Original Article
Clin Infect Immun. 2018;3(2):52-59
Treatment of Viral Hepatitis C by the Sofosbuvir and Ledipasvir With or Without Ribavirin Combination in Cameroon: Efficiency, Tolerance and Significant Predictors of SVR12 Servais Albert Fiacre Bagnaka Eloumoua, b, i, Adele II Ndoumbe Moutoa, Winnie Nga Bekolob, Gabin Kenfacka, Dominique Noah Noahb, Isabelle Dang Timba Babagnac, Agnes Malonguea, Mauriceau Kamchouing Fodjod, Sylvie Tamufe Takue, Gislaine Ngatcha Epse Eloundouc, Dietith Kemayouf, Jean Jacques N Noubiapg, Michelle Sartre Tagnic, Christian Tzeutona, f, Henry Namme Lumaa, h
Abstract Background: There has been a revolution in the treatment of hepatitis C virus (HCV) infection since the introduction of new direct-acting antivirals agents (DAAs) in 2014. About 95% of the patients have a sustained virological response (SVR) after 12 weeks with DAAs. The aim of this study was to evaluate the SVR after 12 weeks of treatment with the combination of sofosbuvir (SOF)/ledipasvir (LDV) +/- ribavirin (RBV) among a cohort of Cameroonian HCV carriers. Methods: This was a cross-sectional study in HCV treatment centers in Cameroon health facilities in Yaounde and Douala. It focused on patients with chronic HCV of genotypes 1 and 4 treated with the SOF/ LDV +/- RBV combination for 12 weeks. The virological response after 4 and 12 weeks of treatment was determined. SVR indicating recovery was determined 12 weeks after the end of treatment (SVR12). Results: A total of 111 patients with chronic HCV were included. There was female predominance with a proportion of 58.6%. The average age of the patients was 58.8 ± 8.2 years. Genotype 1 was the most frequent with 68.5% of the cases. The SVR was 93.7% (95% CI Manuscript submitted December 31, 2017, accepted March 20, 2017 aService
bFaculty
of Internal Medicine, General Hospital of Douala, Douala, Cameroon of Medicine and Pharmaceutical Sciences of Douala, Douala, Cam-
eroon cCathedrale Medical Center of Yaounde, Yaounde, Cameroon dJoss Medic Clinic of Douala, Douala, Cameroon eDigestive Diseases Medical Center of Douala, Douala, Cameroon fCapucines Medical Center of Douala, Douala, Cameroon gDepartement of Medecine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa hFaculty of Medicine and Biomedical Sciences of Yaounde, Yaounde, Cameroon iCorresponding Author: Servais Albert Fiacre Bagnaka Eloumou, BP 2701 FMSP, Universite de Douala, Douala, Cameroon. Email:
[email protected] doi: https://doi.org/10.14740/cii76e
52
(87.4% - 97.4%)) regardless of protocol and genotype. HCV infection without cirrhosis was associated with good SVR (aOR = 0.1, 95 CI (0.1 - 0.9), P = 0.02). The most common clinical adverse reaction was asthenia with 12.5% (n = 10). Conclusions: The SVR12 in Cameroonian patient infected with HCV genotypes 1 and 4 treated with the combination SOF/LDV +/- RBV was 93.7%. Cirrhosis is a factor of poor response. Keywords: Sofosbuvir; Ledipasvir; Ribavirin; Viral hepatitis C; Sustained virological response; Cameroon
Introduction Viral hepatitis C is a global public health problem [1]. In 2015, according to the World Health Organization (WHO), 3% of the world’s population i.e. about 185 million individuals were carriers of hepatitis C virus (HCV) [1]. Africa is the second most affected continent [1]. The estimated prevalence is 2.9% of the world population [2]. In Cameroon, the prevalence is estimated at 13.8% making about 2 million people [2]. The treatment of HCV management is imperative given severe complications such as cirrhosis and liver cancer [3]. The main objective of the treatment is the eradication of the virus [4]. A few years ago, the reference therapy was bitherapy with pegylated interferon and RBV with a sustained virological response (SVR) varying between 36.1 and 44% [5, 6]. There were numerous adverse effects that sometimes led to discontinuation of treatment [6]. Currently, the treatment is based on direct-acting antiviral agents (DAAs) [7]. This treatment is highly effective, well tolerated and associated with the use of short-lived oral therapeutic combinations [8, 9]. The evaluation of the treatment of viral hepatitis C is based on SVR obtained [4]. This is defined as the persistence of undetectable HCV RNA 12 to 24 weeks after the end of treatment [4].
