|Year : 2018 | Volume
| Issue : 3 | Page : 376-380
Hepatitis C virus and its genotypes in chronic liver disease patients from Meghalaya, Northeast India
Bhupen Barman1, Kaustubh Bora2, Kryshanlang G Lynrah1, W Valarie Lyngdoh3, Mohammad Jamil1
1 Department of General Medicine, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Shillong, Meghalaya, India
2 ICMR-Regional Medical Research Centre, N. E. Region, Dibrugarh, Assam; Department of Biochemistry, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Shillong, Meghalaya, India
3 Department of Microbiology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Shillong, Meghalaya, India
|Date of Web Publication||14-Nov-2018|
Dr. Kaustubh Bora
ICMR-Regional Medical Research Centre, N.E. Region, Dibrugarh - 786 001, Assam
Source of Support: None, Conflict of Interest: None
Background and Objectives: Hepatitis C virus (HCV) is an important cause of chronic liver disease (CLD). Although Northeast India is believed to be a HCV hotspot, the proportion of HCV infection and the distribution of HCV genotypes in CLD cases from the region are not known. The objectives of the study were to determine the proportion of HCV infection in newly diagnosed CLD patients from Meghalaya, Northeast India, and further investigate the HCV genotype distribution in those patients. Materials and Methods: The aetiology of CLD was evaluated in 196 newly diagnosed patients, recruited consecutively over a period of 1 year in a medical college hospital from Meghalaya. Those positive for HCV infection were genotyped, and the mode of transmission of the virus was investigated. Results: A considerable proportion (43 patients, 21.9%) of CLD patients were positive for HCV (95% confidence interval [CI]: 16.7%–28.2%). Other leading causes of CLD were alcohol (36.32%) and hepatitis B virus infection (39.3%). Genotype 3 was the most prevalent (48.7%, 95% CI: 33.9%–63.8%), followed by genotype 6 (30.8%, 95% CI: 18.6%–46.6%) and genotype 1 (20.5%, 95% CI: 10.8%–35.5%). The frequency of genotype 6 was remarkably higher than in the other regions of India. Injecting drug use appeared to be the most common mode (28 patients) of acquiring HCV. This was true irrespective of the genotype. Conclusions: The presence of HCV in newly diagnosed CLD cases from Meghalaya was considerable. The genotype distribution of HCV was distinct from the other regions of India.
Keywords: Chronic hepatitis, genotype, hepatitis C, India, liver disease
|How to cite this article:|
Barman B, Bora K, Lynrah KG, Lyngdoh W V, Jamil M. Hepatitis C virus and its genotypes in chronic liver disease patients from Meghalaya, Northeast India. Indian J Med Microbiol 2018;36:376-80
|How to cite this URL:|
Barman B, Bora K, Lynrah KG, Lyngdoh W V, Jamil M. Hepatitis C virus and its genotypes in chronic liver disease patients from Meghalaya, Northeast India. Indian J Med Microbiol [serial online] 2018 [cited 2019 Dec 11];36:376-80. Available from: http://www.ijmm.org/text.asp?2018/36/3/376/245376
| ~ Introduction|| |
Chronic liver disease (CLD) is a major cause of morbidity and mortality worldwide. Infection by hepatitis C virus (HCV) stands out as a major cause of CLD (estimated global HCV prevalence 2%–3%, i.e., 130–170 million people)., Annually, around 700,000 people die of HCV-related liver disease. Belonging to the family Flaviviridae, HCV is a hepatotropic ribonucleic acid (RNA) virus that is notorious for its propensity for chronicity. Only in ~25% of the patients infected with HCV, the infection is self-limiting with spontaneous clearance and undetectable HCV RNA levels in blood. In the majority of the cases (~75%), the virus persists and establishes chronic infection, which causes progressive liver damage that may eventually lead to a spectrum of pathologies, namely chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.,,
India, which contributes significantly to the global HCV burden, is believed to harbour 12–18 million HCV-infected people. The estimated prevalence of HCV in India is 0.5%–1.5% (though variations may be seen across geographical regions)., The prevalence of HCV is believed to be high in states of Northeast India,, which may represent HCV hotspots.
Meghalaya in Northeast India is predominantly inhabited by hill tribes belonging to the Austro-Asiatic and Tibetan-Burmese stock. Studies on HCV in CLD patients from Meghalaya are unavailable. There is also a paucity of data on HCV seroprevalence and genotype distribution from Meghalaya in general. Few reports on HCV seroprevalence in specific groups such as sex workers, individuals with history of injecting drug use (IDU), blood donors and isolated tribal communities from the adjoining northeastern states of Assam, Arunachal Pradesh, Nagaland, Mizoram and Manipur are present, which point toward a substantial HCV burden.,,, Limited studies also indicate marked genotypic heterogeneity of HCV in the northeastern region, which is in stark contrast to the other parts of India.,,
With this background, we investigated the proportion of HCV infection in newly diagnosed CLD patients from Meghalaya. In addition, we determined the HCV genotypes and examined their relevance with respect to the clinicolaboratory presentation.
| ~ Materials and Methods|| |
The study was approved by the Institutional Ethics Committee, vide letter no. NEIGR/IEC/2013/101. Informed written consent was procured from all the participants.
