Efficacy of a moisturizer for pruritus accompanied by xerosis in patients undergoing dialysis: A multicenter, open-label, randomized verification study.

Xerosis and pruritus are common in patients undergoing dialysis. These symptoms are treated with moisturizers, but limited evidence supports the efficacy of such treatment. Our exploratory study suggested the effectiveness of a heparinoid-containing product for xerosis in dialysis patients. We conducted a multicenter, open-label, randomized, before-after, parallel-group comparative study to verify the exploratory study results (Clinical Trial Registry: UMIN000029360). Seventy-one Japanese patients undergoing dialysis with chronic kidney disease and xerosis were randomly assigned to receive a heparinoid-containing product for 2 weeks (group A [n = 36]) or 8 weeks (group B [n = 35]). Patients were instructed to apply the study product based on the fingertip unit method. The efficacy endpoints were the water content of the stratum corneum (WCSC), skin dryness score, pruritus visual analog scale score, and Dermatology Life Quality Index. Safety was assessed by monitoring adverse events. The mean WCSC (arbitrary units) was 26.0 ± 9.6 in group A and 25.2 ± 10.0 in group B at the start of treatment (week 0), significantly increased to 39.0±12.5 in group A and 38.5 ± 11.0 in group B (P < 0.0001 for both vs week 0) by week 2, and then decreased only in group A. Thus, the WCSC at week 4 (the primary endpoint) remained significantly higher in group B (36.4 ± 12.2 vs 28.8 ± 10.4; P = 0.0068). Other endpoints improved during treatment with the study product. One patient developed a rash and erythema as treatment-related adverse events. In conclusion, 8 weeks' application of a heparinoid-containing product was effective for xerosis in patients undergoing dialysis.

Association of adipocytokines with peritoneal function.

BACKGROUND: Preservation of peritoneal function is crucial for the continuation of peritoneal dialysis (PD). A previous study suggested that blood cholesterol is involved in the preservation of peritoneal function; therefore, we determined whether adipocytokines can predict peritoneal function preservation. METHODS: Eighty patients were enrolled. Serum adiponectin, leptin, apelin, various blood components, and estimated glomerular filtration rate (eGFR) (mL/min/m2) were measured. In addition, the duration of PD, presence or absence of peritonitis and diabetes mellitus, body mass index, urine output, peritoneal Kt/V, renal Kt/V, weekly Kt/V, peritoneal creatinine clearance rate (CCr), renal CCr, weekly CCr, use or nonuse of statin products, dialysate volume, glucose exposure, and use or nonuse of icodextrin dialysate were assessed. Peritoneal equilibration tests were performed at 6-month intervals, and dialysate-to-plasma [D/P] ratio and glucose uptake ratio [D/D0] were measured. Associations of the baseline values and their percent changes with various adipocytokines and test items were evaluated. RESULTS: Multiple regression analyses identified adiponectin (p = 0.0392, p = 0.0348) as a significant predictive factor of D/P and D/D0 ratios. eGFR was identified as a significant predictive factor (p = 0.015) of percent change in the D/P ratio. Apelin (p = 0.0484), high-density lipoprotein cholesterol (p = 0.0066), dialysate volume (p = 0.0223), and urine output (p = 0.0020) were identified as factors affecting the duration of PD. CONCLUSIONS: Adipocytokines are a predictive factor of peritoneal function and the duration of PD in patients undergoing PD.

Lipopolysaccharide directly inhibits bicarbonate absorption by the renal outer medullary collecting duct.

Acidosis is associated with E. coli induced pyelonephritis but whether bacterial cell wall constituents inhibit HCO3 transport in the outer medullary collecting duct from the inner stripe (OMCDi) is not known. We examined the effect of lipopolysaccharide (LPS), on HCO3 absorption in isolated perfused rabbit OMCDi. LPS caused a ~ 40% decrease in HCO3 absorption, providing a mechanism for E. coli pyelonephritis-induced acidosis. Monophosphoryl lipid A (MPLA), a detoxified TLR4 agonist, and Wortmannin, a phosphoinositide 3-kinase inhibitor, prevented the LPS-mediated decrease, demonstrating the role of TLR4-PI3-kinase signaling and providing proof-of-concept for therapeutic interventions aimed at ameliorating OMCDi dysfunction and pyelonephritis-induced acidosis.

Correction to: Pharmacokinetics and Dialyzability of a Single Oral Dose of Amenamevir, an Anti-Herpes Drug, in Hemodialysis Patients.