Articles © The authors | Journal compilation © Clin Infect Immun and Elmer Press Inc™ | www.ciijournal.org This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited
Eloumou et al
Clin Infect Immun. 2018;3(2):52-59
Cameroon is one of the 60 countries in the world chosen by WHO that can benefit from a reduction in the cost of treating viral hepatitis C [10]. Since March 2016, two DAAs are available in Cameroon under the galenical presentation of a tablet combining 400 mg of sofosbuvir (SOF) and 90 mg of ledipasvir (LDV) after the signature of an agreement between the Gilead laboratory and the state [11]. The cost of this treatment in Cameroon is 453 US dollar (USD) per month compared to Western countries where it is 49,000 USD per month [11, 12]. In 2012 the Ministry of Health in Cameroon set up two approved treatment centers (ATCs). There has been a revolution in the treatment of HCV since the introduction of DAAs in 2014 [4]. The SVR after 12 weeks of treatment varies between 93-99% in developed countries in clinical trial [13]. However, few real world studies on the treatment of HCV infection with DAAs in the context of “real life” have been performed in our environment. The aim was to evaluate the SVR to the combination of SOF/LDV +/- ribavirin (RBV) by investigating efficacy, predictive factors for response and tolerance.
Methods Type, location and period of study This was a cross-sectional study carried out in the following health facilities: Douala General Hospital (DGH), Capucine Medical Center, Joss Medic Clinic, Polyclinique Marie O and Digestive Disease Medical Center in Douala and in Yaounde at the Cathedrale Medical Center from the January 1, 2016 to April 30, 2017. These health facilities have the particularity of having at least one hepatologist with an active line of patients followed for chronic HCV infection. DGH is one of the reference hospitals in Cameroon with a capacity of 320 beds. It also acts as a university teaching hospital. It houses one of the two ATCs in Cameroon. Other clinics, such as the Capucine Medical Center, the Joss Medic Clinic, the Polyclinique Marie O and the Digestive Diseases Medical Center of Douala, and the Cathedrale Medical Center in Yaounde are private clinics, each of which is affiliated to an ATC. The choice of health facilities was made with agreement if the latter. These health facilities are each affiliated with the ATCs set up by the Ministry of Health in Cameroon in 2012 either in Yaounde or Douala. The initiation of treatment was discussed in the different ATCs for each eligible patient. The treatment protocols used were chosen according to the European Association for the Study of Liver (EASL) recommendations 2015 [14]. Data collection The study population consisted of HCV-infected patients followed at one of the study sites. We included patients with HCV genotypes 1 and 4 treated with the combination of SOF/LDV +/- RBV for 12 weeks and achieved SVR12. Patients with a combination of interferon or other direct-acting antivirals agents (DAAs) were excluded. The variables of interest were: socio-demographic char-
acteristics and comorbidities (age, sex, marital status, occupation, care financing, obesity, diabetes, alcohol consumption, HBV co-infection, drug addiction IV, HIV co-infection); clinical characteristics (cirrhosis or not); biological characteristics (HCV viral load, genotype, full blood count, transaminases, degree of liver fibrosis, treatment (duration, treatment protocol, various adverse effects), and SVR 12 weeks after the end of treatment (viral load presented negativity 12 weeks after the end of treatment). Alcohol consumption was rated yes and no. Care financingwas made either personally or by insurance. The marital status was subdivided into two (married and unmarried). The occupation was subdivided into three (salaried, self-employed and unemployed). The diagnosis of diabetes was made by an endocrinologist. The diagnosis of cirrhosis was documented on the basis of signs of hepatocellular insufficiency and portal hypertension. The genotype and quantification of HCV RNA was done by a real-time PCR (RT-PCR reverse-hybridization LiPA and RT-PCR Cobas 8800 Roches, Cerba, France). RNA quantification, blood count, transaminases and creatinine were performed after 4, 12 and 24 weeks of onset of treatment. The detection threshold for HCV RNA was less than 15 IU/mL. A value of hemoglobin less than 12 g/dL was considered anemia. Normal values of transaminases were less than or equal to 40 IU/L, creatinine less than or equal to 12 mg/L, and thrombocytopenia was observed when platelets were less than or equal to 100,000 cells/mm3. Viral load was considered high when it was greater than 800,000 IU/mL or low when less than 800,000 IU/mL. The evaluation of fibrosis was done using the Fibrostest® in the Cerba laboratory in France (BioPredictive, Paris France) or by transient elastography (Fibroscan 502®). Fibrosis was classified according to the Metavir score by a significant fibrosis (greater than or equal to F2) and not significant (less than F2). Cirrhosis was defined by fibrosis equal to F4. The virological response was sought after 4 and 12 weeks of treatment. Definition of terms Rapid virological response (RVR) was defined as the negativity of the charge at the 4th week of treatment. The end-of-treatment response (ETR) was defined as an undetectable viral load at the 12th week of treatment. SVR at 12 weeks (SVR12) was defined as an undetectable viral load 12 weeks after the end of treatment. Response was defined as the undetectable viral load after the end of treatment. Non-response was defined as a detectable viral load at the end of treatment and 12 weeks after the end of treatment. Relapse was defined as an undetectable viral load at the end of treatment and then reappeared 2 weeks after the end of treatment. Statistical analysis Statistical analysis was carried out using software R version 3.2.4. Qualitative variables were presented as frequencies and percentage whereas quantitative variables were presented as
Articles © The authors | Journal compilation © Clin Infect Immun and Elmer Press Inc™ | www.ciijournal.org
53
Treatment of HCV by SOF/LDV +/- RBV
Clin Infect Immun. 2018;3(2):52-59
Table 1. General Characteristics of the Study Population Parameters
Values
Age (years)
60.5 ± 8.2
Sex (female)
N = 65(58.6%)
Occupation (employee)
N = 73(55.0%)
Marital status (married)
N = 81(72.9%)
Insurance (not insured)
N = 77(69.4%)
Alcohol consumption
N = 34(33.3%)
Diabetes
N = 19(18.6%)
HIV co-infection
N = 2(2.0%)
HBV co-infection
N = 1(1.0%)
Prior surgery
N = 53(47.7%)
Blood transfusion
N = 16(14.4%)
Obese
N = 85(76.6%)
Cirrhosis
N = 7(6.3%)
WBC (cells/mm3)
4,937 ± 2,403.1
Hb (g/dL)
13.4 ± 1.7
PLT (cells/mm3) Neutrophils
192,422.4 ± 86,730.9
(cells/mm3)
2,311.3 ± 1,331.8
Glomerular filtration rate (mL/min)
93.2 ± 36.4
ALAT (UI/L)
40.7 ± 78.5
ASAT (UI/L)
49 ± 78.5
GGT (UI/L)
119.1 ± 203.8
AP (UI/L)
117.3 ± 94.7
Albumin (g/L)
32.9 ± 14.7
Total bilirubin (g/L)
43.8 ± 127
Prothrombin (%)
97.9 ± 90.5
Genotype 1
N = 76(68.5%)
HCV RNA (IU/mL) median (IQR)
1,183,000 (1,410 - 24,940,000)
Significant fibrosis (≥ F2)
N = 62 (55.9%)
Therapeutic status before treatment (naive of any treatment)
N = 82 (73.9%)
Treatment protocol (SOF/LDV)
N = 92 (73.9%)