Study design and participants
We carried out a prospective study of 1-year duration from July 2015 to June 2016 in a medical college hospital from Meghalaya. Newly diagnosed CLD patients during that period were recruited consecutively. The diagnosis of CLD was on the basis of history, clinical examination and ultrasound and biochemical findings. History about amount and duration of alcohol abuse, if any, was taken. All the patients were screened for seropositivity of hepatitis B virus (HBV), HCV and human immunodeficiency virus (HIV). Those seropositive for HCV were further subjected to HCV RNA level estimation and HCV genotyping. They were also interviewed about history of transfusion of blood/blood products, procedures such as dental extraction, surgeries and dialysis and high-risk behaviours such as IDU, sexual promiscuity, sharing of blades/razors and tattooing to elucidate the mode of HCV transmission. Body mass index (BMI) was assessed as per the World Health Organization protocol.
Commercially available diagnostic kits were used to test for HCV (Erba Lisa HCV Gen3 v2, Transasia Bio-Medicals Ltd., Daman, India), HBV (Erba Lisa SEN HBsAg, Transasia Bio-Medicals Ltd., Daman, India) and HIV (Comb AIDS RS Advantage HIV 1 + 2 Immunodot test kit, Span Diagnostics Ltd., Surat, India; HIV-1/2 Trispot Test Kit® AIDSCAN, Bhat Bio-Tech India Pvt. Ltd., Bangalore, India and SD BIOLINE HIV-1/2 3.0, Standard Diagnostics, Inc., Gyeonggi-do, South Korea). Besides, the HCV RNA load estimation (COBAS® AmpliPrep/COBAS® TaqMan 48 HCV test) and HCV genotyping (nested reverse transcriptase polymerase chain reaction) were carried out at SRL Diagnostics, Super Religare Laboratories Ltd., Mumbai, India. Biochemical estimations included serum alanine transaminase (ALT), aspartate transaminase (AST) and total bilirubin assays using photometric kits in AU 2700 plus clinical chemistry autoanalyser (Beckman Coulter, USA). Haemoglobin (Hb) percentage, white blood cell (WBC) count and platelet count were determined in LH 750 haematology analyser (Beckman Coulter, USA). Prothrombin time with international normalised ratio (PT-INR) was determined using STA Compact Max® analyser (Diagnostica Stago Inc., New Jersey, USA).
The statistical analyses were performed in SPSS 17.0 (Chicago, IL, USA). The categorical variables were tabulated as counts and percentages, along with 95% confidence intervals (CIs), whenever appropriate. The Kolmogorov–Smirnov test revealed non-Gaussian distribution of the continuous variables, and hence, they were expressed as median (maximum–minimum value). Comparison of continuous data across the HCV genotypes was performed by the non-parametric Kruskal–Wallis test by ranks, while categorical data were compared by Chi-square test (with Yates's correction). A two-sided P < 0.05 was set as the level of statistical significance in all the analyses.
| ~ Results|| |
A total of 196 patients were newly diagnosed with CLD during the 1-year study period. Gender preponderance (165 males, 31 females) was seen. The age ranged from 17 to 78 years (median = 40 years). From an aetiological perspective, CLD was attributed to HCV infection cases in 43 patients (21.9%, 95% CI: 16.7–28.2) [Table 1]. Two patients with HCV were concurrently seropositive for HIV. HBV infection (77 patients [39.3%, 95% CI: 32.7–46.3]) and alcohol (71 patients [36.2%, 95% CI: 29.8–43.2]) were the other leading causes of CLD in our sample. For five patients, the CLD aetiology was classified as cryptogenic.
|Table 1: Aetiology of chronic liver disease in the current study (n=196)|
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Of the 43 HCV-infected cases, four patients did not undergo HCV genotyping. Genotyping in the remaining 39 cases revealed that majority of them were infected by genotype 3 (48.7%, 95% CI: 33.9–63.8), followed by genotype 6 (30.8%, 95% CI: 18.6–46.6) and genotype 1 (20.5%, 95% CI: 10.8–35.5) [Table 2]. Genotypes 2, 4 and 5 were not detected in our study.
