Long-term benefit of interferon alpha therapy of chronic hepatitis D: regression of advanced hepatic fibrosis.
OBJECTIVE
Little is known about the long-term effects of interferon alpha on clinical outcome and survival of patients with chronic hepatitis D.


METHODS
Thirty-six patients with chronic hepatitis D who participated in a randomized controlled trial of a 48-week course of high (9 million units) or low (3 million units) doses of interferon alpha or no treatment were followed for an additional 2 to 14 years.


RESULTS
Long-term survival was significantly longer in the high-dose group than in untreated controls (P = 0.003) or in the low-dose group (P = 0.019) but did not differ between patients treated with 3 million units and controls. Among surviving patients at 12 years of follow-up, a biochemical response was present in 7 of 12 treated with 9 million units, in 2 of 4 who received 3 million units, and in none of 3 controls. Long-term alanine aminotransferase (ALT) normalization correlated with improved hepatic function and loss of IgM antibody to hepatitis delta antigen (anti-HD). Patients in the high-dose group had a sustained decrease in HDV replication (P = 0.008), leading to clearance of HDV RNA and, eventually, hepatitis B virus (HBV) in some patients, as well as a dramatic improvement in liver histology with respect to activity grade (P = 0.0004) and fibrosis stage (P = 0.007). Strikingly, we documented an absence of fibrosis in the final biopsy of 4 patients with a long-term biochemical response and an initial diagnosis of active cirrhosis.


CONCLUSIONS
High doses of interferon alpha-2a significantly improved the long-term clinical outcome and survival of patients with chronic hepatitis D, even though the majority had active cirrhosis before the onset of therapy.
Farci
Patrizia
P
Dipartimento di Scienze Mediche, Università di Cagliari, SS 554 Bivio Sestu, 09042 Cagliari, Italy. farcip@pacs.unica.it
Roskams
Tania
T
Chessa
Luchino
L
Peddis
Giovanna
G
Mazzoleni
Anna Paola
AP
Scioscia
Rosetta
R
Serra
Giancarlo
G
Lai
Maria Eliana
ME
Loy
Maurizio
M
Caruso
Luciano
L
Desmet
Valeer
V
Purcell
Robert H
RH
Balestrieri
Angelo
A
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006514:Hepatitis B Surface Antigens / Q000097:blood; D019701:Hepatitis D, Chronic / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D003698:Hepatitis Delta Virus / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D008297:Male; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis; D016019:Survival Analysis; D013997:Time Factors
D000970:Antineoplastic Agents; D006514:Hepatitis B Surface Antigens; D016898:Interferon-alpha; D012367:RNA, Viral; D000410:Alanine Transaminase