mean with their standard deviation or median with interquartile range. The univariate analysis revealed the association or link between the variables through the calculation of the odds ratio (OR) with its 95% confidence interval (CI) or the exact Fisher test in the case where an OR was not applicable. Regression model has enabled to obtain adjusted ORs. The threshold for statistical significance was set at 0.05. Ethical Considerations This work was carried out in accordance with the Helsinki declaration. Ethical clearance was obtained from the Institutional Ethical Committee of the University of Douala with reference number IEC-Udo/799/16/2017/T. 54
Results Characteristics of the population case study We included a total of 111 patients who met the inclusion criteria. The sex ratio was 0.7 with a female predominance of 65 participants (58.6%) (Table 1). The mean age was 60.5 ± 8.2 years with a range of 32 - 78 years (Table 1). The most frequent comorbidities were alcohol in 34 patients (33.3%) and diabetes in 19 patients (18.6%) (Table 1). The main risk factors for transmission were past history of surgery (47.7%) followed by a blood transfusion (14.4%) (Table 1). Eleven participants were grossly overweight (13.1%) and seven (6.3%) patient had cirrhosis (Table 1). Twenty patients (21.7%) had anemia at
Articles © The authors | Journal compilation © Clin Infect Immun and Elmer Press Inc™ | www.ciijournal.org
Eloumou et al
Clin Infect Immun. 2018;3(2):52-59
Table 2. Global Virologic Response Virologic response
SOF/LDV
SOF/LDV + RBV
Total
Effective (n)
Frequency (%)
Effective (n)
Frequency (%)
Effective (n)
Frequency (%)
Non responders
7
8.5
0
0
7
6.3
Responders
75
91.5
29
100
104
93.7
Total
82
100
29
100
111
100
Non responders
2
2.4
1
3.4
3
2.7
Responders
80
97.6
28
96.6
108
97 .3
Total
82
100
29
100
111
100
Non responders
13
15.8
4
13.7
17
15 .3
Responders
69
84.2
25
86.5
94
84.7
Total
82
100
29
100
111
100
SVR12
ETR
RVR
treatment initiation. The mean estimated glomerular filtration rate was 93.2 ± 26.4 mL/min (Table 1). In this study, two patients had stage 3 chronic kidney disease (3.6%). In this study, the initial ALT level was above normal in 66 patients (59.5% of the cases). Patients infected with HCV genotype 1 accounted for 68.5% of the study population (76 patients) (Table 1). The median (IQR) of the initial viral load was 1,183,000 IU/ mL (1,410 - 24,940,000) (Table 1). A high viral load was found in 62 patients (55.9%). Sixty-two patients (55.9%) had significant fibrosis (≥ F2) (Table 1). Regarding the status of patients treated, 82 patients (73.9%) were naive to treatment against chronic viral hepatitis C (Table 1). The SOF/LDV treatment protocol alone was undertaken in 82 patients, i.e. 73.9% of the cases (Table 1). Efficiency and significant predictors In this study, the SVR12 regardless of the treatment protocol was 93.7% (95% CI (87.4 - 97.4)), i.e. 104 respond-
ers (Table 2). The SVR12 for the SOF/LDV protocol was 91.5% (95% CI (83.2 - 96.5)), i.e. 75 patients (Table 2). The SVR12 for the SOF/LDV + RBV protocol was 100%, i.e. 29 patients (Table 2). The SVR12 for genotypes 1 and 4 was 92.1% (95% CI (83.6 - 97.1)) and 97.4% (95% CI (85.1 99.9)) respectively (Fig. 1). There was no significant difference between SVR12 for genotype 1 or 4 (P = 0.8). Patients treated with the SOF/LDV protocol had an SVR12 of 90% and 95%, respectively, for genotypes 1 and 4 (Fig. 2). In addition, patients treated with the SOF/LDV + RBV protocol had a 100% SVR12 regardless of the genotypes (Fig. 2). However, there was no association between genotypes and virological response for each protocol (P = 0.9, P = 0.8) (Fig. 2). Cirrhotic patients had a SVR12 of 71.4% versus 95. 2% for non-cirrhotic patients (P = 0.004) (Fig. 3). Patient with diabetes, had 89.5% SVR12 versus 94.6% in non-diabetic patients (P = 0.75) (Fig. 4). After multivariate analysis, cirrhosis was an independent factor associated with poor SVR for SOF/LDV (non-cirrhotic: OR = 0.1, 95% CI (0.1 - 0.09), P = 0.02).
