Systemic inflammation score as a predictor of death within one year after esophagectomy.

BACKGROUND: After radical resection for esophageal cancer, death within 1 year of surgery can occur due both to recurrence and to other diseases, even after postoperative complications have been overcome. This study identified risk factors for early death within 1 year of esophagectomy for reasons other than death in hospital in patients undergoing esophagectomy for esophageal cancer or esophagogastric junction cancer. METHODS: We reviewed 366 patients who underwent esophagectomy without adjuvant treatment between January 2009 and July 2022 for thoracic esophageal cancer or esophagogastric junction cancer. Patients who died within 1 year excluding in-hospital death were compared with those who did not. Multivariable logistic regression analysis was used to identify predictors of death within 1 year after surgery. RESULTS: Death within 1 year occurred in 32 of 366 patients, 24 from primary disease and 8 from other diseases. Deaths within 1 year were significantly older than the other cases, had significantly lower % vital capacity (%VC), and occurred significantly more often in cases in advanced stages of disease. In a multivariable analysis, a systemic inflammation score (SIS) based on serum albumin level and lymphocyte-to-monocyte ratio was identified as an independent predictor of death within 1 year. As SIS increased, %VC decreased significantly, and CRP level and neutrophil-lymphocyte ratio increased significantly. There was no relationship between SIS and pN. Death within 1 year increased as SIS increased (p = 0.001 for trend). CONCLUSION: SIS assessment undertaken before beginning esophageal cancer treatment is a useful predictor of death within 1 year of surgery.

Fibroblast-specific PRMT5 deficiency suppresses cardiac fibrosis and left ventricular dysfunction in male mice.

Protein arginine methyltransferase 5 (PRMT5) is a well-known epigenetic regulatory enzyme. However, the role of PRMT5-mediated arginine methylation in gene transcription related to cardiac fibrosis is unknown. Here we show that fibroblast-specific deletion of PRMT5 significantly reduces pressure overload-induced cardiac fibrosis and improves cardiac dysfunction in male mice. Both the PRMT5-selective inhibitor EPZ015666 and knockdown of PRMT5 suppress α-smooth muscle actin (α-SMA) expression induced by transforming growth factor-ß (TGF-ß) in cultured cardiac fibroblasts. TGF-ß stimulation promotes the recruitment of the PRMT5/Smad3 complex to the promoter site of α-SMA. It also increases PRMT5-mediated H3R2 symmetric dimethylation, and this increase is inhibited by Smad3 knockdown. TGF-ß stimulation increases H3K4 tri-methylation mediated by the WDR5/MLL1 methyltransferase complex, which recognizes H3R2 dimethylation. Finally, treatment with EPZ015666 significantly improves pressure overload-induced cardiac fibrosis and dysfunction. These findings suggest that PRMT5 regulates TGF-ß/Smad3-dependent fibrotic gene transcription, possibly through histone methylation crosstalk, and plays a critical role in cardiac fibrosis and dysfunction.

Risk factors for glioblastoma in adults in Japan: an exploratory cohort study based on the Shizuoka Kokuho Database, the Shizuoka study.

PURPOSE: To elucidate the risk factors associated with the onset of glioblastoma (GBM) utilizing a comprehensive administrative claims database from a major governmental district in Japan. METHODS: Using the Shizuoka Kokuho Database (SKDB) for the period from April 2012 to September 2021, we conducted a retrospective analysis of 1,465,353 participants, identifying GBM cases using specific Japanese disease codes in conjunction with associated treatments. Risk factors were assessed using both univariable and multivariable Cox proportional hazards models. RESULTS: Within the cohort, 182 participants (0.012%) received a GBM diagnosis during the study period, resulting in an incidence rate of 2.1 per 100,000 person-years. The multivariable analysis revealed that older age, male sex, and peripheral vascular disease (PVD) significantly influenced the risk of GBM onset. No clear link was found between allergic conditions and GBM risk, in contrast to some previous research. CONCLUSION: Employing a robust health insurance database, this study revealed significant associations between GBM and factors such as age, male sex, and PVD within the Japanese population. It provides key insights into GBM epidemiology and underscores the potential of health insurance databases for large-scale oncological research.

A snare maneuver to reposition self-expandable aortic valve after transcatheter replacement of surgically implanted valve.

