Generalized eczematoid eruption induced by PEGylated interferon-alpha 2a therapy for chronic hepatitis B

( Yeason Lee ),( Dongjin Kim ),( Chanho Na ),( Minsung Kim ),( Bongseok Shin ) 대한피부과학회 2016 대한피부과학회 학술발표대회집 Vol.68 No.1

Interferon (IFN)-a, an immune-modulating agent, has several therapeutic indications, including in the treatment of hepatitis B and C. Cutaneous side effects have been reported and include vasculitis, necrosis, ulceration and alopecia. New onset or exacerbation of lichenoid drug eruption is a rare complication after administration of PEGylated interferon-alpha. Herein, we present a case of lichenoid drug eruption during PEGylated interferon-alpha 2a therapy for chronic hepatitis B. Our patient was a 29-year-old woman with chronic hepatitis B. She was anti HAV(+), HBeAg(+), HBV DNA 28341231 IU/ml. She was started on PEGylated interferon-alpha 2a 180 mcg/week subcutaneous injection with non specific skin lesion. After 36th weeks of treatment, she presented focal alopecia and pruritic erythema on abdomen. After 38th weeks of treatment, generalized pruritic fine scaly erythematous maculoplaques appeared on whole body and she was consulted to our department. These lesions were compatible with lichenoid eruptions. Owing to the intolerable adverse effects and significant worsening of lechenoid eruptions, pegylated IFN-α 2a injection was discontinued. Oral corticosteroid and antihistamine treatment plus daily phototherapy were started. Lichenoid lesions had partially regressed after two weeks of treatment and completely resolved with slight hyperpigmentation.

Efficacy and Tolerability of Pegylated Interferon-α_2a plus Ribavirin versus Pegylated Interferon-α_2b plus Ribavirin in Treatment-Naive Chronic Hepatitis C Patients

Lee, Seok,Kim, In Hee,Kim, Seong Hun,Kim, Sang Wook,Lee, Seung Ok,Lee, Soo Teik,Kim, Dae Ghon,Lee, Chang Seop,Choi, Chang Soo,Cho, Eun Young,Kim, Haak Cheoul S. Karger AG 2010 Intervirology Vol.53 No.3

<P><I>Objectives:</I> The authors compared the efficacies and tolerabilities of pegylated interferon-α<SUB>2a</SUB> (PEG-IFN-α<SUB>2a</SUB>) + ribavirin and pegylated interferon-α<SUB>2b</SUB> (PEG-IFN-α<SUB>2b</SUB>) + ribavirin for the initial treatment of chronic hepatitis C. <I>Methods:</I> A total of 126 treatment-naive patients (29.4% genotype 1, 70.6% genotype non-1) were treated with PEG-IFN-α<SUB>2a</SUB> 180 μg/week (group A, n = 79) or PEG-IFN-α<SUB>2b</SUB> 1.5 μg/kg/week (group B, n = 47) with ribavirin (800 mg/day for genotype non-1 or 1,000-1,200 mg/day for genotype 1) for 24 (genotype non-1) or 48 weeks (genotype 1). <I>Results:</I> End-of-treatment virologic response, sustained virologic response, and biochemical response were not significantly different in groups A and B (84.8 vs. 89.4%, 70.9 vs. 72.3%, and 70.9 vs. 74.5%, respectively; p > 0.05). In patients with the HCV genotype 1 or non-1, treatment responses were not significantly different. Multivariate analysis showed that HCV genotype only was an independent factor that affected sustained virologic response (p = 0.048). The proportions of treatment discontinuations in groups A and B were similar (10.1 vs. 10.6%; p = 1.000). <I>Conclusions:</I> PEG-IFN-α<SUB>2a</SUB> or PEG-IFN-α<SUB>2b</SUB> + ribavirin combination therapies showed similar efficacies and tolerabilities as initial treatments for chronic hepatitis C.</P><P>Copyright © 2010 S. Karger AG, Basel</P>

Case Report : Acute pancreatitis associated with pegylated interferon-alpha-2a therapy in chronic hepatitis C

