Assessment of Patients With Hepatitis C Virus Related Liver Cirrhosis After Sustained Response to Direct Acting Anti Viral Drugs.

• Conditions: Hepatitis C; Liver Cirrhosis
• Interventions: Diagnostic Test: Abdominal ultrasound .; Diagnostic Test: Model for End-Stage Liver Disease; Diagnostic Test: Fibro Scan.; Diagnostic Test: Child-Turcotte-Pugh score.

• Registration Number: NCT03241823
• Lead Sponsor: Assiut University

Brief Summary

Hepatitis C Virus (HCV) infection is a major global health challenge; it is estimated that more than 80 million people are chronically infected worldwide, with 3-4 million new infections and 350,000 deaths occurring each year because of HCV-related complications .

Detailed Description

In 2015, a national Egyptian health issue survey was conducted to describe the prevalence of hepatitis C virus infection. The prevalence of hepatitis C virus antibody was found to be 10.0% and that of Hepatitis C virus Ribonucleic acid (HCV RNA ) to be 7.0% in the age group between 15-59 years. While In children, 1-14 years old, the prevalence of Hepatitis C virus (HCV) antibody and Hepatitis C virus Ribonucleic acid (HCV RNA) were 0.4% and 0.2% respectively.

The primary goal of HCV therapy is to cure the infection, i.e. to achieve a sustained virological response (SVR) defined as undetectable Hepatitis C virus Ribonucleic acid (HCV RNA )12 weeks or 24 weeks after treatment completion. The infection is cured in more than 99% of patients who achieve asustained virological response (SVR). Asustained virological response (SVR) is generally associated with normalization of liver enzymes and improvement or disappearance of liver necroinflammation and fibrosis in patients without cirrhosis. Patients with severe liver disease remain at risk of life-threatening complications; however hepatic fibrosis may regress and the risk of complications such as hepatic failure and portal hypertension is reduced .

Previous data suggest that the risk of Hepatocellular carcinoma and all-cause mortality is significantly reduced, but not eliminated, in cirrhotic patients who clear Hepatitis C Virus compared to untreated patients and non-sustained virological responders . Hepatitis C Virus is also associated with a number of extrahepatic manifestations and effective viral suppression induces reversal of most of them .

Studies in those with hepatitis C-related decompensated cirrhosis have demonstrated that sustained virological response can indeed be achieved in the majority of these individuals, and short-term follow-up from these studies has shown that Sustained virological response is often accompanied by improvement in measures of decompensation including Model for End-Stage Liver Disease (MELD) score and Child-Turcotte-Pugh (CPT) score. Moreover, because hepatitis C recurrence after Orthotopic liver transplantation is associated with worse outcomes, achieving Sustained virological response before transplant in a decompensated population with chronic hepatitis C will likely allow these patients to achieve long-term outcomes not different from non-Hepatitis C virus-infected populations .

In the SOLAR-1 and SOLAR-2 studies, those with decompensated cirrhosis with genotypes 1 and 4 were randomized to receive sofosbuvir/ledipasvir with low-dose ribavirin for 12 or 24 weeks . No difference was seen in Sustained virological response in the 12- or 24-week arms, and the therapy was well tolerated. Moreover, these studies both reported improvement in Model for End-Stage Liver Disease (MELD) score and Child-Turcotte-Pugh (CPT) scores 4 weeks after therapy had been stopped with longer-term follow-up results expected.

Liver stiffness measurement by transient elastography is a noninvasive, painless, rapid, and objective method for the evaluation of fibrosis or cirrhosis . Systemic reviews and meta-analyses have demonstrated the high sensitivity and specificity of Liver stiffness measurement in the diagnosis of hepatic cirrhosis.

In a systematic review conducted at 2007, repoted that at a threshold of approximately 0.60, the sensitivity and specificity of the FibroTest were 47% (35-59%) and 90% (87-92%). For FibroScan (threshold approximately 8 kPa), corresponding values were 64% (50-76%) and 87% (80-91%), respectively.

In another systematic review conducted at 2010, reported that the pooled estimates for sensitivity of fibroscan were 87% (84%-90%), specificity 91% (89%-92%) in stage IV fibrosis (cirrhosis). While in patients with stages II-IV fibrosis, they reported that the pooled estimates for sensitivity were 70% (67%-73%), specificity 84% (80%-88%).

Multicenter observational, cohort, prospective study included 90 patients with hepatitis C genotype 1 treated with telaprevir or boceprevir who had advanced fibrosis evidenced by liver stiffness and achieved Sustained virological response reported that liver stiffness was significantly reduced 2 weeks after treatment. This suggested the possibility of liver cirrhosis regression evidenced by liver stiffness after sustained virological response in a significant proportion of patients .