In this case, we successfully repositioned the transcatheter heart valve (THV) by pulling it with a snare inserted via the right brachial artery. Attempting to pull the THV via the femoral approach was not successful, due to the vector of the pulling force not being coaxial. Changing the direction of the force by switching to an approach from the right brachial artery successfully prevented perivalvular leakage. While there are previous case reports of repositioning an implanted transcatheter valve in a native valve using a gooseneck snare, to our knowledge, this is the first case of successfully repositioning an implanted transcatheter valve in a valve-in-valve procedure using the precise assessment that can be achieved with intra-procedural transesophageal echocardiography. Learning objective: Perivalvular leakage (PVL) is a major problem after transcatheter aortic valve replacement. In this case, we experienced PVL after implantation of self-expandable transcatheter heart valve (THV) inside the previously inserted Mosaic bioprosthetic valve. Depth of the implanted valve was too low into left ventricle accessed with transesophageal echocardiogram. It is barely known whether THV in surgical implanted aortic valve could be repositioned using snare maneuver, but we successfully pulled the valve via brachial artery and PVL was controlled.

Craniocervical Junction Dural Arteriovenous Fistula and Pial Arteriovenous Fistula Presenting Concomitantly in Separate Locations with Subarachnoid Hemorrhage.

Craniocervical junction dural arteriovenous fistula and pial arteriovenous fistula are rare cerebrovascular lesions. While their pathophysiology is different, both conditions can cause intracranial hemorrhage attributable to venous congestion. We present, to our knowledge, the first case report of craniocervical junction dural arteriovenous fistula and pial arteriovenous fistula presenting concomitantly in separate locations with subarachnoid hemorrhage. This case appears to have been due to increased venous hypertension caused by a merging of the venous drainage of the 2 lesions, resulting in hemorrhage.

6-Shogaol, an Active Component of Ginger, Inhibits p300 Histone Acetyltransferase Activity and Attenuates the Development of Pressure-Overload-Induced Heart Failure.

Hypertrophic stress-induced cardiac remodeling is a compensatory mechanism associated with cardiomyocyte hypertrophy and cardiac fibrosis. Continuation of this response eventually leads to heart failure. The histone acetyltransferase p300 plays an important role in the development of heart failure, and may be a target for heart failure therapy. The phenolic phytochemical 6-shogaol, a pungent component of raw ginger, has various bioactive effects; however, its effect on cardiovascular diseases has not been investigated. One micromolar of 6-shogaol suppressed phenylephrine (PE)-induced increases in cardiomyocyte hypertrophy in rat primary cultured cardiomyocytes. In rat primary cultured cardiac fibroblasts, 6-shogaol suppressed transforming growth factor-beta (TGF-ß)-induced increases in L-proline incorporation. It also blocked PE- and TGF-ß-induced increases in histone H3K9 acetylation in the same cells and in vitro. An in vitro p300-HAT assay revealed that 6-shogaol suppressed histone acetylation. The mice underwent transverse aortic constriction (TAC) surgery, and were administered 0.2 or 1 mg/kg of 6-shogaol daily for 8 weeks. 6-shogaol prevented TAC-induced systolic dysfunction and cardiac hypertrophy in a dose-dependent manner. Furthermore, it also significantly inhibited TAC-induced increases in histone H3K9 acetylation. These results suggest that 6-shogaol may ameliorate heart failure through a variety of mechanisms, including the inhibition of p300-HAT activity.

Administration of Tranexamic Acid After Burr Hole Craniotomy Reduced Postoperative Recurrence of Chronic Subdural Hematoma in a Japanese Regional Population.

BACKGROUND: Although tranexamic acid (TXA) has occasionally been used to prevent postoperative recurrence of chronic subdural hematoma (CSDH) after burr hole craniotomy (BC), robust evidence of its efficacy has been lacking. OBJECTIVE: To assess the efficacy and safety of postoperative oral administration of TXA after BC for CSDH among the elderly. METHODS: This retrospective, propensity score-matched cohort study was carried out with a large Japanese local population-based longitudinal cohort in the Shizuoka Kokuho Database between April 2012 and September 2020. Patients included were age 60 years or older and had undergone BC for CSDH but were not undergoing dialysis. Covariates were collected from records of the preceding 12 months from the month of first BC, and patients were followed up for 6 months after surgery. The primary outcome was repeat surgery, and the secondary outcome was death or the onset of thrombosis. Data on postoperative TXA administration were collected and compared with controls using propensity score matching. RESULTS: Of the 8544 patients who underwent BC for CSDH, 6647 were included, with 473 placed in the TXA group and 6174 placed in the control group. After 1:1 matching, repeated BC was found to have been performed in 30 of 465 patients (6.5%) in the TXA group and in 78 of 465 patients (16.8%) in the control group (relative risk, 0.38; 95% CI, 0.26-0.56). No significant difference was observed for death or the onset of thrombosis. CONCLUSION: Oral administration of TXA reduced the occurrence of repeat surgery after BC for CSDH.