Figure 1. Virological response according to HCV genotype.
Articles © The authors | Journal compilation © Clin Infect Immun and Elmer Press Inc™ | www.ciijournal.org
55
Treatment of HCV by SOF/LDV +/- RBV
Clin Infect Immun. 2018;3(2):52-59
Figure 2. Virological response of HCV according to the protocole of treatment.
Treatment tolerance Asthenia was the most common adverse reaction regardless of the protocol, i.e. 76.9% for the SOF/LDV protocol and 23.1% for the SOF/LDV + RBV protocol (Table 3). Anemia was more common in patients treated with SOF/LDV + RBV, or 60.9% of the cases (Table 3).
Discussion The aim of this study was to evaluate the efficacy, tolerance and predictive factors of treatment with SOF/LDV +/- RBV in Cameroon. It appears that the female sex is the most predominant; the average age is high at 60.12 years. The overall SVR12 was 93.7%, decreases to 91.5% for the SOF/LDV protocol and increases to 100% when RBV was added. Non-cirrhotic patients responded better to the treatment with 95.2%. Asthenia was the most common side effect. Cirrhosis was found as the only independent factor associated with poor SVR12. The distribution of the study population in relation to sex and age shows a female predominance (56 women for 42 men) and an average age 60.12 ± 8.2 years. This is similar to literature in Cameroon. Indeed, studies in Cameroon and China have shown a female predominance and a high average age at more than 50 years [15-17]. The average age of the patients treated is explained by an old exposure to HCV during the care of mass anti-trypanosomiasis campaigns in the years 1930 -
1960 [18-20]. The most common risk factors for transmission in this study were a surgical history in 45 patients (46.1%) and a blood transfusion in 16 patients (16.3%). This is consistent with the work of Luma et al [15]. Like blood transfusion, surgery at a time when hepatitis C virus was not routinely tested could explain the high frequency of C viral hepatitis in these patients. The most common comorbidity was diabetes in 11.1% of cases. These results are consistent with literature [15-17]. The national prevalence of diabetes in Cameroon was 6.5% in 2015; this high frequency in patients with chronic C viral hepatitis is due to HCV-induced insulin resistance [21, 22]. The median pre-therapeutic viral load was 1,183,000 IU/ mL and 58.2% of patients had a high viral load (≥ 800,000). This result was similar to that found by Werner et al which found an initial high viral load at 65% of cases [23]. This high mean viremia in this study population could be explained by the selection of severe patients in the indexed study. These severe patients appear to have high viremia. Among the patients included in this study, significant fibrosis was found in 55.1% of cases. This result differs from that of Luma et al in 2016, where in a population of 524 patients with HCV, 47% of severe fibrosis or cirrhosis [15]. The selection of severe patients by the therapeutic committee in this work and the search for fibrosis in some patients in Luma’s work may explain this difference. Globally, we were able to obtain three types of virological response, the RVR was 84%, the ETR was 97% and finally the sustained virological response 12 weeks after the end of treat-
Figure 3. Virological response of HCV patients according to cirrhotic status.
56
Articles © The authors | Journal compilation © Clin Infect Immun and Elmer Press Inc™ | www.ciijournal.org
Eloumou et al
Clin Infect Immun. 2018;3(2):52-59
Figure 4. Virological response of HCV patients according to diabetes status.
