Case Study Clinical Case Reports International Published: 18 Feb, 2020

Eosinophilic Complicating Perforation in a C Patient Treated with Direct-Acting Antivirals

Ming X Huang1, Chun N Li1, Ruo M Ke1, Zuo Q Zhang2, Zhe Zhu3 and Xiao M Peng1,4* 1Department of Infectious Diseases, Sun Yat-Sen University, China

2Department of Radiology, Sun Yat-Sen University, China

3Department of Medicine, University of California, USA

4Central Laboratory, Sun Yat-Sen University, China

Abstract The Direct-Acting Antiviral (DAA) therapy of (HCV) has demonstrated excellent efficacy and safety profile. Based on large cohort studies, Serious Adverse Events (SAEs) are rare [1,2]. Here, we reported the first case of a patient with alcoholic liver super infected by HCV presenting with a SAE of Eosinophilic Gastro (EGE) complicating perforation during daclatasvir plus sofosbuvir therapy.

Abbreviations CT: Computed Tomography; DAA: Direct-Acting Antiviral; EGE: Eosinophilic Gastro Enteritis; HCV: ; SAE: Serious Adverse Event Case Presentation A 58-year-old Chinese man with history of alcoholic liver cirrhosis (Child-Pugh A) more than 10 years had been diagnosed with HCV infection (serum HCV RNA 6.85 logIU/mL, genotype 6a) and was treated with daclatasvir plus sofosbuvir. (Velpanat composed of velpatasvir 100 mg plus sofosbuvir 400 mg) The patient’s virological response was achieved at week 7, but his peripheral eosinophils rose from normal baseline to 2.79 × 109/L (Figure 1). Since the patient was asymptomatic, OPEN ACCESS the dual therapy was continued. On September 24, 2017 (about at week 8), the man was hospitalized *Correspondence: due to sudden severe right upper , abdominal distention and a of 38.9°C. 9 9 Xiao M Peng, Department of Infectious Blood examination showed elevated leukocytes of 13.06 × 10 /L and eosinophils of 2.64 × 10 /L, and Diseases, Central Laboratory, Sun Yat- slightly decreased hemoglobin and platelets. Erect plain abdominal radiograph showed free air in Sen University, 52 East Meihua Road, subphrenic space and hepatic hilar region (Figure 2A). Abdominal CT showed intraperitoneal free Zhuhai, Guangdong, 519000, China, air, perforation in duodenal bulb and thickened gastric and duodenal wells (Figure 2B-2E). Since Tel: +86-7562528500; the patient refused gastrointestinal endoscopy and surgical operation, symptomatic and supportive E-mail: [email protected] treatments and discontinuation of DAAs were conducted after specialist consultations. The patient’s abdominal symptoms alleviated and free air disappeared on the third day after the suddenness Received Date: 24 Jan 2019 (Figure 2F), the peripheral eosinophils almost restored to normal level on the fifth day (Figure 1), Accepted Date: 13 Feb 2020 and the patient was discharged with negative serum HCV RNA and normal eosinophils on the Published Date: 18 Feb 2020 twelfth day. After discharged, the patient was asymptomatic and the negative serum HCV RNA and Citation: Huang MX, Li CN, Ke RM, Zhang ZQ, Zhu Z, Peng XM. Eosinophilic Gastroenteritis Complicating Perforation in a Hepatitis C Patient Treated with Direct-Acting Antivirals. Clin Case Rep Int. 2020; 4: 1140. Copyright © 2020 Xiao M Peng. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work Figure 1: Clinical course of the patient. Daclatasvir and Sofosbuvir (DAAs); Gastro Intestinal (GI) perforation occurred on September 24th. is properly cited.

