Rashiti-Bytyçi A, Ramadani N, Kalaveshi A, Muçaj S, Gashi L, Rashiti P. Hepatitis C in several risk groups: literature review (Review article). SEEJPH 2021, posted: 31 May 2021. DOI: 10.11576/see- jph-4487 P a g e 1 | 19 REVIEW ARTICLE Hepatitis C in several risk groups: Literature review Albiona Rashiti-Bytyçi1, Naser Ramadani1,2, Ariana Kalaveshi1,2, Sefedin Muçaj1,2, Luljeta Gashi1, Premtim Rashiti2 1 National Institute of Public Health in Kosovo, Prishtina, Kosovo; 2 University of Prishtina “Hasan Prishtina”, Prishtina, Kosovo. Corresponding author: Prof. Dr. Naser Ramadani, MD, PhD, MPHE, CMIS, CIEH; Address: Rr. Nëna Tereze p.n., Rrethi i Spitalit, 10.000, Prishtina, Kosovo; Telephone: +38338551431; Email: naser.ramadani@uni-pr.edu Rashiti-Bytyçi A, Ramadani N, Kalaveshi A, Muçaj S, Gashi L, Rashiti P. Hepatitis C in several risk groups: literature review (Review article). SEEJPH 2021, posted: 31 May 2021. DOI: 10.11576/see- jph-4487 P a g e 2 | 19 Abstract Aim: The objective of this study was to assess the distribution of hepatitis C in selected risk groups such as haemodialysis patients, pregnant women, healthcare workers, HIV-HCV co-in- fected patients, patients with mental health diseases and piercing and tattoo procedures. Further- more, it aimed at evidencing common transmitting routes and highlighting the importance of pre- ventive measures among these groups. Methods: The literature review was conducted using online databases (Medline) with search query involving the keyword “hepatitis C” in conjunction with keywords describing risk groups such as "dialysis", or "haemodialysis", or "pregnancy", or "pregnant", or "mental health", or "tat- too", or "piercing", or "HIV", or "health professionals”. Results: After assessing all the retrieved publications, 39 of them were considered for inclusion: 17 on haemodialysis patients, 7 on pregnant women, 8 on HIV-HCV co-infection and 7 publica- tions on health professionals, patients of mental health wards and piercing and tattoo procedures. The high rate of hepatitis C is still a high problem and in some cases it is considered as a new is- sue, as in the case of pregnancy. Some of the transmission routes have been identified earlier, such as the HIV-HCV co-infection but some, such as piercing and tattoo, are becoming new transmission routes. Health professionals are still identified as high risk group while mental health patients are a potentially high risk group. Conclusion: Even though some patients are routinely screened for hepatitis C, there are indica- tions for performing such a routine test in other groups. In almost all of the risk groups, it is ad- vocated to use stricter preventive measures and to disseminate knowledge on risks of hepatitis C. Keywords: haemodialysis, healthcare workers, hepatitis C, human immunodeficiency virus, mental health diseases, piercing and tattoo, pregnancy. Conflict of interest: None declared. Rashiti-Bytyçi A, Ramadani N, Kalaveshi A, Muçaj S, Gashi L, Rashiti P. Hepatitis C in several risk groups: literature review (Review article). SEEJPH 2021, posted: 31 May 2021. DOI: 10.11576/see- jph-4487 P a g e 3 | 19 Introduction Hepatitis C, as a liver infection, is caused by the Hepatitis C Virus (HCV), blood borne vi- rus. The virus can cause both acute and chronic hepatitis, ranging in severity from a mild illness lasting a few weeks to a serious, lifelong illness. Approximately 60%-80% of infected people may progress to chronic liver disease and 20% of them will develop cirrho- sis (1). According to WHO, globally, an esti- mated 71 million people have chronic hepati- tis C infection (2). An estimated 3.5 million people in the United States have chronic hep- atitis C (3). Globally, morbidity and mortality from hep- atitis C virus infection (HCV) is increasing. According to estimation from recent studies, more than 185 million people around the world are infected with hepatitis C virus (1). Total global prevalence of HCV is 2.5%, var- ying from 2.9% in Africa to 1.3% in America, with global viremic rate 67% (118.9 million HCVRNA positive cases), varying from 64.4% in Asia to 74.8% in Australasia (4). In Europe, the prevalence of hepatitis C (HCV) is estimated to be around 1.7% and in- cludes 13 million cases, the lowest preva- lence (0.9%) is reported in Western Europe (except some rural regions in South of Italy and Greece) and the highest prevalence in central Europe (3.1%) specifically in Roma- nia and Russia (5). According to estimation from Global Burden of Disease study, deaths rate from hepatitis C was 333000 in 1990, 499000 in 2010 and 704000 in 2013 (6). These cases of deaths are result of complica- tions from HCV, including liver cirrhosis, hepatocellular carcinoma and liver failure (7). The following groups are at increased risk for HCV infection:  Current or former injection drug us- ers;  Chronic haemodialysis patients;  People with known exposures to HCV, such as (health care workers af- ter needle sticks involving HCV-pos- itive blood, recipients of blood or or- gans from a donor who tested HCV- positive);  People with HIV infection;  Children born to HCV-positive moth- ers;  Patients of mental health wards And also were at risk:  Recipients of clotting factor concen- trates made before 1987, when less advanced methods for manufacturing those products were used;  Recipients of blood transfusions or solid organ transplants prior 1992, be- fore better testing of blood donors be- came available (8); Conversely, the transmission routes and epi- demiology include:  Intravenous drug use;  Non-intravenous recreational drug exposure;  Healthcare procedures;  Accidental exposure;  Mother to child vertical transmission;  Sexual exposure etc. (8). Methods Search and study identification The aim of the study was to identify, through literature review, studies addressing the fol- lowing: - cases of Hepatitis C, - most common transmitting route, - the importance of preventive measures, among several risk groups such as: haemodi- alysis patients, pregnant women, healthcare Rashiti-Bytyçi A, Ramadani N, Kalaveshi A, Muçaj S, Gashi L, Rashiti P. Hepatitis C in several risk groups: literature review (Review article). SEEJPH 2021, posted: 31 May 2021. DOI: 10.11576/see- jph-4487 P a g e 4 | 19 workers, HIV-HCV co-infected patients, pa- tients with mental health diseases and practi- tioners of piercing and tattoo. Articles published were identified by litera- ture survey in online database Medline through PubMed interface, using keywords: "hepatitis C" AND ("dialysis" OR "haemodialysis" OR "preg- nancy" OR "pregnant" OR "mental health" OR "psychiatry" OR "tattoo" OR "piercing" OR "HIV" OR "health professionals" OR "health workers"). From the search query, 1788 publications were identified and from these only original publications were included. The following data were excluded from our analysis: data with unclear definition of HCV infection, du- plicated data, all short communications or re- views. Next, the remaining 688 publications were selected and after removing publica- tions without abstract, there were left 617 of them. After reading abstracts of 617 publica- tions we selected 150 publications that ful- filled our research interests. All 150 publica- tions were studied and publications that dealt with detailed treatments, or included other groups of interests were excluded. Finally, we selected 39 publications for analysing and presenting their results, as presented in Fig- ure 1. Figure 1. Search and study identification Rashiti-Bytyçi A, Ramadani N, Kalaveshi A, Muçaj S, Gashi L, Rashiti P. Hepatitis C in several risk groups: literature review (Review article). SEEJPH 2021, posted: 31 May 2021. DOI: 10.11576/see- jph-4487 P a g e 5 | 19 Overview of the results After a full text screening, as presented in Figure 2, a total of 39 articles were consid- ered for inclusion: 17 on haemodialysis pa- tients, 7 on pregnant women, 8 on HIV-HCV coinfection and in total 7 publications on health professionals, patients of mental health wards and piercing and tattoo proce- dures. In following sections, each group will be discussed and in the end of each section, a short conclusion will be presented. Figure 2. Publications with HCV data by risk groups Results on Haemodialysis / HCV From 17 publications on HCV and haemodi- alysis, 10 of the publications included on their results prevalence of HCV on Haemodi- alysis centres, while 7 other publications in- cluded on their result other findings or asso- ciation of HCV with other factors. For HCV, prevalence