Formal proof of the requirement of MESP1 and MESP2 in mesoderm specification and their transcriptional control via specific enhancers in mice.

MESP1 and MESP2 are transcriptional factors involved in mesoderm specification, somite boundary formation and somite polarity regulation. However, Mesp quadruple mutant zebrafish displayed only abnormal somite polarity without mesoderm specification defects. In order to re-evaluate Mesp1/Mesp2 mutants in mice, Mesp1 and Mesp2 single knockouts (KOs), and a Mesp1/Mesp2 double KO were established using genome-editing techniques without introducing selection markers commonly used before. The Mesp1/Mesp2 double KO embryos exhibited markedly severe mesoderm formation defects that were similar to the previously reported Mesp1/Mesp2 double KO embryos, indicating species differences in the function of MESP family proteins. However, the Mesp1 KO did not display any phenotype, including heart formation defects, which have been reported previously. We noted upregulation of Mesp2 in the Mesp1 KO embryos, suggesting that MESP2 rescues the loss of MESP1 in mesoderm specification. We also found that Mesp1 and Mesp2 expression in the early mesoderm is regulated by the cooperation of two independent enhancers containing T-box- and TCF/Lef-binding sites. Deletion of both enhancers caused the downregulation of both genes, resulting in heart formation defects. This study suggests dose-dependent roles of MESP1 and MESP2 in early mesoderm formation.

[Rectal cancer with multiple metastases complicated by Crohn's disease 5 years after surgery:a case report].

In recent years, with the rising incidence of patients having long-term Crohn's disease, there has been an increase in the number of reports of carcinogenesis from dysplasia with chronic inflammation as the primary pathogenic factor. We hereby report a case of multiple metastases that appeared 5 years after surgery, in a patient with rectal cancer who had Crohn's disease. A man in his 50s was diagnosed with Crohn's disease which affected his small and large intestines 21 years back. The patient was being treated with oral steroids, 5-aminosalicylic acid, and modified nutrition. Infliximab was added to the treatment after it was introduced 11 years ago. He also had a history of rectal cancer and had undergone surgery for the same 5 years back. He was diagnosed with stage II cancer, and had not received any adjuvant chemotherapy. However, 5 years after surgery, multiple metastases recurred, and chemotherapy with mFOLFOX6 was administered. Additionally, for treating his Crohn's disease, which was also active, infliximab was changed to vedolizumab;however, the patient died a year later. Colorectal cancer accompanied with Crohn's disease has a higher risk of developing metastasis and is associated with poorer prognosis as compared to the noncomplicated colorectal cancer. Regarding treatment modalities, while searching for multidisciplinary treatment methods centered on surgical treatment in collaboration with medical oncologists and radiologists, the safety of treatment for Crohn's disease in patients with cancer must be borne in mind. The rising prevalence of cases of colorectal cancer with Crohn's disease is expected to lead to the formulation of specialized diagnostic and treatment strategies for these patients.

Vascular endothelial growth factor-A is an Immunohistochemical biomarker for the efficacy of bevacizumab-containing chemotherapy for duodenal and jejunal adenocarcinoma.

BACKGROUND: The efficacy and safety of bevacizumab-containing chemotherapy for patients with metastatic duodenal and jejunal adenocarcinoma (mDJA) are unclear. The present study aimed to evaluate the efficacy of bevacizumab and to explore immunohistochemical markers that can predict the efficacy of bevacizumab for patients with mDJA. METHODS: This multicentre study included patients with histologically confirmed small bowel adenocarcinoma who received palliative chemotherapy from 2008 to 2017 at 15 hospitals. Immunostaining was performed for vascular endothelial growth factor-A (VEGF-A), TP53, Ki67, ß-catenin, CD10, MUC2, MUC5AC, MUC6, and mismatch repair proteins. RESULTS: A total of 74 patients were enrolled, including 65 patients with mDJA and 9 with metastatic ileal adenocarcinoma. Patients with mDJA who received platinum-based chemotherapy with bevacizumab as first-line treatment tended to have a longer progression-free survival and overall survival than those treated without bevacizumab (P = 0.075 and 0.077, respectively). Multivariate analysis extracted high VEGF-A expression as a factor prolonging progression-free survival (hazard ratio: 0.52, 95% confidence interval: 0.30-0.91). In mDJA patients with high VEGF-A expression, those who received platinum-based chemotherapy with bevacizumab as a first-line treatment had significantly longer progression-free survival and tended to have longer overall survival than those treated without bevacizumab (P = 0.025 and P = 0.056, respectively), whereas no differences were observed in mDJA patients with low VEGF-A expression. CONCLUSION: Immunohistochemical expression of VEGF-A is a potentially useful biomarker for predicting the efficacy of bevacizumab-containing chemotherapy for patients with mDJA.

