Interferon-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients: a preliminary matched case-control study / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

BACKGROUND@#Currently, there are no drugs that have been proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of its broad antiviral activity, interferon (IFN) should be evaluated as a potential therapeutic agent for treatment of coronavirus disease 2019 (COVID-19), especially while COVID-19-specific therapies are still under development.@*METHODS@#Confirmed COVID-19 patients hospitalized in the First Affiliated Hospital, School of Medicine, Zhejiang University in Hangzhou, China, from January 19 to February 19, 2020 were enrolled in a retrospective study. The patients were separated into an IFN group and a control group according to whether they received initial IFN-α2b inhalation treatment after admission. Propensity-score matching was used to balance the confounding factors.@*RESULTS@#A total of 104 confirmed COVID-19 patients, 68 in the IFN group and 36 in the control group, were enrolled. Less hypertension (27.9% vs. 55.6%, P=0.006), dyspnea (8.8% vs. 25.0%, P=0.025), or diarrhea (4.4% vs. 19.4%, P=0.030) was observed in the IFN group. Lower levels of albumin and C-reactive protein and higher level of sodium were observed in the IFN group. Glucocorticoid dosage was lower in the IFN group (median, 40 vs. 80 mg/d, P=0.025). Compared to the control group, fewer patients in the IFN group were ventilated (13.2% vs. 33.3%, P=0.015) and admitted to intensive care unit (ICU) (16.2% vs. 44.4%, P=0.002). There were also fewer critical patients in the IFN group (7.4% vs. 25.0%, P=0.017) upon admission. Although complications during admission process were comparable between groups, the discharge rate (85.3% vs. 66.7%, P=0.027) was higher and the hospitalization time (16 vs. 21 d, P=0.015) was shorter in the IFN group. When other confounding factors were not considered, virus shedding time (10 vs. 13 d, P=0.014) was also shorter in the IFN group. However, when the influence of other factors was eliminated using propensity score matching, virus shedding time was not significantly shorter than that of the control group (12 vs. 15 d, P=0.206).@*CONCLUSIONS@#IFN-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients.

Primary scrotal melanoma: it is time to destigmatize genital lesions

Abstract Primary male genital melanomas are very rare; they are associated with high mortality and late detection. Scrotal melanoma is the least common presentation and only 23 cases have been reported. Herein, the authors present a 30-year-old patient with stage IIIC (T4b, N2a, M0) scrotal melanoma in order to report the characteristics, treatment, and outcome, as well as to emphasize the importance of examination of the genitals, education of patients about self-examination and destigmatizing genital lesions to increase the likelihood of earlier detection.

24 Weeks Treatment with Pegylated Interferon Alfa Plus Ribavirin May Be Possible in Genotype 1 Chronic Hepatitis C Patients with Rapid Virological Response Who Have Low Pretreatment Viremia / 대한소화기학회지

BACKGROUND/AIMS: The standard treatment for chronic hepatitis C infected with hepatitis C virus (HCV) genotype 1 is a combination of pegylated interferon alfa and ribavirin over a 48 weeks period. It is unclear if 24 weeks treatment is possible for patients showing a rapid virological response (RVR) without compromising the sustained virological response (SVR) in Korea. METHODS: Between June 2005 and September 2008, among patients chronically infected with the HCV genotype 1 who were treated with pegylated interferon alfa subcutaneously once weekly plus ribavirin based on body weight, 55 patients who had low pretreatment viral load (<600,000 IU/mL) and RVR were enrolled. A total of 55 patients were divided into 24 weeks treatment group (n=29) and the standard treatment group (n=26). The HCV RNA was quantitatively assessed before treatment, and after 12 weeks of treatment, and also qualitatively assessed after 4 weeks of treatment, at end of treatment (24 weeks), and 24 weeks after end of treatment. RVR was defined as undetectable HCV RNA at the 4 weeks of treatment. RESULTS: Among the 55 patients, SVR was achieved in 100% (29/29) of the patients in 24 weeks treatment and 96.2% (25/26) of the patients in the standard treatment (p=0.473). CONCLUSIONS: HCV genotype 1 infected patients with a low baseline HCV RNA concentration who become HCV RNA negative at week 4 may be treated for 24 weeks without compromising sustained virlolgical response. However, an additional trial will be needed to optimize the treatment duration.