estimates that were considered representative for haemodialysis centres were available for 10 countries as presented in Table 1. A prospective study conducted in Japan in 2016 (9) included 41 haemodialysis centres, with total of 2986 haemodialysis pa- tients. The aim of the study was to screen for HCV antibody, and HCV RNA, but as well to determine genotype of hepatitis C and the treatment of HCV patients. In its findings, au- thors have reported that 5.02% of patients were HCV Ab positive and from this number 72.31% were HCV RNA positive. Another interesting conclusion of the study, was that 62.1% of tested patients were HCV genotype 1 and that the combined therapy of Daclatas- vir and Asunaprevir was effective at HCV positive patients in haemodialysis. Another study performed in Japan, but this time a ret- rospective one (10), included 3064 patients on haemodialysis. The aim of the study was to find the association of hepatitis C virus in- fection with the prognosis of chronic haemo- dialysis patients. The results of the study sug- gested that of those patients, 14.0% were HCV RNA positive, while 2.4% were HBsAg positive and 0.3% were double posi- tive. Also in the study, it was reported that by 2010, 49% of haemodialysis patients were deceased. From that percentage, 60% of them were HCV RNA positive, and 47% HCV RNA negative. A prospective study was con- 17 7 8 3 2 2 0 2 4 6 8 10 12 14 16 18 Rashiti-Bytyçi A, Ramadani N, Kalaveshi A, Muçaj S, Gashi L, Rashiti P. Hepatitis C in several risk groups: literature review (Review article). SEEJPH 2021, posted: 31 May 2021. DOI: 10.11576/see- jph-4487 P a g e 6 | 19 ducted in Brazil (11) that included 798 hae- modialysis patients, with the aim of determi- nation of prevalence of HCV infection and genotypes in patients undergoing haemodial- ysis. The study found that performing ELISA test, 8.4% of the patients resulted HCV posi- tive, while 86.1% of them had determined vi- ral genotype 1 and 11.6% determined geno- type 2 and 2.3% determined genotype 3. One of the suggestions of the authors was to strengthen the control strategies for hepatitis C in haemodialysis centres. A cross-sectional study conducted in China in 2013 (12), in- cluded 2120 patients on haemodialysis and 409 patient partners. This study investigated the prevalence and risk factors of HCV and HBV infection and the distribution of HCV genotypes among haemodialysis patients and their spouses. Authors findings were that 6.1% of the patients were anti-HCV positive, 4.6% of them were HCV RNA and 7.0% of them resulted in HBsAg positive. Regarding the prevalence of their partners, it resulted that 0.5% of them were anti-HCV positive, while 0.2% RNA HCV positive and 4.2% HBsAg positive. Some of the risk factors that authors have mentioned were: the duration of dialysis and blood transfusion. The predomi- nant genotype was 1b with 89% while 2a had 7.7% and genotype 3a, 3b, 6a each by1.1%. Authors’ suggestion, due to the persistence of nosocomial infection, were strict infection control measures to be strengthened with the aim of reducing the transmission of HCV. Another prospective study, that involved 170 patients on haemodialysis, was performed in US (13), with the aim to overview the inci- dence and preventive measures for HCV in the haemodialysis centre. The study resulted in finding 5.4% new HCV cases, from which 4 cases were genotype 1a, 2 cases of geno- type 1b. The other 37.6% of old cases, 29 cases were genotype 1a, 16 cases were geno- type 1b, and 2 cases were genotype 3a. Cross sectional survey in Sudan included 353 patients of haemodialysis, aiming to deter- mine the seroprevalence and risk factors for hepatitis C and hepatitis B in their dialysis centres (14). Their finding resulted in 16 cases that were HBsAg positive and 30 cases that were anti-HCV positive. The long dura- tion of dialysis and surgical intervention, were most common risk factors, related to in- fection. In the Middle East, authors (15) con- ducted a prospective investigation, to find the impact of an identical isolation policy on in- cidence of nosocomial HCV infection in hae- modialysis centre. Study was conducted in two phases, phase one involving 189 patients and phase two involving 198 patients af- fected of haemodialysis. Their