Thirty-two years' experience of treating fulminant hepatitis in a Japanese single center.

AIM: The prognosis of patients with acute liver failure has improved dramatically in the past three decades due to advances in medical critical care and use of liver transplantation (LT) in Western countries, where the etiology of acute liver failure is different from that in Japan. We analyzed patients with fulminant hepatitis (FH) and late-onset hepatic failure (LOHF) admitted to our unit over a 32-year period to clarify the nature of Japanese patients with FH and LOHF. METHODS: A total of 137 Japanese patients with FH and LOHF between 1986 and 2017 were analyzed for etiologies, disease types, treatment protocols, and outcome. RESULTS: Of 137 patients, 124 were FH (53 acute type and 71 subacute type) and 13 LOHF. The major etiology was due to viral infections in 48% of patients. A total of 23.4% of patients recovered without LT, 7.3% received LT, and 69.3% died without LT. The number of patients showed rise and fall without an evident decrease during the period. Patients with autoimmune hepatitis increased after the establishment of autoimmune hepatitis criteria in 1999 (p < 0.001), and that with indeterminate cause decreased (p < 0.01). The mean age was older in the last decade than in the first decade (p = 0.036). Spontaneous and overall survival rates were not different during the period. CONCLUSIONS: The prognosis of our patients with FH and LOHF has not improved, probably because of aging and the increasing proportion of etiologies with poor prognosis and difficult-to-treat patients without response to medications regardless of advancement of clinical management, including artificial liver support devices and LT.

Diagnostic value of peroral cholangioscopy in addition to computed tomography for indeterminate biliary strictures.

BACKGROUND: Peroral cholangioscopy (POCS) has been used to overcome the difficulty in diagnosing indeterminate biliary stricture or tumor spread. However, the value of adding POCS to computed tomography (CT) remains unclear. Our aim was to evaluate the diagnostic value of adding POCS to CT for indeterminate biliary stricture and tumor spread by interpretation of images focusing on the high diagnostic accuracy of visual findings in POCS. METHODS: We retrospectively identified 52 patients with biliary stricture who underwent endoscopic retrograde cholangiography (ERC) at our institution between January 2013 and December 2018. Two teams, each composed of an expert endoscopist and surgeon, performed the interpretation independently, referring to the CT findings of the radiologist. The CT + ERC + POCS images (POCS group) were evaluated 4 weeks after the evaluation of CT + ERC images (CT group). A 5-point scale (1: definitely benign to 5: definitely malignant) was used to determine the confident diagnosis rate, which was defined as an evaluation value of 1 or 5. Tumor spread was also evaluated. RESULTS: In the evaluation of 45 malignant diagnoses, the score was significantly closer to 5 in the POCS group than in the CT group in both teams (P < 0.001). The confident diagnosis rate was significantly higher for the POCS group (92% and 73%) than for the CT group (25% and 12%) in teams 1 and 2, respectively (P < 0.001). We found no significant difference in diagnostic accuracy for tumor spread between the groups. CONCLUSION: Visual POCS findings confirmed the diagnosis of biliary strictures. POCS was useful in cases of indefinite diagnosis of biliary strictures by CT.

Liver cirrhosis is a risk factor for poor prognosis of acute cholangitis caused by choledocholithiasis.

INTRODUCTION AND OBJECTIVES: Acute cholangitis, which is characterized by biliary infection and acute liver injury, may impact cirrhosis prognosis. However, the prognosis itself remains unclear. MATERIALS AND METHODS: This multicenter retrospective cohort study compared the mortality and liver function change between patients with and without cirrhosis who underwent endoscopic treatment for acute cholangitis caused by choledocholithiasis between January 2004 and December 2019. RESULTS: We analyzed 699 patients, 44 of whom had cirrhosis. The cirrhotic group had a significantly higher 30-day mortality rate than the noncirrhotic group (14% vs. 1%; P < 0.001). The cirrhotic group also had significantly lower total bilirubin and albumin recovery. However, all patients with cirrhosis who survived achieved total-bilirubin recovery, and 91% achieved albumin recovery within 90 days. In multivariable Cox regression analysis, the independent risk factors for total-bilirubin recovery included cirrhosis (hazard ratio, 0.37; 95%CI, 0.24‒0.58; P < 0.001) and high total-bilirubin level (0.46; 95%CI, 0.34‒0.60; P < 0.001), whereas those for albumin recovery were cirrhosis (0.51; 95%CI, 0.33‒0.79; P = 0.002), high age (0.62; 95%CI, 0.47‒0.82; P < 0.001), organ dysfunction (0.62; 95%CI, 0.39‒0.96; P = 0.03), low albumin level (0.57; 95%CI, 0.36‒0.91; P = 0.02), and high C-reactive protein level (0.73; 95%CI, 0.56‒0.95; P = 0.02). CONCLUSIONS: Patients with cirrhosis complicated with acute cholangitis had poor prognosis. Recovery of liver function after endoscopic treatment was slow; nevertheless, most patients who survived could recover within 90 days.

