Case Report

Successful treatment of chronic hepatitis C in a hemodialysis

Ivana Milošević1,2, Uroš Karić1, Ivana Pešić-Pavlović3, Goran Stevanović1,2, Aleksandra Barać1,2,
Marijana Smiljanić4, Aleksandra Arsenović4, Olja Stevanović1, Miljana Đonin-Nenezić1, Branko
Brmbolić1,2
1 Hospitalfor Infectious and Tropical Diseases, Clinical Centre of Serbia, Belgrade, Serbia
2 Medical Faculty, University of Belgrade, Serbia
3 Virusology Laboratory, Department of Microbiology, Clinical Center of Serbia, Belgrade, Serbia
4 Special Clinic for Endemic Nephropathy, Lazarevac, Serbia

Abstract
We present the first case of successful direct acting antiviral therapy of chronic hepatitis C in a hemodialysis patient in Serbia. The patient
infected with genotype 1a has been successfully treated with Paritaprevir/Ritonavir/Ombitasvir/Dasabuvir and Ribavirin. There are only a
few real world reports regarding this therapeutic option in hemodialysis patients.

Key words: chronic hepatitis C; hemodialysis; 3D regimen.

J Infect Dev Ctries 2018; 12(2):142-145. doi:10.3855/jidc.10257

(Received 12 February 2018 – Accepted 17 February 2018)

Copyright © 2018 Milošević et al. 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 is properly cited.

Introduction other anti-HCV positive patients. Genotype 1 (GT1)

We are witnessing a revolution in chronic hepatitis HCV was determined, and the HCV RNA viral load
C (CHC) therapy in the last few years. Direct acting was 2,265,000 copies/mL. She was treated with
antivirals (DAAs) provide shorter treatment duration pegylated interferon-a2a (peg-IFN-a2a, 135 mcg SC
with higher sustained virological response (SVR) rates, once weekly) and ribavirin (200 mg PO 3 times per
greater efficacy and safety, and less adverse events week) for 48 weeks during 2008/2009 and she tolerated
(AE) in comparison to interferon-based therapy [1]. the regimen well. Although HCV RNA was
DAAs can be used in patients with comorbidities, in undetectable at the end of treatment (EOT), she
which interferon-based therapy was unsuccessful or experienced relapse during the 24-week follow-up
contraindicated [1]. Patients with chronic kidney period. During 2017 she underwent a reevaluation of
disease (CKD), including those on hemodialysis (HD), CHC. A liver stiffness of 5.5 kPa, corresponding with
can be treated successfully with DAAs [2]. We present minimal or no liver fibrosis (F0/F1), was identified by
a case of a young woman with CHC on HD successfully transient elastography. The HCV RNK viral load and
treated with the 3D regimen - GT were reassessed before DAAs treatment and were
Paritaprevir/Ritonavir/Ombitasvir and Dasabuvir. found to be 1,158,000 IU/mL and GT1a, respectively
(COBAS HCV 4800, ROCHE Diagnostics, Branchburg
Case Report NJ, USA).
We present a case of 31 year-old female with CHC She was treated with a 12-week 3D regimen
and stage 5 CKD. She was diagnosed with hypertension consisting of 2 tablets taken once daily and each
and CKD in 2003, when she was 18 years old. She containing 75 mg of paritaprevir, 50 mg of ritonavir,
didn't undergo a renal biopsy and the etiology of CKD and 12,5 mg of ombitasvir, together with a 250 mg
remains elusive. Her average diuresis was less than 1.5 tablet of dasabuvir taken twice daily, in combination
L/day when she became HD-dependent in 2008. Her with ribavirin (July - September 2017). Serum
current average diuresis is less than 50 mL/day and she hemoglobin was 10 g/dL prior to DAAs therapy. The
has three four-hour HD sessions weekly. She had been initial ribavirin dose was 200 mg 3 times per week after
diagnosed with CHC soon after she had started HD, so HD, with hemoglobin concentration monitoring before
she was transferred to an isolation HD unit, along with each dose. The patient received erythropoietin (20,000
Milošević et al. – Chronic hepatitis C in hemodialysis patients J Infect Dev Ctries 2018; 12(2):142-145.

