https://doi.org/10.

1186/s12879-019-4741-5

Tsertsvadze et al. BMC Infectious Diseases (2020) 20:30

RESEARCH ARTICLE Open Access

Treatment outcomes of patients with

chronic hepatitis C receiving
sofosbuvirbased combination therapy
within national hepatitis C elimination
program in the country of Georgia
Tengiz Tsertsvadze1,1*, Amiran Gamkrelidze3, Muazzam Nasrullah4, Lali Sharvadze1,2,5, Juliette Morgan4,
Shaun Shadaker4, Lia Gvinjilia6, Maia Butsashvili7, David Metreveli8, Vakhtang Kerashvili1, Marina Ezugbaia1,
Nikoloz Chkhartishvili1, Akaki Abutidze1, Valeri Kvaratskhelia9 and Francisco Averhoff4

Abstract
Background: Georgia has one of the highest HCV prevalence in the world and launched the world’s first national
HCV elimination programs in 2015. Georgia set the ambitious target of diagnosing 90% of people living with HCV,
treating 95% of those diagnosed and curing 95% of treated patients by 2020. We report outcomes of Sofosbuvir
(SOF) based treatment regimens in patients with chronic HCV infection in Georgia.
Methods: Patients with cirrhosis, advanced liver fibrosis and severe extrahepatic manifestations were enrolled in
the treatment program. Initial treatment consisted of SOF plus ribavirin (RBV) with or without pegylated interferon
(INF). Sustained virologic response (SVR) was defined as undetectable HCV RNA at least 12 weeks after the end of
treatment. SVR were calculated using both per-protocol and modified intent-to-treat (mITT) analysis. Results for
patients who completed treatment through 31 October 2018 were analyzed.
Results: Of the 7342 patients who initiated treatment with SOF-based regimens, 5079 patients were tested for SVR.
Total SVR rate was 82.1% in per-protocol analysis and 74.5% in mITT analysis. The lowest response rate was
observed among genotype 1 patients (69.5%), intermediate response rate was achieved in genotype 2 patients
(81.4%), while the highest response rate was among genotype 3 patients (91.8%). Overall, SOF/RBV regimens
achieved lower response rates than IFN/SOF/RBV regimen (72.1% vs 91.3%, P < 0.0001).
In multivariate analysis being infected with HCV genotype 2 (RR =1.10, CI [1.05–1.15]) and genotype 3 (RR = 1.14,
CI [1.11–1.18]) were associated with higher SVR. Patients with cirrhosis (RR = 0.95, CI [0.93–0.98]), receiving
treatment regimens of SOF/RBV 12 weeks, SOF/RBV 20 weeks, SOF/RBV 24 weeks and SOF/RBV 48 weeks (RR =
0.85, CI [0.81–0.91]; RR = 0.86, CI [0.82–0.92]; RR = 0.88, CI [0.85–0.91] and RR = 0.92, CI [0.87–0.98], respectively)
were less likely to achieve SVR.
Conclusions: Georgia’s real world experience resulted in high overall response rates given that most patients had
severe liver damage. Our results provide clear evidence that SOF plus IFN and RBV for 12 weeks can be considered
a treatment option for eligible patients with all three HCV genotypes. With introduction of next generation DAAs,
significantly improved response rates are expected, paving the way for Georgia to achieve HCV elimination goals.
Keywords: HCV, Elimination, DAAs, SVR, Georgia

* Correspondence: [email protected]

1 Ivane Javakhishvili Tbilisi State University, Faculty of Medicine, Tbilisi, Georgia

Full list of author information is available at the end of the article

© The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License
(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate
credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public
Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Tsertsvadze et al. BMC Infectious Diseases (2020) 20:30 Page 2 of 8

