الفهرس 
INTRODUCTION TO HEPATITIS C VIRUS (HCV)
CLINICAL PICTURE : SYMPTOMS AND SIGNSOnly 14 pages are availabe for public view
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Abstract
According to the WHO there are 185 million people infected with HCV in the world.
Egypt has the highest prevalence of hepatitis C virus (HCV) in the world reaching
13% equating to an estimated 12 million Egyptians . HCV is one of the main causes of
liver cirrhosis and hepatocellular carcinoma.
HCV can develop kidney disease because of extrahepatic manifestations of HCV or as
a disease process independent of the HCV infection.In addition, hemodialysis has been
a risk factor for acquiring HCV infection. The prevalence of HCV infection is high in
patients with ESRD, on hemodialysis ranges from 6% to 60% in different parts of the
world. Several studies show that patients on hemodialysis have an increased overall
mortality risk if they have chronic HCV when compared with those on dialysis who do
not have HCV.
Antiviral treatment in CKD patients can be complicated because many of the agents
used for anti-HCV therapy can accumulate to toxic levels in the setting of renal
impairment. Treatment of HCV compensated cirrhosis with the new DAA therapy
Qurevo “ombitasvir/ paritaprevir/ritonavir” with ribavirin in ESRD was approved in
many countries.
Based on that, the current study was conducted aiming to evaluate the efficacy and
safety of Qurevo /Ribavirin regimen in ESRD Egyptian patients on regular
hemodialysis who are infected with hepatitis C virus (HCV) . 50 ESRD patients on
regular hemodialysis with a mean age of 51.4 years ,range from 23-77 years, 25 (50%)
males, 25(50% females) were enrolled in a prospective cohort study. The study took
place at the hepatic virology clinic at Ain Shams University hospital over a period of 15
months( from December 2016 to February 2018) .
Patients with Child’s C cirrhosis patients, platelet count <50000 /mm3, HCC , extrahepatic
malignancy ,pregnancy or inability to use effective contraception,
inadequately controlled diabetes mellitus (HbA1c> 9%) were all excluded.
All patients were subjected to full history taking( including renal condition and
hepatitis C infection) , full clinical examination ,baseline laboratory investigations
(CBC, serum creatinine ,HCV Ab, HBsAg, PCR for HCV, liver functions “Total & direct bilirubin/serum albumin/ INR”, liver enzymes “AST/ALT”, alpha feto
protein, pelvi-abdominal ultrasound).
Treatment with daily fixed-dose combination of 2 tabs Qurevo “ombitasvir (12.5
mg,NS5A inhibitor)/paritaprevir (75 mg, NS3/4A protease inhibitor) /ritonavir (50
mg)” with meal + 200 mg ribavirin daily for 12 weeks was done. The primary
endpoint was sustained virologic response 12 weeks after end of therapy (SVR12).
Also, tracing the incidence of adverse events according to checklist (by symptoms,
signs, investigations) and follow-up CBC, liver enzymes,liver functions at weeks 4,
8 and 12 were done.
The results revealed, regarding the efficacy, SVR12 rate was 96% (48/50); 2 patients
had virologic failure. This goes in line with the RUBY-I and RUBY-II trials
presented at the meeting of the American Association for the Study of Liver
Diseases (AASLD) held in Boston in November 2016, in which SVR12 rate was
96%(46/48) in RUBY-I, 94% (17/18) in RUBY-II. Also, like the study in Japan by
Atsukawa in 2017, SVR12 rate was 96.8%(30/31) and like study in Egypt by Hanno
year 2018, SVR12 was also 96%(48/50) .It was similar to study in USA by Eric year
2018, SVR12 rate was 95%(63/66) and another study in Japan by Arai year 2018,
SVR12 was 98.7%
As regards safety and adverse events ,the most frequent was fatigue/asthenia in 44
patients (88%) and worsening anemia (Hb dropped to <10 g/dl) in 42 patients (84%).
