Short‐ and long‐term effects of treatment of chronic hepatitis B and delta virus by IFN

Abstract

Chronic hepatitis B virus (HBV) infection is a common infectious disease in the world. Two percent of the patients with chronic HBV infection will develop cirrhosis each year, and will die prematurely from cirrhosis or hepatocellular carcinoma. So far interferon alfa and lamivudine are the only effective drugs. Interferon alfa can be used at the dosage of 9-10 million units thrice a week for 4-6 months either intramuscularly or subcutaneously for standard treatment. Interferon provides sustained response in 1/3 of the patients when HBe Ag is (+). Response rate to interferon therapy in HBe Ag(-) patients was similar to that reported in HBe Ag(+) ones. However the responses were not sustained in many patients, serum HBV-DNA reappear in most after stopping the treatment. Extension of therapy to 1 year may be needed in patients who are unresponsive to therapy and having HBV-DNA levels <10 pg/ml and ALT >100 IU. Establishment of unresponsiveness in early phases of the therapy is important and careful follow up of serum HBe Ag may be helpful. Interferon alfa treatment of chronic HDV infection may result in temporary normalization of ALT values. Disappearance of HBV-DNA and HBs Ag from the serum upon completion of therapy dictates sustained response in chronic HDV infection. The long term effect of interferon with respect to virological and histopathological responses is poor in HDV infection and longer periods of therapy in higher doses may be beneficial.

Effect of adjuvant interferon therapy on hepatitis B virus-related hepatocellular carcinoma: a systematic review

“…On the other hand, some studies found that the efficacy of IFN on inducing hepatitis Be antigen (HBeAg) seroconversion is not so good [ 28 ] and the sustained virologic response rate was only 25 % [ 29 ]. But, the main effects of interferon are antiviral, immune regulation, and antiproliferative agents rather than the integration of HBV gene inhibitors [ 30 ]. Interferon treatment improves liver fibrosis and liver function by reducing active hepatitis [ 31 ], and it can improve overall survival by reducing the severity of the recurrence of the tumor, so it is suitable for secondary therapeutic ablation or resection [ 32 ].…”

A meta-analysis and systematic review: adjuvant interferon therapy for patients with viral hepatitis-related hepatocellular carcinoma

“…Many researchers have found that the efficacy of IFN on inducing Hepatitis Be Antigen (HBeAg) seroconversion is far from satisfactory [25], but we should realize that IFN acted mainly as an antiviral, immunomodulatory and antiproliferative agent and not as an inhibitor of the integration of HBV DNA [26]. IFN therapy improves overall survival through relieving active hepatitis, improving hepatic fibrosis and liver function [27] as well as decreasing the severity of a recurrent tumor and thus be amenable to secondary curative ablation or resection [28].…”

Adjuvant interferon therapy after surgical treatment for hepatitis B/C virus‐related hepatocellular carcinoma: A meta‐analysis

“…Four, most Asian patients with CHB were probably infected by mother‐to‐child transmission, and longer duration of infection may have permitted integration of HBV DNA into the host genome: The mechanism of carcinogenesis involves many factors that are particularly complex in patients with chronic viral hepatitis and cirrhosis. It had been reported that integrated HBV DNA could be detected both in HBsAg carriers and in anti‐hepatitis B core positive patients without HBsAg, however, IFN acts mainly as antiviral, immunomodulatory and antiproliferative agents but not as an inhibitor of integration of HBV DNA . The reasons IFN therapy improves overall survival include: (i) relieving active hepatitis and improving hepatic fibrosis and liver function; (ii) decreasing the severity of a recurrent tumor and thus be amenable to secondary curative ablation or resection; and (iii) survival gain comes in part from a significantly improved recurrence survival in patients treated with IFN (standard IFN treatment for 12 months can induce sustained off‐treatment response in patients with HBeAg positive chronic hepatitis B).…”

“…It had been reported that integrated HBV DNA could be detected both in HBsAg carriers and in anti-hepatitis B core positive patients without HBsAg, 38 however, IFN acts mainly as antiviral, immunomodulatory and antiproliferative agents but not as an inhibitor of integration of HBV DNA. 39 The reasons IFN therapy improves overall survival include: 40,41 (i) relieving active hepatitis and improving hepatic fibrosis and liver function; (ii) decreasing the severity of a recurrent tumor and thus be amenable to secondary curative ablation or resection; and (iii) survival gain comes in part from a significantly improved recurrence survival in patients treated with IFN (standard IFN treatment for 12 months can induce sustained off-treatment response in patients with HBeAg positive chronic hepatitis B). From the above, we can conclude that although IFN does not prevent recurrence in HBV-related HCC patients, it still shows long-term beneficial effects in HBV-related HCC in other ways.…”