A comparison of 24- vs. 48-week peginterferon plus ribavirin in patients with genotype 1 chronic hepatitis C / 대한간학회지

BACKGROUND/AIMS: The standard therapy for patients with genotype 1 chronic hepatitis C (CHC) is a combination of peginterferon and ribavirin for 48 weeks. However, the most appropriate duration of treatment remains to be established because of treatment-related side effects and cost. The aim of this study was to compare the efficacies of 24- and 48-week treatments, and to assess the efficacy of split 24-week therapy (a further 24 weeks of treatment in patients with relapse after the initial 24 weeks of treatment). METHODS: A total of 130 patients with genotype 1 CHC was treated between June 2004 and December 2006. Patients with undetectable HCV RNA at 24 weeks of treatment (as assessed by qualitative PCR assay; n=101 patients) were allowed to choose either 24 or 48 weeks as the duration of their treatment; 51 patients chose the 24-week treatment regimen and the remainder chose the 48-week regimen. Patients who relapsed after 24 weeks of treatment were treated for further 24 weeks. The sustained virologic response (SVR) of each treatment group was analyzed. RESULTS: The SVR rate was higher in patients treated for 48 weeks than in those treated for 24 weeks (74.0% vs. 52.9%, P=0.028). In the multivariate analysis, age or = 150,000/mm3, and treatment duration for 48 weeks remained significant independent predictors of SVR. Fourteen of the 24 patients who relapsed in the 24-week treatment group received split 24-week therapy, and 6 patients (42.9%) achieved SVR. The overall SVR rate did not differ significantly between the 24-week treatment group, including those who underwent 24-week split therapy (64.7%), and the 48-week treatment group (64.7% vs. 74%, P=0.311). CONCLUSIONS: The 24-week plus additional split 24-week therapy following failure is a useful treatment strategy for patients with genotype 1 CHC.

Assessment of the Efficacy of Reducing Peginterferon Alfa-2a and Ribavirin Dose on Virologic Response in Koreans with Chronic Hepatitis C

BACKGROUND/AIMS: The virologic response of Koreans to combination therapy for chronic hepatitis C is similar to westerns; however, dose modification occurs more frequently in Koreans. We evaluated the rates of peginterferon alpha-2a and ribavirin dose modifications and their effect on the virologic response in Koreans. METHODS: Patients with detectable HCV RNA and enrolled from multicenters were treated with peginterferon alpha-2a (180 microgram/week) and ribavirin (800 mg/day) for 24 weeks (genotype non-1, n=37) or peginterferon alpha-2a (180 microgram/week) and ribavirin (1,000-1,200 mg/day) for 48 weeks (genotype 1, n=55). RESULTS: Early virologic response (EVR) and sustained virologic response (SVR) were 77.2% (genotype 1, 75%; non-1, 81%) and 66.3% (genotype 1, 56%; non-1, 81%), respectively. The frequency of dose modification was 32.6% within the first 12 weeks and 52.2% during the entire treatment period. No difference was found in SVR regardless of dose modification. However, the SVR for patients using > or =80% of the peginterferon dose was significantly higher than for those using <80% (81.3 vs. 50.0%, p=0.007), despite varying ribavirin doses. No difference was found in SVR regardless of whether the ribavirin dose was <80% or not. These results did not change based on genotype. CONCLUSIONS: We suggest that using at least 80% of the peginterferon alpha-2a dose in Koreans not only maintains SVR but also reduces drug side effects during the entire treatment period. A lower dose of ribavirin may be as efficacious as a standard dose.

Treatment of chronic hepatitis C: Efficacy of initial treatment of peginterferon alpha-2a versus peginterferon alpha-2b plus ribavirin in naive chronic hepatitis C patients / 대한간학회지

No abstract available.