1
Infectious Diseases, AIDS and Clinical Immunology Research Center, Tbilisi,
Georgia
Background experts. Based on eligibility of interferon therapy all
Globally, an estimated 71 million people are chronically HCV genotype 1 and 3 patients received SOF plus,
infected with hepatitis C virus (HCV), and 400, 000 die Pegylated interferon (IFN) and RBV for 12 weeks or
annually from hepatitis C-related liver diseases [1]. SOF plus RBV for 24 weeks.
Management of HCV infection has been revolutionized HCV genotype 2 treatment naïve patients without
after the availability of direct acting antivirals (DAAs), cirrhosis were treated with the 12-week combination of
and Sofosbuvir (SOF) was the first widely introduced SOF plus RBV, while cirrhotic patients and those with
DAA [2, 3]. Clinical trials have demonstrated high prior treatment failure received the 12-week regimen of
efficacy of SOF-based regimens in patients infected with SOF plus IFN and RBV or the 20-week regimen of SOF
genotypes 1–6 [4–8]. plus RBV based on eligibility of interferon. Patients with
Georgia has one of the highest HCV prevalence rates decompensated cirrhosis received SOF plus RBV for 48
among general population in the world [9], and launched weeks.
the world’s first national HCV elimination program in Treatment was initially limited to four sites in Tbilisi,
2015 [10]. The elimination program has adopted a and later expanded with sites from other cities within
comprehensive strategy that addresses both prevention Georgia; by October 2018, 31 sites were providing HCV
and treatment of HCV infection. A key component of the treatment in the country. The HCV treatment program
program is the provision of DAAs free of charge to all providers also participated in Project ECHO (Extension
Georgian citizens; this was made possible through an for Community Healthcare Outcomes).
agreement with Gilead Sciences to donate DAAs. A national HCV treatment database was established,
Georgia has set itself the ambitious target of diagnosing which collected standard data for each patient enrolled in
90% (135,000 persons) of people living with HCV, treatment program. Each treatment site was responsible
treating 95% (128,000 persons) of those diagnosed and for data entry for each enrolled patient. Data were de-
curing 95% (121000) of treated patients by 2020 [9]. We identified and sociodemographic, clinical and laboratory
report outcomes of SOFbased treatment regimens in data were extracted from national HCV treatment
patients with chronic HCV infection in the country of database. Characteristics measured included: age, gender,
Georgia. HCV RNA, FIB-4 test score, METAVIR score, HBsAg,
treatment regimen, HCV genotype and city where
Methods treatment was provided. Sustained virologic response
All Georgians aged 18 years or older that are infected (SVR) was defined as undetectable HCV RNA at least 12
with HCV are eligible for the free of charge treatment weeks after the end of treatment. The presence of
program. The hepatitis C elimination program was cirrhosis was confirmed by vibration-controlled transient
launched on 28 April 2015. All patients treated from elastography or acoustic radiation force impulse
launch through 31 October 2018 are included in the elastography (ARFI) compatible with stage F4 fibrosis
analysis. Treatment-naive and experienced patients with (≥14.5 kpa)_by METAVIR. Decompensated cirrhosis
cirrhosis (including decompensated cirrhosis), advanced was defined as the presence of current or past ascites,
liver fibrosis, severe extrahepatic manifestations, HCV hepatic encephalopathy and variceal haemorrhage etc.
re-infection after liver transplantation and HIV- SVRs were calculated using both per-protocol and
coinfection were prioritized for enrollment in the modified intent-to-treat (mITT) analysis. Per-protocol
treatment program. Initially, DAA treatment was approach included only those with complete SVR data,
exclusively SOF based and included ribavirin (RBV) while in mITT analysis persons discontinuing treatment
with or without pegylated interferon, depending on the were also included. Persons who died or had no SVR test
HCV genotype, per national guidelines. From February > 24 weeks after completing treatment were excluded
2016, more effective, interferon free DAA combination - from analysis.
sofosbuvir and ledipasvir (SOF/LDV) was introduced,
and treatment regimens were revised. Beginning in June Statistical analysis
2016, treatment criteria were relaxed allowing enrollment All analyses were performed with SAS version 9.3
of all HCV infected persons regardless of level of liver software (SAS Institute, Inc., Cary, NC, USA). Variables
fibrosis, to be treated. Treatment guidelines were were categorized as follows: age category: 18–44, 45–60,
established by a committee composed of treatment and > 60; HCV RNA category: < 800,000 IU/mL vs.
experts from Georgia in consultation with international ≥800, 000 IU/mL; FIB-4 test: <1.45, 1.45–3.25 and >
Tsertsvadze et al. BMC Infectious Diseases (2020) 20:30 Page 3 of 8