Remedy Publications LLC., | http://clinicalcasereportsint.com/ 1 2020 | Volume 4 | Article 1140 Xiao M Peng, et al., Clinical Case Reports International - Infectious Diseases

Figure 2: Radiological manifestations in the of the patient. A) Free air (*) in subphrenic space and hepatic hilar region (on September 24th, erect plain abdominal radiograph). (B and C) Intraperitoneal free air (*), air in enteric cavity (#), perforation (white arrow) and thickened gastric well (on September 24th, abdominal cross-sectional CT images. D) Intraperitoneal free air (*), air in enteric cavity (#), duodenum perforation (white arrow) and thickened duodenal well (on September 24th, abdominal vertical CT images). E) Intraperitoneal free air completely disappeared (on September 26th, erect plain abdominal radiograph). F) Irritated duodenal bulb (white circle) (on October 3rd, barium meal examination). normal peripheral eosinophils were monitored at week 12 (Figure 1). significance of comprehensive monitoring. Life-threatening SAE Discussion may occur in patients only with history of profound liver damage. In this case, to identify EGE by noticing peripheral eosinophilia and EGE is usually diagnosed by endoscopic biopsies showing conducting endoscopy earlier, and to discontinue the therapy in time eosinophilic infiltration. In this case, acute duodenal perforation might prevent the life-threatening acute duodenal perforation. stopped endoscopists from conducting endoscopy. However, Learning Points abdominal pain, thickened gastric and duodenal walls in CT images with peripheral eosinophilia and no evidence of parasitic or extra • When using DAAs, the comprehensive monitoring of intestinal disease met all of the three criteria established by Talley et adverse drug reaction is required. al. [3] in addition, fast healing and no history and symptoms of peptic • EGE is usually diagnosed by endoscopic biopsies showing ulcer excluded the perforation secondary to peptic ulcer or cancer. eosinophilic infiltration. Concordantly, a case with EGE presenting with gastric perforation has been reported. • EGE induced by DAAs is uncommon but can be present, thus emphasizing the need to notice peripheral eosinophilia and EGE is speculated to be induced by some allergens in the diet or conduct endoscopy earlier. air. In this case, daclatasvir or sofosbuvir was highly suspected since peripheral eosinophilia occurred at week 2 during their exposure and References disappeared within five days after their with drawl without corticoid 1. Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein or anti allergic therapy. Although EGE induced by DAAs has not T, Jacobson I, et al. Daclatasvir plus sofosbuvir for previously treated or been reported in the literature so far, drug-induced EGE correlated untreated chronic HCV infection. N Engl J Med. 2014;370(3):211-21. with minocycline and celecoxib has been reported. Compared with 2. Fazel Y, Lam B, Golabi P, Younossi Z. Safety analysis of sofosbuvir and daclatasvir, sofosbuvir with much better safety profile constituted the ledipasvir for treating hepatitis C. Expert Opin Drug Saf. 2015;14(8):1317- “backbone” of most combination treatments [4]. Thus, EGE in this 26. case was perhaps related to daclatasvir. It is well known that additional 3. Talley NJ, Shorter RG, Phillips SF, Zinsmeister AR. Eosinophilic cautions are needed in dealing with special patient populations (e.g. gastroenteritis: a clinicopathological study of patients with disease of the with end-stage renal disease or decompensated cirrhosis) [4]. It means mucosa, muscle layer, and subserosal tissues. Gut. 1990;31(1):54-8. that the history of alcoholic liver cirrhosis perhaps enhanced the susceptibility. Concordantly, a patient with Child-Pugh A cirrhosis 4. Behara R, Reau N. Updates on hepatitis C virus therapy in the direct-acting antiviral era. Curr Opin Gastroenterol. 2017;33:115-9. secondary to HCV genotype 3 suffered from an acute kidney injury after treatment with daclatasvir plus sofosbuvir [5]. 5. Ashraf T, Majoni W. Acute Interstitial Nephritis Associated with Sofosbuvir and Daclatasvir. ACG Case Rep J. 2017;4:e84. DAA therapy largely simplifies the treatment of HCV infection. However, this case indicates that some DAAs needs further clinical assessment of their safety and also reminds us to re-emphasize the

Remedy Publications LLC., | http://clinicalcasereportsint.com/ 2 2020 | Volume 4 | Article 1140