Analysis of circulating cell-free DNA after endoscopic ultrasound-guided fine needle aspiration in pancreatic ductal adenocarcinoma.

BACKGROUND/OBJECTIVES: Recently, increase in cell-free DNA (cfDNA) concentration or newly detected KRAS mutation after endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy were reported to be related to the occurrence of new distant metastasis. In this study, we investigated whether cfDNA concentration increased with the release of tumor components into the blood after EUS-FNA and whether its increase was related to prognosis. METHODS: Sixty-eight patients underwent EUS-FNA and were pathologically confirmed as having pancreatic ductal adenocarcinoma (PDAC). We measured plasma cfDNA concentration and the copy number of KRAS mutation in 68 patients and circulating tumor cells in 8 before and after EUS-FNA. RESULTS: The average cfDNA concentration after EUS-FNA (672.5 ± 919.6 ng/mL) was significantly higher than that before EUS-FNA (527.7 ± 827.3 ng/mL) (P < 0.001). KRAS mutation in plasma was detected in 8 patients (11.8%), however a significant increase in cfDNA concentration after EUS-FNA was not related to the change in KRAS-mutant copy number. Minimal increase in circulating tumor cells was observed in 3 of 8 patients. New distant metastasis was observed within 286 days to initial metastasis detection in 6 of 12 patients with ≥2-fold increase in cfDNA concentration and 26 of 56 patients with <2-fold increase within 185 days. In 32 patients who underwent surgery, ≥2-fold increase in cfDNA did not affect early recurrence. CONCLUSIONS: The increase in cfDNA concentration after EUS-FNA was not caused by tumor cell components released into blood vessels. Hence, the risk of seeding via the blood stream after EUS-FNA may need not be considered.

Sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a multicenter retrospective study in Japan.

Background Conversion from sorafenib to regorafenib is primarily an evidence-based treatment strategy in patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess the safety and efficacy of sequential therapy with sorafenib and regorafenib in patients with advanced HCC by analysis of outcomes in clinical practice with the aim to complement phase III findings. Methods The medical records of patients with advanced HCC receiving regorafenib were retrieved to collect data on sorafenib administration at seven Japanese institutions. Radiological responses and adverse events were evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1 and the Common Terminology Criteria for Adverse Events version 4.0, respectively. Results Before March 2018, 44 patients were administered regorafenib for advanced HCC. The median sorafenib treatment duration was 8.4 months. The most common adverse events were similar to those reported by the RESORCE trial. The median overall survival (OS) was 17.3 months (95% confidence interval [CI] 11.4-22.9), and 17 of 37 patients (45.9%) discontinued regorafenib and received sequential systemic therapy after regorafenib. These patients had significantly longer OS than those who were treated by the best supportive care or sub-optimal therapy (not reached versus 8.7 months [95% CI 5.8-11.7]; P < 0.001). Conclusion The results based on Japanese clinical practices verified the tolerability of regorafenib in advanced HCC. Major regorafenib-associated adverse events were similar to those related to sorafenib. OS was significantly longer than expected, which might be associated with the sequential systemic therapies after regorafenib, mainly lenvatinib.

Diverse transitions in diabetes status during the clinical course of patients with resectable pancreatic cancer.