3.25; METAVIR score: <F4 and F4. We used the chi- Overall, SOF/RBV regimens achieved lower response
square or Fisher’s exact to compare differences in rates than IFN/SOF/RBV regimen (72.1% vs 91.3%, P <
categorical variables with SVR. We performed a 0.0001). This difference was seen in all genotypes
multivariate logistic-regression analysis involving (57.0% vs 80.8%, P < 0.0001 for genotype 1; 76.9% vs
baseline demographic, clinical and laboratory 96.3%, P < 0.0001 for genotype 2 and 82.5% vs 96.9%, P
characteristics to identify independent predictors of SVR. < 0.0001 for genotype 3 respectively) (Fig. 1).
A p-value < 0.05 was considered significant. The final Multivariate analysis (Table 2) showed that when
model included variables associated (p < 0.05) with SVR controlling those factors which were significantly
in the bivariate analysis. The results are presented with a associated with SVR in bivariate analysis, being infected
Risk ratio (RR) and 95% Confidence intervals (CIs). with HCV genotype 2 (RR =1.10, CI [1.05–1.15], P =
Results for patients who completed treatment and tested 0.001) and genotype 3 (RR = 1.14, CI [1.11–1.18], P <
for SVR through 31 October 2018 were analyzed. The 0.0001) were associated with higher SVR. Patients with
study was approved by the Institutional review board of cirrhosis (RR = 0.95, CI [0.93–0.98], P < 0.0001),
the Infectious Diseases, AIDS and Clinical Immunology receiving treatment regimens of SOF/RBV 12 weeks,
Research Center, Tbilisi. SOF/RBV 20 weeks, SOF/RBV 24 weeks and SOF/RBV
48 weeks (RR = 0.85, CI [0.81–0.91], P < 0.0001; RR =
Results 0.86, CI [0.82–0.92], P < 0.0001; RR = 0.88, CI [0.85–
A total of 7342 patients with chronic HCV infection 0.91], P < 0.0001 and RR = 0.92, CI [0.87–0.98], P =
received SOF-based therapy from April 28, 2015 until 0.005, respectively) were less likely to achieve SVR.
October 31, 2018 and 5079 had complete SVR data.
The pretreatment demographics, clinical and laboratory Discussion
characteristics of patients with complete SVR data are This study from Georgia is one of the largest realworld
described in Table 1. Most patients, 2838 (55.9%) were cohorts examining outcomes of HCV treatment with SOF
age 45–60 years, 4381 (86.3%) were males and 2783 based regimens, among patients with severe liver disease.
(57.9%) had stage F4 fibrosis (by METAVIR). Overall, We assessed real-world efficacy of SOF plus RBV with
1724 (33.9%) of the patients had HCV genotype 1, or without IFN in these difficult-to-treat patients with
followed by HCV genotype 3, 2305 (45.4%) and HCV chronic hepatitis C. Our study demonstrated that SOF-
genotype 2, 1047 (20.6%). Only 3 patients were infected based regimens can result in high overall SVR rates,
with HCV genotype 4. Majority of patients were treated similar to SVR rates achieved in clinical trials [11, 12].
with IFN/SOF/RBV for 12 weeks (52.1%), followed by While newer combination DAAs are now available, SOF
SOF/RBV for 24 weeks (27.9%), SOF/RBV for 20 weeks is now one of the most readily available DAAs
(7.8%), SOF/RBV for 12 weeks (7.2%), and SOF/RBV worldwide, at affordable prices in many low middle
for 48 weeks (5.0%). income countries, and as such, these findings have
A total of 521 persons discontinued treatment, with the relevance today. In particular, the acceptable SOF plus
most common causes for not completing treatment being RBV outcomes among the most severely ill patients,
death (48.8%; n = 254), self-discontinuation (19.6%; n = regardless of genotype are highly relevant.
102), and loss to follow up (15.9%; n = 83). Among those In our study response rates among patients with HCV
who died during treatment, the majority 299/521 (57.4%) genotype 2 were lower than reported in clinical trials and
had severe liver disease (METAVIR scores of F3 or F4). real-life studies which showed high efficacy of SOF plus
A total of 5079 persons with complete SVR data and RBV combination treatment among HCV genotype 2
521 persons who discontinued treatment, were included patients including those with cirrhosis and/or treatment
in treatment efficacy analysis (total 5600 persons). Total experience [8, 12–15]. Lower efficacy of treatment in
SVR rate was 82.1% (4170/5079) in per-protocol genotype 2 patients may have been associated with a
analysis and 74.5% (4170/5600) in mITT analysis. reported high prevalence of HCV recombinant form 2
Of those with an SVR12, the lowest response rate was k/1b among Georgian HCV genotype 2 patients [16];
observed among genotype 1 patients (1198/1724; 69.5%), these patients do not respond well to standard treatment
intermediate response rate was achieved in genotype 2 for genotype 2 and regimens used for genotype 1 seem to
patients (852/1047; 81.4%), while the highest response be more effective [17]. Therefore there is a need for
rate was among genotype 3 patients (2117/2305; 91.8%). reassessing existing modalities for the management of
There were only 3 patients with genotype 4 and all were HCV genotype 2 infection, especially in areas with high
cured. prevalence of HCV recombinant form 2 k/1b [18].
Tsertsvadze et al. BMC Infectious Diseases (2020) 20:30 Page 4 of 8

