Keywords
hepatitis C virus - direct acting antiviral - hepatitis C virus genotype - National
Viral Hepatitis Control Program
Introduction
Globally 110 million people are seropositive for hepatitis C virus (HCV) antibodies
and about 80 million people have chronic HCV infection.[1] In India, the prevalence of HCV infection is about 0.5 to 1.5%.[2] Prevalence among hemodialysis (HD) patients is 27.7%,[3] in renal transplant recipients 26.2 to 55.9%,[4] in health care workers 0 to 4%,[5] and among intravenous drug users (IVDUs) it is up to 55%.[6] HCV has six major genotypes (GT) 1 to 6. GT 3 is most common genotype from India,
accounting for 54 to 80% of cases.[7]
[8] Direct-acting antivirals (DAAs) have greatly simplified treatment of HCV infection
with cure rate of 90%; however, awareness of the risk factors for infection, access
to diagnostic modalities, and RNA testing and treatment facilities are low.[9]
No data is available on sociodemographic profile, HCV genotype, and response to therapy
of HCV infection from Himachal Pradesh (HP), a hilly state in the sub-Himalayan ranges
of North India. So, this study was conducted to determine the sociodemographic profile
of HCV-infected patients along with risk factors for HCV transmission, HCV genotype,
and treatment response to new oral DAAs in HP.
Methods
In this single-center study, we retrospectively analyzed data of HCV infected patients
treated in our institution in HP from September 2019 to March 2022. All patients were
treated with oral DAA drugs free-of-cost treatment under National Viral Hepatitis
Control Program.
All patients with HCV infection diagnosed on third-generation ELISA (HCV ELISA- J
Mitra and Co. Pvt Ltd, J Mitra and Co Pvt limited. A-180-181, Okhla Industrial Area,
Phase-1, New Delhi-110020, INDIA) followed by confirmatory HCV-RNA quantification
(by COBAS Ampliprep/COBAS TaqMan HCV Test, ver 2.0 Roche Molecular Systems, Inc.,
Branchburg, New Jersey, United States, with lower limit of quantitation of 15 IU/mL).
HCV genotype and subtype were determined using LiPA 2.0 genotyping assay or by Sanger
sequencing. We excluded those with concomitant infection with hepatitis B and/or human
immunodeficiency virus, acute liver failure, aminotransferases more than 10 × upper
limit of normal, prior liver transplantation, hepatocellular carcinoma, and previous
treatment with DAA was excluded from the study. Plasma HCV RNA levels were evaluated
at baseline and then after 12 weeks of completion of treatment for documenting sustained
virological response (SVR) at week 12.
The sociodemographic parameters including age, gender, locality, educational status,
occupation and addiction patterns of the included patients were studied. Data regarding
risk factors for the transmission of HCV infection like IVDU, needle stick injury,
high-risk sexual behavior, spouse with HCV infection, body piercing, tattooing, HD,
history of blood transfusion, surgery, organ transplantation, injection drug treatment,
and hospitalization were analyzed. Evidence of cirrhosis included: AST to Platelet
Ratio Index (APRI) score more than 2, or liver stiffness measurement of more than
12.5 kPa on transient elastography and clinical evidence of cirrhosis (e.g., liver
nodularity and/or splenomegaly on imaging, platelet count < 150,000/mm3).[10]
The drug regimen used for the treatment of HCV infection was as per national guidelines.[10] Those who did not have underlying cirrhosis received sofosbuvir plus daclatasvir
for 12 weeks. Sofosbuvir plus velpatasvir for 12 weeks was administered to those with
compensated cirrhosis. Those with decompensated cirrhosis were treated either with
sofosbuvir plus velpatasvir plus ribavirin for 12 weeks or sofosbuvir plus velpatasvir
for 24 weeks, depending on ribavirin tolerance. Those patients who achieved SVR 12
(HCV RNA < lower limit of quantitation 12 weeks after completion of the treatment)
were recorded as treatment responders. Statistical analysis was performed using statistical
package for social sciences (SPSS) version 22.0 for Windows (SPSS, Chicago, Illinois,
United States). Results are displayed in tables and figure, with the categorical variables
presented as numbers and percentages and mean ± standard deviation, as appropriate.
Results
A total of 189 HCV infected patients were included in the study, with a mean age of
30.9 ± 13.8 years (range: 16–75 years; [Table 1]). Most were males (91%) aged between 11 and 30 years (71.4%), and they were students
(71.9%) predominantly from urban (61.9%) background ([Table 1]). Patients had come from all 12 districts of the state and mostly from districts
Shimla (57.1%), Solan (10.6%), and Bilaspur (7.9%). Students constituted the predominant
(40.7%) patient population, followed by unemployed adults (37%; [Table 1]). Predominant risk factors for HCV transmission were IVDU (61.4%), tattooing (11.7%),
and HD (11.1%; [Table 1]).