GIT upset occurred in 10 patients (20%), sleep disorders in 8 patients (16%) ,decreased
appetite in 8 patients (16%),respiratory distress in 6 patients (12%) ,headache,
dizziness in 6 patients(12%). Muscle spasms in 4 patients (8%). Itching(pruritis)
occurred in 3 patients(6%).2 patients (4%) were non-responders to treatment and
another 2 (4%) were relapsers.Death was reported in 4 patients (8%), post treatment
probably unrelated to treatment, due to myocardial infarction, pulmonary edema, severe
hypotension on hemodialysis sessions, shock due to blood loss in retroperitoneal
hematoma following peritoneal dialysis.Hepatic decompensation, hypersenisitivity
(angioedema), teratogenicity and drug interactions did not occur in any patient
(0%).Other events occurred in 11 patients (22%)% during therapy, not yet proved to be
related or not to the drug. They were parenchymal liver changes in ultrasound at the end
of therapy after being normal before therapy (in 3 patients), thrombocytopenia,
increased alkaline phosphatase, hiccough, deterioration of hypertension, urinary tract
infection, lower limb cellulitis, vaginal bleeding, chest infection(in 1 patient each).
These results go in line with RUBY-I trial and Eric study in USA, 2018 in which anemia was the most common adverse event .But, unlike study of Atsukawa 2017 in Japan,
which used RBV free regimen and Hanna 2018 in Egypt, which enrolled different CKD
stages (2-5) in which pruritis was the most common adverse event.
As regards follow-up CBC, liver enzymes and liver functions week 4,8 and 12, it was
found that HGB levels decrease, total and indirect bilirubin increase due to RBV
associated hemolysis. AST,ALT and INR levels decrease .This is in agreement with
Hanno study in Egypt 2018.
As regards anemia being the most common adverse event, several studies including the
current study confirm 2 observations .First, anemia during HCV treatment occurs higher
with more advanced renal failure(More in CKD 5 dialysis patients than CKD 2-5 than
non-CKD). Second, it occurs in majority of the studies with ribavirin including
regimens.This was obvious in the current study which included both advanced renal
failure, ESRD patients on regular hemodialysis and ribavirin including regimen.
To overcome anemia in ESRD patients receiving HCV therapy, ribavirin dose is 200
mg/day (typically starting at 200 mg three times weekly and titrating up to 200 mg/day
as tolerated). Ribavirin should be discontinued if the hemoglobin level decreases by
more than 2 g/dL despite the use of erythropoietin according to (AASLD)
guidelines.SVR12 rate in the current study was achieved in 100% of patients who had to
stop or modify ribavirin dose ;this means that RBV absence didn’t affect the SVR12 in
these patients. This leads us to think of RBV-free regimens in ESRD patients as a safer
option of treatment to avoid severe hemolytic anemia with Ribavirin that occurs with
these patients despite various anemia mangements during therapy.
Current guidelines recommend two RBV-free regimens for patients with HCV infection
and stage 4 or 5 CKD, elbasvir/grazoprevir, which is approved for the treatment of
patients with GT1 or 4 infection, and glecaprevir/pibrentasvir, which has pangenotypic
activity. Both show high efficacy(SVR12) with no anemia as adverse event in ESRD.
For this reason, the regimen used in the current study ombitasvir/paritaprevir/ritonavir
and ribavirin would be considered to be alternative to the 2 recommended regimens.
However, these 2 regimens are not yet available in Egypt.
The current study had 2 non-responders and 2 relapsers.The study tried to correlate
between them and RBV dose modification and also HCV viral load but there was no
statistical significant relation between them.
The results confirm the efficacy of Qurevo “ombitasvir/ paritaprevir/ritonavir” with
Ribavirin combination therapy in ESRD patients on regular hemodialysis with HCV
infection, with anemia as the most frequent adverse event. However, the effect of this
regimen in CKD staging, different HCV genotypes and causes of virologic
failure/relapse couldn’t be studied.