Efficacy of initial treatment with peginterferon alpha-2a versus peginterferon alpha-2b in combination with ribavirin in naive chronic hepatitis C patients living in Daejeon and Chungcheong Province in Korea: A comparative study / 대한간학회지

BACKGROUNDS/AIMS: Peginterferon alpha-2a or -2b is the standard treatment regimen in chronic hepatitis C. However, there have been few comparative studies of the efficacies of these two types of peginterferon. We evaluated their efficacies in combination with ribavirin as a initial treatment for chronic hepatitis C. METHODS: Ninety-seven patients were treated with peginterferon alpha-2a (180 microgram/week, n=48) or peginterferon alpha-2b (1.5 microgram/kg/week, n=49) plus ribavirin (800 mg/day for 24 weeks in genotype non-1 or 1,000-1,200 mg/day for 48 weeks in genotype 1). Virologic responses including the early virologic response (EVR), end-of-treatment response (ETR), sustained virologic response (SVR), and adverse effects were analyzed retrospectively. RESULTS: The virologic response rates did not differ significantly between peginterferon alpha-2a and -2b: 89.6% and 89.7% for EVR, 79.2% and 79.5% for ETR, 72.9% and 73.5% for SVR, respectively. Analysis of the virologic responses according to genotype also revealed no significant differences in SVR between peginterferon alpha-2a and -2b (59.3% vs. 59.7% for genotype 1 and 90.5% vs. 83.3% for genotype non-1, respectively), or in adverse effects including flu-like symptom, rash, itching, neutropenia, and thrombocytopenia. CONCLUSIONS: We found no significant differences in therapeutic efficacies and adverse effects between the alpha-2a and -2b types of peginterferon as the initial treatment regimen in naive chronic hepatitis C patients.

Treatment with pegylated interferon and ribavirin in a patient with fibrosing cholestatic hepatitis due to recurrent hepatitis C after liver transplantation / 대한간학회지

Fibrosing cholestatic hepatitis (FCH) is the most devastating manifestation of recurrent hepatitis C in transplant recipients with hepatitis C virus (HCV), possibly leading to death or retransplantation. Although FCH was first described as a complication of hepatitis B, this manifestation has been well documented in association with HCV in the setting of liver transplantation, bone marrow transplantation, heart transplantation, and end-stage human immunodeficiency virus infection. We report the clinical course and antiviral response in a patient with FCH due to recurrent hepatitis C after cadaveric liver transplantation who was treated with pegylated interferon alpha-2a and ribavirin.

Effects of pegylated interferon and ribavirin in Korean patients with chronic hepatitis C virus infection / 대한간학회지

BACKGROUND/AIMS: We assessed the efficacy and safety of pegylated interferon (peginterferon) plus ribavirin and identified the predictors of a sustained virologic response (SVR) in Korean patients with chronic hepatitis C virus infection. METHODS: A total of 192 patients with chronic hepatitis C, treated with both peginterferon (n=141) or conventional interferon (n=51) and ribavirin, were analyzed retrospectively. Peginterferon alfa-2a (180 microgram/week) or -2b (1.5 microgram/kg/week) or interferon alfa-2a (3 MIU thrice weekly) was administered in combination with ribavirin at 1,000-1,200 mg/day for 48 weeks for genotype 1 and at 800 mg/day for 24 weeks for genotypes 2 and 3. RESULTS: The overall SVR rate was 80.9% (114/141) in the peginterferon group and 52.9% (27/51) in the interferon group (P=0.0001). The SVR rate in genotype 1 was 69.5% (41/59) in the peginterferon group and 31.6% (6/19) in the interferon group (P=0.0033), whereas in genotype 2 or 3 it was 89.0% (73/82) in the peginterferon group and 65.6% (21/32) in the interferon group (P=0.0032). The predictors of SVR in the peginterferon group were genotype, absence of cirrhosis, and early virologic response (P<0.05). CONCLUSIONS: In Korean patients with chronic hepatitis C, a regimen of peginterferon and ribavirin was more effective than a regimen of conventional interferon and ribavirin. This result is comparable to those from studies on Western patients as an initial treatment for chronic hepatitis C.