In the original article, there is incorrect text has published as "The hemodialysis clearance, elimination fraction percentage, and amount of amenamevir removed were 37.8 mL/min, 28.1%, and 132.0 µg, respectively".

Practice Advisory on the Appropriate Use of NSAIDs in Primary Care.

Cyclo-oxygenase (COX)-2 selective and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are important in managing acute and chronic pain secondary to inflammation. As a greater understanding of the risks of gastrointestinal (GI), cardiovascular (CV) and renal events with NSAIDs use has emerged, guidelines have evolved to reflect differences in risks among NSAIDs. Updated guidelines have yet to reflect new evidence from recent trials which showed similar CV event rates with celecoxib compared to naproxen and ibuprofen, and significantly better GI tolerability for celecoxib. This practice advisory paper aims to present consensus statements and associated guidance regarding appropriate NSAID use based on a review of current evidence by a multidisciplinary group of expert clinicians. This paper is especially intended to guide primary care practitioners within Asia in the appropriate use of NSAIDs in primary care. Following a literature review, group members used a modified Delphi consensus process to determine agreement with selected recommendations. Agreement with a statement by 75% of total voting members was defined a priori as consensus. For low GI risk patients, any nonselective NSAID plus proton pump inhibitor (PPI) or celecoxib alone is acceptable treatment when CV risk is low; for high CV risk patients, low-dose celecoxib or naproxen plus PPI is appropriate. For high GI risk patients, celecoxib plus PPI is acceptable for low CV risk patients; low-dose celecoxib plus PPI is appropriate for high CV risk patients, with the alternative to avoid NSAIDs and consider opioids instead. Appropriate NSAID prescription assumes that the patient has normal renal function at commencement, with ongoing monitoring recommended. In conclusion, appropriate NSAID use requires consideration of all risks.

Pharmacokinetics and Dialyzability of a Single Oral Dose of Amenamevir, an Anti-Herpes Drug, in Hemodialysis Patients.

INTRODUCTION: Amenamevir (ASP2151), a herpesvirus helicase-primase inhibitor, is currently used for the treatment of herpes zoster in Japan. Amenamevir is mainly metabolized in the liver, and urinary excretion of amenamevir is approximately 10% in healthy adults. The increase of systemic exposure in non-dialysis patients with severe renal impairment was much less than that associated with nucleoside antiviral agents. The aim of this study was to evaluate the pharmacokinetics and dialyzability of a single oral dose (400 mg) of amenamevir in hemodialysis patients. METHODS: This was a single-arm, open-label, multicenter clinical pharmacology study. Nine patients aged 20-80 years with end-stage kidney disease and undergoing maintenance hemodialysis three times weekly were enrolled. Pharmacokinetics and dialyzability were investigated by serial collection of blood samples until 48 h post-dose during the study. RESULTS: The maximum plasma concentration and time to reach maximum plasma concentration during 24 h post-dose were 1585 ng/mL and 6.2 h, respectively. The area under the plasma concentration-time curve (AUC) from time zero to 24 h was 23,890 ng h/mL. The median terminal elimination half-life within 24 h before, during, and after hemodialysis was 14.7, 15.2, and 12.4 h, respectively. The AUC in hemodialysis patients was approximately double that in healthy adults. This increase in AUC was much less than that reported in nucleoside antiviral agents. The hemodialysis clearance, elimination fraction percentage, and amount of amenamevir removed were 37.8 mL/min, 28.1%, and 132.0 µg, respectively. The amount of amenamevir removed by hemodialysis was minimal. None of the hemodialysis parameters were associated with serum albumin. This study revealed no clinically relevant safety concerns. CONCLUSION: There were no clinically relevant safety concerns when 400 mg of amenamevir was administered as a single dose to hemodialysis patients without dose adjustment and/or modification of the dosing schedule. TRIAL REGISTRATION: JapicCTI-184242.

Effective improvement of minimal change nephrotic syndrome with uncontrollable high low-density lipoprotein cholesterol level using evolocumab accompanied by the development of acute pancreatitis.