Risk Factors for Delayed Bleeding after Therapeutic Gastrointestinal Endoscopy in Patients Receiving Oral Anticoagulants: A Multicenter Retrospective Study.

BACKGROUND/AIMS: Delayed bleeding is among the adverse events associated with therapeutic gastrointestinal endoscopy. The aim of this study was to evaluate risk factors for delayed bleeding after gastrointestinal endoscopic resection in patients receiving oral anticoagulants as well as to compare the rates of occurrence of delayed bleeding between the oral anticoagulants used. METHODS: We retrospectively analyzed a total of 772 patients receiving anticoagulants. Of these, 389 and 383 patients were receiving direct oral anticoagulants (DOACs) and warfarin, respectively. Therapeutic endoscopic procedures performed included endoscopic submucosal dissection (ESD), endoscopic mucosal resection, polypectomy, and cold polypectomy. RESULTS: Delayed bleeding occurred in 90 patients (11.7%) with no significant difference between the DOAC and warfarin groups (9.5 and 13.8%, respectively). Delayed bleeding occurred significantly more frequently with apixaban than with rivaroxaban (13.5 vs. 6.4%; p < 0.05). A multivariate analysis identified continued anticoagulant therapy (OR 2.29), anticoagulant withdrawal with heparin bridging therapy (HBT; OR 2.18), anticoagulant therapy combined with 1 antiplatelet drug (OR 1.72), and ESD (OR 3.87) as risk factors for delayed bleeding. CONCLUSION: This study identified continued anticoagulant therapy, anticoagulant withdrawal with HBT, anticoagulant therapy combined with 1 antiplatelet drug, and ESD as risk factors for delayed bleeding after therapeutic endoscopy in patients receiving oral anticoagulants. Delayed bleeding rates were not significantly different between those receiving DOACs and warfarin. It was also suggested that the occurrence of delayed bleeding may vary between different DOACs and that oral anticoagulant withdrawal should be minimized during therapeutic gastrointestinal endoscopy, given the thromboembolic risk involved.

[A case of severe colitis induced by the administration of pembrolizumab for pulmonary adenocarcinoma in a patient with ulcerative colitis].

Pembrolizumab is an immunoglobulin G4 isotype antibody that targets the programmed cell death protein 1 (PD-1) receptor of lymphocytes. It is used in the treatment of advanced non-small cell lung cancer (NSCLC). The safety and efficacy of immunotherapy for autoimmune disease are currently unknown;immune-related adverse events induced by immune checkpoint inhibitors (ICIs) have been reported. We report a case of severe colitis induced by the administration of pembrolizumab for pulmonary adenocarcinoma in a patient with ulcerative colitis. A 72-year-old man with a 3-year history of ulcerative colitis maintained clinical remission with mesalazine. The recurrence of lung adenocarcinoma was diagnosed and treated with pembrolizumab as second-line treatment. Diarrhea and bloody stool recurred 5 months after the first administration of pembrolizumab. The colitis did not respond to corticosteroids and infliximab. Because of the recurrence of ulcerative colitis, treatment of the lung adenocarcinoma was discontinued, and the patient died 1 year after the first administration of pembrolizumab. Few cases of severe colitis induced by the administration of pembrolizumab in patients with ulcerative colitis have been reported. This case suggests that the clinical stratification of autoimmune disease and typical standards of effectiveness of treatment are needed for patients with autoimmune disease who are treated with ICIs.

Endoscopic alterations in Peyer's patches in patients with ulcerative colitis: A prospective, multicenter study.