Amongst the different risk factors, IDU was found to be the chief mode of HCV transmission in our patients (28/43) [Table 3]. This was true irrespective of the detected HCV genotypes. History of transfusion of blood/blood-related products and tattooing was present in four and three patients, respectively, while only one patient (infected with genotype 1) had history of sexual promiscuity. Another patient (infected with genotype 1) had both IDU and tattoo exposure, whereas a patient (infected with genotype 6) had history consistent with blood-borne as well as sexual transmission. In eight patients (out of 43), the mode of transmission could not be ascertained.
|Table 3: Modes of transmission and distribution of hepatitis C virus genotypes|
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The age and gender composition of the patients did not differ significantly (P > 0.05) according to the genotypes [Table 4]. BMI values were also comparable amongst patients infected by the three genotypes. Relationship of the genotypes with laboratory parameters was studied too. However, none of the liver function tests (namely total bilirubin, AST, ALT and PT-INR) differed significantly (P > 0.05) across the three genotypes. Significant differences in Hb concentration and blood cell counts (WBC and platelets) were absent (P > 0.05) as well. Patients infected by genotype 1 appeared to have a higher viral load than those infected with genotype 6, to be followed by the ones infected with genotype 3. However, these differences did not assume statistical significance (P > 0.05).
|Table 4: Clinical and laboratory parameters across the detected hepatitis C virus genotypes|
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| ~ Discussion|| |
Our study provides an insight into the aetiology of CLD in patients from Meghalaya. More specifically, we provide insights into the burden of HCV and the distribution of its genotypes in newly diagnosed CLD patients from the region. Although most of the cases of CLD in our study were alcohol and HBV infection related, the proportion of HCV infection was considerable (~22%). It was substantially higher than that reported from nearby Dibrugarh in Northeast India (~11%) and Kolkata in East India (~15%). The HCV seroprevalence in our CLD patients was also higher than that in North India (~14%). In reports from South India, an even higher seroprevalence of HCV (33%–43%) in CLD patients had been documented.,
Most of the HCV-infected patients in our study belonged to genotype 3 (~49%). This is in contrast to global data, according to which genotype 1 is the major variety worldwide. However, other studies from India have documented genotype 3 as the predominant HCV genotype that accounts for ~64% of the cases, followed by genotype 1 that constitutes ~26% of the cases., A very recent report by Patil et al. also found genotype 3 (68%) to be the most common and genotype 1 (32%) to be the next common genotype in HCV-infected cases from rural Maharashtra. The other HCV genotypes were not detected in their study. However, surprisingly, in our study, genotype 6 was found to be the second common genotype (~31%), to be followed by genotype 1 (~20%). Although the cases of genotype 6 in India are mostly described from the northeastern states,, such high preponderance as in our study has been to the best of our knowledge hitherto unreported. In fact, a recent study by Medhi et al. in a predominantly tribal population from Northeast India (Assam and Manipur) found genotype 4 to be the most common HCV genotype (~31%). Genotypes 3 (~20%) and 1 (~15%) also outranked genotype 6 in that study, with the latter detected in ~ 14% of the cases. In contrast, no case of genotype 4 was detected in our study. Information about distribution of HCV genotype is of epidemiological value. It has important implications in relation to diversity of the circulating genotypes, sources, modes of transmission and monitoring changes in their pattern of distribution over a period of time.,, There is a scarcity of literature on HCV genotype 6 as compared to the other genotypes. The high frequency of genotype 6 in our participants may be due to the geographical proximity and ethnic relatedness of Northeast India with the Southeast Asian nations. It is increasingly believed that this genotype has circulated, adapted and evolved in Southeast Asia for a long time. Pybus et al. estimated that all genotype 6 infections had descended from a common ancestor around 1100–1350 years ago and that its distribution in Southeast Asia is characterised by substantial phylogeographic structure and two distinct phases of epidemic history before and during the 20th century.
The risk factors of HCV transmission include blood and blood product transfusion, unsafe sexual practices, IDU and unsafe injection practices, tattooing and acupuncture. In our study, IDU was found to be the most common mode of HCV transmission. Intravenous and percutaneous drug abuse is a significant problem in the northeastern states. This is often attributed to the proximity of the region to the infamous 'Golden Triangle' (Myanmar, Laos and Thailand), world's major hub of illicit drug production and trafficking. Further, IDUs from Northeast India are at a high risk of contracting HCV infection due to unsafe injecting practices. The genotype distribution did not appear to be influenced by the mode of transmission of the virus too. IDU was the major mode of transmission for all the detected genotypes. This is in contrast to the report by Medhi et al. where IDU was found to be the most common mode of transmission for genotype 4a, whereas exposure to multiple sexual partners and professional barbers were the major modes of transmission for genotypes 1a and 1c, respectively. From a therapeutic perspective, however, the current treatment for HCV infection is pan-genotypic. Therefore, the need to determine HCV genotype except in difficult to treat patients is becoming obsolete.
| ~ Conclusions|| |
This study contributes toward understanding the burden of HCV in newly diagnosed CLD patients. It also describes for the first time the diversity of HCV genotypes associated with CLD cases from Meghalaya. Genotype 3 was the most common HCV variant. Genotype 6 which was the next frequent HCV variant also had a substantial presence in our patients. History of IDU exposure appeared to be the chief mode for HCV transmission.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]