Nephrotic syndrome is sometimes refractory; however, it is rarely accompanied by acute pancreatitis. A 47-year-old Japanese woman complaining of limb edema was diagnosed with nephrotic syndrome. Blood and urine examinations suggested minimal change nephrotic syndrome (MCNS), and pulse intravenous methylprednisolone was administered, followed by oral prednisolone. Although proteinuria improved, the patient's condition remained unchanged, and diuresis was insufficient. As in patients with other nephrotic syndromes, this patient showed significant dyslipidemia. Atorvastatin was started for remarkable dyslipidemia since her admission, but her low-density lipoprotein cholesterol (LDL-C) level did not improve significantly. During the clinical course, she developed acute pancreatitis, and large-volume fluid replacement was performed. Although diuretic levels were increased in response to the increased fluid volume, diuresis was not enough, and lung edema developed. Extracorporeal ultrafiltration was started to ameliorate the lung edema. With the onset of pancreatitis, oral intake, including atorvastatin, was discontinued, and prednisolone was administered intravenously. To treat the high-LDL cholesterolemia, 140 mg of evolocumab was injected subcutaneously. Nausea slightly decreased on the following day, and the administration of 150 mg cyclosporine was initiated. LDL-C levels, proteinuria, and renal function promptly ameliorated. The results of a renal biopsy suggested MCNS. On the 44th day of hospitalization, she had complete remission. Evolocumab is potentially effective for severe nephrotic syndrome with uncontrollable dyslipidemia.

Modified forearm ischemic test in hypouricemic patients.

Renal hypouricemia sometimes leads to exercise-induced acute kidney injury (EIAKI) of unknown pathogenesis. In order to elucidate the various pathological conditions associated with hypouricemia, we analyzed the effects of low uric acid level on energy metabolism. We have modified semi-ischemic forearm exercise test and performed this test in one Japanese healthy volunteer, three patients with hereditary renal hypouricemia and one patient with hereditary xanthinuria of Czech origin. Forearm exercise was performed by squeezing a hand dynamometer with the sphygmomanometer cuff pressure kept at the mean arterial pressure. Venous blood was drawn five times (before exercise, 3, 10, 30, 45 minutes after the start of exercise) in each tests. The mean plasma lactate concentration increased from a baseline of 1.3 (range 0.7-1.8 mmol/L) to 4.0 (range 2.0-5.5 mmol/L) at 3 minutes after the start of exercise. The plasma hypoxanthine concentrations were quite low before exercise (0-2.9 µmol/L), but increased markedly to a range of 13.6-28.8 µmol/L after 10 minute forearm ischemia. Our protocol allowed us to conclude that the load was sufficient for observing metabolic changes in temporally hypoxia and in following recovery phase. The test was well tolerated and safe, we did not observe any adverse reactions including EIAKI.

Recent approaches to gout drug discovery: an update.

INTRODUCTION: Inflammation induced by urate deposition in joints causes gout. Healthy individuals maintain serum levels of urate by balancing urate production/excretion, whereas a production/excretion imbalance increases urate levels. Hyperuricemia is diagnosed when the serum urate level is continuously above 7 mg/dl as the solubility limit, and urate accumulates in the kidneys and joints. Because hyperuricemia increases the risk of gout, therapies aim to eliminate urate deposition to prevent gouty arthritis and kidney injury. AREAS COVERED: This review discusses the mechanism underlying hyperuricemia with respect to urate production and urate transport, along with urate-lowering therapeutics, including urate synthesis inhibitors, uricolytic enzymes, and uricosuric agents. The authors asses published data on relevant commercial therapy development projects and clinical trials. EXPERT OPINION: Available treatment options for hyperuricemia are limited. Allopurinol, a urate synthesis inhibitor, is generally administered at a reduced dosage to patients with renal impairment. Some URAT1 inhibitors have an unfavorable side effect profile. A promising strategy for treatment is the use of uricosuric agents that inhibit transporters (e.g. URAT1, URATv1/GLUT9, OAT10) which reabsorb urate from the urine.

Interleukin-36α as a potential biomarker for renal tubular damage induced by dietary phosphate load.

Excessive intake of phosphate has been known to induce renal tubular damage and interstitial inflammation, leading to acute kidney injury or chronic kidney disease in rodents and humans. However, sensitive and early biomarkers for phosphate-induced kidney damage remain to be identified. Our previous RNA sequencing analysis of renal gene expression identified interleukin-36α (IL-36α) as a gene significantly upregulated by dietary phosphate load in mice. To determine the time course and dose dependency of renal IL-36α expression induced by dietary phosphate load, we placed mice with or without uninephrectomy on a diet containing either 0.35%, 1.0%, 1.5%, or 2.0% inorganic phosphate for 10 days, 4 weeks, or 8 weeks and evaluated renal expression of IL-36α and other markers of tubular damage and inflammation by quantitative RT-PCR, immunoblot analysis, and immunohistochemistry. We found that IL-36α expression was induced in distal convoluted tubules and correlated with phosphate excretion per nephron. The increase in IL-36α expression was simultaneous with but more robust in amplitude than the increase in tubular damage markers such as Osteopontin and neutrophil gelatinase-associated lipocalin, preceding the increase in expression of other inflammatory cytokines, including transforming growth factor-α, interleukin-1ß, and transforming growth factor-ß1. We conclude that IL-36α serves as a marker that reflects the degree of phosphate load excreted per nephron and of associated kidney damage.

