Epclusa® (SOF/VEL), Harvoni® (LDV/SOF), Sovaldi® (SOF), Vosevi® (SOF/VEL/VOX)

Liver Disease and Liver Fibrosis Regression

This document is in response to your request for information regarding liver disease and fibrosis regression after the use of sofosbuvir-based regimens, including Epclusa® (sofosbuvir/velpatasvir [SOF/VEL]), Harvoni® (ledipasvir/sofosbuvir [LDV/SOF]), Sovaldi® (sofosbuvir [SOF]), and Vosevi® (sofosbuvir/velpatasvir/voxilaprevir [SOF/VEL/VOX]).

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Summary

Clinical Registries: Liver Disease and Liver Fibrosis Regression With SOF-Based Regimens

In two Cirrhosis Registry studies, most participants maintained or improved SVR, CPT scores, and MELD scores. Liver stiffness or fibrosis assessments by transient elastography improved in both studies.1,2

Clinical Data on Liver Disease and Liver Fibrosis Regression With SOF-Based Regimens

Across several studies, including prospective trials and retrospective chart reviews, treatment with SOF-based regimens resulted in a majority of participants who had improvements or no changes in various clinical parameters, such as MELD scores, CPT scores, and liver stiffness or fibrosis assessments, including APRI, FIB-4, FibroScan, and transient elastography.3-15

Clinical Registries: Liver Disease and Liver Fibrosis Regression With SOF-Based Regimens

Cirrhosis Registry1

Study design and demographics

The Cirrhosis Registry was conducted to assess the worsening or improvement of clinical liver disease after achievement of SVR, to determine SVR durability, and to evaluate if the presence of detectable HCV RNA is representative of late relapse or reinfection (as determined by phylogenetic sample analysis) in 1245 participants. The median (range) follow‑up time in this interim analysis was 71 (1–146) weeks.

Figure 1. Study Design (Mangia et al)1

Table 1. Baseline Demographics and Disease Characteristics (Mangia et al)1

Results

SVR was maintained in all participants, except one (CPT Class A cirrhosis and reinfection with GT 1a 96 weeks after SOF/VEL treatment completion). Nearly all participants (99%) with CPT Class A cirrhosis pretreatment remained within CPT Class A (Figure 2). In participants with CPT Class B or C and a MELD score <15 at pretreatment, 95% maintained a MELD score <15 at Week 96 (Figure 3). FibroScan measurements improved early during the Cirrhosis Registry and were maintained through Week 96.

Figure 2. Change in CPT Class in Participants With Pretreatment CPT Classes B or C Cirrhosis (Mangia et al)1

Figure 3. Change in MELD Score in Participants with CPT Classes B and C Cirrhosis (Mangia et al)1

Cirrhosis Registry–Cirrhosis Regression Study2

Study design and demographics

Changes in non-invasive tests for participants in the Cirrhosis Registry were evaluated. The median time between SVR achievement and registry enrollment was 38 weeks. To assess the course of cirrhosis regression, investigators assessed the reduction in ELF scores of ≥0.5 units, reduction in liver stiffness by transient elastography of ≥25%, and shifts in CPT class from registry enrollment to Week 144.

Table 2. Baseline Demographics and Disease Characteristics (Jacobson et al)2

Results

In participants with CPT Class A at Week 144 (n=543), 533 participants (98%) remained classified as CPT Class A, and 10 participants (2%) shifted to CPT Class B/C. In participants with CPT Class B/C (n=43), 21 participants (49%) improved to CPT Class A, and 22 participants (51%) remained classified as CPT Class B/C.

According to ELF score, F3 fibrosis was present in 38% of participants (594/1575), and F4 fibrosis was present in 16% of participants (247/1575) at registry enrollment. Improvement was seen in participants with F3 and F4 through follow-up at Week 144 (Figure 4). Improvements in fibrosis according to ELF response were significantly associated with younger age, higher ELF score, lower BMI, lower bilirubin level, lower FIB-4 score, and lower liver stiffness by transient elastography at enrollment.