Clinical outcome of pegylated interferon and ribavirin therapy for chronic hepatitis C / 대한간학회지

BACKGROUND/AIMS: The purpose of this study is to elucidate the efficacy and safety of combined peginterferon and ribavirin therapy in Korean patients with chronic HCV infection. METHODS: We retrospectively analyzed the clinical records of 84 patients. Thirty five patients with genotype 1 HCV infection were treated with peginterferon alpha-2a 180 microgram/week and ribavirin 1,000-1,200 mg/day for 48 weeks, and 49 patients with genotype non-1 were treated with peginterferon alpha-2a 180 microgram/week and ribavirin 800 mg/day for 24 weeks. RESULTS: An early virologic response was seen in 87.0% of patients with genotype 1 HCV. An end of treatment response (ETR) was seen in 82.6% and 97.6% of patients with genotype 1 and genotype non-1, respectively. An overall sustained virologic response (SVR) was seen in 53 patients (82.8%) of the 64 patients: in 16 (69.6%) of 23 patients with genotype 1 and in 37 (90.2%) of 41 patients with genotype non-1. An end of treatment biochemical response was seen in 58 patients (90.6%) [genotype 1, 20 patients (87.0%); genotype non-1, 38 patients (92.7%)], and a sustained biochemical response was achieved in 49 patients (76.6%) [genotype 1, 14 patients (60.9%); genotype non-1, 35 patients (85.4%)]. Independent factors affecting an SVR were HCV genotype and the baseline HCV RNA level. CONCLUSIONS: This study shows that a combination therapy of peginterferon and ribavirin is highly effective for chronic HCV infection, producing a high SVR and ETR.

Comparison of therapeutic results between combination therapy of peginterferon alpha-2a plus ribavirin and interferon alpha-2b plus ribavirin according to treatment duration in patients with chronic hepatitis C / 대한간학회지

BACKGROUND/AIMS: This study compared the efficacy and safety of combined peginterferon alfa (PEG-IFN) and ribavirin with that of combined interferon alpha (IFN-alpha) and ribavirin, according to the treatment duration in Korean patients with chronic hepatitis C. METHODS: Medical records of 86 patients treated with PEG-IFN and ribavirin (mean age, 50.7 years; males/females, 57/29; genotypes 1/2, 59/27) and 134 patients treated with IFN-alpha and ribavirin (mean age, 50.9 years; males/females 74/60; genotypes 1/2, 79/55) were reviewed. Ribavirin was administered at doses of 600-1,200 mg and 600-800 mg in patients with genotypes 1 and 2, respectively. RESULTS: Sustained virological responses (SVRs) were evident in 68.4% and 41.7% of genotype 1 patients treated for 48 weeks in the PEG-IFN and IFN-alpha groups, respectively (P=0.021), and in 94.1% and 64.9% of genotype 2 patients treated for 24 weeks (P=0.026). Some genotype 1 patients treated for 24 weeks in the PEG-IFN group, who all exhibited negative HCV PCR results at week 12, showed an SVR of 87.5% (7/8). CONCLUSIONS: The rate of SVRs in Korean patients with chronic hepatitis C was higher for combined PEG-IFN and ribavirin than for combined IFN-alpha and ribavirin. Further study is needed to clarify the outcome of short-term therapy in patients with a rapid or early virological response.

Pulmonary Toxicity by Pegylated Interferon alpha-2a in a Patient with Chronic Hepatitis C / 대한간학회지

The combination therapy with pegylated interferon alpha and ribavirin has increasingly prescribed for chronic hepatitis C. Although many side effects of interferon such as flu-like symptoms, gastrointestinal and neuropsychiatric symptoms are well known, only several cases of interferon-induced pulmonary toxicity have been reported. Interferon-induced pulmonary toxicity usually develops from 2 weeks to 12 weeks after treatment for HCV infection. Diagnosis is commonly based on clinical findings such as a dry cough, dyspnea, hypoxemia, and a restrictive pattern in pulmonary function testing, bilateral diffuse parenchymal infiltrations, histopathological findings of interstitial pneumonitis, and exclusion of any other causative agents. Prompt withdrawal of the drug is the cornerstone of treatment. We report a case of PEG-IFN alpha-2a induced pulmonary toxicity in a 50-year-old male patient with hepatitis C. To our knowledge, this is the first case of pegylated interferon alpha-2a induced pulmonary toxicity in Korea.

Treatment of Chronic Hepatitis C: Shorter Treatment Duration for Genotype 2 or 3 Infection / 대한간학회지

No abstract available.