Medical and Dental Visits of Chronic Kidney Disease-Diagnosed Participants Analyzed From the Specific Health Checkups Results in Japan: TAMA MED Project-CKD.

BACKGROUND: Since 2012, Tama City has promoted the early detection of chronic kidney disease (CKD), through an initiative that measures serum creatinine as part of the specific health checkups. We examined preventive measures against CKD deterioration based on the outcomes of this initiative. METHODS: The complications, medication status, body mass index, smoking status and other determining factors were surveyed among CKD-diagnosed participants over 3 years between 2013 and 2015. Moreover, factors aggravating CKD were investigated via a survey of medical and dental visits based on health insurance claim data over the same period. RESULTS: There was an increased rate of comorbid hypertension with each increase in the CKD stage. Comorbidity rates of diabetes mellitus, dyslipidemia, obesity, and smoking increased until CKD stage G4, and then decreased from stage G5. A substantial number of participants with CKD stage G3b and above were not medicated despite comorbidities like hypertension, diabetes mellitus and dyslipidemia. While the rate of regular visits at medical institutions was seen to increase significantly in accordance with the worsening degree of CKD, there were also individuals who, despite having severe CKD, did not visit medical institutions specializing in internal medicine. The rate of dental visits decreased as the CKD stage increased, and further decreased as the diabetic control status worsened. CONCLUSIONS: CKD patients should become aware of the importance of the dental visit because only a limited number of patients with advanced CKD received dental care.

Primary Tumor Infiltration and Severe Acute Kidney Injury in Patients with Acute Myeloblastic Leukemia.

In patients with hematologic malignancies, acute kidney injury (AKI) is the most common kidney complication requiring nephrologist consultation. Although the causes of AKI are multifactorial, primary tumor infiltration is rare in patients with acute myeloblastic leukemia (AML). This makes it challenging to determine the cause of AKI and the optimal chemotherapy regimen for AML. We describe two cases of AML (French-American-British classification: M2, M4) in patients with AKI requiring hemodialysis. We successfully identified the cause of AKI as primary leukemic infiltration and started induction chemotherapy in the setting of hemodialysis. This treatment significantly improved renal function and resulted in AML remission. In this report, we describe several clinical characteristics of AKI due to primary tumor infiltration. In addition, we emphasize the importance of onconephrology, a new subspecialty concerned with the complex relationship between the kidneys and cancer.

A case of female Fabry disease revealed by renal biopsy.

Fabry disease (FD) is an X-linked inherited glycosphingolipid metabolism disorder, therefore, heterozygous female FD patients display highly variable clinical symptoms, disease severity, and pathological findings. This makes it very challenging to diagnosing female patients with FD. A 69-year-old Japanese female was introduced to the nephrologist for the evaluation of proteinuria. A renal biopsy was performed. Although the light microscopic examinations revealed that most of the glomeruli showed minor glomerular abnormalities, however, vacuolation was apparently found in the tubular epithelial cells. Immunofluorescence staining for globotriaosylceramide was positively detected in some podocytes and distal tubular epithelial cells. In addition, myelin-like structure (zebra body) was detected by electron microscopy. Pathological findings were most consistent with FD. Consequently, biochemical and genetic analysis confirmed the diagnosis of female FD. Enzyme replacement therapy was performed in conjunction with renin-angiotensin aldosterone system inhibitors and beta-blockers. The patient's family members received the analysis, and the same DNA missense mutation was detected in the patient's grandson. The enzyme replacement therapy was introduced to the grandson. The present case showed that renal biopsy can contribute towards a correct diagnosis for FD. Particularly, in female FD patients, careful examination of pathological changes is essential, for example, vacuolation of any type of renal cells may be a clue for the diagnosis.

Inhibition of tissue-nonspecific alkaline phosphatase protects against medial arterial calcification and improves survival probability in the CKD-MBD mouse model.