Figure 4. Improvement in Fibrosis Class According to ELF Score (Jacobson et al)2

According to transient elastography, F3 fibrosis was present in 57% of participants, and F4 fibrosis was present in 17% of participants at registry enrollment. Improvement was seen in both F3 and F4 participants through follow-up at Week 144 (Figure 5). Improvements in fibrosis according to liver stiffness response were significantly associated with absence of ascites before treatment and higher liver stiffness according to transient elastography at registry enrollment. From registry enrollment to the end of the follow-up period, a reduction of ≥25% in liver stiffness by transient elastography was observed in 37% of participants (433/1178) with available data.

Figure 5. Improvement in Fibrosis Class According to Liver Stiffness by Transient Elastography (Jacobson et al)2

Clinical Data on Liver Disease and Liver Fibrosis Regression With SOF-Based Regimens

SOLAR-1, -2 and ASTRAL-4

Study designs

SOLAR-1 and -2 were phase 2, open‑label studies that evaluated the safety and efficacy of LDV/SOF + RBV for 12 or 24 weeks in participants with GT 1 or 4, who were TN or TE, pre‑transplant CPT Class B and C (n=215) and post-transplant F0–F3/CPT A (n=330) and CPT Classes B and C (n=114).3-6 ASTRAL-4 was a phase 3, open-label study that evaluated the safety and efficacy of 12 (n=90) or 24 (n=90) weeks of SOF/VEL vs 12 weeks of SOF/VEL + RBV (n=87) in TN and TE participants with HCV GTs 1 to 6 and CPT Class B decompensated cirrhosis.7

SOLAR-1 and -2 CPT and MELD changes

Of participants with CPT Class B or C cirrhosis who achieved SVR12 with a baseline MELD score <15 (n=199), the majority (56%) improved or had no change (18%) in MELD scores from baseline to follow-up at Week 24. Most participants (89%) with CPT Class B or C who achieved SVR12 with a baseline MELD score >15 (n=72) improved (76%) or had no change (13%) in MELD scores from baseline to Week 24. No Week 24 follow-up assessment was available for 9 participants in either arm. Participants with CPT Class B or C decompensated cirrhosis who achieved SVR12 also had statistically significant improvements from baseline to Week 24 in total bilirubin, albumin, and INR (each, P<0.001). Participants with fibrosing cholestatic hepatitis had rapid and sustained improvements in liver function as assessed with MELD score.4-6

ASTRAL-4 CPT and MELD changes8

CPT and MELD scores either improved or did not change in most participants who achieved SVR12 (Table 3 and Table 4).

Table 3. CPT Change From Baseline in Participants Who Achieved SVR12 and SVR248

Of the participants who achieved SVR24, 39% of participants (84/213) had an improvement in albumin, 16% of participants (35/213) had an improvement in bilirubin, 2% of participants (5/213) had an improvement in INR, 15% of participants (32/213) had an improvement in ascites, and 9% of participants (20/213) had an improvement in encephalopathy.

Table 4. Changes in MELD Score in Participants Who Achieved SVR24 With Baseline MELD Scores <15 or ≥158

Improvements in MELD score were driven largely by improvements in total bilirubin.

In an analysis of baseline characteristics that might potentially predict improvements in MELD score among patients who achieved SVR, improvements in MELD score at post‑treatment Weeks 12 and 24 were more common in patients with higher MELD scores, lower BMI (<30 kg/m2), and absence of encephalopathy at baseline.

Retrospective and Prospective Observational Study in Switzerland9

Study design and demographics

A multicenter, retrospective and prospective, observational study was performed in patients with HCV (N=392) to assess the reduction in liver stiffness measured by transient elastography after treatment with DAA, to identify the factors associated with transient elastography regression, and to correlate the transient elastography results with FIB‑4 and APRI scores. LSMs by transient elastography were taken the day before patients initiated DAA therapy and 12 weeks after therapy. The primary outcome was a decrease in transient elastography after DAA treatment, and secondary outcomes were decreases in APRI and FIB‑4 scores after treatment.