( Jong Wook Choi ),( June Sung Lee ),( Woo Hyun Paik ),( Tae Jun Song ),( Jung Wook Kim ),( Won Ki Bae ),( Kyung-ah Kim ),( Jung Gon Kim ) 대한간학회 2016 Clinical and Molecular Hepatology(대한간학회지) Vol.22 No.1

Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea. (Clin Mol Hepatol 2016;22:168-171)

Generalized flare of pustular psoriasis induced by pegylated interferon alfa-2b therapy for chronic hepatitis C

( Joo Hee Lee ),( Hyuk Sun Kwon ),( Ji Hae Lee ),( Jung Min Bae ),( Gyong Moon Kim ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.1

Pegylated interferon (IFN)-α2b is a form of recombinant human IFN with immune-modulating functions. The use of IFN-α2b and ribavirin is considered standard therapy for chronic hepatitis C. New onset or exacerbation of psoriasis vulgaris has been reported in a small number after IFN-α2b therapy. Herein, we report a case of flare of pustular psoriasis induced by IFN-α2b in a 43-year-old woman with pustular psoriasis and chronichepatitis C. A 43-year-old woman with chronic hepatitis C and pustular psoriasis presented with a generalized flare of her pustular psoriasis. She had been suffered from pustular psoriasis for 18 years and worsen abruptly after 4 weeks of IFN-α2b treatment.Examination revealed extensive coalescing erythematous, edematous plaques studded with numerous pinhead-sized pustules over the anterior trunk, bilateral arms, buttocks and bilateral inner thighs. Previously, the patient had several episodes of generalized flares, mostly in association with infections and/or the administration of antibiotics. Before IFN-α2b therapy, the patient’s psoriasis had been under control with oral cyclosporine 100 mg/day and topical steroids for sporadic pustular lesions. Interferon- α therapy was discontinued and the rash resolved after treatment with cyclosporine and systemic methylprednisolone. The potential side effect of IFN-α2b should be kept in mind when treating patients with a history of psoriasis or pustular psoriasis.

ORiginal Article : Association of IL28B Genotypes and Baseline Serum Interferon-γ-Inducible-Protein-10 Levels with Treatment Response in Hepatitis C Virus Patients in China

( Renwen Zhang ),( Cuiping Shao ),( Na Huo ),( Minran Li ),( Xiaoyuan Xu ) 대한간학회 2016 Gut and Liver Vol.10 No.3

Background/Aims: Several studies have demonstrated that serum interferon-γ-inducible-protein-10 (IP-10) levels at baseline and single nucleotide polymorphisms (SNPs) near the IL28B gene were associated with viral response and treatment outcomes. Our purpose was to assess the combination of pretreatment IP-10 levels with IL28B SNPs as predictors of treatment response to pegylated interferon α-2a plus ribavirin in patients infected with genotype 1 hepatitis C virus in China. Methods: Seventy-two patients with chronic hepatitis C without fibrosis/cirrhosis were enrolled in the study. The virologic parameters and baseline serum IP-10 levels were determined. IL-28B genotypes were determined by sequencing. Results: In this cohort, serum baseline IP-10 levels lower than 426.7 pg/mL could predict rapid virological response/ sustained virological response (SVR). Patients carrying favorable IL28B SNP genotypes had higher SVRs than did those carrying unfavorable variants (IL28B rs12979860, p=0.002; IL28B rs8099917, p=0.020). Combining both baseline IP- 10 and IL28B SNPs could improve the prediction of SVR in favorable allele carriers of IL28B, rs12979860 CC and rs8099917 TT. Serum baseline IP-10 levels and IL28B genotypes were independent predictors of SVR. Conclusions: Our study shows that the combination of baseline serum IP-10 levels and the determination of IL28B SNPs increase the predictability of SVR rates in this cohort. (Gut Liver 2016;10:446-455)

Application of Stopping Rule of Pegylated Interferon-Alpha 2a Therapy to Korean Patients with Chronic Hepatitis B

