Effect of iron overload on the response to recombinant interferon-alfa treatment in transfusion-dependent patients with thalassemia major and chronic hepatitis C

Clemente, Maria Grazia; Congia, Mauro; Lai, Maria Eliana; Lilliu, F.; Lampis, Rosanna; Frau, Franco; Frau, Maddalena; Faa, Gavino; Diana, Giuseppe; Dessì, Carlo; Melis, Andrea; Mazzoleni, Anna Paola; Cornacchia, Giovanna; A, Cao; Virgiliis, Stefano De

doi:10.1016/s0022-3476(94)70138-5

Cited by 117 publications

(49 citation statements)

References 19 publications

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“…Some clinical studies 34, [78][79][80][81][82][83][84] showed that ␣-interferon monotherapy administered for 6 to 15 months induces a sustained biochemical response and SVR in 40% to 50% of thalassemia patients with HCV-related chronic hepatitis. The absence of cirrhosis, low iron hepatic concentration, and infection by HCV genotype other than 1b are the main clinical and virologic findings that predict a good response to therapy.…”

Section: Recommendations For Virologic and Clinical Evaluation Of Thamentioning

confidence: 99%

Management of chronic viral hepatitis in patients with thalassemia: recommendations from an international panel

Marco

Capra²,

Angelucci³

et al. 2010

Blood

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IntroductionIn the last 4 decades, regular blood transfusions and chelation therapy have improved the survival of patients with thalassemia major. 1-3 Despite the progress on chelation therapy, cardiac complications remain the main cause of death among transfusiondependent thalassemia patients related to the susceptibility of cardiac cells to iron overload toxicity. 4,5 The interest in the clinical management of chronic liver diseases has been increasing, however, because of the high prevalence of viral infections in adult transfusion-dependent thalassemia patients and the central role of the liver in regulating the iron metabolism. 5,6 The assessment of heart and liver iron overload is required to tailor iron chelation therapy. Furthermore, the diagnosis of hepatitis B virus (HBV)-or hepatitis C virus (HCV)-related chronic hepatitis is required to identify patients who have a high risk of developing liver complications and who may obtain a benefit by antiviral therapy.The goals of this paper are to summarize the epidemiology and the risks of transmission of viral infections, to analyze invasive and noninvasive methods for the diagnosis of chronic liver disease, to report the knowledge on clinical course of chronic viral hepatitis, and to suggest the management of antiviral therapy. For personal use only. on May 12, 2018. by guest www.bloodjournal.org From An expert hepatologist prepared an initial draft based on systematic review of published literature by Medline search on viral hepatitis in thalassemia patients, examined recently published guidelines on the diagnosis, management, and treatment of chronic hepatitis B and chronic hepatitis C edited by the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Asian-Pacific Association for the Study of the Liver 7-10 and the Consensus Development Conference sponsored by the National Institutes of Health. 11 Recommendations of the panel of experts were based insofar as possible on evidence from publications that reported data on thalassemia patients. If evidence from thalassemia patients was unavailable, the panel selected recommendations from published guidelines that were suitable for thalassemia patients. Recommendations were evaluated according to the Grading of Recommendations Assessment Development and Evaluation system and classified into 3 levels: high, moderate, or low 12 (Table 1). For each recommendation, the level of evidence (high, moderate, or low) and population studied (general population of patients with viral chronic hepatitis or thalassemia patients) was specified. The panel of experts discussed the draft issue by issue, and 3 experts on blood transfusion, iron metabolism, and viral hepatitis management reviewed the recommendations. Finally, 8 international external experts in pediatrics, hematology, and viral hepatitis reviewed and criticized the recommendations. Methods Results What proportion of thalassemia patients have chronic viral infections?Worldwide, from 0.3% to 5.7% of thala...