Skeletal Muscle Loss During Neoadjuvant Chemotherapy Predicts the Incidence of Postoperative Infectious Complications in Esophageal Cancer Patients Undergoing Esophagectomy.

BACKGROUND/AIM: Malnutrition, immune deficiency, and skeletal muscle loss are associated with a risk of postoperative complications in patients with various types of cancer. This study evaluated whether malnutrition, immunological deficiencies, and skeletal muscle loss during neoadjuvant chemotherapy (NAC) predict postoperative complications in patients with esophageal cancer. PATIENTS AND METHODS: We retrospectively reviewed 123 patients with esophageal squamous cell carcinoma treated with NAC and esophagectomy at our hospital between 2014 and 2019. Patients were divided into two groups based on the presence or absence of postoperative infectious complications, such as pneumonia, anastomotic leakage, surgical site infections, pyothorax, acalculous cholecystitis, and peripheral phlebitis. Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and Onodera prognostic nutritional index were used as indicators of systemic inflammation and nutritional status. Skeletal muscle mass was evaluated using the skeletal muscle index (SMI), calculated by evaluating the total cross-sectional area of muscle tissue at the third lumbar level in computed tomography imaging. Univariable and multivariable logistic regression analyses were used to identify predictors of postoperative infectious complications. RESULTS: Postoperative infectious complications occurred in 41 patients (33.3%). A reduction in SMI was observed in 105 patients (87.8%) during NAC. Univariable and multivariable analyses indicated that the reduction in SMI during NAC was an independent predictor of postoperative complications (odds ratio=0.89; 95% confidence interval=0.79-0.99; p=0.048). CONCLUSION: Skeletal muscle loss during NAC is a useful predictor of postoperative complications in patients with esophageal cancer undergoing esophagectomy.

Intratumoral Air Bubbles and Hematemesis As Predictors of Pseudoaneurysm Rupture in Unresected Pancreatic Cancer.

Objective Pseudoaneurysm rupture associated with unresected pancreatic cancer can cause rare but fatal hemobilia and gastrointestinal bleeding. This study aimed to identify factors predicting pseudoaneurysm rupture. Methods We conducted a single-center case-control study of unresected pancreatic cancer patients treated at Shizuoka General Hospital between January 2011 and July 2020 using a retrospective cancer registry database. Included in the study were 611 consecutive patients with unresected pancreatic cancer, of whom 55 developed overt upper gastrointestinal bleeding or hemobilia. Twenty patients were excluded, as they had not undergone contrast-enhanced computed tomography (CT) or angiography. Patients were classified into pseudoaneurysm and non-pseudoaneurysm groups. One patient with arterial bleeding but without obvious pseudoaneurysm was included in the pseudoaneurysm group. Factors predicting pseudoaneurysm rupture at the onset of overt gastrointestinal bleeding were investigated using a logistic regression analysis. CT findings revealing air bubbles inside the tumor were described as intratumoral air bubbles. Results Thirty-five patients were included (15 in the pseudoaneurysm group, 20 in the non-pseudoaneurysm group). In the multivariate analysis, intratumoral air bubbles [odds ratio (OR), 12.9; 95% confidence interval (CI), 2.14-77.9; p=0.005] and hematemesis (OR, 6.30; 95% CI, 1.03-38.6; p=0.047) were independent predictors of pseudoaneurysm rupture. In addition, patients who experienced successful hemostasis and were re-administered chemotherapy survived more than six months. Conclusion This study reveals that intratumoral air bubbles and hematemesis may predict pseudoaneurysm rupture at the onset of overt gastrointestinal bleeding. For patients presenting these findings, an examination with conventional or CT angiography may lead to an early diagnosis and improve the patient prognosis.

Risk factors for gallstone disease onset in Japan: Findings from the Shizuoka Study, a population-based cohort study.