international units) twice per week through the entire anemia, yet the treating physicians decided not to
course of the treatment, except on the few occasions in interrupt ribavirin because the bleeding ended on the
which the hemoglobin concentration exceeded 11g/dL. day the hemoglobin concentration fell below 8.5g/dL.
Ribavirin was not administered if serum hemoglobin Sure enough the hemoglobin concentration started to
was lower than 8.5 g/dL. She was also treated for rise spontaneously after day 49 of therapy. Figure 1
hypertension with metoprolol 90mg, methyldopa 500 illustrates the hemoglobin concentration dynamics in
mg and ramipril 5 mg. All drugs taken as a single daily conjunction with RBC transfusions and ribavirin doses.
dose were administered after HD. The patient complained of pruritus without any
The treating clinicians actively evaluated the patient noticeable skin lesions, from the 4th to the 10th day
for AEs daily from the start of DAA therapy until 30 (week 1-2) of DAA treatment. Pruritus was due to
days after the EOT. The most important and serious AE xerosis and it resolved with frequent moisturization.
observed during treatment was ribavirin- There were no other significant AEs.
induced/exacerbated anemia. After the 5th dose of The viral load was assessed at week 4 of antiviral
ribavirin (week 2 of antiviral therapy) there was a treatment and was found to be <15 IU/mL. HCV RNA
significant drop in the serum hemoglobin concentration was undetectable at the EOT and after 12 weeks of
to 8.3 g/dL, at which point ribavirin was interrupted. follow-up (SVR12). The patient was transferred to a
The patient subsequently received 2 pools of red blood general HD unit for anti-HCV negative patients as soon
cells (RBCs). After the hemoglobin concentration as HCV RNK became undetectable.
increased to 10.2 g/dL ribavirin was reintroduced
during week 3 of therapy. From that point until EOT, Discussion
the patient received 200 mg of ribavirin weekly. At HCV infection is one of the most important causes
week 7 since the beginning of therapy the patient had of chronic liver diseases, liver cirrhosis and
profuse menstrual bleeding and developed severe hepatocellular carcinoma, as well as liver-related

Figure 1. Serum hemoglobin dynamics during the course of treatment.

dot-dash line represents a RBC transfusion; dotted lines frame the time period when the patient had profuse menstrual bleeding; white dot – HD and no
ribavirin; black dot – HD and a single ribavirin dose.

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Milošević et al. – Chronic hepatitis C in hemodialysis patients J Infect Dev Ctries 2018; 12(2):142-145.