Short-term Therapy with Pegylated Interferon plus Ribavirin for the Chronic Hepatitis C Genotype 2 Patients / 대한간학회지

BACKGROUND/AIMS: The standard treatment for chronic hepatitis C patients infected with HCV genotype-2 is a combination of pegylated interferon alfa and ribavirin over a 24 week period. It is unclear if a shorter treatment duration is possible for patients showing a rapid virological response (RVR) without compromising the sustained virologic response (SVR) in Korea. METHODS: 42 patients chronically infected with the HCV genotype-2 were treated with peginterferon alfa-2a 180 mcg/wk plus ribavirin 800 mg/d for 24 weeks and followed up for 24 weeks. The HCV RNA was qualitatively assessed after 4 weeks of treatment, and RVR was defined as undetectable HCV RNA at the 4th week. Retrospectively, 26 patients were treated with the standard treatment strategy (> or =80% of the intended duration and dosage), 14 patients with a short-term treatment strategy (<80% intended duration and dosage) and 2 patients were excluded. RESULTS: Among the 42 patients, 35 patients (83%) had RVR and 38 patients (90%) had a sustained virologic response (SVR). All 7 patients without RVR were treated with the standard treatment strategy, in whom 6 patients (86%) had SVR. Among the 35 patients with RVR, 14 patients were treated with short-term treatment and 19 patients were treated with the standard treatment. SVR was obtained in 12 out of the 14 patients (86%) in the short-term treatment group and 18 out of the 19 (95%) in the standard treatment group (P=0.373). CONCLUSION: HCV genotype-2 patients who have RVR with peginterferon and ribavirin treatment can be treated with a short-term treatment without compromising the chances for SVR. However, an additional trial will be needed to optimize the treatment duration.

Comparison of lamivudine and alpha-interferon combination with alpha-interferon alone in the treatment of HBeAg-positive chronic hepatitis B.

AIM: To compare the efficacy of a combination of a-interferon (IFN-a) and lamivudine with IFN-a alone in the treatment of patients with HBeAg-positive chronic hepatitis B (CHB). METHODS: Sixty-eight treatment-naove patients with HBeAg-positive CHB were randomized to receive either 9 MU of IFN-a2a three times a week and lamivudine 100 mg daily (Group 1), or IFN-a2a alone in the same dosage (Group 2), for 12 months. Serum ALT, HBeAg, anti-HBe and HBV DNA were tested at the end of treatment and 6 months later. Complete response was defined as normal ALT, negative HBeAg and negative HBV DNA, six months after stopping treatment. RESULTS: Of the 68 patients, 64 completed the study. In Group 1 (n=31), mean (SD) ALT levels decreased from 124 (59) IU/L to 39 (18) IU/L at 12 months; corresponding values in Group 2 (n=33) were 128 (57) and 56 (11) IU/L (p< 0.05). Absence of HBV DNA at the end of treatment was more common in Group 1 (28/31) than in Group 2 (22/33; p< 0.022). The number of patients with seroconversion to anti-HBe (4/31 [13%] vs. 4/33 [12%], respectively; p>0.05), as also those with complete response (4/31 [13%] and 4/33 [12%], respectively; p>0.05) six months after completion of treatment was similar in Group 1 and Group 2. CONCLUSION: Combination treatment with IFN-a and lamivudine was better than IFN-a monotherapy in normalization of ALT and clearance of HBV DNA; however, it did not have a better sustained response rate than IFN-a alone.

Peginterferon Alfa-2a plus Ribavirin for Initial Treatment of Chronic Hepatitis C in Korea / 대한간학회지