( Tae Seop Lim ),( Young Seok Kim ),( Tae-hun Kim ),( Sang Goon Shim ),( Eun Young Cho ),( Tae Hee Lee ),( Seung Ha Park ),( Yeon Seok Seo ),( Ki Tae Yoon ),( Hyung Joon Kim ),( Byung Seok Lee ),( Yan 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: In pegylated interferon-alpha 2a (PEG-IFN) of chronic hepatitis B (CHB), the decline of hepatitis B surface antigen (HBsAg) titers after 12-week therapy has been considered as a potent predictor that can determine discontinuation of therapy. In this study, we evaluated treatment response in Korean patients with CHB after 12-week PEG-IFN therapy. Methods: 100 patients with CHB were prospectively analyzed from April 2015 to September 2016 in multi-centers. After 12-week use of PEG-IFN, we evaluated the changes of HBsAg, heapatitis B virus (HBV) DNA, and other liver-related markers in patients with CHB. Results: Of 100 patients with CHB, heapatitis B e antigen (HBeAg)- positive patients were 75, and HBeAg-negative patients were 25. After 12-week PEG-IFN therapy, the number of HBeAg-positive patients with HBsAg less than 20,000 IU/mL was 61 (82.43%), and the number of HBeAg-negative patents with declined HBsAg titers or decreased HBV DNA levels more than 2 log IU/mL was 19 (76.00%). In HBeAg-positive patients, the decline of HBV DNA and HBsAg levels after 12 weeks was 1.83 ± 2.05 log10 IU/mL (p < 0.0001) and 6452.33 ± 11266.74 IU/mL (p <0.0001), respectively. In HBeAg-negative patients, the decrease of HBV DNA and HBsAg levels after 12 weeks was 2.55 ± 2.11 log10 IU/mL (p < 0.0001) and 1940.71 ± 5071.62 IU/mL (p < 0.0001), respectively. The number of patients with HBsAg titers less than 1,500 IU/mL after 12 weeks was 14 (18.92%) in HBeAg-positive patients and 17 (68.00%) in HBeAg-negative patients, respectively. Conclusions: As applying 12-week stopping rule, early anti-viral response rate of PEG-IFN was confirmed in Korean patients with CHB, and we could apply this results to determine patients who will continue long-term PEG-IFN therapy in the early period of treatment.

FCT 7 : Treatment of Kaposi Sarcoma with intralesional injection of Pegylated Interferon-alpha

( Young In Jeong ),( Joon Won Huh ),( Geon Kim ),( Hyun Chul Shim ),( Eun Jung Kim ),( Hyang Joon Park ),( Mihn Sook Jue ) 대한피부과학회 2013 대한피부과학회 학술발표대회집 Vol.65 No.2

Background: Kaposi sarcoma (KS) is a rare lymphoangioproliferative disease often caused by human herpesvirus 8 (HHV-8). There are 4 known variants of KS: AIDS-associated KS, African KS, iatrogenic posttransplantation KS, and classic KS (CKS). CKS is usually chronic, persisting over many years, but not life threatening. Because the natural history of KS is variable, the therapeutic options for CKS vary and the assessment of therapeutic results may be difficult. Objectives: To evaluate the efficacy of intralesional injection of Pegylated(Peg) Interferon(INF)-α, which is a long-lasting form of INF, on the KS. Methods: The study included 3 patients with CKS who showed no history of immunosuppression and HIV infections, and no metastasis detected by PET-CT scanning from Jan 2012 to June 2012. We treated them with intralesional Peg INF-α 2a injections of 180mcg/0.5ml once a week for 4 months. Results: In all of 3 cases, the size and induration of the lesions much reduced and the colors faded away. Histological examination of the resolving lesions revealed no evidence of KS with negative HHV-8. There were no serious complications. Conclusion: Intralesional injection of Peg INF-α is effective for the treatment of CKS.

Changes of HBsAg Quantity and its Relation with HBeAg Seroconversion Following 48 Weeks Pegylated-interferon-alpha Treatment in Patients with HBeAg Positive Chronic Hepatitis B after Long Term Nucleos(t)ide Analogue Maintenance Therapy; Roll Over Trial