Medial arterial calcification (MAC) is a major complication of chronic kidney disease (CKD) and an indicator of poor prognosis. Aortic overexpression of tissue-nonspecific alkaline phosphatase (TNAP) accelerates MAC formation. The present study aimed to assess whether a TNAP inhibitor, SBI-425, protects against MAC and improves survival probability in a CKD-mineral and bone disorder (MBD) mouse model. CKD-MBD mice were divided in three groups: vehicle, SBI-10, and SBI-30. They were fed a 0.2% adenine and 0.8% phosphorus diet from 14 to 20 weeks of age to induce CKD, followed by a high-phosphorus (0.2% adenine and 1.8% phosphorus) diet for another 6 weeks. At 14-20 weeks of age, mice in the SBI-10 and SBI-30 groups were given 10 and 30 mg/kg SBI-425 by gavage once a day, respectively, while vehicle-group mice were given distilled water as vehicle. Control mice were fed a standard chow (0.8% phosphorus) between the ages of 8 and 20 weeks. Computed tomography imaging, histology, and aortic tissue calcium content revealed that, compared to vehicle animals, SBI-425 nearly halted the formation of MAC. Mice in the control, SBI-10 and SBI-30 groups exhibited 100% survival, which was significantly better than vehicle-treated mice (57.1%). Aortic mRNA expression of Alpl, encoding TNAP, as well as plasma and aortic tissue TNAP activity, were suppressed by SBI-425 administration, whereas plasma pyrophosphate increased. We conclude that a TNAP inhibitor successfully protected the vasculature from MAC and improved survival rate in a mouse CKD-MBD model, without causing any adverse effects on normal skeletal formation and residual renal function. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Risk Factors for Acute Kidney Injury and Chronic Kidney Disease following Allogeneic Hematopoietic Stem Cell Transplantation for Hematopoietic Malignancies.

BACKGROUND: Acute kidney injury (AKI) and chronic kidney disease (CKD) are considered common complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). OBJECTIVES AND METHOD: In this study, 114 patients who had undergone allo-HSCT were retrospectively analyzed to investigate the risk factors for onset of posttransplant AKI and CKD as defined by the new Kidney Disease Improving Global Outcomes criteria. RESULTS: Seventy-four patients (64.9%) developed AKI and 25 (21.9%) developed CKD. The multivariate analysis showed that the risk factors for developing stage 1 or higher AKI were age ≥46 years at the time of transplant (p = 0.001) and use of ≥3 nephrotoxic drugs (p = 0.036). For CKD, the associated risk factors were disease status other than complete remission at the time of transplantation (p = 0.018) and onset of AKI after transplant (p = 0.035). The 5-year overall survival (OS) was significantly reduced by development of AKI (p < 0.001), but not CKD. Posttransplant AKI significantly increased the 5-year nonrelapse mortality (p < 0.001), whereas posttransplant CKD showed an increasing tendency, but the difference was not significant. CONCLUSIONS: Posttransplant AKI impacts OS, significantly increases the risk of CKD, and is significantly associated with disseminated intravascular coagulation and use of ˃3 nephrotoxic drugs.

Renal Complications after Hematopoietic Stem Cell Transplantation: Role of Graft-Versus-Host Disease in Renal Thrombotic Microangiopathy.

Hematopoietic stem cell transplantation (HSCT) is a widely accepted treatment for mainly hematopoietic disorders. Recent advances in transplantation techniques have increased the number of long-time survivors with chronic kidney disease (CKD). The presence of CKD affects outcomes and is associated with high mortality rates. Therefore, physicians treating transplant survivors should consider renal complications and optimize management of patients with CKD after HSCT. The pathology of CKD after HSCT is affected by many factors, and the causes of renal thrombotic microangiopathy (TMA) are diverse and complicated. We have treated patients who underwent allogeneic HSCT and developed late-stage renal TMA possibly associated with graft-versus-host disease (GVHD). Administration of immunosuppressive drugs, such as calcineurin inhibitors, is typically reduced in patients with TMA. However, if renal TMA is caused by renal GVHD, the use of immunosuppressive drugs should be increased, contradicting conventional thinking. On the basis of previous findings and our own observations, we review the pathology of renal complications after HSCT and focus on the role of GVHD in the development of renal TMA.

A case of membranous nephropathy diagnosed with lupus nephritis 11 years after onset.