study resulted in finding 83 (43.9%) phase one patients with anti HCV positive, while the remaining 106 (56.1%) patients resulted as anti HCV nega- tive. An interesting fact is the correlation be- tween HCV positivity and the dialytic age (of 83 patients who had positive results for anti- HCV antibodies had a mean dialytic age of 48.5 ± 14.2 months, compared with 25.0 ± 8.6 months among the 106 anti-HCV-nega- tive patients). In phase II, they had similar re- sults, 85 (42.9%) of 198 patients had anti- HCV positive results, and 113 (57.1%) con- tinued to have a negative status for anti-HCV antibodies. Interesting relation between phase one and two is the addition of two new anti-HCV positive cases (none of them be- longing to the added 9 after phase one), that occurred over 12 months of study period, leading to an HCV seroconversion rate of 1.01% per year (15). Netherlands conducted a nationwide prospective study on the preva- lence and incidence of Hepatitis C virus in- fections among dialysis patients in 1996 (16). In 34 haemodialysis centres, a total of 2281 patients were included, dividing the research into two phases: the first phase with 2281 pa- tients – where the HCV RNA positive rate was 2.9%, and the second phase after one Rashiti-Bytyçi A, Ramadani N, Kalaveshi A, Muçaj S, Gashi L, Rashiti P. Hepatitis C in several risk groups: literature review (Review article). SEEJPH 2021, posted: 31 May 2021. DOI: 10.11576/see- jph-4487 P a g e 7 | 19 year with the sample of 2286 patients, where 3.4% of the cases were HCV RNA positive. Main risk factors were also identified by the study, and those being: haemodialysis before 1992, kidney transplantation before 1994, birth in other countries, and receiving dialysis abroad during vacations. Another cross sec- tional study was conducted in Canada, aim- ing to study Hepatitis C prevalence and risk factors in dialysis population, with 336 pa- tients included in the study (17). The study resulted in finding that prevalence of anti- HCV antibody was 6.5% (22/336), 77.2% (17/22) of cases that were anti-HCV positive resulted HCV RNA positive. Another pro- spective study was conducted with 128 pa- tients in USA, with findings of 25% of them positive HCV EIA (18), but tests were not specific because in 6 cases it was detected and resulted negative, which speaks about past infection. It is known that PCR remains the only reliable test to determine the pres- ence of the virus. Table 1. Hepatitis C in haemodialysis centres Paper Year Country Study design Study sample Laboratory tests HCV Ab Positive HCV RNA positive (9) 2016 Japan Prospective 2986 HCV anti- body, HCV RNA 5.02% From total of HCV Ab posi- tive cases, 72.31% were HCV RNA positive (10) 2010 Japan Retrospective 3064 HCV RNA / 14.00% (11) 2013 Brazil Prospective 798 HCV anti- body 8.40% / (12) 2013 China Cross-sec- tional 2120 HCV anti- body, HCV RNA 6.10% From total of HCV Ab posi- tive cases 4.6% were HCV RNA positive; (13) 2009 USA Prospective 170 HCV RNA / 5.4% new HCV cases and 37.6% older HCV cases (14) 2010 Sudan Cross- sec- tional 353 HCV anti- body 8.50% / (15) 2003 Arabia Retrospective and prospec- tive 189 HCV anti- body Phase I, 43.9% Phase II, 42.9% / (16) 1996 Netherlands Prospective 2281 (phase I) 2286 (phase II) HCV RNA / First phase 2.9%; Second phase 3.4% (17) 1997 Canada Cross- sec- tional 336 HCV anti- body, HCV RNA 6.5% HCV From total of HCV Ab posi- tive cases 77.2% were Rashiti-Bytyçi A, Ramadani N, Kalaveshi A, Muçaj S, Gashi L, Rashiti P. Hepatitis C in several risk groups: literature review (Review article). SEEJPH 2021, posted: 31 May 2021. DOI: 10.11576/see- jph-4487 P a g e 8 | 19 HCV RNA positive (18) 1998 USA Prospective 128 HCV anti- body 25% / In relation to haemodialysis patients, some other studies were conducted to find the con- nection between haemodialysis patients and HCV and other risk factors. Since that con- nection is believed to be of importance, find- ings of those studies are briefly presented in the following paragraphs. One of the studies investigated bleeding epidemic that has erupted on September-October 2013, in hae- modialysis unit in Vietnam, involving 119 patients with 9 positive HCV cases and 9 pos- itive HBV cases. Authors found that HCV prevalence in the epidemic