OBJECTIVE: Pancreatic cancer and diabetes status have complex bilateral interactions; therefore, understanding their clinical features is essential for the clinical management of pancreatic cancer patients. We aimed to evaluate the diabetes status before diagnosis, after resection and until the time of recurrence in patients with resectable pancreatic cancer and to clarify the correlations among the clinical course of pancreatic cancer, operative procedure and diabetes status. METHODS: Between 2011 and 2016, we retrospectively identified 189 pancreatic cancer patients who underwent pancreatoduodenectomy or distal pancreatectomy at our institution. The entire clinical course of each patient was retrieved from the medical records, and the diabetes status in the longest possible duration was assessed. RESULTS: Among 115 pancreatic cancer patients who had normal glucose tolerance at the time of resection, 22 (19.1%) developed type 2 diabetes after resection. In a multivariate analysis, distal pancreatectomy was strongly associated with the development of postoperative diabetes. On the other hand, 74 pancreatic cancer patients had already been diagnosed with type 2 diabetes at the time of resection. During the follow-up period, 15 patients were noted to have diabetes resolution after resection; interestingly, the majority of these patients had newly diagnosed diabetes, which was defined as the diagnosis of diabetes within 3 months before resection. Moreover, newly diagnosed diabetes was an independent factor for diabetes resolution after resection. CONCLUSIONS: In pancreatic cancer patients who underwent pancreatectomy, distal pancreatectomy was correlated with postoperative diabetes, and newly diagnosed diabetes had a high probability of resolution after resection.

Long-term administration of Tolvaptan to patients with decompensated cirrhosis.

Aim: Tolvaptan, an oral vasopressin-2 antagonist, sometimes improves hepatic edema including ascites in patients with decompensated cirrhosis. In this study, we examined the effectiveness and survival advantage in patients with the long-term administration of tolvaptan. Methods: A total of 115 patients with refractory ascites who were treated with tolvaptan were retrospectively analyzed based on their clinical records. Patients with a decrease in body weight of ≥1.5 kg from the baseline on day 7 were determined as responders. Re-exacerbation was defined as a return to the baseline BW, dose escalation of conventional diuretics, or abdominal drainage. Results: Of the 115 patients, 84 were included in this analysis. Response to tolvaptan treatment was observed in 55 out of the 84 patients (65.5%), with a mean weight reduction of 2.52 kg. Multivariate analyses demonstrated that body mass index (≥24) and urinary specific gravity (≥1.018) were significant predictors of the response to tolvaptan. However, cumulative re-exacerbation rates in responders at 6 and 12 months were 42.4 and 60.1%, respectively. Child-Pugh (classification C), HCC complication, and serum sodium levels (≥133 mEq/L) were determined as independent prognostic factors impacting overall survival (OS). Although there were no significant differences in OS between tolvaptan responders and non-responders, the responders without re-exacerbation within 3 months showed significantly longer OS than those with re-exacerbation within 3 months. Conclusion: A persistent therapeutic response, but not early response to tolvaptan, was associated with favorable survival of decompensated cirrhotic patients.

High recovery rate of consciousness by high-volume filtrate hemodiafiltration for fulminant hepatitis.

AIM: An artificial liver support (ALS) system sustaining patients with acute liver failure (ALF) in good condition until recovery of the native liver or performance of liver transplantation (LT), is essential for the improvement of the poor prognosis of ALF despite the lack of survival benefit. We aimed to investigate the efficacy of various ALS systems for fulminant hepatitis (FH) carried out in our liver unit so far, focusing on the restoration of consciousness from hepatic encephalopathy. METHODS: One hundred and ten consecutive adult Japanese patients with FH admitted to Chiba University Hospital (Chiba, Japan) between 1988 and 2016 who received ALS were analyzed. RESULTS: Recovery rate of consciousness improved with the increased dialysate flow rate and filtrate rate: 37.5% by plasma exchange (PE), 51.9% by PE + continuous hemodiafiltration (CHDF), 57.7% by slow PE (sPE) + high-flow CHDF (HFCHDF) (QD = 300 mL/min), 88.6% by HFCHDF (QD = 500 mL/min) (+ sPE), and 92.9% by on-line HDF (OLHDF) (+ sPE). All patients except one, who could not be fully treated because of circulatory failure, recovered consciousness by OLHDF, including those whose liver function were completely abolished. Superiority of HFCHDF (QD = 500 mL/min) and OLHDF was also shown in patients who died without LT or received LT. CONCLUSIONS: More effective ALS should be recognized considering the extremely high recovery rate of consciousness. In particular, OLHDF with predilution reduces the cost of substitution fluid by supplying an unlimited amount of dialysate as substitution fluid prepared using an on-line system, and simplifies the procedure for the management.

Characteristics of patients with sorafenib-treated advanced hepatocellular carcinoma eligible for second-line treatment.

