Pegylated Interferon Alfa 2a Treatment in Patients with Chronic Hepatitis B and Genotype D in Jordan

Research Article

J Hepat Res. 2014;1(2): 1009.

Pegylated Interferon Alfa 2a Treatment in Patients with Chronic Hepatitis B and Genotype D in Jordan

Hamoudi Waseem1*, Mirela Maria H, Al-Azizi Moath, Al Sheikh Mahmoud, Shabaan Hamdi, Laswi Eyad RN and Al Hamed Ahmad RN

Internal Medicine department, Al Bashir Hospital, Jordan

*Corresponding author: Hamoudi Waseem, Internal Medicine department, Gastroenterology & Hepatology unit - Al Bashir Hospital, Amman - Jordan

Received: August 01, 2014; Accepted: August 20, 2014; Published: August 21, 2014


Background & Aims: To evaluate the efficacy of immune-modulation therapy using pegylated interferon Alfa 2a in the treatment of patients infected with HBV.

Patients, Methods: 103 patients diagnosed with chronic hepatitis B at the Gastroenterology & Hepatology unit in Al Bashir Hospital Amman-Jordan between the years 2006 and 2013 were treated with pegylated interferon Alfa 2a 180 mcg once weekly for 48 weeks, 54.3% (56/103) were of male gender and 45.6% (47/103) were female.45 (43.6%) patients were HBeAg negative, 58 (56.3%) were HBeAg positive.

ALT, HBV DNA levels, HBeAg seroconversion, HBsAg seroconversion were investigated at 12, 24, 36, 48 and 72 weeks. Non responders were defined failure to decrease in the viral load at least 2 logs at 24 weeks of treatment, responders were defined as HBV DNA load less than 2000 IU/ml at week 48, sustained responders were defined as patients who sustained their viral load less than 2000 after 72 weeks of treatment. HBeAg seroconversion was defined as disappearance of HBeAg and seroconvertion to HBeAb. HBsAg clearance was defined as disappearance of HBsAg. HBsAg seroconversion was considered as disappearance of HBsAg and seroconversion to HBsAb. Relapsers were those responders that had HBV DNA increase more than 2000 IU/ml and ALT flair after end of treatment.

All patients were of genotype D.

Results: 5.8% of treated patients were sustained responders (6/103), of them 33.3% (2/6) were HBeAg negative patients and 66.6% (4/6) were HBeAg positive patients.

Non-responders counted 68.9% (71/103), of them 53.3% (24/45) were HBeAg negative patients and 46.6% (21/45) were HBeAg positive patients. Relapsers were 25.2% (26/103) (16 HBeAg negative patients and 10 HBeAg positive patients). One patient seroconverted HBsAg to HBsAb (0.9%), and two patients obtained HBsAg clearance (1.9%).

Conclusion: Pegylated interferon therapy for patients with chronic hepatitis B in Jordan showed that the response to this treatment is unsatisfactory, mostly due to high prevalence of genotype D in Jordan.

Longer duration of treatment or sequential therapy may be of help in order to obtain more positive results. More studies regarding treatment with immune modulation therapy are warranted to obtain more representative data.

Keywords: Chronic Hepatitis B; Pegylated Interferon; Genotype D; Sustained responders; Jordan


Chronic hepatitis B is prevalent in the world, with estimated chronic carriers of more than 350 millions worldwide [1]. Currently, pegylatedinterferon alfa 2a or oral nucleos(t)ides are approved for the treatment of chronic hepatitis B with the aim of HBV DNA negatitivity, HbeAg seroconversion, normalization of ALT and ultimatly HbsAg clearnce and seroconversion [2,3].

Pegylated interferon-alfa 2a (PEG-IFN) provides potential advantages over nucleos(t)ides analogues in the treatment of Chronic Hepatitis B (CHB) given its finite course, durability and lack of drug resistance [2,3].

Best predictors of good response for treatment with interferon / Pegylated interferon based treatment are HBeAg positive patients, low viral load, high serum ALT levels, HBV genotype A , B and high activity in liver biopsy [2,3].

The predominant HBV genotype in Middle Eastern countries including Jordan is genotype D [4,5]. Also Jordan has high prevalence of HBsAg negative individuals, which may raise questions regarding efficacy of treatment with immune modulators for patients with Chronic Hepatitis B.

Jordan has high prevalence of HBV infected people reaching in the med eighties of the last century around 10% (carriers and diseased) [6,7,8], it is estimated now that this prevalence has dropped to 3% due to introduction of vaccination in the med nighties and other measurement to control this disease [9,10]. In order to clarify the issue of efficacy of treating chronic hepatitis B patients with Pegylated Interferon Alfa 2a and its cost effectiveness, we concluded this study over a period of 8 years in order to investigate the efficacy and tolerability of Pegylated Interferon Alfa 2a in chronic hepatitis patients in a clinical setting.

Methods & Material

This study included all eligible chronic hepatitis B patients for treatment who choose treatment with Pegylated interferon therapy and addressed Al Bashir Teaching Hospital - Gastroenterology & Hepatology unit between the years 2006 and 2013; they were offered to choose between nucleotide / nucleoside analogues or treatment with Pegylated Interferon Alfa 2a 180 mcg weekly for 48 weeks after explaining advantages and disadvantages of both regimens.

Al Bashir Teaching Hospital is the biggest tertiary hospital in Jordan that serves more than 40% of Jordanians. This study included all patients who accepted treatment with pegylated interferon 180 mcg. Demographic data, HBV markers including HBeAg, HBV DNA by PCR, ALT levels, synthetic function of the liver and imagistic studies were recorded prior to treatment. HBV genotyping was done for all studied patients.

Follow up tests with HBV DNA by PCR, HBsAg, HBsAb ,HBeAg, HBeAb status and ALT levels were recorded at 12, 24, 48 weeks of treatment and 6 months after ending treatment. Complete blood count was investigated weekly for every patient for the first two months then monthly. Side effects were recorded for every patient also. Cirrhotic patients were not included in this study.

Patients who responded favorably to treatment at 6 months or less (decrease in HBV DNA with at least 2 logs and/or seroconverted HBeAg to HBeAb and normalization of ALT) continued treatment for another 24 months (total treatment regimen of 48 weeks) and were considered responders. Patients who did not achieve the treatment endpoints at 6 months were considered non-responders while patients who did respond to treatment regimen and relapsed after stopping the treatment were considered relapses.

The ultimate goal of the treatment was HBsAg clearance and seroconversion to HBsAb.

Other goals of treatment were sustained HBeAg seroconversion to HBeAb in HBeAg positive patients, decrease /undetectably of HBV DNA and normalization of ALT.

Treated patients (responders, non-responders and relapsers) after completion of treatment regimen were tested yearly for liver function tests and HBV status.

Non-responders and relapses were offered alternative therapy using nucleoside/nucleotide analogues.

One hundred and three patients were included in this study; 56 (54.3%) were of male gender and 47 (35.6%) were female.

Fifty eight patients (56.3%) were HBeAg positive and 45 patients (43.6%) were HBeAg negative. Patient's age ranged between 18 and 60 years with median range of 42.1 years (SD=11) (Table 1).