Table 5. Baseline Demographics and Disease Characteristics (Bachofner et al)9

Results

The median time between biopsy and start of therapy was 2.01 years, and the mean duration of therapy for all patients was 15.7 weeks. The median time between EOT and post-therapy LSM by transient elastography was 16.1 weeks. Within 12 weeks after therapy, the overall median (IQR) LSM decreased from 12.65 to 8.55 (5.93–15.25) kPa (P<0.001). Overall, median (IQR) APRI scores decreased from 1.1 (0.65–2.43) to 0.43 (0.3‑‑0.79), and FIB-4 scores decreased from 2.54 (1.65–4.43) to 1.8 (1.23–2.84). While improvement was observed in both those who achieved SVR and those who did not, significant reductions in LSMs and APRI and FIB‑4 scores were found only among patients who achieved SVR. There was a median decrease in LSM by transient elastography of >30% in patients who achieved SVR.

A subgroup of 143 patients had their liver stiffness measured by transient elastography twice after they stopped therapy to assess whether the observed decrease in liver stiffness was maintained. The median (IQR) LSM for the subgroup was 14.3 (10.25–21.15) kPa at baseline, 10.2 (6.8–16.9) kPa at first measurement (mean time between EOT and measurement, 15 weeks), and 9.1 (6.1–13.9) kPa for the second measurement (mean time between EOT and measurement, 40 weeks). The decrease in LSMs between the first and second post-treatment follow-up visits was statistically significant for all 137 patients who achieved SVR (P<0.001). No significant differences in LSMs were observed between treatment regimens or HCV GT.

One patient died due to a cause unrelated to DAA therapy, 4 patients had liver transplants during therapy, and 31 patients were lost to follow-up.

Prospective Cohort Study in Georgia10

Study design and demographics

A prospective, observational, cohort study in adults with HCV and advanced liver fibrosis or cirrhosis evaluated changes in liver stiffness, as measured by transient elastography, to determine the effect of DAA therapy on liver fibrosis regression (N=304). Participants were treated with either PEG-IFN α-2a or α‑2b + SOF + RBV for 12 weeks; SOF + RBV for 12, 20, or 24 weeks; or LDV/SOF ± RBV for 12 or 24 weeks. Liver stiffness was measured by transient elastography within 3 months prior to the start of therapy, at EOT, and at Weeks 12 and 24 after EOT. The primary outcome was an improvement in liver stiffness at Week 24, as measured with a ≥20% decrease in liver stiffness and a decrease from baseline in the median LSM. Participants with a history of liver transplant, co‑infection with HBV or HIV, decompensated liver cirrhosis, unexplained elevations in liver enzyme levels, or those being treated with hepatotoxic medications were excluded from this study.

Table 6. Baseline Demographics and Disease Characteristics (Dolmazashvili et al)10

Results

SVR was achieved in 84.5% of participants (257/304) overall; 98.5% who received LDV/SOF ± RBV, 89.5% who received PEG‑IFN + SOF + RBV, and 64.3% who received SOF + RBV achieved SVR. Participants who did not achieve SVR also had significant decreases in liver stiffness.

Overall, significant decreases in liver stiffness from baseline were observed at EOT and Weeks 12 and 24 after EOT. Liver stiffness decreased from a median (IQR) baseline score of 16.9 (11.8–27.7) kPa to a Week 24 post-treatment score of 11.9 (8.2–20.9) kPa (P<0.0001). By Week 24 post-treatment, only those who achieved SVR had a significant decrease in liver stiffness from pretreatment values (SVR, P<0.001; no SVR, P=0.27;
Table 7).