deaths. Global prevalence is 1.0%, with 71.1 million treated with DAAs in Serbia, all of them with the 3D
infected people worldwide, 399,000 of which die due to regimen. Only one of them was on HD.
this infection every year [3,4]. It is important to emphasize that co-administration
Patients with CKD stages 4-5 have a higher of ribavirin is recommended for infection with GT1a
prevalence of HCV infection compared to the general HCV, which poses an additional challenge in ESRD
population. The prevalence of HCV infection among patients due to preexisting anemia and their limited
HD patients varies widely, ranging from 5% to ability to excrete ribavirin [2,13]. The Ruby-I study
approximately 40%, depending on the geographic analyzed the 3D regimen in treatment-naïve GT1
region. Thus, these patients still represent a high risk patients with stage 4-5 CKD, 14 of which were HD
group for the acquisition of HCV infection [5-7]. patients. Results were encouraging with SVR12 rate of
Prevalence of anti-HCV positive patients among those 90%. Anemia was the main AE and it was considered a
on HD in Serbia was found to be high, but showing consequence of ribavirin treatment [2]. Here, ribavirin
tendency to decrease (31-23%) [8]. was interrupted if hemoglobin concentrations fell below
HCV infection is associated with significant 10g/dl which is a more conservative approach than ours
morbidity and mortality in HD patients, especially due was.
to cardiovascular diseases [9,10]. In addition, various Data from Spain showed that all HD patients with
histological types of glomerulopathies are associated GT1 and 4 achieved SVR regardless of DAA regimen
with HCV infection (membranoproliferative [19]. In 15 cases, ribavirin was co-administrated with
glomerulonephritis is the most common). Therefore, DAAs and anemia was found to be the most important
patients with stages 4 and 5 of CKD have to be AE. Ribavirin treatment should be interrupted if
considered priority patients for HCV therapy. hemoglobin levels fall by more than 2g/dL or to less
Achieving a SVR could also slow the progression of than 8.5g/dL, which is exactly what happened in the
CKD stages 1-3 [11,12]. case presented here [2,13]. It is interesting that
The introduction of DAAs offers new therapeutic treatment discontinuation and blood transfusion were
avenues for previously difficult-to-treat patients, not necessary in a cohort of Spanish patients which had
including those with ESRD. Furthermore, DAAs could no significant drop in hemoglobin concentration
lead to eradication of HCV infection among them. The because they had received high doses of erythropoietin.
3D regimen, grazoprevir / elbasvir and glecaprevir / It poses a reasonable preventive measure for ribavirin-
pibrentasvir are all drugs with a predominant hepatic induced/exacerbated anemia in patients on HD [19].
metabolism and excretion and as such are ideal in the Although blood transfusion and erythropoietin were
CKD setting [13,14]. Thousands of patients were permitted in the Ruby-I study, ribavirin treatment had
treated with the 3D protocol worldwide, but few reports to be discontinued in nine GT1a infected patients.
deal with HD patients, and most present a relatively Ribavirin was reintroduced in three patients after
small number of cases. Glecaprevir / pibrentasvir improvement of hemoglobin concentrations, and the
achieved high SVR12 rates and was well tolerated in same was done in the Serbian patient.
three difficult-to-treat patient subgroups with limited Ribavirin should be used with 3D regimens and
treatment options (DAA-experienced patients, patients grazoprevir/elbasvir in GT1a and GT4 patients with
with CKD) [15]. Grazoprevir / elbasvir has also been ESRD with individual dose modification [13].
demonstrated to be an efficacious and safe option in HD Although this could be challenging in patients with
patients [16]. Unfortunately, DAAs are very expensive, cirrhosis, Ponziani et al. showed that the 3D regimen is
and their price is an issue in both developed and effective and well tolerated in patients with GT1 and
developing countries. GT4 on HD and with compensated cirrhosis, including
Peg-IFN with ribavirin is still the most common those requiring administration of ribavirin [20].
therapeutic option in Serbia. Few Serbian hemodialysis Ribavirin is minimally eliminated by HD, and doses
patients were treated with these medications, with should be individually adjusted based on careful
modest results, so the majority remains treatment naïve. hemoglobin concentration monitoring. Recommended
Interferon based therapy is neither effective (a SVR rate ribavirin doses range from 200mg per week to 200 mg
of 40-58%) nor safe (a 26.9% withdrawal rate due to daily [21]. There are patients, as the one presented here,
side-effects) in patients with end stage renal disease who tolerate only minimal ribavirin doses (200 mg per
(ESRD) [17,18]. Sofosbuvir / ledipasvir, grazoprevir / week), but still benefit from them.
elbasvir and 3D regimen were approved for clinical use
in Serbia during 2016/17. Thus far just 23 patients were

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Patients with ESRD are not difficult-to-treat CHC treatment of the hepatitis C virus-infected patient with chronic
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Hepatol 66 :153-194.
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Artif Organs 25: 852-859. Ivana Milošević, MD, PhD
9. Ozer Etik D, Ocal S, Boyacioglu AS (2015) Hepatitis C Medical Faculty, University of Belgrade, Serbia
infection in hemodialysis patients: A review. World J Hospital for Infectious and Tropical Diseases, Clinical Center of
Hepatol7: 885–895. Serbia,
10. Kalantar-Zadeh K, McAllister CJ, Miller LG (2005) Clinical Bulevar oslobođenja 16, 11 000 Belgrade, Serbia
characteristics and mortality in hepatitis C-positive Phone. +381 11 2683366
haemodialysis patients: a population based study. Nephrol Dial Email: ivana.s.milosevic@mfub.bg.ac.rs
Transplant 20: 1662-1669.
Conflict of interests: No conflict of interests is declared.

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