BACKGROUND AND AIM: Peyer's patches (PPs) play a major role in intestinal mucosal immunity; however, their role in ulcerative colitis (UC) is not well investigated. We evaluated endoscopic features of PPs on narrow-band imaging with magnifying endoscopy (NBI-ME) and investigated their association with clinical factors. METHODS: We prospectively recruited 105 patients with UC, 18 with Crohn's disease, 16 with disease control, and 33 healthy control subjects at three institutions from 2014 to 2017. NBI-ME images of the villi of PPs were evaluated according to the Villi Index, and patients were divided into the Villi Index low (L) and high (H) types. The 1-year sustained clinical remission rate was evaluated between L-type and H-type PPs in patients with UC. RESULTS: The proportions of patients with H-type PPs were significantly higher among UC, Crohn's disease, and disease control patients than among healthy control patients (P = 0.0125, 0.018, 0.0007). In UC, age, gender, endoscopic score, and extent of disease involvement were not significantly different between L-type and H-type PPs, whereas the sustained clinical remission rate was significantly higher in L-type PPs than in H-type PPs (88% [57/65] vs 65% [17/26], P = 0.019). Multivariate analysis revealed that the L type of PPs was a significant factor for sustained clinical remission (odds ratio 3.8, 95% confidence interval 1.1-12.9, P = 0.033). CONCLUSIONS: Patients with UC showed endoscopic alterations in PPs on NBI-ME, and highly altered appearance of PPs can be associated with a high risk of clinical relapse in patients with UC.

Continuous Anticoagulation and Cold Snare Polypectomy Versus Heparin Bridging and Hot Snare Polypectomy in Patients on Anticoagulants With Subcentimeter Polyps: A Randomized Controlled Trial.

Background: Management of anticoagulants for patients undergoing polypectomy is still controversial. Cold snare polypectomy (CSP) is reported to cause less bleeding than hot snare polypectomy (HSP). Objective: To compare outcomes between continuous administration of anticoagulants (CA) with CSP (CA+CSP) and periprocedural heparin bridging (HB) with HSP (HB+HSP) for subcentimeter colorectal polyps. Design: Multicenter, parallel, noninferiority randomized controlled trial. (University Hospital Medical Information Network Clinical Trials Registry: UMIN000019355). Setting: 30 Japanese institutions. Patients: Patients receiving anticoagulant therapy (warfarin or direct oral anticoagulants) who had at least 1 nonpedunculated subcentimeter colorectal polyp. Intervention: Patients were randomly assigned to undergo HB+HSP or CA+CSP and followed up 28 days after polypectomy. Measurements: The primary end point was incidence of polypectomy-related major bleeding (based on the incidence of poorly controlled intraprocedural bleeding or postpolypectomy bleeding requiring endoscopic hemostasis). The prespecified inferiority margin was -5% (CA+CSP vs. HB+HSP). Results: A total of 184 patients were enrolled: 90 in the HB+HSP group, 92 in the CA+CSP group, and 2 who declined to participate after enrollment. The incidence of polypectomy-related major bleeding in the HB+HSP and CA+CSP groups was 12.0% (95% CI, 5.0% to 19.1%) and 4.7% (CI, 0.2% to 9.2%), respectively. The intergroup difference for the primary end point was +7.3% (CI, -1.0% to 15.7%), with a 0.4% lower limit of 2-sided 90% CI, demonstrating the noninferiority of CA+CSP. The mean procedure time for each polyp and the hospitalization period were longer in the HB+HSP than in the CA+CSP group. Limitation: An open-label trial assessing 2 factors (anticoagulation approach and polypectomy procedure type) simultaneously. Conclusion: Patients having CA+CSP for subcentimeter colorectal polyps who were receiving oral anticoagulants did not have an increased incidence of polypectomy-related major bleeding, and procedure time and hospitalization were shorter than in those having HB+HSP. Primary Funding Source: Japanese Gastroenterological Association.

[A case of idiopathic thrombocytopenic purpura development after total colectomy for ulcerative colitis].