Table 3. Clinical and Biological Tolerance During Treatment SOF/LDV
Side effects
SOF/LDV + RBV
Effective (n)
Frequency (%)
Effective (n)
Frequency (%)
No effect
55
68.7
26
83.9
Asthenia
10
12.5
3
9.7
Headaches
6
7.5
1
3.2
Abdominal pain
7
8.6
2
6.5
Itching
0
0
0
0
Joint pain/bone pain
6
7.5
1
3.2
Insomnia
1
1.3
1
3.2
Nausea
1
1.3
0
0
Diarrhea
1
1.3
0
0
Dyspnea
0
0
0
0
Skin rash
0
0
0
0
Visual impairment
0
0
0
0
Anorexia
0
0
1
3.2
Hair loss
0
0
0
0
Nervousness
0
0
0
0
Tachycardia
0
0
0
0
Depression/fear
0
0
0
0
Clinical
Biological Hb12(g/dL) 40
2
3.8
2
18.2
ASAT12 (UI/L) > 40
2
3.8
1
9.1
Creat12(mg/L) > 12
3
8.8
2
22.2
Hb12: hemoglobin at the 12th week of treatment; Plt12: platelet at the 12th week of treatment; Neutrophils12: neutrophilic polynuclear at the 12th week of treatment; ALAT12: ALAT at the 12th week of treatment; ASAT12: ASAT at the 12th week of treatment; Creat12: creatinine at the 12th week of treatment.
Articles © The authors | Journal compilation © Clin Infect Immun and Elmer Press Inc™ | www.ciijournal.org
57
Treatment of HCV by SOF/LDV +/- RBV ment was 93.7% to 95% (87.4% - 97.4%). These results were lower than those of Afdhal et al in 2014 in the United States, which found 99% at 4 weeks, 100% at 12 weeks and 98% on the SVR12 [24]. This difference could be explained by the fact that their study population consisted mainly of patients naive of any anti viral C treatment and not cirrhotic. The SVR12 according to the SOF/LDV protocol was 91.5% against 100% when RBV was added. There was no association between the SVR12 and the protocol used. These results were close to Younossi et al in 2016 in Japan, which found a 100% SVR12 for the SOF/LDV + RBV protocol [16]. But our results were different from those of Younossi et al when using SOF/LDV alone. Patients with genotype 4 were more responsive to treatment with 97% SVR12. However, the difference in SVR12 was not significant between genotypes. These results were close to those found by Werner et al in 2016 in Germany, which found a 98% SVR12 for genotype 4 [23]. Cirrhotic patients responded significantly less well with 71% SVR12. These results were close to those of Werner et al which found SVR12 to be significantly lower in cirrhotic patients at 87% compared to non-cirrhotic patients [23]. The low response of cirrhotic patients could be explained by the scarred fibrosis installed and the functional deficiency of the hepatocytes induced by cirrhosis. Patients with diabetes responded less well to SVR treatment at 89%, however, the association between SVR12 and the presence or absence of diabetes was not significant. These results were similar to those of Backus et al which found SVR in diabetics to be 87% [25]. Type 2 diabetes is a factor in the progression of liver fibrosis. In multivariate analysis it was found that cirrhotic patients treated with the SOF/LDV protocol had a SVR that was significantly lower than in non-cirrhotic patients (adjusted OR = 0.1). Cirrhosis is therefore an independent factor of poor response to treatment. These results are similar to those of Terrault et al in 2016 who found cirrhosis as a predictor of poor response to treatment [26]. The most common side effect was asthenia at 10.6% of all adverse reactions, regardless of the treatment regimen. These results were consistent with those of Zeng et al in 2017 in China, which found asthenia in 27% of cases as the most common clinical adverse reaction [17]. Anemia was encountered in 60.9% of patients treated with SOF/LDV + RBV. This was in accordance with data from literature that revealed the hematological toxicity of RBV. This study did not take into account all the centers of treatment of HCV in Cameroon. The study being retrospective was based on the exploitation of medical records so some data were missing, finally, the delay between the introduction of the DAAs in Cameroon. The accomplishment of this work contributed to limiting the size of the sample obtained. All this led to a small sample whose small size limited the research of the determinants of the SVR due to the weakness of the statistical tests used. Conclusions The SVR12 in Cameroon with the SOF/LDV +/- RBV protocol is 93.7% (95% CI (87.4% -97.4%)). This SVR is better when carrying genotype 4 with 97.7%. The addition of RBV makes 58
Clin Infect Immun. 2018;3(2):52-59 the response even better and it goes up to 100% whatever the genotype. This therapeutic combination has good clinical as well as biological tolerance.
