The French experience of treatment of chronic type D hepatitis with a 12‐month course of interferon alpha‐2B. Results of a randomized controlled trial

Abstract

Hepatitis due to hepatitis delta virus (HDV) infection is generally associated with severe histological abnormalities and rapid progression of the disease. To assess the efficacy of recombinant interferon‐a2b in treatment of chronic delta hepatitis, 22 patients were entered into a randomized controlled trial: 11 received interferon‐a2b subcutaneously three times weekly for 12 months (5 MU/m2 for 4 months and then 3 MU/ m2 for a further 8 months) and 11 were untreated. All patients were followed up for 6 months after the completion of therapy. Nine treated patients completed the trial: one was withdrawn with hyperthyroidism and one committed suicide. Serum ALT levels were normalized or significantly reduced, always within 3 months of initiating treatment, and remained so in 73% of treated patients at the 4th month and in 54.5% at the 12th month, compared with 18% and 18%, respectively, in the untreated group. Moreover, in seven of nine treated patients, interferon was associated with the clearance of serum HDV‐RNA, associated with amelioration of the histological picture, whereas this occurred in only four of 11 untreated patients. On cessation of therapy, all patients but one experienced a biological and/ or virological relapse over the 6‐month follow up. In conclusion, our data confirm that HDV is sensitive to inhibition by interferon‐a2b, although the schedule used did not achieve permanent control of the disease. The adverse effects of interferon require consideration; in particular, care will be needed to avoid serious psychiatric side effects.

Delta Hepatitis

“…This response rate is lower than the study by Castelnaue et al, probably due to the high prevalence of cirrhosis (28/38, 73%) in this study [61]. Several nucleos(t)ide analogs effectively used for HBV infection were found ineffective in the treatment of HDV infection [3,65,70]. Lamivudine and famciclovir had no significant antiviral activity against HDV infection [70][71][72].…”

“…If fulminant hepatitis occurs during the acute hepatitis D, liver transplantation is the only treatment option [3,5,6,63]. At present, interferon is the only option for the treatment of chronic hepatitis D. Since most patients have advanced disease and cirrhosis, the response rate to interferon (IFN) therapy is not high (less than 10% with 1-year IFN therapy [63][64][65]). Therapeutic efficacy increases when higher dose of interferon alpha is administered for prolonged periods (12-24 months) [63][64][65][66].…”

“…At present, interferon is the only option for the treatment of chronic hepatitis D. Since most patients have advanced disease and cirrhosis, the response rate to interferon (IFN) therapy is not high (less than 10% with 1-year IFN therapy [63][64][65]). Therapeutic efficacy increases when higher dose of interferon alpha is administered for prolonged periods (12-24 months) [63][64][65][66]. As described in an interesting case report a 12-year high-dose IFN treatment resulted in the complete resolution of HDV infection with remission of liver fibrosis and disappearance of HBV and HDV from serum [67].…”

Elevated cytokine expression in the orbitofrontal cortex of victims of suicide

“…The most common consequence of administering cytokines is the triggering of symptoms of depression (1)(2)(3)(4). In addition, other serious mental complications are the occurrence of suicidal ideation, suicidal attempts, and completion (5)(6)(7)(8). Case reports worldwide have documented death by suicide in patients receiving cytokines as immune boosting therapy to treat a variety of diseases including melanoma, hepatitis C, HIV infections, and multiple sclerosis (5)(6)(7)(8)(9).…”

“…In addition, other serious mental complications are the occurrence of suicidal ideation, suicidal attempts, and completion (5)(6)(7)(8). Case reports worldwide have documented death by suicide in patients receiving cytokines as immune boosting therapy to treat a variety of diseases including melanoma, hepatitis C, HIV infections, and multiple sclerosis (5)(6)(7)(8)(9). While there is a growing recognition of the participation of cytokines in the etiology of mood disorders, their role as pro-suicidal factors has been less studied (10,11).…”