BACKGROUND/AIMS: Combination therapy with peginterferon and ribavirin is a standard therapy for western patients with chronic hepatitis C; however, its efficacy remains unclear in East Asian patients. We evaluated the efficacy and safety of administering peginterferon alfa-2a plus ribavirin in native Korean patients with chronic hepatitis C. METHODS: Seventy-five patients with detectable HCV RNA (52.0% male, median age: 50.8 years) were eligible for the study. The patients were treated with peginterferon alfa-2a 180 mcg/week plus ribavirin 800 mg/day for 24 weeks (for genotype non-1, n=46) or 1000-1200 mg/day for 48 weeks (for genotype 1, n=29). The early virologic response (EVR), the end of treatment virologic response (ETVR), the sustained virologic response (SVR), the biochemical response and the adverse event were analyzed. RESULTS: EVR was seen in 86.2% of the patients with genotype 1. The ETVR was 58.6% in the genotype 1 group and 84.8% in the genotype non-1 group (P=0.02). The overall SVR was 70.7%: 55.2% in the genotype 1 group and 80.4% in the non-1 group (P=0.04). The sustained biochemical response was 64.0%. Multivariate analysis showed that the baseline HCV RNA level (Odds ratio: 0.045, 95% CI: 0.011-0.183, P<0.001) and genotype (Odds ratio: 0.247, 95% CI: 0.063-0.969, P=0.045) had an independent effect on the SVR. Neutropenia, anemia, flu-like symptoms and itching were the common adverse events. Aggravated liver function led to discontinuation of therapy for six patients. Dose modification in twenty-nine patients was effective without producing a significant reduction of the SVR. CONCLUSIONS: Our data suggest that the efficacy of peginterferon plus ribavirin therapy in Koreans is comparable to those from studies on Western patients as an initial treatment for chronic hepatitis C patients. The baseline HCV RNA level and the genotype can be significant factors influencing the SVR.

Treatment of Chronic Hepatitis C / 대한소화기학회지

Chronic infection with HCV represents second most common cause of end-stage liver diseases and hepatocellular carcinoma in Korea. The introduction of new agents and regimens for the treatment of chronic hepatitis C, such as pegylated forms of interferon-alpha (Peg-IFN) and combination with oral ribavirin has resulted in substantial improvement in sustained virologic response (SVR) rates. SVR rate of Peg-IFN and ribavirin combination therapy can be 40-46% of individuals infected with genotype 1 and approximately 75-85% with genotype 2 and 3. Peg-IFN/ribavirin combination therapy represents current standard therapy of chronic hepatitis C. This article reviews the treatment objectives, outcomes, optimal regimens, efficacy and predictors of response, monitoring during treatment, adverse events, retreatment of persons who failed to respond to previous treatments, and treatment of special patient groups in chronic hepatitis C.

The combined treatment of interferon alpha-2a and thymosin alpha 1 for chronic hepatitis C: the 48 weeks end of treatment results.

The efficacy and safety of IFN alpha 2a and Thymosin alpha1 combination therapy in patients with chronic hepatitis C were determined. Twelve chronic hepatitis C patients (9 M, 3F), with positive HCV-RNA and histology compatible with chronic hepatitis C were included in this open, prospective study. Each patient received a combination therapy of IFN alpha 2a 3 mU s.c. TIW and Thymosin alpha1 1.6 mg s.c. twice a week for 52 weeks. Up to the present, 11 patients are still being followed-up after the end of 52 weeks' treatment. One patient dropped out after 32 weeks of follow-up due to noncompliance. Responses to treatment were evaluated by measuring serum HCV-RNA levels determined by RT-PCR. and serum amino transferases at the end of 48 weeks of treatment (end of treatment response: ETR). There were 8 naive and 4 previously IFN treated patients with partial response with a mean age of 45.0 +/- 10.1 (mean +/- SD). The mean duration from diagnosis until treatment was 25.1 +/- 22.9 months. The mean AST, ALT, and HCV-RNA levels before treatment were 79.5 +/- 36.8 U/L, 128.3 +/- 68.5 U/L, and 3.9+1.9 x 10(5) copies/ml respectively. Serum AST, ALT, and HCV-RNA levels were significantly lower at week 24 and 48 after treatment compared to before treatment (p<0.05). Of 11 cases, complete HCV-RNA clearance at week 24 was noted in 33.3 per cent, whereas, normal alanine aminotransferase values (ALT < 40 U/L) were observed in 41.7 per cent of patients. Complete HCV-RNA clearance and normal alanine aminotransferase at week 48 were seen in 45.5 per cent of the patients. At the end of week 48, complete response occurred in 4 of 5 naive patients. Minor side effects were observed during treatment with this combination therapy and these included myalgia (33.3%), mild form of alopecia (33.3%), and weight loss (8.3%). In patients with chronic hepatitis C, Interferon alpha 2a and Thymosin alpha1 combination therapy produced a good response rate especially in naive patients with acceptable safety profile. The sustained response will be determined after the completion of follow-up for another 6 months.