In a study included 182 Egyptian patients with HCV infection to validate and compare the diagnostic performance of Fibroscan , APRI Score , FIB4 for the prediction of hepatic fibrosis and treatment outcome in HCV infected patients receiving pegylated interferon and ribavirin, the authors reported that Fibroscan and noninvasive scores as APRI , FIB4 can be used as good predictors of liver fibrosis in chronic hepatitis C. However, they are not good predictors of response to pegylated interferon and ribavirin .

In a study 2010, they concluded that liver stiffness measurement can be useful for monitoring regression of liver fibrosis during entecavir treatment in patients with chronic hepatitis B virus infection.

A few studies showed a consistent relationship between Doppler Ultrasonography findings and liver histology. showed that Doppler Ultrasound findings are sensitive to haemo dynamic changes in liver fibrosis. Doppler Ultrasonography scoring was significantly related to liver fibrosis staging.

The Doppler Ultrasound signs for portal hypertension are: (1) reduced portal vein blood flow velocity (time-averaged mean vel. \< 14-16 cm/s2), with sensitivity and specificity between 80-88% and 80-96%, respectively; (2) portal vein congestion index \> 0.08. This parameter, however, is not used routinely, probably due to its being difficult to measure and its lower reproducibility; and (3) measurements of the hepatic arterial Resistive Index are less useful. In the course of Liver cirrhosis, the appearance of clinically significant portal hypertension worsens prognosis and Doppler ultrasound is very useful in evaluating portal hypertension. . astudy showed a significant reverse correlation between the velocities of the main portal vein and fibrous staging of the liver.

Study Timeline

• Status Verified: 2017-08
• Study First Submitted: 2017-08-03
• Study First Submitted QC: 2017-08-05
• Last Update Submitted: 2017-08-05
• Study First Posted: 2017-08-08
• Last Update Posted: 2017-08-08
• Study Start: 2017-12-01
• Primary Completion: 2019-01
• Study Completion: 2019-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Age: ≥ 18 years.
2. Disease status: patients with hepatitis C Virus related liver cirrhosis child A& B (scores 5-9).
3. Previous treatment: treatment naïve and treatment experienced.
4. HCV RNA: Negative at any point between 12-24 weeks post treatment to confirm successful eradication of the virus.
5. Negative HBsAg and HIV antibody.
6. Normal kidney function test

Read More

Exclusion Criteria

1. Child C liver cirrhosis (Child score ≥ 10).
2. HCV coinfection with HBV or HIV.
3. Patients with high risk of infection (I.V drug users, patients with blood disease requiring blood transfusion).

Read More

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with hepatitis c virus related liver cirrhosis	Model for End-Stage Liver Disease	Patients with chronic hepatitis C virus whose ultrasound shows liver cirrhosis, fibroscan "F3 and F4, Child score "A and B", of any MELD score, who achieved Sustained Virological Response after direct acting antiviral drugs (Sofosbuvir, Daclatasvir ± Ribavirin).
Patients with hepatitis c virus related liver cirrhosis	Abdominal ultrasound .	Patients with chronic hepatitis C virus whose ultrasound shows liver cirrhosis, fibroscan "F3 and F4, Child score "A and B", of any MELD score, who achieved Sustained Virological Response after direct acting antiviral drugs (Sofosbuvir, Daclatasvir ± Ribavirin).
Patients with hepatitis c virus related liver cirrhosis	Child-Turcotte-Pugh score.	Patients with chronic hepatitis C virus whose ultrasound shows liver cirrhosis, fibroscan "F3 and F4, Child score "A and B", of any MELD score, who achieved Sustained Virological Response after direct acting antiviral drugs (Sofosbuvir, Daclatasvir ± Ribavirin).
Patients with hepatitis c virus related liver cirrhosis	Fibro Scan.	Patients with chronic hepatitis C virus whose ultrasound shows liver cirrhosis, fibroscan "F3 and F4, Child score "A and B", of any MELD score, who achieved Sustained Virological Response after direct acting antiviral drugs (Sofosbuvir, Daclatasvir ± Ribavirin).

Primary Outcome Measures

Name	Time	Method
Changes in liver fibrosis	1 year.	Using non-invasive measures "Fibroscan"

Secondary Outcome Measures

Name	Time	Method
Changes occurring in liver haemodynamics	1 year.	Using Doppler ultrasound.
Changes in severity of liver disease	1 year	Using Child-Pugh score.

Trial Locations

Locations (1)

Assuit Unit of Treatment of Viral Hepatitis.; 🇪🇬 Assuit, Egypt