Background Regorafenib has been investigated for its efficacy and safety as a second-line treatment in patients with advanced hepatocellular carcinoma (HCC). We assessed the characteristics of patients with HCC treated with sorafenib who might be eligible for second-line treatment in general and regorafenib in particular. Methods Patients with HCC treated with sorafenib were retrospectively analyzed. We defined second-line candidate patients as maintaining Child-Pugh A and ECOG-PS ≤1 at the time of sorafenib failure. We also defined regorafenib candidate patients as follows: 1) continuing sorafenib at the time of radiological progression, 2) maintaining Child-Pugh A and ECOG-PS ≤ 1 at the time of sorafenib failure, and 3) continuing sorafenib 400 mg or more without intolerable adverse events at least 20 days of the last 28 days of treatment. Results Of 185 patients, 130 (70%) and 69 (37%) were candidates for second-line treatment and regorafenib. Child-Pugh score 6 and ECOG-PS 1 at the time of starting sorafenib were significantly lower in both second-line treatment and regorafenib candidate patients. Moreover, hand-foot skin reaction and liver failure during sorafenib treatment were associated with significantly low and high probabilities, respectively, of both Child-Pugh score > 6 and ECOG-PS > 1 at the time of sorafenib failure. Conclusion Regorafenib candidate patients after sorafenib failure are limited, and generally fewer than those who are candidates for second-line treatment. A lower Child-Pugh score and a better ECOG-PS were predictors of eligibility for second-line therapy and regorafenib treatment in sorafenib-treated patients with advanced HCC patients.

Immunohistochemical analysis of IMP3 and p53 expression in endoscopic ultrasound-guided fine needle aspiration and resected specimens of pancreatic diseases.

BACKGROUND: Insulin-like growth factor II messenger ribonucleic acid-binding protein 3 (IMP3) is a valuable marker that distinguishes malignant from benign lesions and predicts prognosis. METHODS: First, we evaluated IMP3 expression in 77 resected specimens of pancreatic ductal adenocarcinoma (PDAC), intraductal papillary mucinous neoplasm (IPMN), and chronic pancreatitis (CP). Eleven PDAC patients preoperatively underwent endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Survival analysis of IMP3 and clinicopathological factors was performed. IMP3 and p53 expression was evaluated in another 127 EUS-FNA samples of solid pancreatic masses to compare the diagnostic value of routine and immunohistochemical staining. RESULTS: IMP3 expression was detected in 72.3%, 50%, 20%, and 0% of PDAC, malignant IPMN, benign IPMN, and CP, respectively. Evaluation of IMP3 expression in EUS-FNA specimens coincided with that in resected specimens in 10 of 11. IMP3 expression correlated with tumor differentiation in PDAC samples (p = .006) and with poor prognosis through univariate analysis (p = .045). Tumor differentiation and lymph node metastasis were significantly associated with poor prognosis through multivariate analysis. In EUS-FNA specimens, the sensitivity, specificity, and accuracy of cytohistological analysis were 80.8%, 100%, and 85.0%, respectively. IMP3 and p53 expression were detected in 80.8% and 44.9% of malignant and 0% and 5% of benign lesions. Combined with IMP3 immunostaining, the sensitivity, specificity and accuracy of cytohistological analysis significantly increased to 87.9%, 100%, and 90.8% (p = .016), respectively. Meanwhile, p53 staining had no impact on the results. CONCLUSIONS: IMP3 immunohistochemical staining can improve the diagnostic accuracy of EUS-FNA for malignant pancreatic tumors.

Transpancreatic precut papillotomy versus double-guidewire technique in difficult biliary cannulation: prospective randomized study.

BACKGROUND AND STUDY AIMS: Difficult biliary cannulation and unintentional pancreatic duct cannulation are thought to be important contributors to pancreatitis occurring after endoscopic retrograde cholangiopancreatography. Our aim was to compare and evaluate the rates of success and complications of transpancreatic precut papillotomy (TPPP) and the double-guidewire technique (DGT), both with prophylactic pancreatic stenting. PATIENTS AND METHODS: From April 2011 to March 2014, patients with difficult biliary cannulation, in whom we planned to first position a guidewire in the pancreatic duct, were enrolled, and 68 patients were prospectively randomly allocated to two groups (TPPP 34, DGT 34). We evaluated the rates of success and complications for each group. RESULTS: TPPP had a significantly higher success rate (94.1 %) than DGT (58.8 %). The rate of post-ERCP pancreatitis was 2.9 % in both groups. There was no significant difference between the two groups in the overall rate of complications related to cannulation. CONCLUSION : If biliary cannulation cannot be achieved, TPPP should be selected first after unintentional pancreatic duct cannulation.