Table 7. Liver Stiffness by Transient Elastography by SVR Achievement
(Dolmazashvili et al)10

All treatment regimens demonstrated a significant reduction in liver stiffness score (P-values not provided). Between regimens, a significant difference in liver stiffness reduction was noted between LDV/SOF ± RBV (median [IQR] reduction: 4.7 [2.9–8] kPa) and SOF + RBV (median [IQR] reduction: 3.4 [0.6–7.5] kPa; Table 8).

Table 8. Liver Stiffness by Transient Elastography by Treatment Regimen (Dolmazashvili et al)10

Overall, a ≥20% reduction in LSM from baseline to Week 24 was observed in 65.1% of participants. The achievement of a 20% reduction from baseline in liver stiffness was significantly associated with achievement of SVR (P<0.0001), and it was not significantly associated with an IFN-free or IFN-containing regimen (P=0.06). At Week 24 post-treatment, fibrosis stage improvement to below F3 was observed in 37.2% of participants.

Comparative Study in Cairo, Egypt11

Study design and demographics

A comparative study in participants with HCV was performed to evaluate the effect of DAA therapy compared with IFN-based therapy on liver fibrosis regression and to analyze the relationship between fibrosis and treatment response. Liver stiffness was measured using transient elastography, and APRI and FIB-4 scores were calculated. Participants were divided into 3 treatment groups: 1) PEG-IFN + RBV for 48 weeks, 2) SOF + RBV for 24 weeks, or 3) PEG-IFN + SOF + RBV for 12 weeks. Follow-up occurred 3 months after treatment was complete.

Table 9. Baseline Demographics and Disease Characteristics (El-Raziky et al)11

Results

SVR achievement rates between treatment groups did not significantly differ; SVR was achieved by 78.3% of participants (n=54) who received treatment with SOF + RBV and by 73.1% of participants (n=49) who received treatment with PEG‑IFN + SOF + RBV.

Fibrosis regression was assessed by monitoring transient elastography, APRI, and FIB‑4 scores, and there were no significant differences between treatment regimens (Table 10).

Table 10. Overall Pre- and Post-Treatment APRI, FIB-4, and Liver Stiffness and by SOF‑Based Treatment Group (El‑Raziky et al)11

Abbreviation: BL=baseline.

Table 11. APRI, FIB-4, and Liver Stiffness Changes by SOF-Based Treatment Group
(El-Raziky et al)11

Assessment of Liver Fibrosis Regression Using SWE12

Study design and demographics

The magnitude of liver fibrosis regression was evaluated using SWE in adult participants with HCV GT 4 after treatment with a SOF‑based DAA regimen for 12 weeks (N=165). Participant laboratory characteristics, FIB-4, APRI, and liver stiffness by SWE were evaluated at study baseline, EOT, and Weeks 24 and 36. Participants received treatment with SOF/DCV ± RBV (n=134), SOF/SMV ± RBV (n=21), or LDV/SOF ± RBV (n=10).

Table 12. Baseline Demographics and Disease Characteristics (Kohla et al)12

Results

SVR12 was achieved by all participants. At Week 36, APRI scores decreased to 0.23, and FIB-4 scores decreased 0.99 (P<0.001 for both). Mean liver stiffness by SWE also improved to 7.01 kPa at EOT, 6.18 kPa at Week 24, and 5.74 kPa at Week 36. Fibrosis improvement was reflected in the increase in the proportion of participants with F0/F1 fibrosis at baseline (50.9%) vs EOT (75.8%).

From baseline to Week 36, AST and ALT levels decreased, and platelet count increased (each, P<0.001).

Retrospective Canadian Cohort Study13

Study design and demographics

A retrospective study at a tertiary referral, university-affiliated clinic in Vancouver, Canada, was conducted in chronic HCV patients who achieved SVR12 after treatment with DAAs between March 2013 and December 2016. FibroScan results from pre- and post-treatment were recorded.