Ulcerative colitis (UC) is known to be associated with extraintestinal manifestations. However, idiopathic thrombocytopenic purpura (ITP) has rarely been reported as one of the extraintestinal manifestations in UC. In most cases, ITP develops as an extraintestinal manifestation during the treatment for UC. After treatment with medications or colectomy, there is often a remission of UC and ITP. However, we experienced a case of ITP development after total colectomy for UC. An 83-year-old man was diagnosed as having UC and started treatment with medications. After 3 years, total colectomy and ileostomy were performed to prevent UC remission. Subsequently, no further treatment was provided. Two years later, he presented to the hematology department in our hospital with the chief complaint of thrombocytopenia and was diagnosed as having ITP. ITP was treated with steroids, and his platelet count increased to within the normal range. Immunological abnormalities may be involved in the development of extraintestinal manifestation, including UC-associated ITP. In previous reports, ITP was cured by colectomy for UC. In contrast, peripheral arthritis is a common extraintestinal manifestation of UC, and it is known that 75% of these patients develop or continue to experience such symptoms after colectomy. Some extraintestinal manifestations may equally persist after colectomy. However, the underlying mechanisms are poorly understood. Ileitis and small intestinal and duodenal inflammation are all known bowel complications associated with colectomy, and some immunological mechanisms have been suggested to be involved. Therefore, careful monitoring in these patients is necessary to detect any possibility of developing extraintestinal manifestations after colectomy. Further studies to examine the mechanisms underlying the immunological abnormality between UC and extraintestinal manifestations such as ITP are needed.

Application of artificial intelligence using convolutional neural networks in determining the invasion depth of esophageal squamous cell carcinoma.

OBJECTIVES: In Japan, endoscopic resection (ER) is often used to treat esophageal squamous cell carcinoma (ESCC) when invasion depths are diagnosed as EP-SM1, whereas ESCC cases deeper than SM2 are treated by surgical operation or chemoradiotherapy. Therefore, it is crucial to determine the invasion depth of ESCC via preoperative endoscopic examination. Recently, rapid progress in the utilization of artificial intelligence (AI) with deep learning in medical fields has been achieved. In this study, we demonstrate the diagnostic ability of AI to measure ESCC invasion depth. METHODS: We retrospectively collected 1751 training images of ESCC at the Cancer Institute Hospital, Japan. We developed an AI-diagnostic system of convolutional neural networks using deep learning techniques with these images. Subsequently, 291 test images were prepared and reviewed by the AI-diagnostic system and 13 board-certified endoscopists to evaluate the diagnostic accuracy. RESULTS: The AI-diagnostic system detected 95.5% (279/291) of the ESCC in test images in 10 s, analyzed the 279 images and correctly estimated the invasion depth of ESCC with a sensitivity of 84.1% and accuracy of 80.9% in 6 s. The accuracy score of this system exceeded those of 12 out of 13 board-certified endoscopists, and its area under the curve (AUC) was greater than the AUCs of all endoscopists. CONCLUSIONS: The AI-diagnostic system demonstrated a higher diagnostic accuracy for ESCC invasion depth than those of endoscopists and, therefore, can be potentially used in ESCC diagnostics.

Favorable outcome with direct-acting antiviral treatment in hepatitis C patients coinfected with HIV.

AIM: To investigate the efficacy and safety of all-oral direct-acting antiviral treatments in patients coinfected with hepatitis C virus (HCV) and HIV. METHODS: In all, 35 patients with HCV/HIV coinfection (22 patients with HCV genotype 1 infection, 6 with genotype 2, and 7 with genotype 3) were treated with sofosbuvir and ledipasvir (for genotype 1 patients) or sofosbuvir and ribavirin (for genotypes 2 and 3). Sustained virological response (SVR) at 24 weeks after end of treatment and adverse events were assessed. RESULTS: The overall SVR rate was 91.4% (32/35). One patient with genotype 1 infection discontinued treatment on day 2 due to severe headache, which subsided after the cessation of medication; all other patients completed their treatment without severe adverse events. Two patients who had a relapse of HCV were infected with a genotype 3 strain. We observed hyperbilirubinemia in a patient with genotype 3, who was under antiretroviral therapy including atazanavir. He completed the treatment and achieved SVR. CONCLUSION: Direct-acting antiviral treatment for patients coinfected with HCV/HIV is as effective as in patients infected only with HCV. It was generally well tolerated, except in one patient who discontinued the treatment due to severe headache.

[A case of refractory pouchitis following surgery for ulcerative colitis successfully treated with adalimumab].