Corticosteroid might reduce serum levels of pro-inflammatory cytokines in fulminant hepatitis: A case series.

AIM: There are no beneficial therapies except for emergency liver transplantation for acute liver failure (ALF). However, in Japan, which has a serious problem in the shortage of donor livers, therapies other than transplantation must be further investigated for patients with ALF. Pro-inflammatory cytokines promoting tissue destruction are predominant at an early phase of ALF. Corticosteroid (CS) influences monocyte/macrophage differentiation, by suppressing pro-inflammatory genes, indicating CS treatment might be beneficial during the early phase of ALF. Our aim was to elucidate the efficacy of CS pulse therapy in decreasing pro-inflammatory cytokine levels in the early stage of ALF. METHODS: Ten consecutive adult Japanese patients with fulminant hepatitis in the early stage, three treated with artificial liver support (ALS) and CS pulse therapy (ALS + CS group) and seven treated with ALS (ALS group), were enrolled. Clinical and biochemical data on admission were matched between the groups and retrospectively analyzed for serum concentrations of interleukin-6, tumor necrosis factor-α, and interleukin-1ß over a 2-week period. RESULTS: Mean cytokine levels on admission were not different between the two groups. Tumor necrosis factor-α was significantly reduced on day 7 in patients with CS. Serum levels of pro-inflammatory cytokines tended to be reduced in patients with CS compared to those without during the observation period, although the differences were not significant. CONCLUSIONS: It might be possible that introduction of CS pulse therapy in the early stage of ALF could reduce levels of pro-inflammatory cytokines, which might inhibit the cascade of progression of ALF.

Association of IFNL3 Genotype with Hepatic Steatosis in Chronic Hepatitis C Patients Treated with Peginterferon and Ribavirin Combination Therapy.

BACKGROUND: Genetic variation near the interferon lambda 3 (IFNL3) is known to be associated with response to pegylated interferon (pegIFN) and ribavirin combination therapy in patients with chronic hepatitis C virus (HCV) infection which is often accompanied by hepatic steatosis. AIMS: We examined whether this genetic variation is associated with host lipids and treatment response. METHODS: A total of 101 Japanese patients who had underwent liver biopsy before treatment with pegIFN and ribavirin for HCV genotype 1b infection were retrospectively analyzed for association between IFNL3 genotypes (rs8099917) and clinical factors including histopathological features of the liver. The presence of >5% steatosis in the liver specimen was defined as hepatic steatosis. RESULTS: Forty patients (40%) had liver steatosis before therapy. Patients with IFNL3 minor genotype (non-TT) showed lower low-density lipoprotein cholesterol level (p=0.0045), higher γ-glutamyl transpeptidase level (p=0.0003) and higher prevalence of hepatic steatosis (p=0.0002). Advanced fibrosis [odds ratio (OR) 4.63, p=0.03] and IFNL3 major genotype (OR 0.13, p=0.001) were 2 independent factors for determining the presence of hepatic steatosis. Among the factors associated with sustained virological response, IFNL3 genotype was the most significant predictor, as per multivariate analysis. CONCLUSIONS: Our results confirmed that IFNL3 genotype is associated with hepatic steatosis as well as IFN response.

Discrepancy between Hepatitis C Virus Genotypes and NS4-Based Serotypes: Association with Their Subgenomic Sequences.

Determination of hepatitis C virus (HCV) genotypes plays an important role in the direct-acting agent era. Discrepancies between HCV genotyping and serotyping assays are occasionally observed. Eighteen samples with discrepant results between genotyping and serotyping methods were analyzed. HCV serotyping and genotyping were based on the HCV nonstructural 4 (NS4) region and 5'-untranslated region (5'-UTR), respectively. HCV core and NS4 regions were chosen to be sequenced and were compared with the genotyping and serotyping results. Deep sequencing was also performed for the corresponding HCV NS4 regions. Seventeen out of 18 discrepant samples could be sequenced by the Sanger method. Both HCV core and NS4 sequences were concordant with that of genotyping in the 5'-UTR in all 17 samples. In cloning analysis of the HCV NS4 region, there were several amino acid variations, but each sequence was much closer to the peptide with the same genotype. Deep sequencing revealed that minor clones with different subgenotypes existed in two of the 17 samples. Genotyping by genome amplification showed high consistency, while several false reactions were detected by serotyping. The deep sequencing method also provides accurate genotyping results and may be useful for analyzing discrepant cases. HCV genotyping should be correctly determined before antiviral treatment.