Acknowledgments The authors would like to thank the external consultation staff and the archives of all health facilities that participated in this work for their contribution to the data collection.
Ethical Clearance This work has received approval from the Institutional Ethics Committee of the University of Douala.
Conflict of Interest This work was not funded. The authors do not declare any conflict of interest.
Author Contributions SAFBE, AMN, DNN, HNL designed the study. SAFBE, AMN, WBN, GK, DNN, IDBT, AM, MFK, STT, GNE, KD, CT, HNL collected the data. SAFBE, AMN analyzed the data and wrote the manuscript. SAFBE, AMN, DNN, JJNN, HNL re-read and corrected the manuscript. All authors agree with the final version of the manuscript for submission to the publication.
Abbreviations DAA: direct-acting antivirals; AFP: alpha-feto-protein; ALAT: alanine aminotransferase; RNA: ribonucleic acid; ASAT: aspartate aminotransferase; BILI C: conjugated bilirubin; BILI T: total bilirubin; ATC: agreed treatment center; VL: viral load; eGFR: estimated glomerular filtration rate; ELISA: enzymelinked immunosorbent assay; WBC: white blood cells; GGT: gamma glutamyl transpeptidase; Hb: hemoglobin; HCV: hepatitis C virus; CI: confidence interval; BMI: body mass index; LDV: ledipasvir; FBC: full blood count; WHO: World Health Organization; OR: odds ratio; PCR: polymerase chain reaction; PLT: platelet; PNN: neutrophils polynuclear; RBV: ribavirin; SVR: sustained virological response; SVR12: sustained virological response 12 weeks after discontinuation of therapy; SOF: sofosbuvir; SOF/LDV: sofosbuvir + ledipasvir; TP: prothrombin time; HBV: hepatitis B virus; HCV: hepatitis C virus; HIV: human immunodeficiency virus
References 1. World Health Organization. Guidelines for the screening care and treatment of persons with chronic hepatitis C in-
Articles © The authors | Journal compilation © Clin Infect Immun and Elmer Press Inc™ | www.ciijournal.org
Eloumou et al
2.
3. 4. 5.
6.
7. 8. 9.
10. 11. 12.
13.
14.
Clin Infect Immun. 2018;3(2):52-59
fection. Geneva: WHO Document Production Services. 2016;140. Petruzziello A, Marigliano S, Loquercio G, Cozzolino A, Cacciapuoti C. Global epidemiology of hepatitis C virus infection: An up-date of the distribution and circulation of hepatitis C virus genotypes. World J Gastroenterol. 2016;22(34):7824-7840. Desenclos JC. L’infection par le virus de l’hepatite C dans le monde: importance en sante publique, modes de transmission et perspectives. Virologie. 2003;7(3):177-191. Leroy V. le traitement de l’hepatite C en 2016. POST’U. 2016:127-132. Njoya O, Djoukam T, Mawaguiawoguia JP, Tagni SM, Essi MJ, Ombotto S et al. Safety of the association of pegylated interferon and ribavirin in the treatment of chronic viral hepatitis C in the blacks: a ten year observation. Gastroenterology & Hepatology. 2015;2(5). Yee BE, Nguyen NH, Zhang B, Lin D, Vutien P, Wong CR, Lutchman GA, et al. Sustained virological response and its treatment predictors in hepatitis C virus genotype 4 compared to genotypes 1, 2, and 3: a meta-analysis. BMJ Open Gastroenterol. 2015;2(1):e000049. EASL recommendations on treatment of hepatitis C 2016. J Hepatol. 2017;66(1):153-194. Darius M, Beat M. Hepatite C: traitement actuel. Revue Medicale Suisse. 2015;471:902-906. Lawitz E, Poordad FF, Pang PS, Hyland RH, Ding X, Mo H, Symonds WT, et al. Sofosbuvir and ledipasvir fixeddose combination with and without ribavirin in treatmentnaive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014;383(9916):515523. Medecins du Monde. Nouveaux traitements de l’hepatite C:Strategies pour atteindre l’acces universel. Paris: Medecins du monde. 2014:24. Ministere de la Sante publique du Cameroun. Cout du traitement des hepatites. Yaounde: Imprimerie nationale; 2016:3. Bach TA, Zaiken K. Real-world drug costs of treating hepatitis C genotypes 1-4 with direct-acting antivirals: initiating treatment at fibrosis 0-2 and 3-4. J Manag Care Spec Pharm. 2016;22(12):1437-1445. Ahmed H, Elgebaly A, Abushouk AI, Hammad AM, Attia A, Negida A. Correction: Safety and efficacy of sofosbuvir plus ledipasvir with and without ribavirin for chronic HCV genotype-1 infection: a systematic review and meta-analysis. Antivir Ther. 2017;22(5):457. European Association for Study of Liver. EASL Recommendations on Treatment of Hepatitis C 2015. J Hepatol. 2015;63(1):199-236.