In the research literature on factors associated with gallstones, large population-based cohort studies are rare. We carried out a study of this type to explore risk factors for the onset of gallstones. This study included Japanese participants aged 40-107 years who were followed prospectively from January 2012 to September 2020 using a dataset composed of two individually linked databases, one containing annual health checkup records and the other containing medical claims for beneficiaries of the National Health Insurance System and the Medical Care System for Elderly in the Latter Stage of Life in Shizuoka Prefecture, Japan. Among the 611,930 participants in the analysis set, 23,843 (3.9%) were diagnosed with gallstones during the observational period (median [max]: 5.68 [7.5] years). Multivariate analysis revealed that risk of gallstone disease was increased by male sex, cerebrovascular disease, any malignancy, dementia, rheumatic disease, chronic pulmonary disease, hypertension, and H. pylori-infected gastritis. These findings provide essential insights into the etiology of cholelithiasis and may contribute to efforts to reduce the incidence of the disease.

The impact of the American Society of Anesthesiology-Physical Status classification system on the treatment and prognosis of patients with esophageal cancer undergoing esophagectomy.

BACKGROUND: The American Society of Anesthesiologists-Physical Status (ASA-PS) classification system has been shown to predict morbidity and mortality after surgery. However, the impact of the ASA-PS on esophageal cancer treatment remains unclear. This study examined both the impact of the ASA-PS on treatment, including surgery and perioperative chemotherapy, and the prognostic effects of ASA-PS class in patients who had undergone esophagectomy for thoracic esophageal cancer or esophagogastric junction cancer. METHODS: ASA-PS status was collected for 301 patients who had undergone esophagectomy between January 2007 and June 2016 for thoracic esophageal cancer or esophagogastric junction cancer at a single institution. As the ASA-PS was updated in 2014, the previous classifications of all patients were reevaluated using the updated standard by a surgeon with the previous classifications masked. The dose intensity of preoperative chemotherapy was also compared across classes. Multivariate Cox regression analysis was used to analyze the association between ASA-PS class and overall survival. RESULTS: Patients whose reevaluations had placed them in a more severe ASA-PS class showed significantly poorer overall and cancer-specific survival rates. The dose intensities of cisplatin and 5-fluorouracil for preoperative chemotherapy were significantly lower in patients in the more severe ASA-PS classes. Multivariate analysis showed that ASA-PS class was an independent prognostic factor for overall survival. CONCLUSION: Preoperative ASA-PS classification may influence the intensity of perioperative treatment and may be a valuable long-term prognostic factor for patients with esophageal cancer undergoing esophagectomy.

Ecklonia stolonifera Okamura Extract Suppresses Myocardial Infarction-Induced Left Ventricular Systolic Dysfunction by Inhibiting p300-HAT Activity.

Ecklonia stolonifera Okamura extract (ESE) has been reported to have various bioactive effects, but its effects on cardiovascular disease have not yet been investigated. First, primary neonatal rat cultured cardiomyocytes were treated with ESE and stimulated with phenylephrine (PE) for 48 h. ESE (1000 µg/mL) significantly suppressed PE-induced cardiomyocyte hypertrophy, hypertrophy-related gene transcription, and the acetylation of histone H3K9. An in vitro p300-HAT assay indicated that ESE directly inhibited p300-HAT activity. Next, one week after myocardial infarction (MI) surgery, rats (left ventricular fractional shortening (LVFS) < 40%) were randomly assigned to three groups: vehicle (saline, n = 9), ESE (0.3 g/kg, n = 10), or ESE (1 g/kg, n = 10). Daily oral administration was carried out for 8 weeks. After treatment, LVFS was significantly higher in the ESE (1 g/kg) group than in the vehicle group. The ESE treatments also significantly suppressed MI-induced increases in myocardial cell diameter, perivascular fibrosis, hypertrophy- and fibrosis-related gene transcription, and the acetylation of histone H3K9. These results suggest that ESE suppressed both hypertrophic responses in cardiomyocytes and the development of heart failure in rats by inhibiting p300-HAT activity. Thus, this dietary extract is a potential novel therapeutic strategy for heart failure in humans.

Chrysanthemum morifolium Extract Ameliorates Doxorubicin-Induced Cardiotoxicity by Decreasing Apoptosis.