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is widely accepted as the operation of choice for refractory ulcerative colitis (UC), UC with dysplasia or cancer, or familial adenomatous polyposis. Pouchitis is the most frequent complication after IPAA for UC. Although the pathogenesis of pouchitis remains unclear, current evidence suggests that dysbiosis and mucosal immune response are important mechanisms. Antibiotics are the first-line treatment for the condition, but some patients develop chronic refractory pouchitis. Such cases can be treated with regimens such as longer courses of antibiotic combinations, mesalazine, corticosteroids, probiotics, or biologics. But if pouch inflammation is not ameliorated, a permanent ileostomy may be required. A 40-year-old man had undergone IPAA for UC and was diagnosed with pouchitis according to the Pouchitis Disease Activity Index. Antibiotics, mesalazine, and corticosteroids were given, but the inflammation was difficult to control. He developed chronic refractory pouchitis associated with perianal abscesses and anal fistulae. Following a seton procedure for fistulae, adalimumab (ADA) was administered. After 42 weeks, the ulcers in the pouch became scarred, and the anal fistulae were closed endoscopically. After remission was induced, it has been maintained. ADA is a fully human anti-tumor necrosis factor-α (TNF-α) monoclonal antibody that has been successfully used to treat refractory Crohn disease of the ileoanal pouch. Although some studies report that infliximab, a chimeric anti-TNF-α monoclonal antibody, is efficacious in patients with refractory pouchitis, clinical evidence for the use of ADA is limited. This case illustrates achievement of induction and maintenance of remission of refractory pouchitis with ADA. It is possible that patients with this condition can avoid a permanent ileostomy with anti-TNF-α therapy. In the near future, further study of long-term clinical outcomes of anti-TNF-α therapy is expected.

Colonic stenting as a bridge to surgery for obstructive colorectal cancer: advantages and disadvantages.

PURPOSE: To clarify the advantages and disadvantages of stenting as a bridge to surgery (BTS) by comparing the clinical features and outcomes of patients who underwent BTS with those of patients who underwent emergency surgery (ES). METHODS: We assessed technical success, clinical success, surgical procedures, stoma formation, complications, clinicopathological features, and Onodera's prognostic nutritional index (OPNI) in patients who underwent BTS and those who underwent ES. RESULTS: Twenty-six patients underwent stenting, which was successful in 22 (BTS group). The remaining four patients with unsuccessful stenting underwent emergency surgery. A total of 22 patients underwent emergency surgery (ES group). The rates of technical and clinical success were 85.0 and 81.0 %, respectively. The proportion of patients able to be treated by laparoscopic surgery (P = 0.0001) and avoid colostomy (P = 0.0042) was significantly higher in the BTS group. Although the incidence of anastomotic leakage in the two groups was not significantly different, it was significantly reduced by colonoscopic evaluation of obstructive colitis (P = 0.0251). The mean number of harvested lymph nodes (P = 0.0056) and the proportion of D3 lymphadenectomy (P = 0.0241) were significantly greater in the BTS group. Perineural invasion (PNI) was noted in 59.1 and 18.2 % of the BTS group and ES group patients, respectively (P = 0.0053). OPNI and serum albumin decreased significantly after stenting (P = 0.0084). CONCLUSIONS: The advantages of stenting as a BTS were that it avoided colostomy and allowed for laparoscopic surgery and lymphadenectomy, whereas its disadvantage lay in the decreased PNI and OPNI levels. A larger study including an analysis of prognosis is warranted.

[Squamous cell carcinoma of the anal canal treated with chemoradiotherapy in a patient with HIV].

Since the introduction of combination antiretroviral therapy (ART), the life expectancy has increased for patients infected with human immunodeficiency virus (HIV). This has been associated with reductions in the incidences of some AIDS-defining malignancies, such as Kaposi sarcoma and non-Hodgkin lymphoma, but has coincided with an increased incidence of non-AIDS-defining malignancies, such as anal cancer. However, anal cancers are rare in patients with HIV in Japan. We report the case of an HIV-infected patient with anal cancer treated with chemoradiotherapy. A 37-year-old man receiving ART for HIV infection presented with a 1-month history of left inguinal lymphadenopathy and anal pain. Magnetic resonance imaging and computed tomography revealed a 56-mm mass, left inguinal lymphadenopathy, and left external iliac lymphadenopathy. The mass had infiltrated from the anal canal to the right levator ani and corpus spongiosum. Colonoscopy revealed a tumor with an ulcer in the anal canal. Histological examination of the tumor biopsy specimens confirmed the diagnosis of squamous cell carcinoma. The patient was diagnosed with anal cancer (T4N2M1 stage IV), and he received 5-fluorouracil (1000mg/m(2) on days 1-4 and 29-32) plus mitomycin C (10mg/m(2) on days 1 and 29) and concurrent radiotherapy (total dose, 59.4Gy in 33 fractions) along with ART. The treatment-related adverse events were grade 4 leukopenia and neutropenia, grade 3 thrombocytopenia, and grade 2 radiation dermatitis. Moreover, CD4 suppression was observed:the CD4 count decreased from 190 cells/µl before chemoradiotherapy to 138 cells/µl after 3 months, but increased to 210 cells/µl after 1 year. Because of the grade 4 leukopenia and neutropenia, the dose of 5-fluorouracil was reduced to 800mg/m(2) on days 29-32. A complete response was confirmed on magnetic resonance imaging, and colonoscopy confirmed the disappearance of the anal cancer. The patient is living with no signs of recurrence at 2 years after chemoradiotherapy. When treating HIV-infected patients with anal cancer by chemoradiotherapy and ART, clinicians should be aware of the possibility of CD4 suppression.

