MELD Score as a Predictor of Treatment Response of ‘ Difficult to Treat ’ Chronic HCV Patients

hepatitis C, MELD, Child score, antiviral Background and study aim: The introduction of direct acting antiviral agents shifted the management of chronic hepatitis C virus (HCV) infection to a new level. Pretreatment predictors of benefit are needed to help the selection of patients for treatment. The aim of this work is to study if Model for End Stage Liver Disease (MELD) score can be reliably used as a predictor of response to treatment with direct acting antivirals (DAAs) in „difficult to treat‟ chronic HCV patients.


Background and study aim:
The introduction of direct acting antiviral agents shifted the management of chronic hepatitis C virus (HCV) infection to a new level.Pretreatment predictors of benefit are needed to help the selection of patients for treatment.The aim of this work is to study if Model for End Stage Liver Disease (MELD) score can be reliably used as a predictor of response to treatment with direct acting antivirals (DAAs) in "difficult to treat" chronic HCV patients.

INTRODUCTION
Chronic hepatitis C virus (HCV) infection is a major health problem affecting more than 170 million infected individuals worldwide.Liver cirrhosis is a real threat in 2-35% of the patients after 20-25 years of chronic infection [1].The classical treatment for HCV infection was the dual therapy with pegylated interferon (Peg-IFN) α-2a or -2b combined with the guanosine analog ribavirin giving sustained virologic response (SVR) rate of only about 50% [2].A new era of direct acting antivirals (DAAs), with SVR rate of about 90%, has emerged.Multiple regimens with various combinations of these drugs, without the use of IFN, proved to be effective and well tolerated, even among patients with advanced liver disease

PATIENTS AND METHODS
A retrospective cohort study was conducted as a collaborate work between Tropical Medicine Department, Faculty of Medicine, Zagazig University and Viral Hepatitis Treatment Unit, Al Ahrar Teaching Hospital.Ninety-one patients who were selected and categorized as "difficult to treat" were included in this study.Their files were randomly selected from the follow up clinic -in Al Ahrar hospital-till the completion of sample size from July 2017 to January 2018.

RESULTS
Ninety-one patients who were categorized as "difficult to treat" were included in this study.Their files were selected randomly from the follow up clinic till the completion of sample size from July 2017 to January 2018.
59.3% of patients were males and 40.7 % were females.The mean age was 53.52 (53.52 ± 8.48) years and 11% only had prior HCV treatment.AFP level was 23.90 ± 18.40 ng/ml and HCV RNA level was 6.35 ± 4.17 million IU/ml (Table 2).
After treatment, MELD score improved in about 28.6% of patients, remained stable in 57.1 % and worsen in 14.3 % (Table 3).
There was no significant difference in the mean values of MELD score between patients with and without SVR before treatment and also after treatment (Table 4).
MELD score was improved in 27.9% of patients who had SVR.Despite that 40% of patients without SVR showed improvement of their MELD scores.There were no significant differences between both groups regarding percentage of improved, stable and worsen cases (Table 5).
MELD score"s mean was higher among patients with complications when compared with those without complications before and after treatment with significant statistical differences.The patient without complications showed highly significant decrease in their mean MELD after treatment, while patients with complications showed nonsignificant increase of their mean MELD score.Five patients (5.5%) were complicated by variceal bleeding (one case), hepatic encephalopathy grade 2 (one case) and HCC (one case) (Table 6).
In patients without complications, MELD scores were improved in 30.2% and worsen in about 10.5%, while in patients with complications; MELD scores did not improve in any one and worsen in 80% with highly significant difference (Table 7).In this study, before treatment, mean MELD score in patients who reported complications during treatment was significantly higher when compared with patients without complications indicating that the high MELD score is a predictor of occurrence of complication.However, because of the small number of patients with complications (n=5), the exact predictive cutoff value of MELD cannot be calculated by the specific statistical tests used for this purpose.A similar result was reported by Manns et  In this study, before treatment, mean MELD score in patients who achieved SVR didn"t show significant difference when compared with patients who didn"t achieve SVR indicating that MELD score cannot be used as a predictor of response to DAAs.This result can be explained by the significant decrease in the mean MELD score in patients with SVR and the unchanged score of patients without SVR after treatment.This result is not matching with that of Carrillo et al. who reported that decompensated cirrhosis (CTP B/C) at baseline was associated with lower rates of virologic response compared with patients with less advanced cirrhosis (CTP A).Carrillo and his colleague put Child B/C patients in one group leading to decreased response rate of this group.In addition, 67% of Child B patients in that study had score 7 which is the nearest score to Child A making those to achieve high SVR rate near to that of Child A [15].

CONCLUSION
Baseline MELD score cannot predict the response to treatment of "difficult to treat" chronic HCV patients but can predict the occurrence of complications.

Ethical approval:
The research protocol was approved by the Institutional Review Board (IRB), the ethical committee of Zagazig University Hospitals.

Conflicts of interest:
None.
[3].Despite the poor treatment outcome in patients with decompensated cirrhosis (Child-Pugh B/C) compared to patients with compensated cirrhosis (Child-Pugh A), safety issues regarding the use of DAAs among those patients with the most advanced liver disease have arisen [4].Successful treatment of patients with decompensated liver disease due to HCV has two potential benefits.First, it could result in resolution of complications of endstage liver disease and improve survival resulting in delisting patients awaiting liver transplantation.Second, perhaps successful treatment of HCV could result in better post-transplant outcomes [5].

Table ( 2
): Basic characteristics of the studied patients

Table ( 3
): Change in MELD score among the studied patients

Table ( 5
): Comparison between patients with and without SVR as regard MELD score changes after treatment [16]who observed that the patients with baseline MELD score <15 reported more improvement of their MELD after treatment and rarely develop complications while those who had baseline MELD score ≥15 were in the opposite side[16].