It is well known that the anthracycline anticancer drug doxorubicin (DOX) induces cardiotoxicity. Recently, Chrysanthemum morifolium extract (CME), an extract of the purple chrysanthemum flower, has been reported to possess various physiological activities such as antioxidant and anti-inflammatory effects. However, its effect on DOX-induced cardiotoxicity is still unknown. An 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT)assay revealed that 1 mg/mL of CME reduced DOX-induced cytotoxicity in H9C2 cells but not in MDA-MB-231 cells. A TUNEL assay indicated that CME treatment improved DOX-induced apoptosis in H9C2 cells. Moreover, DOX-induced increases in the expression levels of p53, phosphorylated p53, and cleaved caspase-3,9 were significantly suppressed by CME treatment. Next, we investigated the effect of CME in vivo. The results showed that CME treatment substantially reversed the DOX-induced decrease in survival rate. Echocardiography indicated that CME treatment also reduced DOX-induced left ventricular systolic dysfunction, and a TUNEL assay showed that CME treatment also suppressed apoptosis in the mouse heart. These results reveal that CME treatment ameliorated DOX-induced cardiotoxicity by suppressing apoptosis. Further study is needed to clarify the effect of CME on DOX-induced heart failure in humans.

Serum carnitine as a biomarker of sarcopenia and nutritional status in preoperative gastrointestinal cancer patients.

BACKGROUND: Sarcopenia is an important factor in the postoperative outcome of gastrointestinal cancer patients. However, little research has been carried out on potential biomarkers of sarcopenia. Carnitine is an amino acid derivative that is stored in skeletal muscle and is essential for muscle energy metabolism. The primary purpose of this study was to investigate whether serum carnitine level is a biomarker of sarcopenia in preoperative patients with gastrointestinal cancer. The secondary purposes were (i) to examine the associations between carnitine, nutritional status, and albumin level, and (ii) to determine whether carnitine is a prognostic factor for postoperative complications. METHODS: One hundred fourteen patients scheduled to undergo gastroenterological surgery between August 2016 and January 2017 were enrolled. Their mean age was 68.4 ± 10.5, and 64.9% were male. Serum carnitine fractions [total carnitine (TC), free l-carnitine (FC), and acylcarnitine (AC)] were measured prior to surgery. The correlation between carnitine level and a variety of clinical features was analysed, including skeletal muscle index (SMI), sarcopenia, prognostic nutritional index (PNI), and postoperative complications. RESULTS: Tumour locations included the oesophagus (n = 17), stomach (n = 16), pancreas (n = 20), bile duct (n = 9), liver [n = 33; primary liver cancer (n = 18), liver metastasis (n = 15)], and colorectal region (n = 19). TC and FC levels varied significantly by tumour location. TC and FC showed significant positive correlations with SMI [TC (r = 0.295, P = 0.0014), FC (r = 0.286, P = 0.0020)] and PNI [TC (P = 0.0178, r = 0.222), FC (P = 0.0067, r = 0.2526)]. These levels were significantly lower in the sarcopenia group (TC, P = 0.0124; FC, P = 0.0243). In addition, TC and FC showed significant positive correlations with ALB level [TC (P = 0.038 r = 0.19), FC (P = 0.016 r = 0.23)]. When patients were divided into high ALB (≥3.5 g/dL, 96 patients) and low ALB (<3.5 g/dL, 18 patients) groups, these correlations were no longer significant, but in the low ALB group there was a tendency towards a negative relationship between ALB level and both TC and FC. No significant relationship was found between postoperative complications and carnitine level. CONCLUSIONS: This study suggests that carnitine level is a biomarker of sarcopenia and nutritional status. However, it did not find an association between carnitine level and postoperative complications.

Pregnancy and delivery in women receiving maintenance hemodialysis in Japan: analysis of potential risk factors for neonatal and maternal complications.

