treatment of chronic hepatitis c can improve glycemic ...case report treatment of chronic hepatitis...

Case ReportTreatment of Chronic Hepatitis C Can Improve GlycemicControl in Patients with Type 2 Diabetes

Nalan Okuroglu , Meltem Sertbas, and Ali Ozdemir

University of Health Sciences, Fatih SultanMehmet Training and ResearchHospital, Department of InternalMedicine, Istanbul, Turkey

Correspondence should be addressed to Nalan Okuroglu; [email protected]

Received 10 July 2018; Accepted 12 August 2018; Published 17 September 2018

Academic Editor: Tawesak Tanwandee

Copyright © 2018 NalanOkuroglu et al.This is an open access article distributed under the Creative CommonsAttribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

A 73-year-old female patient with a history of type 2 DM for seven years was admitted to our out-patient clinic with a complaint offrequent hypoglycemic episodes. She was receiving basal- bolus insulin treatment. She underwent liver transplantation 20 monthsago due to end stage liver disease caused by HCV infection genotype 1b. While she was still on tacrolimus for liver transplantation,she received direct acting antiviral agents including fix dose ledipasvir-sofosbuvir with ribavirin. Biochemical analysis showedfasting plasma glucose of 105mg/dl and postprandial glucose of 200mg/dl, glycosylated hemoglobin A1c of 4.8%, and c-peptide of3.17 ng/ml. After achieving successfully virologic response with antiviral therapy, the patient stayed euglycemic and was no longerin need to anymedication including insulin and the patient was followed only by dietary regulation. Achievement of the virologicalresponse in treatment of HCV infection can improve not only the liver status, but also the extrahepatic manifestations includingtype 2 DM.

1. Introduction

Hepatitis C virus (HCV) infection which has a prevalence of2.8% is one of the major causes of hepatitis, cirrhosis, andhepatocellular carcinoma [1]. Several studies have reportedthat the prevalence of diabetesmellitus (DM) is higher amongHCV-associated hepatitis compared to other viral hepatitis.The underlying mechanisms of DM development can belisted as HCV-associated glucose intolerance, insulin resis-tance (IR), increased inflammatory response, liver fibrosis,and the direct effect of HCV on insulin signaling. Recently,a few clinical trials and cases showed improvement of theregulation of DM after antiviral treatment. We report a casewith type 2 DMwho had liver transplantation due to chronicHCV infection 20 months ago and undergoing basal-bolusinsulin therapy already. After achieving successfully virologicresponse with antiviral therapy the patient stayed euglycemicand was no longer in need to any medication includinginsulin.

2. Case Presentation

A 73-year-old female patient with type 2 DM was referredto our clinic for low sugar episodes. She had been

receiving insulin therapy for 7 years. In medical history livertransplantation was performed 20 months ago due to endstage liver disease caused by HCV infection genotype 1b.She had a body mass index (BMI) of 31.9 kg/m2 and wasusing intensive subcutaneous insulin injections four timesdaily: insulin glargine 24 U at bedtime and insulin aspart16U three times a day before each meal. While she was stillon tacrolimus 2.5mg and mycophenolate mofetil 1000mgdaily, after liver transplantation for nearly 20 months, shereceived direct acting antiviral agents (DAAs) including fixdose combination ledipasvir-sofosbuvir (90mg-400mg) plusribavirin, for 24weeks, and achieved virologic response. AfterDAAs and ribavirin treatment was completed, she began toexperience severe hypoglycemia and therefore the insulinaspart was stopped. Since hypoglycemia persists, she alsodiscontinued insulin glargine 1 week ago. Her vital signswere normal and physical examination was unremarkable.Biochemical analysis showed fasting plasma glucose (FG) of105mg/dl and postprandial glucose of 200mg/dl. Surpris-ingly, glycosylated hemoglobin A1c (HbA1c) was 4.8% and c-peptide was 3.17 ng/ml. Liver and renal function test resultswere in the normal reference range. Home blood glucose

HindawiCase Reports in HepatologyVolume 2018, Article ID 5260510, 2 pageshttps://doi.org/10.1155/2018/5260510

http://orcid.org/0000-0002-0814-2359https://doi.org/10.1155/2018/5260510

2 Case Reports in Hepatology

measurements also showed a normal course of glucose andthe patient was followed only by dietary regulation.

3. Discussion

The development of diabetes in HCV infection is well knownand is called ”hepatogenos diabetes”. The main reason for thepathogenesis of ”hepatogenous diabetes” is especially IR asso-ciated with impaired insulin secretion and sensitivity. Also,IR has been shown to increase liver fibrosis, reduce antiviraltreatment response, and increase hepatocellular carcinoma(HCC). IR and hepatic steatosis are the characteristic featuresofHCV. IRwas an independent risk factor in the developmentof fibrosis in patients with chronic HCV infection [2].There are two types of IR: metabolic and viral. Comparedto other inflammatory liver diseases, hepatosteatosis wasfound to be more common in chronic hepatitis C virusinfection. The direct effect of hepatitis C virus core proteininduces fat accumulation in hepatocytes and causes hepaticsteatosis. Both fat accumulation and hepatosteatosis havebeen related to elevations of serum aminotransferase levelsin HCV infections rather than DM. It has been reported thatnonstructural protein 5A (NS5A) encoded by the HCV RNAgenome is involved in insulin receptor substrate-1 (IRS-1)phosphorylation and regulates the insulin signaling pathway[3]. In addition, NS5A transfected cells, decreased the levelsof serin phosphorylation that facilitate gluconeogenesis, andinhibited the synthesis of glycogen.

Moreover, Massini et al. showed that HCV can affectpancreatic 𝛽-cells and inducemorphological cell changes [4].In another study Wang suggested that HCV infection maycause pancreatic beta cells death by an endoplasmic reticulum(ER) stress-involved effect [5].

By the clinical use of novel DAAs including proteaseinhibitors, and nucleotide and non-nucleotide polymeraseinhibitors like NS5a-Ns5b inhibitors, with or without rib-avirin, high HCV clearance rates have been achieved. Thereare clinical case reports showing that FG and HbA1c recoverafter HCV eradication has been achieved [6, 7]. It has beensuggested that coexisting diabetes or hyperlipidemia mightinteract with the response to DAAs and patients with bloodglucose

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