We observed high cure rates in HCV genotype 3 combination with IFN that patients who were treated with
patients that are one of the most challenging SOF and RBV alone [12].
subpopulations to treat [19]. IFN-based regimens were Our findings support use of a 12 week regimen of SOF
superior to SOF/RBV alone. The results of clinical trials plus RBV in combination with IFN as a treatment option
showed that HCV genotype 3 patients achieved higher for eligible HCV genotype 3 patients in settings, where
SVR12 rates with a 12 week SOF and RBV in
Table 1 Baseline characteristics of adult persons with complete SVR data treated with SOF-based regimens by HCV genotypes
within the national hepatitis C elimination program, April 28, 2015 – October 31, 2018

Characteristic TOTAL Genotype 1 Genotype 2 Genotype 3 Genotype 4

n % n % n % n % n %

Age category, n (%)

18–45 1635 32.2 386 22.4 299 28.6 948 41.1 2 66.7
45–60 2838 55.9 944 54.8 630 60.2 1264 54.8 . .
60+ 606 11.9 394 22.9 118 11.3 93 4.0 1 33.3
Gender, n (%)
Female 698 13.7 486 28.2 101 9.6 110 4.8 1 33.3
Male 4381 86.3 1238 71.8 946 90.4 2195 95.2 2 66.7
HCV RNA categories, n (%)
100.
< 800,000 IU/mL 2922 57.7 901 52.5 625 59.8 1393 60.5 3 0
≥ 800,000 IU/mL 2145 42.3 816 47.5 420 40.2 909 39.5 . .
FIB-4 Test
< 1.45 200 5.7 65 6.0 51 7.0 84 5.0 . .
1.45–3.25 1763 50.2 491 45.0 403 55.1 868 51.5 1 50.0
> 3.25 1546 44.1 535 49.0 277 37.9 733 43.5 1 50.0
Metavir score
< F4 2021 42.1 676 39.8 516 50.9 827 39.6 2 66.7
F4 2783 57.9 1021 60.2 497 49.1 1264 60.4 1 33.3
Liver function tests, n (%) 100.
ALT >2 X ULN 2585 51.0 731 42.5 466 44.6 1385 60.2 3 0
AST >2 X ULN 2604 51.4 783 45.6 442 42.3 1376 59.8 3 100.
0
Billirubin >1.1 mg/dL 4423 87.3 1520 88.5 928 88.8 1972 85.7 3 100.
0
Albumin < 35 g/L 2001 39.5 670 39.0 469 44.9 862 37.4 . .
INR >1.49 687 13.6 260 15.1 132 12.6 295 12.8 . .
Co-infections, n (%)
HBsAg+ 108 2.2 28 1.7 19 1.9 61 2.8 . .
HBsAg- 4777 97.8 1666 98.3 985 98.1 2123 97.2 3 100.
0
Treatment regimen, n (%)
IFN/SOF/RBV (12 wk) 2646 52.1 905 52.5 240 22.9 1500 65.1 1 33.3
SOF/RBV (12 wk) 364 7.2 3 0.2 360 34.4 1 0 . .
SOF/RBV (20 wk) 395 7.8 3 0.2 392 37.4 . . . .
Tsertsvadze et al. BMC Infectious Diseases (2020) 20:30 Page 5 of 8