Table 1
Baseline sociodemographic characteristics and risk factors for HCV infection in study
population
|
Parameter
|
Number (n)
|
Percentage (%)
|
|
Gender
|
|
Male
|
172
|
91.0
|
|
Female
|
17
|
9.0
|
|
Age group (y)
|
|
11–30
|
135
|
71.4
|
|
31–50
|
29
|
15.3
|
|
51–70
|
20
|
10.6
|
|
>70
|
5
|
2.6
|
|
Educational status
|
|
Literate
|
182
|
96.3
|
|
Illiterate
|
7
|
3.7
|
|
Locality
|
|
Urban
|
117
|
61.9
|
|
Rural
|
72
|
38.1
|
|
Occupation
|
|
Students
|
77
|
40.7
|
|
Unemployed
|
70
|
37.0
|
|
Government employee
|
10
|
5.3
|
|
Self-employed
|
32
|
17
|
|
Risk factors for HCV transmission
|
|
|
|
Intravenous drug abuse
|
116
|
61.4
|
|
Tattooing
|
22
|
11.7
|
|
Hemodialysis
|
21
|
11.1
|
|
Prior surgery
|
8
|
4.2
|
|
No risk factor found
|
7
|
3.7
|
|
Blood transfusion and therapeutic injections
|
5
|
2.6
|
|
Sexual exposure
|
5
|
2.6
|
|
Needle stick injury
|
4
|
2.1
|
|
Organ transplant
|
1
|
0.5
|
Abbreviation: HCV, hepatitis C virus.
Most (95.2%) patients were without cirrhosis, so sofosbuvir plus daclatasvir for 12
weeks was the most common regimen used. The predominant HCV genotype was GT 3a followed
by GT 3b, GT1a, GT 1b, and GT 4 ([Table 2]). HCV genotype could not be determined in 19 patients due to logistic issues. SVR
was achieved in most patients (94.7%; [Table 2]). In five patients, SVR could not be achieved. Five patients got lost to follow-up
and SVR could not be documented on them.
Table 2
Liver cirrhosis, hepatitis C virus genotype, and sustained virological response of
study population
|
Parameter
|
Number (n)
|
Percentage (%)
|
|
Cirrhosis
|
No
|
180
|
95.2
|
|
Yes
|
9
|
4.8
|
|
Hepatitis C virus genotype
|
1a
|
14
|
7.4
|
|
1b
|
10
|
5.3
|
|
3a
|
125
|
66.1
|
|
3b
|
16
|
8.5
|
|
4
|
5
|
2.6
|
|
Not available
|
19
|
10.1
|
|
Sustained virological response
|
Achieved
|
179
|
94.7
|
|
Not achieved
|
5
|
2.6
|
|
Not available (lost to follow-up)
|
5
|
2.6
|
Discussion
In this study, HCV-infected patients were mostly males (91%) and aged between 11 and
30 years (71.4%). Most were students and predominantly from an urban background. Previous
studies from Punjab and West Bengal reported high prevalence of HCV infection in the
age group of 41 to 60 years and over 60 years, respectively.[11]
[12] This difference could be due to the predominant IVDUs and students in our study.
A study conducted in the neighboring states of Punjab and Haryana revealed most IVDUs
in age group of 18 to 30 years.[13] In a recent study of the prevalence of hepatitis C among IVDUs from Shimla, HP,
all patients were males aged between 21 and 40 years.[14] In a recent study, IVDU as risk factor for HCV transmission was more common in younger
adults with age less than or equal to 30 years in Punjab and Haryana.[15]
Predominant risk factors for HCV transmission were IVDU (61.4%), tattooing (11.7%),
and HD (11.1%). This is in contrast to previous studies which suggest that the predominant
mode of HCV transmission in India is unsafe therapeutic injections and blood transfusion.3In a study from Northern India, the most common risk factors for HCV transmission
were a history of dental treatment and therapeutic injections.8In a recent study, common risk factors for HCV transmission in Punjab and Haryana
were previous surgery and IVDU.[15] This contrast in risk factors may be a true epidemiological difference or may be
skewed due to the nonepidemiological nature of our study that included only those
patients who came to us for treatment. Tattooing has been observed as a common risk
factor in our study. Tattooing is prevalent among youth in HP, especially in tourist
areas. Most (95.2%) patients had infection with HCV without underlying cirrhosis,
so sofosbuvir plus daclatasvir was the most common regimen used for treatment. Most
(94.7%) patients achieved SVR. Similar high effectiveness of DAA-based treatment of
up to 90% has been reported in other studies, even in public health programs.[11]
Though the present study is not a true epidemiological study, it may reflect the current
trend of acquiring HCV infection through intravenous drug abuse and tattooing among
youth. HCV infection in HP is common among young school and college-going male students,
and there is a need to combat the menace of intravenous drug abuse to ensure that
HCV infection can be controlled.
Authors' Contributions
Brij Sharma, Vishal Bodh, Rajesh Sharma, Ashish Chauhan, and Vineeta Sharma conceptualized
the study and designed the protocol. Amit Sachdeva, Rajesh Kumar, Vishal Bodh, Tahir
Majeed, Mir Bilal, and Dikshant Sharma collected and analyzed the data. Vishal Bodh,
Rajesh Kumar, and Brij Sharma prepared initial draft of the manuscript. Vishal Bodh,
Rajesh Sharma, and Tahir Majeed critically revised the manuscript. Brij Sharma and
Vineeta Sharma provided administrative, technical, and material support. Brij Sharma,
Vishal Bodh, Rajesh Sharma, and Vineeta Sharma supervised the study.