Table 13. Baseline Demographics and Disease Characteristics (Bollu et al)13

Results

Significant reductions in FibroScan scores were observed post-treatment overall (P=0.004) and by fibrosis stage (Figure 6). At a median (range) follow-up of 35 (14–80) weeks, 42/81 patients (52%) with baseline F3/4 fibrosis had a reduction in fibrosis stage by 1 stage, and 28 patients’ fibrosis score was reduced by ≥2 stages. At a median (range) follow-up of 36 (12–112) weeks, 24/31 patients (77%) with baseline F2 fibrosis had a downgraded fibrosis score.

Figure 6. FibroScan Scores at Baseline and Follow-Up (Bollu et al)13

Chinese HCV GT 3 Cohort Study14

Study design and demographics

A retrospective cohort study was conducted in TN patients with HCV GT 3 and compensated cirrhosis who received ≥12 weeks of SOF-based treatment between January 2016 and May 2017. Patients received either SOF/VEL for 12 weeks or SOF + DCV + RBV for 12 or 24 weeks. Patients who also had HBV or HIV‑1, advanced liver disease (including decompensated cirrhosis), HCC, or impaired renal function were excluded. The primary endpoint was the proportion of participants who achieved SVR24, and the secondary endpoints were non-invasive scores of liver fibrosis (FIB-4 and APRI), EVR (undetectable serum HCV RNA at Week 4 of treatment), and serious AEs.

Table 14. Baseline Demographics and Disease Characteristics (Tao et al)14

aVariables are presented as mean (95% CI) for normally distributed quantitative values, median (IQR) for non‑normally distributed values, and count for categorical variables, unless otherwise noted.

Efficacy

Overall, 90% of patients (92/102) achieved SVR24, and no significant differences for each SOF-based regimen were noted for the proportion of patients who achieved SVR24 (P=0.226). SVR24 rates by treatment regimen included the following: SOF/VEL, 100% (21/21); SOF + DCV, 86% (49/57); and SOF + DCV + RBV, 92% (22/24; Figure 7). No significant differences between those with cirrhosis and those without cirrhosis were noted in the proportion of patients who achieved EVR and SVR24 (P=0.237 and P=0.073, respectively; Figure 8).

Overall, FIB‑4 and APRI scores were significantly lower at SVR24 compared with those at baseline (P<0.001, for each comparison). Those who achieved SVR24 and those who relapsed had significantly lower FIB‑4 scores at the SVR24 time point compared with baseline (P<0.001 and P=0.002, respectively); similarly, APRI scores were reduced significantly at the SVR24 time point compared with baseline in both groups (P<0.001 among those who achieved SVR24 and P=0.002 among those who relapsed).

Figure 7. FIB-4 and APRI Scores at Baseline and SVR24 (Tao et al)14

Figure 8. FIB‑4 and APRI Scores at Baseline and SVR24 by Cirrhosis Status
(Tao et al)14

Safety

No serious AEs occurred during treatment or the follow-up period, and all SOF‑based treatments were well-tolerated.

Adolescent HCV GT 4 Study in Egypt15

Study design and demographics

A single-center, prospective, observational cohort study conducted in Egypt evaluated the changes in LSMs (by vibration-controlled transient elastography) and noninvasive fibrosis scores (by FIB-4 and APRI) in adolescents (aged 11–18 years who weighed ≥35 kg) with HCV GT 4 (N=85). Changes from baseline (prior to treatment) to 12 months in LSMs and noninvasive fibrosis scores were assessed after achievement of SVR12 with 12 weeks of LDV/SOF. The cohort included 58 males (68%). All participants were DAA naïve; however, 16 participants previously received treatment with interferon/RBV. At baseline, ALT and AST levels were >30 IU/mL in 58 participants (68%) and 59 participants (69%), respectively. The median (IQR) LSM was 5.8 (4.2–6.5) kPa. There were 67 participants who had an LSM that correlated with fibrosis stages F0 to F1, 12 participants with an LSM that correlated with F2, 4 with an LSM that correlated with F3, and 2 with an LSM that correlated with F6. The primary outcome was a >30% decrease in LSM from baseline with fibrosis stage regression or non‑progression. The secondary outcome was any post‑treatment change to noninvasive fibrosis scores.