A case report of a duodenal adenocarcinoma: a complication with Crohn's disease.

The prevalence of Crohn's disease (CD) in Japan is increasing, and so is the incidence of colorectal and small bowel cancers associated with CD. However, few reports have described the malignant transformation of duodenal lesions; moreover, such a diagnosis is rarely possible preoperatively. We present a case of malignant degeneration in the duodenal mucosa associated with CD. A 54-year-old man had been receiving treatment for CD for more than 20 years. Seven years ago, he was diagnosed with duodenal stenosis related to CD. He was asymptomatic, and biopsy results from the proximal stricture showed inflammatory changes without malignant transformation. The lesion was then monitored during follow-up. In 2013, he underwent an endoscopy, which revealed an ulcerated, nodular mucosa, immediately proximal to a high-grade obstruction of the descending duodenum. A biopsy of the ulcer lesion confirmed a diagnosis of adenocarcinoma. The patient then underwent duodenopancreatectomy. Histopathological results from the resected duodenum confirmed a poorly differentiated adenocarcinoma that had invaded the subserosa. The patient recovered, and no recurrence has been observed. Although the duodenum can be accessed without difficulty during endoscopy, it is challenging to preoperatively diagnose malignant transformation. There are only four reported cases of duodenal cancer stemming from CD-associated stricture, and only one of them received a preoperative diagnosis of malignancy based on endoscopic biopsy results. Progressive duodenal narrowing and ulceration in patients with CD should indicate a need for careful endoscopic evaluation and biopsy in order to exclude malignant degeneration of Crohn's duodenitis. Early diagnosis of cases of CD-associated cancers is necessary. We report the features of a rare and illustrative case of duodenal adenocarcinoma in a patient with CD.

Administration of low-dose epoetin-alpha facilitates adherence to ribavirin in triple therapy with pegylated interferon-alpha-2b and telaprevir.

AIM: Anemia frequently develops in patients given pegylated interferon, ribavirin (RBV), telaprevir (TVR) triple therapy and restricts treatment by forcing reduction or discontinuation of RBV administration. We investigated whether erythropoietin (EPO) could alleviate RBV-induced anemia to help maintain the RBV dose during the first 12 weeks, the triple therapy phase. METHODS: Twenty-two patients with hepatitis C virus (HCV) genotype 1 were enrolled. Hemoglobin (Hb) concentration was measured every week. If Hb reduction from the baseline was 2 g/dL or more, 12 000 IU of epoetin-α was administrated. When further reduction (≥3 g/dL) was observed, 24 000 IU of epoetin-α was used. Inosine triphosphatase (ITPA) single nucleotide polymorphism (rs1127354) was genotyped for all patients. RESULTS: Among the 22 patients enrolled in this study, three required RBV dose reduction due to anemia, two had to discontinue or reduce TVR and RBV due to creatinine elevation. The remaining 17 patients completed the treatment during the triple therapy phase without reduction of the RBV dose or adverse events attributable to EPO. Regardless of ITPA genotype, Hb decline was well controlled by EPO administration, whereas the total EPO dose tended to be higher in the CC genotype group. The average adherence to RBV during the triple therapy phase was 97.5%. SVR was achieved in 17 patients; two patients had viral breakthrough and three patients had relapse of HCV RNA. CONCLUSION: EPO can be a favorable alternative to reduction of RBV to facilitate the adherence of patients on TVR-based triple therapy.