SOF/RBV (24 wk) 1418 27.9 695 40.3 7 0.7 714 31 2 66.7
SOF/RBV (48 wk) 256 5 118 6.8 48 4.6 90 3.9 . .
City of treatment site, n (%)
Tbilisi 3800 74.8 1294 75.1 819 78.2 1684 73.1 3 100
Kutaisi 362 7.1 148 8.6 72 6.9 142 6.2 . .
Batumi 501 9.9 177 10.3 67 6.4 257 11.1 . .
Zugdidi 328 6.5 90 5.2 81 7.7 157 6.8 . .
Gori 42 0.8 6 0.3 5 0.5 31 1.3 . .
Rustavi 40 0.8 9 0.5 3 0.3 28 1.2 . .
Lanchkhuti 4 0.1 . . . . 4 0.2 . .
Gurjaani 2 0 . . . . 2 0.1 . .
SOF Sofosbuvir, RBV Ribavirin, IFN Interferon
new highly potent and well-tolerated DAAs against the Georgia HCV elimination program, challenges to
genotypes 2 and 3 are not available. Our results suggest Georgia achieving the national targets for HCV
the use of SOF/RBV combination for 24 weeks as an elimination by 2020 remain. Pangenotypic DAAs that are
option for patients who cannot tolerate IFN. effective across the different genotypes of HCV
After examining host and viral factors we found that introduced in late 2018 could have a substantial impact
presence of cirrhosis, and receiving IFN-free regimens on improving access and simplifying diagnosis and
were associated with lower SVR in a multivariable treatment.
model. The low rates of response among cirrhotic
patients is consistent with previous studies.
One strength of this study is the large number of Conclusion
patients as well as standardized treatment guidelines and In conclusion, in this large cohort study, a combination of
standardized data collection. The diversity of our cohort SOF and weight-based RBV with or without IFN
with respect to sex, age, and genotype distribution makes appeared to be an effective regimen to treat chronic
our findings generalizable, reflecting reported real-world HCV-infected patients, especially for HCV Genotype 2
outcomes. Our study has several limitations. First, data and 3 patients. SOF formed the foundation of the HCV
from patients in whom prior treatment had failed, was not elimination program in Georgia. Cure rates in patients
collected. Second, liver fibrosis was assessed by multiple without cirrhosis were high, which are comparable with
noninvasive indices, each of which have limitations on those reported in clinical trials. However, consistent with
accuracy [20–22]. The national treatment database, which previous studies, the presence of liver cirrhosis were
captures information on all hepatitis C patients enrolled associated with lower SVR12 rates. Our results provide
in the program, provides accurate treatment related clear evidence that SOF plus IFN and RBV for 12 weeks
information on a national level. However it does not can be considered a treatment option for eligible patients
contain detailed information on some variables, including with all three HCV genotypes. With the introduction of
comorbidities (diabetes mellitus, kidney failure, next generation DAAs, replacement of IFN-based
extrahepatic manifestations etc.) as well as nature of regimens by IFN-free regimens and significantly
deaths, adverse events and reasons of self- improved response rates are expected, paving the way for
discontinuation. Also data available in the national Georgia to achieve the goal of HCV elimination. High
system has limited ability to answer questions as to why cure rates obtained with SOF/LDV combinations for all
people are lost to follow-up along the continuum of care. HCV genotypes within Georgia program highlights
Significant number of patients who were lost to follow- effectiveness of service delivery model, which is based
up after treatment completion is a serious challenge of the on simplified modalities that can be successfully
treatment program. However, in 2017 the program replicated in non-specialty settings, which is important in
offered SVR assessment free of charge that would lead to light of ongoing decentralization process. Strong
reducing missing SVR data.. Despite notable progress of governmental commitment coupled with effective local
Tsertsvadze et al. BMC Infectious Diseases (2020) 20:30 Page 6 of 8