INTRODUCTION: Average dialysis vintage in Japan is among the longest in the world, providing a unique opportunity to characterize pregnancy under conditions of long dialysis vintage. In 2017, we carried out a nationwide survey following up on a similar survey in 1996, in which we investigated the prevalence and outcomes of pregnancy in women undergoing dialysis and assessed risk factors associated with neonatal and maternal complications. METHODS: The target population was women aged 15-44 years undergoing maintenance dialysis between 2012 and 2016. The survey was conducted in 2693 dialysis units. RESULTS: A response was obtained from 951 dialysis units, yielding a target population of 1992 women of childbearing age receiving hemodialysis or peritoneal dialysis. Pregnancy occurred only among women receiving hemodialysis, with 25 pregnancies (1.26% in 5 years) being reported for 20 women. Detailed information about 19 pregnancies (mean age 34.6 ± 5.7 years at conception, mean dialysis vintage 8.4 ± 7.3 years) indicated 4 spontaneous abortions, 1 elective abortion, no neonatal deaths, and 14 surviving infants, including 5 full-term (≥ 37 weeks at birth), 2 late preterm (34-36), and 3 extremely preterm (< 28) cases. Neonatal complications occurred in the offspring of 3 mothers who had end-stage renal disease (ESRD) caused by primary glomerulonephritis and serum albumin levels (sAlb) ≤ 3.2 mg/dL in the first trimester. These mothers had started dialysis at 12, 17, and 30 years of age. ESRD caused by diabetic nephropathy or primary glomerulonephritis, age at conception ≥ 38 years, and sAlb ≤ 3.2 mg/dL were associated with maternal complications, although not significantly. CONCLUSIONS: In this study, the pregnancy rate of Japanese women with ESRD was 0.25% per year. The study generates the hypothesis that ESRD caused by diabetic nephropathy and age at conception ≥ 38 years are potential risk factors for maternal complications but not for neonatal complications in dialysis patients, and that hypoalbuminemia is a potential risk factor for both kinds of complications.

Oxytetracycline-hydrocortisone ointment reduces the occurrence of both dry socket and post-extraction pain after third molar extraction: An observational study.

OBJECTIVES: Dry socket and post-extraction pain are typical discomforts experienced by patients after tooth extraction. In this study, we inserted gauze coated with oxytetracycline-hydrocortisone ointment into the extraction socket immediately after lower third molar extraction and then evaluated the occurrence of dry socket and post-extraction pain compared with gauze non-insertion. METHODS: This retrospective study was carried out on patients undergoing lower third molar extraction in the Department of Oral Surgery at Shizuoka Prefectural General Hospital in Shizuoka, Japan from November 2018 to October 2019. A comparison was carried out between a gauze-insertion group and a non-insertion group. The occurrence versus non-occurrence of dry socket was determined, and degree of pain was assessed based on a visual analogue scale (VAS) and on patients reporting the number of loxoprofen sodium oral analgesic tablets (60mg/tablet) that they had taken. Dry socket was defined as patient-reported spontaneous pain that did not subside 1 to 3 days postoperatively. Spontaneous post-extraction pain was recorded four times: on the operative day, on the first postoperative day (POD1), on POD3, and during suture removal (POD7). RESULTS: The occurrence of dry socket was lower in the gauze-insertion group than in the non-insertion group (0.9%, 2/215 vs. 19.6%, 9/46, p<0.001). The results also showed that both VAS-defined pain level and the number of analgesic tablets taken were lower in the gauze-insertion group than in the non-insertion group on POD3 and POD7. CONCLUSIONS AND CLINICAL RELEVANCE: Inserting gauze coated with oxytetracycline-hydrocortisone ointment into the extraction socket immediately after third molar extraction reduces the occurrence of both dry socket and post-extraction pain.

Comparison of the Safety Profiles of Pegylated Interferon α-2a and α-2b Administered in Combination with Ribavirin for Chronic Hepatitis C Infection: A Real-World Retrospective Cohort Study.

This study compares the safety profiles of pegylated interferon (PEG-IFN) α-2a and α-2b administered in combination with ribavirin, based on the variable of time to withdrawal from treatment due to adverse events. We conducted a real-world retrospective cohort study using the Japanese interferon database. Based on eligibility criteria, individuals with chronic hepatitis C virus (HCV) infection were identified in the database covering the period December 2009 to August 2015. The primary outcome measure was defined as difference in time to withdrawal from treatment due to adverse events between patients receiving PEG-IFN α-2a combined with ribavirin and those receiving PEG-IFN α-2b combined with ribavirin. The difference was analyzed using the multivariate Cox proportional hazards regression model. A frailty model was also applied to consider regional (prefectural) variation. After eligibility evaluation, 11058 individuals were included in the analysis. 3774 were treated with PEG-IFN α-2a, and 6764 with PEG-IFN α-2b, with 11.84 and 12.30% respectively withdrawing from treatment due to adverse events. The Cox model showed no significant difference between the two groups (hazard ratio (HR), 95%CI; 0.918, 0.817 to 1.031; p=0.1475). The results were consistent even when regional variation and other confounding variables were adjusted in the frailty model. In conclusion, there may be no difference in time to withdrawal from treatment due to adverse events between PEG-IFN α-2a and PEG-IFN α-2b combined with ribavirin. Applying the method used here to future studies using novel treatment regimens may also provide important information for the treatment of chronic HCV infection in clinical practice.