A 34-year-old female patient presented to our hospital with lower extremity edema and proteinuria during pregnancy. Renal biopsy was performed and the patient was diagnosed with nephrotic syndrome due to lupus-like membranous nephropathy. This diagnosis was reached upon as laboratory findings upon admission, wherein both anti-nuclear and anti-double-stranded DNA antibodies revealed negative, did not fulfill the criteria for systemic lupus erythematosus (SLE) proposed by the American College of Rheumatology (ACR) and the patient did not reveal any typical physical manifestations of SLE. Methylprednisolone pulse therapy was started followed by oral administration of prednisolone. Urinary protein excretion diminished after 1 year of treatment. Eleven years later, the same patient was admitted to our hospital again with relapse of nephrotic syndrome. Laboratory findings upon second admission, wherein both anti-nuclear and anti-double-stranded DNA antibodies revealed positive, fulfilled the ACR criteria. Renal biopsy was performed again, resulting in a diagnosis of lupus nephritis. Steroid therapy combined with administration of mycophenolate mofetil led to an incomplete remission. Immunofluorescence studies confirmed the presence of IgG, IgM, C3, and C1q in renal biopsy specimens both at first and second admissions. Furthermore, immunofluorescence studies confirmed the presence of IgG1-4 in the first biopsy and tubuloreticular inclusions (TRIs) were revealed using electron microscopy. The present case represents the possibility that characteristic pathological findings of lupus nephritis, including TRIs, can reveal themselves before a diagnosis of SLE.

Metabolomics analysis elucidates unique influences on purine / pyrimidine metabolism by xanthine oxidoreductase inhibitors in a rat model of renal ischemia-reperfusion injury.

BACKGROUND: Clinically applied as anti-gout drugs, xanthine oxidoreductase (XOR) inhibitors, especially the potent, selective, non-purine-analog XOR inhibitors febuxostat and topiroxostat, exert organ-protective effects. We tested the hypothesis that preservation of tissue concentrations of high-energy phosphates, such as ATP and ADP, contributes to organ-protective effects through CE-TOFMS metabolomics. METHODS: Rats were subjected to 30 min of renal ischemia-reperfusion (I/R) injury 60 min after oral administration of 10 mg/kg febuxostat, 10 mg/kg topiroxostat, 50 mg/kg allopurinol, or vehicle. RESULTS: In non-purine-analog XOR inhibitor-treated groups, renal concentrations of high-energy phosphates were greater before and after I/R injury, and renal adenine compounds were less depleted by I/R injury than in the vehicle and allopurinol groups. These findings were well in accordance with the proposed hypothesis that the recomposition of high-energy phosphates is promoted by non-purine-analog XOR inhibitors via the salvage pathway through blockade of hypoxanthine catabolism, whereas non-specific inhibitory effects of allopurinol on purine/pyrimidine enzymes impede this re-synthesis process. CONCLUSIONS: This metabolic approach shed light on the physiology of the organ-protective effects of XOR inhibitors.

Evaluation of 8-week glecaprevir/pibrentasvir treatment in direct-acting antiviral-naïve noncirrhotic HCV genotype 1 and 2infected patients in a real-world setting in Japan.

Based on high efficacy and safety demonstrated in clinical trials, treatment with glecaprevir/pibrentasvir (G/P) for 8 weeks is recommended for hepatitis C virus (HCV)-infected patients who are direct-acting antiviral (DAA) naïve, genotype 1 or 2, and noncirrhotic. The aim of this study was to validate real-world experience with 8-week G/P treatment in Japan. We conducted a prospective observational cohort study in 554 patients who underwent 8-week treatment from among 1,022 patients who initiated G/P therapy. The majority (54.5%) were male, with a median age of 66 years, and HCV genotype distribution was genotype 1, 43.8%; genotype 2, 55.3%; and mixed subtype, 0.9%. Overall, the sustained virologic response rate at 12 weeks (SVR12) was 92.8% (530/571) in the intention-to-treat population and 99.3% (526/530) in the per-protocol population. The SVR12 rates by subgroups were as follows: subtype 1a, 100% (6/6); 1b, 100% (189/189); 2a, 99.3% (150/151); 2b, 99.0% (103/104); and mixed subtype, 50% (2/4). Among four patients with virologic failure following 8-week treatment with G/P, none had baseline polymorphisms or treatment-emergent amino acid substitutions in NS3. However, 2 of 4 patients with virologic failure had treatment-emergent amino acid substitutions in NS5A. Adverse events (AEs) were reported in 21.5% of patients and 1.2% of patients discontinued due to drug-related AEs. In conclusion, G/P treatment for 8 weeks was safe and effective for DAA-naïve noncirrhotic genotype 1 or 2 patients in a real-world clinical setting in Japan.