Fig. 1 SVR rates by treatment regimens and genotype (n = 5076)

and international partnerships provide a basis for turning the ambitious goal of elimination into reality.
Table 2 Treatment outcomes and associated factors among adult persons with complete SVR data receiving SOF-based regimens
within the national hepatitis C elimination program, April 28, 2015 – October 31, 2018
Total N Achieved Bivariate Multivariate analysis
SVR analysis
RR RR 95% CI p value
N % 95% CI p value
Age category
18–45 1635 1440 88.07 1
46–60 2838 2259 79.60 0.90 0.88–0.93 <0.0001

60+ 606 471 77.72 0.88 0.84–0.92 <0.0001

Gender
Female 698 560 80.23 1
Male 4381 3610 82.40 1.03 0.99–1.07 0.18

HCV Genotype
1 1724 1198 69.49 1 1
2 1047 852 81.38 1.17 1.12–1.22 <0.0001 1.10 1.05–1.15 <0.000
1
3 2305 2117 91.84 1.32 1.28–1.37 <0.0001 1.14 1.11–1.18 <0.000
1
4 3 3 100.00 – – – – – –
HCV RNA categories, n (%)
< 800,000 IU/mL 2922 2408 82.41 1
≥ 800,000 IU/mL 2145 1754 81.77 0.99 0.97–1.02 0.56

FIB-4 Tests
< 1.45 200 177 88.50 1 1
1.45–3.25 1763 1573 89.22 1.01 0.96–1.06 0.76 1.00 0.93–1.07 0.95
> 3.25 1546 1166 75.42 0.85 0.80–0.90 <0.0001 0.95 0.87–1.02 0.17
Metavir score
< F4 2021 1761 87.14 1 1
F4 2783 2161 77.65 0.89 0.87–0.97 <0.0001 0.95 0.93–0.98 0.0001
Co-infections
HBsAg- 4777 3897 81.58 1
HBsAg+ 108 89 82.41 1.01 0.92–1.10 0.82

Treatment regimen
IFN/SOF/RBV (12 wk) 2646 2416 91.31 1 1
SOF/RBV (12 wk) 364 276 75.82 0.83 0.78–0.88 <0.0001 0.85 0.81–0.91 <0.000
1
SOF/RBV (20 wk) 395 302 76.46 0.84 0.79–0.89 <0.0001 0.86 0.82–0.92 <0.000
1
SOF/RBV (24 wk) 1418 979 69.04 0.76 0.73–0.78 <0.0001 0.88 0.85–0.91 <0.000
1
Tsertsvadze et al. BMC Infectious Diseases (2020) 20:30 Page 7 of 8

SOF/RBV (48 wk) 256 197 76.95 0.84 0.79–0.90 <0.0001 0.92 0.87–0.98 0.005
City of treatment site
Tbilisi 3800 3127 82.29 1 1
Kutaisi 362 272 75.14 0.91 0.86–0.97 0.004 0.96 0.92–1.01 0.10
Batumi 501 435 86.83 1.06 1.02–1.10 0.005 1.01 0.97–1.05 0.60
Zugdidi 328 258 78.66 0.96 0.90–1.01 0.13 0.96 0.92–1.00 0.07
Gori 42 40 95.24 1.16 1.08–1.24 <0.0001 1.01 0.87–1.17 0.91
Rustavi 40 32 80.00 0.97 0.83–1.14 0.72 0.95 0.80–1.13 0.55
Lanchkhuti 4 4 100.00 – – – – – –
Gurjaani 2 2 100.00 – – – – – –
SOF Sofosbuvir, RBV Ribavirin, IFN Interferon, CI Confidence interval, RR Risk ratio, SVR Sustained virologic response
Abbreviations Program, Tbilisi, Georgia. 7Clinic NeoLab, Tbilisi, Georgia. 8Medical Center
CI: Confidence intervals; DAAs: Direct acting antivirals; HCV: Hepatitis C Mrcheveli, Tbilisi, Georgia. 9Ministry of Labor, Health and Social Affairs of
virus; Georgia, Tbilisi, Georgia.
INF: Pegylated interferon; mITT: modified intent-to-treat; RBV:
Ribavirin; RR: Risk ratio; SOF: Sofosbuvir; SVR: Sustained virologic Received: 17 April 2019 Accepted: 27 December 2019
response