( Hyun Young Woo ),( Jeong Heo ),( Young Joo Park ),( Yu Rim Lee ),( Soo Young Park ),( Jung Gil Park ),( Woo Jin Chung ),( Won Young Tak ),( Young Oh Kweon ),( Heon Ju Lee ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Durable post-treatment response is uncommon in patients with chronic hepatitis B (CHB) on nucleos(t)ide analogue (NA) therapy. The aim of this study is to investigate pegylated interferon (PegIFN) after long term NA therapy might enhance the antiviral efficacy leading to HBeAg seroconversion and eventually HBsAg loss and/or seroconversion. Methods: The patient with HBeAg-positive CHB who had been treated with any NA except telbivudine at least 72 weeks, who have an undetectable HBV DNA (<400 copies/mL) at least 48 weeks, were randomised 1:1 to receive PegIFN alfa-2a 180 ug/week or previous NA for 48 weeks. The primary endpoint was change in log₁₀ HBsAg titer during antiviral therapy (Clinical-Trials.gov: NCT01769833). Post treatment HBsAg titer analysis was performed at every 12 weeks until 96 weeks after end of 48 weeks of PegIFN alfa-2a or NA therapy. Results: Total 150 patients were randomized; 75 received PegIFN alfa-2a. On treatment HBsAg decline from 24 to 48 weeks and was significantly higher in patients who switched to PegIFN alfa-2a than those who continued NA and maximal difference of HBsAg titer was shown at 36 weeks (mean±SD, 0.378±0.572 vs. 0.013±0.241; P< 0.001). However, during follow-up period, this difference in HBsAg titer was disappeared and HBsAg titer became similar between two groups (HBsAg titer at 144 weeks: mean±SD, 0.221±0.526 vs. 0.196±0.163; P=0.243). HBeAg seroconversion was significantly higher in patients receiving PegIFN alfa-2a during [21.2% (14/66) vs 9.7% (5/69) at 48 weeks; P=0.026] and after treatment [28.4% (19/67) vs 8.5% (5/59) at 144 weeks; P=0.006]. HBsAg loss was observed in one patient receiving PegIFN alfa-2a during follow-up period. On-treatment HBV DNA elevation rate ( > 2000 IU/mL) was significantly higher in patients who switched to PegIFN alfa-2a than those who continued NA and its difference was maximal at 48 weeks [35.8% (24/67) vs. 0% (0/65); P<0.001)]. Antiviral treatment was restarted for patients with PegIFN alfa-2a when HBV DNA was elevated with or without ALT flare [92.3% (60/65) at 72 weeks and 95.4% (62/65) at 96 weeks]. Only treatment with PegIFN alfa-2a was significantly associated with HBeAg seroconversion at 48 weeks (P=0.026). PegIFN alfa-2a was well-tolerated. Conclusions: This final analysis showed that, for patients who achieve virological suppression with oral NA, switching to a 48 weeks PegIFN alfa-2a treatment significantly decrease HBsAg titer and increases rates of HBeAg seroconversion. However, HBV DNA elevation was developed frequently during treatment and decrease in HBsAg titer was not maintained during post-treatment follow-up.

HBV : O-001 ; An observational, multicenter, cohort study evaluating the antiviral efficacy, safety, and tolerability in Korean patients with chronic hepatitis B (CHB) receiving pegylated Interferon-alpha 2a (Pegasys®): TRACES STUDY

( Young Eun Chon ),( Dong Joon Kim ),( Sang Gyune Kim ),( In Hee Kim ),( Si Hyun Bae ),( Seong Gyu Hwang ),( Jeong Heo ),( Jeong Won Jang ),( Byung Seok Lee ),( Hyung Joon Kim ),( Dae Won Jun ),( Gang 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.-