Results

LSMs, FIB-4, and APRI scores 12 months post-treatment indicated non‑progression or regression in fibrosis (Table 15 and Table 16).

The primary outcome was met in 62 participants (regression, n=16; non‑progression, n=46; Table 15). A >30% increase in LSM was observed in 23 participants; however, this correlated with increased fibrosis stage only in 7 participants. Fibrosis stage regression post-treatment was more commonly seen in participants with higher LSMs at baseline.

Table 15. Changes in Liver Stiffness From Baseline to 12 Months Post-Treatment (Fahmy et al)15

Table 16. FIB-4 and APRI Scores at Baseline and 12 Months Post-Treatment
(Fahmy et al)15

Of the 67 participants who had an LSM consistent with F0 to F1 at baseline, 62 participants’ scores remained unchanged, and 5 participants experienced an increase in fibrosis stage after treatment: 4 participants’ scores increased to F2, and 1 participant’s score increased to F3. Of the 18 participants who had an LSM consistent with ≥F2, 15 participants’ fibrosis stage improved (11 from F2 to F0–F1, 2 from F3 to F0–F1, and 2 from F6 to F5), 1 participant’s fibrosis stage remained unchanged, and 2 participants experienced an increase in fibrosis stage (1 from F2 to F3 and 1 from F3 to F4) with treatment. All 7 participants who experienced an increase in fibrosis stage had associated comorbidities, and a significant negative correlation was observed between LSM regression and comorbidities (P=0.036).

References

1. Mangia A, Lawitz E, Gane E, et al. Long-Term Follow-up of Patients with Chronic HCV Infection and Compensated or Decompensated Cirrhosis Following Treatment with Sofosbuvir-Based Regimens [Presentation]. Paper presented at: European Association for the Study of the Liver (EASL); 11-15 April, 2018; Paris, France.

2. Jacobson I, Muir AJ, Lawitz EJ, et al. Course of Cirrhosis Regression: Lessons From Patients With HCV Cirrhosis Following Successful Sofosbuvir-Based Treatment [Poster 537]. Paper presented at: AASLD: The Liver Meeting® 2019; 08-12 November, 2019; Boston, MA.

3. Samuel D, Manns M, Forns X, et al. Ledipasvir/Sofosbuvir With Ribavirin Is Safe in >600 Decompensated and Post-Liver Transplantation Patients With HCV Infection: An Integrated Safety Analysis of the SOLAR-1 and SOLAR-2 Trials. Paper presented at: European Association for the Study of the Liver (EASL). The 50th International Liver Congress; April 22-26, 2015; Vienna, Austria.

4. Charlton M, Everson GT, Flamm SL, et al. Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease. Gastroenterology. 2015;149(3):649-659. http://www.ncbi.nlm.nih.gov/pubmed/25985734

5. Manns M, Samuel D, Gane EJ, et al. Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicentre, open-label, randomised, phase 2 trial. Lancet Infect Dis. 2016;16:685-697.

6. Gane E, Manns M, McCaughan G, et al. Ledipasvir/Sofosbuvir With Ribavirin in Patients With Decompensated Cirrhosis or Liver Transplantation and HCV Infection: SOLAR-1 and -2 Trials [Poster 1049]. Paper presented at: American Association for the Study of Liver Diseases (AASLD); 13-17 November, 2015; San Francisco, CA.