Acknowledgements References
Authors gratefully acknowledge Gilead Science for donating Sofosbuvir and 1. WHO Hepatitis C fact sheet. Updated April 2017. http://www.who.int/
Ledipasvir/Sofosbuvir to the national hepatitis C elimination program at no mediacentre/factsheets/fs164/en/. .
cost.
2. Gane EJ, Stedman CA, Hyland RH, et al. Nucleotide polymerase
inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med. 2013;
Authors’ contributions 368(1):34–44.
Concept and design (TT, AG, FA, NC, AA), statistical analyses (SS, NC, AA), 3. Gentile I, Maraolo AE, Buonomo AR, Zappulo E, Borgia G. The
interpretation of the data (TT, AG, MN, LS, JM, SS, LG, MB, DM, VK, ME, NC, discovery of sofosbuvir: a revolution for therapy of chronic hepatitis C.
AA, VK, FA), drafting the manuscript (TT) and critical revision of the Expert Opin Drug Discovery. 2015;10(12):1363–77.
manuscript for intellectual content (TT, AG, MN, LS, JM, SS, LG, MB, DM, 4. Rodriguez-Torres M, Lawitz E, Kowdley KV, et al. Sofosbuvir (GS-7977)
VK, ME, NC, AA, VK, FA). All authors read and approve the final manuscript. plus peginterferon/ribavirin in treatment-naive patients with HCV
genotype 1: a randomized, 28-day, dose-ranging trial. J Hepatol.
Funding 2013;58(4):663–8.
No funding was obtained for this study. 5. Kowdley KV, Lawitz E, Crespo I, et al. Sofosbuvir with pegylated
interferon alfa-2a and ribavirin for treatment-naive patients with
Availability of data and materials hepatitis C genotype1 infection (ATOMIC): an open-label, randomised,
The data that support the findings of this study are property of Georgia’s multicentre phase 2 trial. Lancet. 2013;381(9883):2100–7.
HCV elimination program. In case the data is requested, please contact 6. Lawitz E, Lalezari JP, Hassanein T, et al. Sofosbuvir in combination with
scientific committee of Georgia’s HCV elimination program (Secretary Dr. peginterferon alfa-2a and ribavirin for non-cirrhotic, treatment-naive
Tinatin Kuchuloria, email: [email protected]). patients with genotypes 1, 2, and 3 hepatitis C infection: a
randomised, double-blind, phase 2 trial. Lancet Infect Dis.
Ethics approval and consent to participate 2013;13(5):401–8.
The study was approved by the Institutional review board of the Infectious 7. Lawitz E, Poordad FF, Pang PS, et al. Sofosbuvir and ledipasvir fixed-
Diseases, AIDS and Clinical Immunology Research Center, Tbilisi. dose combination with and without ribavirin in treatment-naive and
previously treated patients with genotype 1 hepatitis C virus infection
Consent for publication Not (LONESTAR): an open-label, randomised, phase 2 trial. Lancet.
Applicable. 2014;383(9916):515–23.
8. Zeuzem S, Dusheiko GM, Salupere R, et al. Sofosbuvir and ribavirin in
HCV genotypes 2 and 3. N Engl J Med. 2014;370(21):1993–2001.
Competing interests
9. Mitruka K, Tsertsvadze T, Butsashvili M, et al. Launch of a Nationwide
The authors declare that they have no competing interests.
Hepatitis C Elimination Program--Georgia, April 2015. MMWR Morb
Author details Mortal Wkly Rep. 2015;64(28):753–7.
1 Infectious Diseases, AIDS and Clinical Immunology Research Center, 10. Nasrullah M, Sergeenko D, Gvinjilia L, et al. The Role of Screening and
Tbilisi, Georgia. 2Ivane Javakhishvili Tbilisi State University, Faculty of Treatment in National Progress Toward Hepatitis C Elimination -
Medicine, Georgia, 2015–2016. MMWR Morb Mortal Wkly Rep.
Tbilisi, Georgia. 3National Center for Disease control and public health, 99, 2017;66(29):773–6.
Kakheti highway, 0198 Tbilisi, Georgia. 4Emerging Infections Program, 11. Stedman C. Sofosbuvir, a NS5B polymerase inhibitor in the treatment
Centers for Disease Control and Prevention (CDC), Division of Viral Hepatitis of hepatitis C: a review of its clinical potential. Ther Adv
Gastroenterol. 2014; 7(3):131–40.
National Center for HIV, Hepatitis, STD&TB Prevention, Atlanta, USA.
5 12. Foster GR, Pianko S, Brown A, et al. Efficacy of sofosbuvir plus ribavirin
Hepatology Clinic
with or without peginterferon-alfa in patients with hepatitis C virus
HEPA, Tbilisi, Georgia. 6CDC Foundation, Georgia Hepatitis C Elimination
genotype 3 infection and treatment-experienced patients with
Tsertsvadze et al. BMC Infectious Diseases (2020) 20:30 Page 8 of 8

