Sofosbuvir-Velpatasvir for Chronic Hepatitis C Virus-Infected Children and Young Adults: Efficacy and Safety

Background: Sofosbuvir-Velpatasvir has a high efficacy in adult patients with chronic hepatitis C infection .In this study, we reported treatment outcome with this drug in children and younger adults in Pakistani population. Objective: To assess the efficacy and safety of Sofosbuvir-velpatasvir in treating HCV-infected children and young adults. Methods: This Interventional(Clinical trial) was done in Hepatitis clinic Jinnah Hospital, Lahore from April 10, 2021 to January 9, 2022.A total of 45 patients aged 6 to 18 years with detectable HCV RNA by PCR were registered. They were evaluated clinically. HCV genotyping was not done as Sofosbuvir – Velpatasvir is pangenotypic. All of the patients were given a single oral dose of Sofosbuvir-velpatasvir per day. Ribavirin was included for patients with compensated cirrhosis and for those who were treatment-experienced .Clinical assessment, CBC, LFT, RFT, and PT were performed monthly to determine side effects and safety. To evaluate treatment efficacy, HCV RNA was measured by PCR at 12 weeks (end of treatment) and 12 weeks post-treatment (sustained virological response). Treatment lasted for 24weeks for those with compensated cirrhosis. (Child Turcotte Pugh score 5 and 6; Child class A) or those who were treatment experienced. SPSS 24 was used for data analysis. Results: Non cirrhotic patients had a mean age of 13.6±1.45 years, while those with compensated cirrhosis had 14.1±2.15 years. There were 63.6% males (28) and 36.4% female (17). 41 patients (91.11%) had undetectable HCV RNA by PCR, 12 weeks after treatment (Sustained virological response), indicating treatment effectiveness. Nine patients had HBV co-infection and took HBV medications as well during HCV treatment. At 12 weeks post-treatment, all HBV-coinfected patients had undetectable HCV RNA by PCR and lower HBV titers. Some of the patients experience minor side effects. However, none of the patients stopped their treatment due to these side effects Thus, this treatment was safe and effective. Conclusion: Sofosbuvir/velpatasvir has effectiveness and safety in treating HCV in children and young adults.


Introduction
T he spread of the hepatitis C virus (HCV) is now recognized as a major public health issue worldwide.Over 71 million people worldwide are afflicted with this virus.HCV antibodies were found in 13.2 1 million youngsters in a recent study.After the first directacting antiviral medication (DAA) was approved in 2 2011, HCV treatment has advanced significantly.More than ten different drug combinations have been approved for the treatment of HCV in adults.With 12 weeks of treatment, these regimens can achieve SVR in >90% of cases.Sofosbuvir-velpatasvir was approved for adults in June 2016 and for children aged 6-17 and 3-5 Given the aforementioned, we examined the efficacy and safety of this combination in treating children over six years old in Pakistan, as to our knowledge no analogous study exists in our population.So this determination can play an important role in making our local guidelines regarding the treatment of children and may help in eradicating the disease and reducing the financial burden on our healthcare system.

Methods
The study's sample size was 45 patients with a 2% margin of error and a 95% confidence level with 80% power of test and taking an expected percentage of efficacy as 90% with Sofosbuvir-Velpatasvir.This Interventional study involved 45 HCV-infected children/young adults referred to the Hepatitis clinic Jinnah Hospital Lahore from April 2021 to January 2022 and their relevant data was recorded.Drug dosage, duration, and side effects and efficacy were determined during and after treatment.We have prepared our own 22 questionnaire based on CLDQ (chronic liver disease questionnaire) .Quality of life in CLD can be evaluated with the help of the CLDQ, which is a disease-specific, well-validated questionnaire.This questionnaire has 22 been pretested in international studies and its chronbach's alpha value is 0.8 .There are 29 total items in it, and they cover digestive issues, lack of energy, systemic symptoms, activity, anxiety and emotional function.The CLDQ results produced a 7-point scale, from "always" to "never," covering the range of possible CLDQ responses.This study only included non-cirrhotic and compensated cirrhosis (Child A) and advanced disease cases with liver decompensation (Child B and C) were excluded.
Children and adults aged 6-18 with detectable HCV RNA by PCR were included.They included treatment naïve and experienced individuals.Clinical assessment, CBC, LFT, RFT, PT and Ultrasound abdomen were done at the start of study and after each month during treatment to assess side effects, safety and fitness of patients for treatment and to exclude decompensated disease from noncirrhotic and compensated disease The patients received Sofosbuvir 400 mg-velpatasvir 100mg daily for 12 weeks (non cirrhotic or treatment Naïve) or 24 weeks(compensated cirrhosis or treatment experienced).Patients under 12years or <30kg received 3 half the dose.(total 32 patients).Treatment-experienced/ compensated cirrhosis patients received Ribavirin 10-

Discussion
This study evaluates the efficacy and safety of Sofosbuvir-Velpatasvir in children and young adults of the Pakistani population.This combination for 12 weeks was found to be highly effective and well-tolerated in pediatric patients without cirrhosis or with compensated cirrhosis In this trial, as in other studies conducted in developing countries, transfusion of blood products was revealed to be the leading cause of HCV acquisi-

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tion.Due to efficient blood screening in affluent countries, vertical transmission is the main route of infection.HBV co-infection is a risk factor for early morbidity.Since DAA treatment may trigger a flare-up of HBV, all patients with HBV co-infection got concurrent anti-HBV medication during HCV treatment and or up to done in connection with the DAA.The treatment in the current study was well tolerated except for minor side effects.However, none of the patients stopped their treatment due to these side effects.SVR 12 in our study was 91.11%, which shows a considerable improvement as compared to INF based treatment where    similar results.
In treatment-experienced/ compensated cirrhosis patients, the 24-week regimen yielded 19 similar results.Data is scarce on the studied subject in our country.However, there are some caveats to our study; small sample size, genotyping was not done as treatment regimen is pangenotypic and due to cost issues.
The study included non-cirrhotic patients and those with compensated cirrhosis (Child class A), but had not included patients with hepatic decompensation.Most of the patients were treatment naïve.These limitations should be addressed in further studies that need to include decompensated patients with large sample sizes.
Our study highlights the need to ensure safe blood screening and transfusion practices.

Conclusion
Sofosbuvir/velpatasvir treats HCV infection in young adults and teens without cirrhosis and those with compensated cirrhosis safely and effectively.This medicine works well for both untreated and previously treated patients who did not respond.
Ethical Approval: Given of Interest: The authors declare no conflict of interest.Funding Source: None

12 , 13 three
months following it.To analyze the effectiveness in relation to viral load, a larger sample size is required.A good response to INF-based therapy is predicted by a decreased viral load, but few studies have been 14-16

Table 1 :
Different Characteristics of Patients without Cirrhosis and in Compensated Cirrhosis

Table 2 :
Treatment Efficacy of Sofosbuvir-Velpatasvir in the Study