7. Curry MP, O'Leary JG, Bzowej N, et al. Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis. N Engl J Med. 2015. http://www.ncbi.nlm.nih.gov/pubmed/26569658

8. O'Leary J, Brown RS, Reddy KR, et al. Baseline Clinical and Laboratory Parameters Associated With Clinical Benefits of Successful HCV Treatment with Sofosbuvir/Velpatasvir in Decompensated Cirrhotic Patients [Poster SAT-169]. Paper presented at: European Association for the Study of the Liver (EASL); 13-17 April, 2016; Barcelona, Spain.

9. Bachofner JA, Valli PV, Kroger A, et al. Direct Antiviral Agent Treatment of Chronic Hepatitis C Results in Rapid Regression of Transient Elastography and Fibrosis Markers Fibrosis-4 Score and Aspartate Aminotransferase-Platelet Ratio Index. Liver Int. 2017;37:369-376. https://www.ncbi.nlm.nih.gov/pubmed/27678216

10. Dolmazashvili E, Abutidze A, Chkhartishvili N, Karchava M, Sharvadze L, Tsertsvadze T. Regression of liver fibrosis over a 24-week period after completing direct-acting antiviral therapy in patients with chronic hepatitis C receiving care within the national hepatitis C elimination program in Georgia: results of hepatology clinic HEPA experience. Eur J Gastroenterol Hepatol. 2017;29(11):1223-1230. http://www.ncbi.nlm.nih.gov/pubmed/28857900

11. El-Raziky M, Khairy M, Fouad A, Salama A, Elsharkawy A, Tantawy O. Effect of Direct-Acting Agents on Fibrosis Regression in Chronic Hepatitis C Virus Patients' Treatment Compared with Interferon-Containing Regimens. J Interferon Cytokine Res. 2018;38(3):129-136. https://www.ncbi.nlm.nih.gov/pubmed/29565743

12. Kohla MAS, Fayoumi AE, Akl M, et al. Early Fibrosis Regression by Shear Wave Elastography after Successful Direct-Acting Anti-HCV Therapy. Clin Exp Med. 2019. https://www.ncbi.nlm.nih.gov/pubmed/31792631

13. Bollu A, Ou G, Ko HH, Feizi J, Wong A, Ramji A. Eradication of Chronic Hepatitis C Infection with Direct Acting Antivirals is Associated with Reduction in Fibrosis by Transient Elastography (FibroScan) [Abstract P1-096]. J Viral Hepatitis. 2018:73.

14. Tao YC, Deng R, Wang ML, et al. Satisfactory Virological Response and Fibrosis Improvement of Sofosbuvir-Based Regimens for Chinese Patients with Hepatitis C Virus Genotype 3 Infection: Results of a Real-World Cohort Study. Virol J. 2018;15:150. https://www.ncbi.nlm.nih.gov/pubmed/30285800

15. Fahmy DM, Shokeir M, El Zeiny SM, Jonas MM, Abdallah A. Changes in Liver Stiffness and Noninvasive Fibrosis Scores in Egyptian Adolescents Successfully Treated with Ledipasvir-Sofosbuvir for Chronic Hepatitis C Virus Infection. J Pediatr. 2020.

Abbreviations

APRI=AST/platelet ratio index
CPT=Child-Pugh Turcotte
DAA=direct-acting antiviral
DCV=daclatasvir
ELF=Enhanced Liver Fibrosis
EOT=end of therapy
EVR=early virological response
F0/1/2/3/4=fibrosis stage 0/1/2/3/4
FIB-4=Fibrosis-4 Index
GT=genotype
HCC=hepatocellular carcinoma
LDV=ledipasvir
LSM=liver stiffness measurement
MELD=Model for End Stage Liver Disease
NS=non-significant
PEG-IFN=pegylated interferon
RBV=ribavirin
SMV=simeprevir
SOF=sofosbuvir
SVR=sustained virologic response
SVR12/24=sustained virologic response 12/24 weeks after end of treatment
SWE=shear wave elastography
TE=treatment experienced
TN=treatment naïve
VEL=velpatasvir
VOX=voxilaprevir
 

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