cirrhosis and hepatitis C virus genotype 2 infection. Gastroenterology.

2015;149(6):1462–70.
13. Lawitz E, Gane EJ. Sofosbuvir for previously untreated chronic
hepatitis C infection. N Engl J Med. 2013;369(7):678–9.
14. Jacobson IM, Gordon SC, Kowdley KV, et al. Sofosbuvir for hepatitis C
genotype 2 or 3 in patients without treatment options. N Engl J Med.
2013; 368(20):1867–77.
15. Welzel TM, Nelson DR, Morelli G, et al. Effectiveness and safety of
sofosbuvir plus ribavirin for the treatment of HCV genotype 2
infection: results of the real-world, clinical practice HCV-TARGET
study. Gut. 2016;66:1844.
16. Karchava M, Waldenstrom J, Parker M, et al. High incidence of the
hepatitis C virus recombinant 2k/1b in Georgia: recommendations for
testing and treatment. Hepatol Res. 2015;45(13):1292–8.
17. Hedskog C, Doehle B, Chodavarapu K, et al. Characterization of
hepatitis C virus intergenotypic recombinant strains and associated
virological response to sofosbuvir/ribavirin. Hepatology.
2015;61(2):471–80.
18. Karchava M, Chkhartishvili N, Sharvadze L, et al. Impact of hepatitis C
virus recombinant form RF1_2k/1b on treatment outcomes within the
Georgian national hepatitis C elimination program. Hepatol Res.
2017;48(1):36.
19. Tapper EB, Afdhal NH. Is 3 the new 1: perspectives on virology, natural
history and treatment for hepatitis C genotype 3. J Viral Hepat.
2013;20(10): 669–77.
20. Lawitz E, Sulkowski MS, Ghalib R, et al. Simeprevir plus sofosbuvir,
with or without ribavirin, to treat chronic infection with hepatitis C
virus genotype 1 in non-responders to pegylated interferon and
ribavirin and treatmentnaive patients: the COSMOS randomised
study. Lancet. 2014;384(9956): 1756–65.
21. Bonder A, Tapper EB, Afdhal NH. Contemporary assessment of hepatic
fibrosis. Clin Liver Dis. 2015;19(1):123–34.
22. Tapper EB, Bacon BR, Curry MP, et al. Real-world effectiveness for 12
weeks of ledipasvir-sofosbuvir for genotype 1 hepatitis C: the trio
health study. J Viral Hepat. Jan 2017;24(1):22–7.

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