donor-positive serology was not an independent risk factor for death, graft loss, or progression to advanced liver disease. Decompensated chronic liver disease occurred in 10.3 percent of the HCV-positive-donor group and 6.2 percent of the HCV-negative-donor group, a difference that was not statistically significant. Post-transplant diabetes occurred more often in the first group, but donor serology was not an independent risk factor, and no difference was found in post-transplant glomerular disease.

The resulting policy remains conditional rather than absolute. Patients with active viremia may be unable to tolerate, refuse, fail, or withdraw from interferon treatment, and treatment may require exclusion from the waiting list while imposing substantial adverse effects, duration, and cost. For these patients, transplantation can still offer a better course than continued dialysis, and an HCV-positive kidney may shorten the wait. At the same time, the decline in active infection among end-stage renal disease patients has made HCV-positive kidneys increasingly surplus organs: one analysis found that they were 2.60 times more likely to be discarded than HCV-negative kidneys. Rostaing's place in the volume is defined by this tension between virologic caution and the human cost of leaving usable organs unused. He presents hepatitis C management not as a single therapeutic decision but as a chain of linked judgments about evidence, timing, graft safety, survival, and access to transplantation.