Background: Until today, there is currently no data available on the efficacy, safety, and tolerability of pegylated interferon alfa 2a (PEG-IFNa-2a) in Korean patients with chronic hepatitis B (CHB), who are known to have mostly HBV genotype C. Methods: We collected data from 18 institutes of 451 Korean patients with CHB who were treated with PEG-IFNa-2a as a first line therapy (370 patients with HBeAg positive and 81 with HBeAg negative). Treatment responses at the end of treatment (ET) and at 6 months post-treatment (PT6) were compared between patients treated for 24 weeks vs. 48 weeks, and adverse events were evaluated. Results: In HBeAg-positive patients, the patients who had received PEG-IFNa-2a for 48 weeks than 24 weeks achieved significantly higher virological response (HBV DNA < 2,000 IU/mL) (48 vs. 24 weeks at ET, 44.4% vs. 27.2%, p = 0.005; at PT6, 46.7% vs. 17.2%, p=0.001). Complete virological response (HBV DNA < 60 IU/mL) at ET was also achieved in more patients with a longer treatment (48 vs. 24 weeks 22.0% vs. 13.0%, p=0.005). HBeAg seroconversion rate at ET was 18.1% with 48 weeks treatment, which is significantly higher than 10.1% (p=0.012) with 24 weeks treatment. This finding was continued to PT6 (23.7% vs. 17.2%, p = 0.028). The rate of ALT normalization was increased from 61.4% at ET to 76.8% at PT6 on 48 weeks-treatment. HBsAg seroconversion was not common (48 vs. 24 weeks at ET, 0.4% vs. 0%; at PT6, 0.8% vs. 0%). In HBeAg-negative patients, virologic response at ET was higher than that in HBeAg-positive patients following 48 weeks treatment (serum HBV DNA< 60 and < 2,000 IU/mL; 60.8% and 87.8%, respectively). HBsAg seroconversion was 1.4% at ET and it was maintained at PT6. Adverse events were typical of those associated with PEG-IFNa-2a. Conclusion: In Korean CHB patients, PEG-IFNa-2a showed substantial treatment response and good tolerability. In patients with HBeAg-positive CHB, the longer treatment of PEG-IFNa-2a (48 weeks rather than 24 weeks) was more efficacious with similar safety profiles.

HBV : O-001 ; An observational, multicenter, cohort study evaluating the antiviral efficacy, safety, and tolerability in Korean patients with chronic hepatitis B (CHB) receiving pegylated Interferon-alpha 2a (Pegasys®): TRACES STUDY

( Young Eun Chon ),( Dong Joon Kim ),( Sang Gyune Kim ),( In Hee Kim ),( Si Hyun Bae ),( Seong Gyu Hwang ),( Jeong Heo ),( Jeong Won Jang ),( Byung Seok Lee ),( Hyung Joon Kim ),( Dae Won Jun ),( Gang 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1

Background: Until today, there is currently no data available on the efficacy, safety, and tolerability of pegylated interferon alfa 2a (PEG-IFNa-2a) in Korean patients with chronic hepatitis B (CHB), who are known to have mostly HBV genotype C. Methods: We collected data from 18 institutes of 451 Korean patients with CHB who were treated with PEG-IFNa-2a as a first line therapy (370 patients with HBeAg positive and 81 with HBeAg negative). Treatment responses at the end of treatment (ET) and at 6 months post-treatment (PT6) were compared between patients treated for 24 weeks vs. 48 weeks, and adverse events were evaluated. Results: In HBeAg-positive patients, the patients who had received PEG-IFNa-2a for 48 weeks than 24 weeks achieved significantly higher virological response (HBV DNA < 2,000 IU/mL) (48 vs. 24 weeks at ET, 44.4% vs. 27.2%, p = 0.005; at PT6, 46.7% vs. 17.2%, p=0.001). Complete virological response (HBV DNA < 60 IU/mL) at ET was also achieved in more patients with a longer treatment (48 vs. 24 weeks 22.0% vs. 13.0%, p=0.005). HBeAg seroconversion rate at ET was 18.1% with 48 weeks treatment, which is significantly higher than 10.1% (p=0.012) with 24 weeks treatment. This finding was continued to PT6 (23.7% vs. 17.2%, p = 0.028). The rate of ALT normalization was increased from 61.4% at ET to 76.8% at PT6 on 48 weeks-treatment. HBsAg seroconversion was not common (48 vs. 24 weeks at ET, 0.4% vs. 0%; at PT6, 0.8% vs. 0%). In HBeAg-negative patients, virologic response at ET was higher than that in HBeAg-positive patients following 48 weeks treatment (serum HBV DNA< 60 and < 2,000 IU/mL; 60.8% and 87.8%, respectively). HBsAg seroconversion was 1.4% at ET and it was maintained at PT6. Adverse events were typical of those associated with PEG-IFNa-2a. Conclusion: In Korean CHB patients, PEG-IFNa-2a showed substantial treatment response and good tolerability. In patients with HBeAg-positive CHB, the longer treatment of PEG-IFNa-2a (48 weeks rather than 24 weeks) was more efficacious with similar safety profiles.