Real-World Experiences with the Combination Treatment of Ledipasvir plus Sofosbuvir for 12 Weeks in HCV Genotype 1-Infected Japanese Patients: Achievement of a Sustained Virological Response in Previous Users of Peginterferon plus Ribavirin with HCV NS3/4A Inhibitors.

The aim of this study was to characterize the treatment response and serious adverse events of ledipasvir plus sofosbuvir therapies in Japanese patients infected with hepatitis C virus (HCV) genotype 1 (GT1). This retrospective study analyzed 240 Japanese HCV GT1 patients treated for 12 weeks with 90 mg of ledipasvir plus 400 mg of sofosbuvir daily. Sustained virological response at 12 weeks post-treatment (SVR12) was achieved in 236 of 240 (98.3%) patients. Among treatment-naïve patients, SVR12 was achieved in 136 of 138 (98.6%) patients, and among treatment-experienced patients, SVR12 was achieved in 100 of 102 (98.0%) patients. In patients previously treated with peginterferon plus ribavirin with various HCV NS3/4A inhibitors, 100% SVR rates (25/25) were achieved. Two relapsers had HCV NS5A resistance-associated variants (RAVs), but no HCV NS5B-S282 was observed after they relapsed. We experienced two patients with cardiac events during treatment. In conclusion, combination of ledipasvir plus sofosbuvir for 12 weeks is a potential therapy for HCV GT1 patients. Caution is needed for HCV NS5A RAVs, which were selected by HCV NS5A inhibitors and cardiac adverse events.

Successful sofosbuvir treatment with ribavirin dose reduction for chronic hepatitis C virus genotype 2 infection in a patient with ulcerative colitis: a case report.

BACKGROUND: Ulcerative colitis is a lifelong, immunologically mediated disease. Direct-acting antivirals (DAAs) are now available for the treatment of chronic hepatitis C virus (HCV) infection. An interferon-free regimen appears useful, safe and effective for many patients for whom interferon-based treatment is contraindicated. CASE PRESENTATION: We studied a 56-year-old treatment-naïve Japanese man with chronic HCV genotype 2b infection who had ulcerative colitis. This patient was treated with sofosbuvir and ribavirin for 12 weeks. During treatment, diarrhoea and bloody faeces were frequent. After ribavirin was reduced to 400 mg daily, these symptoms decreased. Finally, the patient achieved a sustained virologic response 12 weeks after the stoppage of the treatment. CONCLUSION: Clinicians should pay careful attention to the ribavirin dose in the treatment of certain HCV patients with inflammatory bowel disease who are receiving sofosbuvir plus ribavirin.

Daclatasvir plus Asunaprevir Treatment for Real-World HCV Genotype 1-Infected Patients in Japan.

Background. All-oral combination of direct-acting antivirals could lead to higher sustained virologic response (SVR) in hepatitis C virus (HCV)-infected patients. In the present study, we examined the efficacy and safety of the dual oral treatment with HCV nonstructural protein (NS) 5A inhibitor daclatasvir (DCV) plus HCV NS3/4A inhibitor asunaprevir (ASV) for 24 weeks in real-world HCV genotype 1-infected Japanese individuals. Methods. After screening for HCV NS5A resistance-associated variants (RAVs) by PCR invader assay, a total of 54 Japanese patients infected with HCV genotype 1 treated with DCV plus ASV were retrospectively analyzed. SVR12 was used for evaluation of the virologic response. Results. Of the total 54 patients, 46 patients (85.2%) were treated with DCV plus ASV for 24 weeks and achieved SVR12. The other 8 patients (14.8%) discontinued this treatment before 24 weeks due to adverse events. Of these 8 patients, 5 and 3 patients did and did not achieve SVR12, respectively. Finally, 51 of 54 (94.4%) patients achieved SVR12. Conclusion. Treatment with DCV and ASV after screening for HCV NS5A RAVs by PCR invader assay is effective and safe in the treatment of real-world HCV genotype 1-infected patients in Japan.