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Section: Recommendations For Virologic and Clinical Evaluation Of Thamentioning

confidence: 99%

Management of chronic viral hepatitis in patients with thalassemia: recommendations from an international panel

Marco

Capra²,

Angelucci³

et al. 2010

Blood

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“…Other small studies from Europe have shown that rates of response in patients with thalassemia are similar to those of non-thalassemic persons. [37][38][39][40] Combination therapy using interferon and ribavirin has been evaluated in limited studies. An important problem with the use of combination therapy in thalassemic patients is that ribavirin induces a dose-dependent hemolysis and can cause severe anemia in patients with pre-existing hemolytic conditions.…”

Section: Treatment Of Hepatitis C In Understudied Populationsmentioning

confidence: 99%

Understudied populations with hepatitis C

Strader

2002

Hepatology

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Managing patients with hepatitis C virus (HCV) infection consists primarily of antiviral treatment, currently with peginterferon and ribavirin. Unfortunately, treatment recommendations derive largely from trials that have focused on highly selected patient populations. As a consequence of the strict inclusion and exclusion criteria in these studies, more than half of all HCV-infected patients would be ineligible for enrollment. Even among the selected patients enrolled into studies, only 50% achieve a sustained virological response (SVR).Patients not eligible for current therapies include those with mild disease and normal alanine aminotransferase (ALT) levels, patients with advanced and decompensated liver disease, children, the elderly, patients with ongoing or recent alcohol and substance abuse, renal disease, human immunodeficiency virus ( H epatitis C is an important cause of acute and chronic liver disease worldwide and the most common indication for liver transplantation in adults in the United States. Since the discovery of the hepatitis C virus (HCV) in 1989 and its linkage to non-A, non-B hepatitis, there have been major advances in knowledge of the incidence and prevalence of this infection, its clinical manifestations, natural history, molecular virology, histopathology, and treatment. At present, the management of patients with hepatitis C focuses largely on combination antiviral treatment using a 24-or 48-week course of peginterferon and ribavirin. Two large trials evaluating the safety and efficacy of this combination therapy have demonstrated sustained virological responses (SVR) in slightly more than 50% of patients. 1,2 It is important to stress, however, that response rates of 50% in randomized, controlled trials of therapy do not guarantee that 50% of all patients with chronic hepatitis C can be or will be successfully treated. Patients enrolled in the registration trials of combination therapy were highly selected and not fully representative of the broader population of patients with chronic HCV infection. The strict inclusion and exclusion criteria used in registration trials often exclude populations that have high rates of hepatitis C. Furthermore, chronic hepatitis C is common in populations that are not reached by clinical trials of new and investigational therapies. Because patients enrolled in registration trials of new antiviral treatments are a selected group, the applicability of results of these trials to the general population is problematic.

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“…[6][7][8][9][10][11][12] We set out to study whether iron reduction before interferon retreatment would enhance the rate of response to treatment.…”

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confidence: 99%

Iron reduction as an adjuvant to interferon therapy in patients with chronic hepatitis C who have previously not responded to interferon: A multicenter, prospective, randomized, controlled trial

et al. 2000

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Hepatic iron concentration has consistently been observed as being directly correlated with the response to interferon therapy in chronic hepatitis C virus (HCV). We therefore conducted a randomized, controlled trial comparing iron reduction by phlebotomy with iron reduction followed by retreatment with interferon in 96 patients with chronic hepatitis C who had previously not responded to a course of interferon. During the initial phase when all patients were undergoing phlebotomy, we found that serum alanine transaminase (ALT) activities decreased but by less than 50% from baseline in 67 patients (89%), decreased by more than 50% in 12 patients (13%) and became normal in 9 patients (9%) with no overall change in HCV-RNA levels. Subsequently no patient in either treatment group achieved a sustained virologic response. Improvements in necroinflammatory changes were noted in liver biopsy specimens in those patients receiving phlebotomy plus interferon (mean index 8.59 vs. 7.37, P F .05). A slight but not statistically significant decrease in histologic activity index was noted in those subjects treated by phlebotomy alone (mean index 8.4 vs. 7.75, P not significant). We conclude that, although prior phlebotomy therapy does not improve the rate of sustained response to interferon retreatment, it does result in less liver injury manifested by a decrease in serum transaminase activity and a slight improvement in liver histopathology. (HEPATOLOGY 2000;32:135-138.)

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Effect of iron overload on the response to recombinant interferon-alfa treatment in transfusion-dependent patients with thalassemia major and chronic hepatitis C

Cited by 117 publications

References 19 publications

Management of chronic viral hepatitis in patients with thalassemia: recommendations from an international panel

Management of chronic viral hepatitis in patients with thalassemia: recommendations from an international panel

Understudied populations with hepatitis C

Iron reduction as an adjuvant to interferon therapy in patients with chronic hepatitis C who have previously not responded to interferon: A multicenter, prospective, randomized, controlled trial

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