Differential prevalence and geographic distribution of hepatitis C virus genotypes in acute and chronic hepatitis C patients in Vietnam

Abstract

BackgroundThe highest burden of disease from hepatitis C virus (HCV) is found in Southeast Asia, but our understanding of the epidemiology of infection in many heavily burdened countries is still limited. In particular, there is relatively little data on acute HCV infection, the outcome of which can be influenced by both viral and host genetics which differ within the region. We studied HCV genotype and IL28B gene polymorphism in a cohort of acute HCV-infected patients in Southern Vietnam alongside two other cohorts of chronic HCV-infected patients to better understand the epidemiology of HCV infection locally and inform the development of programs for therapy with the increasing availability of directly acting antiviral therapy (DAAs).MethodsWe analysed plasma samples from patients with acute and chronic HCV infection, including chronic HCV mono-infection and chronic Human Immunodeficiency Virus (HIV)-HCV coinfection, who enrolled in four epidemiological or clinical research studies. HCV infection was confirmed with RNA testing. The 5’ UTR, core and NSB5 regions of HCV RNA positive samples were sequenced, and the genotype and subtype of the viral strains were determined. Host DNA from all HCV positive patients and age- and sex-matched non-HCV-infected control individuals were analysed for IL28B single nucleotide polymorphism (SNP) (rs12979860 and rs8099917). Geolocation of the patients were mapped using QGIS.Results355 HCV antibody positive patients were analysed; 54.6% (194/355) and 46.4% (161/355) were acute and chronic infections, respectively. 50.4% (81/161) and 49.6.4% (80/161) of chronic infections had HCV mono-infection and HIV-HCV coinfection, respectively. 88.7% (315/355) and 10.1% (36/355) of the patients were from southern and central regions of Vietnam, respectively. 92.4% (328/355) of patients were HCV RNA positive, including 86.1% (167/194) acute and 100% (161/161) chronic infections. Genotype could be determined in 98.4% (322/328) patients. Genotypes 1 (56.5%; 182/322) and 6 (33.9%; 109/322) predominated. Genotype 1 including genotype 1a was significantly higher in HIV-HCV coinfected patients compared to acute HCV patients [43.8% (35/80) versus 20.5% (33/167)], (p = <0.001), while genotype 6 was significantly higher in chronic HCV mono-infected patients [(44.4% (36/81) versus 20.0% (16/80)] (p = < 0.004) compared to HIV-HCV coinfected patients. The prevalence of IL28B SNP (rs12979860) homozygous CC was 86.46% (83/96) in control individuals and was significantly higher in acutely-infected compared to chronically-infected patients [93.2 (82/88) versus 76.1% (35/46)] (p = < 0.005).ConclusionHCV genotype 6 is highly prevalent in Vietnam and the high prevalence in treatment naïve chronic HCV patients may results from poor spontaneous clearance of acute HCV infection with genotype 6.

Baseline Characteristics and Treatment Cost of Hepatitis C at Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam in Direct-Acting Antiviral Treatment Era

“…Chronic HCV infections are often asymptomatic; it is possible that routine health care or screening for other illness identified these infections. Earlier studies reported a higher prevalence of HCV infection in men, which is contrary to our real-world data [6] . It is possible that female patients are less interested in joining research studies due to fear, stigma, or time limitations to fulfill the study requirement, including follow up visits.…”

“…Genotype 3 patients had significantly higher liver enzymes, a potential marker for liver damage and high BMI, a predictor for poor treatment response. The prevalence of genotype 3 is relatively high in central region and our data is in agreement with earlier studies demonstrating a higher prevalence of genotype 3 in central highland sub-region [6] .…”

“…Genotype 6 contains the highest prevalence of preexisting drug resistance mutations [18] Genotype 6 patients are generally underrepresented in previous clinical trials evaluating the efficacy of DAA regimens [19,20] . Earlier studies from southern Vietnam have shown that the prevalence of genotype 6 is higher in chronic HCV patients compared to acute patients [6] . The high prevalence of genotype 6 among chronic HCV patients in our study may be for several reasons including low spontaneous clearance of acute HCV infection with genotype 6 compared to other genotype or poor response to non-DAA therapy (e.g., PegINF±RBV).…”

“…Genotype 1 has two subtypes; 1a and 1b. Subtype 1a is the most common genotype among injection drug users (IDUs), and HIV-HCV coinfected patients and subtype 1b is common among the general population in Vietnam [6,22] . Subtype 1b is the predominant subtype in Vietnam's neighboring countries, accounting for 66% of HCV infection in China, 64.4% in Japan, and 66% in South Korea [23][24][25] and is also a major subtype in Europe [23] .…”

“…WHO Western Pacific region, including Vietnam, bears the highest burden of HCV, with an estimated 19.2 million infections [5] . Vietnam is amongst the 20 countries with the highest HCV burden, with an estimated 1.5 million chronic HCV infected people (estimated HCV RNA prevalence 1.1%) (https://www.who.int/westernpacific/healthtopics/hepatitis/regional-hepatitis-data) [6] .…”