15. Luma HN, Eloumou SA, Malongue A, Temfack E, Noah DN, Donfack-Sontsa O, Ditah IC. Characteristics of anti-hepatitis C virus antibody-positive patients in a hospital setting in Douala, Cameroon. Int J Infect Dis. 2016;45:53-58. 16. Younossi ZM, Stepanova M, Omata M, Mizokami M, Walters M, Hunt S. Quality of life of Japanese patients with chronic hepatitis C treated with ledipasvir and sofosbuvir. Medicine (Baltimore). 2016;95(33):e4243. 17. Zeng QL, Xu GH, Zhang JY, Li W, Zhang DW, Li ZQ, Liang HX, et al. Generic ledipasvir-sofosbuvir for patients with chronic hepatitis C: A real-life observational study. J Hepatol. 2017;66(6):1123-1129. 18. Nerrienet E, Pouillot R, Lachenal G, Njouom R, Mfoupouendoun J, Bilong C, Mauclere P, et al. Hepatitis C virus infection in cameroon: A cohort-effect. J Med Virol. 2005;76(2):208-214. 19. Biwole-Sida M, Noah D, Eloumou A, Dang I, Talla P, Malongue A et al. Prevalence du portage des anticorps anti VHC dans une population de travailleurs (depistage en milieu professionnel) au Cameroun. JAHG. 2015;9(1):26-29. 20. Pasquier C, Njouom R, Ayouba A, Dubois M, Sartre MT, Vessiere A, Timba I, et al. Distribution and heterogeneity of hepatitis C genotypes in hepatitis patients in Cameroon. J Med Virol. 2005;77(3):390-398. 21. International Diabetes Federation 2017. http://www.idf. org/membership/afr/cameroon. 22. Kaur H, Singh P, Pannu HS, Sood A, Jain NP, Bhoday HS. To study the prevalence of impaired glucose tolerance in patients with hepatitis C virus related chronic liver disease. J Clin Diagn Res. 2015;9(3):OC16-20. 23. Werner CR, Schwarz JM, Egetemeyr DP, Beck R, Malek NP, Lauer UM, Berg CP. Second-generation directacting-antiviral hepatitis C virus treatment: Efficacy, safety, and predictors of SVR12. World J Gastroenterol. 2016;22(35):8050-8059. 24. Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, Romero-Gomez M, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370(20):1889-1898. 25. Backus L, Belperio P, Shahoumian TA, Loomis T, Mole L. Effectiveness of ledipasvir/sofosbuvir in treatment naive genotype 1 patients treated in routine medical practice. Hepatol. 2015;62(Suppl 1):255A. 26. Terrault NA, Zeuzem S, Di Bisceglie AM, Lim JK, Pockros PJ, Frazier LM, Kuo A, et al. Effectiveness of ledipasvir-sofosbuvir combination in patients with hepatitis C virus infection and factors associated with sustained virologic response. Gastroenterology. 2016;151(6):11311140 e1135.
Articles © The authors | Journal compilation © Clin Infect Immun and Elmer Press Inc™ | www.ciijournal.org
59