Reversibility of Cirrhosis in Patients Cured of Thalassemia by Bone Marrow Transplantation

7 May 2002 | Volume 136 Issue 9 | Pages 667-672

Background: Cirrhosis is a well-known complication of thalassemia major. In this context, it is a consequence of iron overload and hepatitis C virus infection and generally seems to be irreversible.

Objective: To determine whether cirrhosis in thalassemia major can be reversible.

Design: Retrospective study.

Setting: Bone Marrow Transplantation Unit and Pathology Service, Pesaro Hospital, Pesaro, Italy.

Patients: 6 patients who developed liver cirrhosis before or after their thalassemia was cured by bone marrow transplantation (age at transplantation, 11 to 25 years). After diagnosis of cirrhosis, the patients received iron depletion and antiviral therapies.

Measurements: Each liver biopsy specimen was coded. A liver pathologist and a member of the transplantation center with expertise in hepatopathology graded the specimens by using the Ishak staging and grading systems. Neither knew the patient's identity or the sequence of biopsy with regard to the time of treatment.

Results: After the patients received iron depletion and antiviral therapies, liver biopsy specimens showed impressive reduction in liver iron stores. In 4 patients, iron removal was complete. Serum aminotransferase levels decreased in all patients and normalized in 5; histologic inflammatory activity decreased in all patients and disappeared in 2. Follow-up biopsies showed regression of incomplete or definite cirrhosis in all patients; 3 patients had presented with portal fibrosis without bridging, and the others had portal fibrosis and portal-to-portal bridging. Several biopsies and the presence of many portal spaces confirmed the diagnosis of cirrhosis; follow-up biopsies confirmed regression of cirrhosis.

Conclusion: In some patients in whom bone marrow transplantation has cured thalassemia, cirrhosis may be reversible after iron removal treatment.

Editors' Notes Context Thalassemia is usually accompanied by conditions that cause cirrhosis, such as iron overload and hepatitis C virus (HCV) infection. Allogeneic bone marrow transplantation can cure thalassemia, and iron removal and treatment of HCV infection after transplantation may eliminate stimuli for fibrosis. Whether cirrhosis can recede after treatment is unknown. Contribution Six selected patients with thalassemia cured by bone marrow transplantation had liver biopsies before and after treatment. Biopsy specimens were evaluated by pathologists blinded to patient identification and sequence of biopsy. Cirrhosis improved substantially in all patients. Implications Cirrhosis (and possibly fibrosis in other organs) may be reversible if underlying profibrotic conditions are eliminated. –The Editors

 

Author and Article Information

From Unità Operativa di Anatomia Patologica and Unità Operativa di Ematologia e Centro Trapianto Midollo Osseo, Azienda Ospedaliera San Salvatore di Pesaro, Italy.

Acknowledgment: The authors thank Professor Stanley L. Schrier for suggestions and for editing of the manuscript.

Requests for Single Reprints: Pietro Muretto, MD, Servizio di Anatomia Patologica, Azienda Ospedaliera San Salvatore di Pesaro, 61100 Pesaro, Italy; e-mail, p.muretto{at}ospedalesansalvatore.it.

Current Author Addresses: Dr. Muretto: Servizio di Anatomia Patologica, Azienda Ospedale San Salvatore di Pesaro, 6110 Pesaro, Italy.

Dr. Angelucci: Unità Operativa di Ematologia e Centro Trapianti Midollo Osseo, Ospedale A Businco, via Edward Jenner, 09121 Cagliari, Italy.

Dr. Lucarelli: Unità Operativa di Ematologia, Azienda Ospedale San Salvatore di Pesaro, 61100 Pesaro, Italy.

Author Contributions: Conception and design: P. Muretto, E. Angelucci.

Analysis and interpretation of the data: P. Muretto, E. Angelucci, G. Lucarelli.

Drafting of the article: P. Muretto, E. Angelucci.

Critical revision of the article for important intellectual content: P. Muretto, E. Angelucci, G. Lucarelli.

Final approval of the article: P. Muretto, E. Angelucci, G. Lucarelli.

Provision of study materials or patients: P. Muretto, E. Angelucci.

Statistical expertise: E. Angelucci.

Obtaining of funding: G. Lucarelli.

Collection and assembly of data: E. Angelucci.