was 6%, which is 7.5 times higher than in the vast population of Vietnam (19). Another retrospective study conducted in USA found correlation between HCV and hepatocellular carcinoma (HCC), when checking 32860 HCV cases, that re- sulted in 262 cases with HCC (20). HCC was 12 times more common in cases of cirrhosis, 3 times more frequent in cases of alcohol con- sumption and 1.3 times higher in cases of di- abetes, with the likelihood of HCC increasing with age. Another correlation, this time lin- ear, between incidence and prevalence, was found in a study in France, concluding that doubling the value of P(C) doubles the inci- dence of cases with hepatitis C (21). A pro- spective study conducted in Spain, found ini- tial prevalence (p <0.0001) and time (p <0.0001) emerging as independent variables associated with the decrease of HCV preva- lence (22). Authors of another study, con- ducted in France, found that HCV serocon- version was associated with the number of hemodialysis sessions undergone on a ma- chine shared with or in the same room as a patient who was anti-HCV (genotype 2a/2c) positive (23). A cross sectional study in USA found by using multivariate logistic regres- sion analysis, that the longer duration of re- ceiving dialysis associated with a history of intravenous drug use, were the only risk fac- tors that remained independently associated with HCV seropositivity (24). Authors of a study in France found that overall, HCV RNA became undetectable in 16 patients (69.6%) 1 month after starting IFN-a therapy and in 21 patients (91.3%) at the end of treat- ment (25). Results on Pregnancy /HCV Conducting the literature review, 7 studies that presented a relation between HCV infec- tion and pregnancy were included, as shown in Table 2. A research conducted in Pakistan (26), enrolled 119 cases of pregnant women with HCV positive, and 238 control cases, from the total of 5621 pregnant women, of whom 5339 were screened. Their result showed that iatrogenic exposure (health care injections, hospitalizations and pregnancies) are the major risk factors for transmission of HCV among pregnant women. Therefore, the authors call for strengthening the prevention aspect of the hepatitis control program to fo- cus on behaviour change for reducing injec- tion reuse and overuse. A study in the USA, which included 1013 obstetric patients iden- tified that use of intravenous drugs resulted as the fastest risk factor (27) in HCV. Authors emphasize that the epidemiologic data are consistent with sexual and parenteral modes of transmission, however, according to them routine screening for hepatitis C is not advo- cated. Another study in the USA, with 599 pregnant hospitalised women, identified Rashiti-Bytyçi A, Ramadani N, Kalaveshi A, Muçaj S, Gashi L, Rashiti P. Hepatitis C in several risk groups: literature review (Review article). SEEJPH 2021, posted: 31 May 2021. DOI: 10.11576/see- jph-4487 P a g e 9 | 19 4.3% were HCV positive, from which 3 pos- itive HIV cases, and 2 of them had coinfec- tion with hepatitis C. Another correlation be- tween hepatitis B and hepatitis C, resulted in 1 coinfection from 5 cases with hepatitis B (28). Another study in Italy, reported that HCV transmission was higher in mothers with fluctuating ALT levels (31/154; 20.1%) when compared with mothers with normal ALT levels (35/292; 12%). The HCV trans- mission was the highest in the group of moth- ers with constantly raised ALT levels (8/31; 25.8%) (29). Vertical transmission of HCV was investigated in three studies. The first study (30), had as a subject 2447 HCV preg- nant women, from whom 78 women (3.2%) were anti-HCV positive, 60 women (2.5% or 77% of all cases of positive anti-HCV) were positive HCV-RNAs. Regarding the new- borns, 60 of them (50%) remained HCV- RNA negative, throughout 22 of them (36.7%) were RNA-HCV positive in one case and 8 of them (13.3%) were RNA-HCV pos- itive at least in the two following tests and only 2 children (3.3%) remained positive RNA-HCV, testing after 8 to 24 months (30). The second vertical transmission study was conducted in Ireland with 36 HCV pregnant women (31). From the study resulted that all 36 cases were positive when tested with Elisa and 26 women (76%) were PCR positive for HCV genotype 1. In terms of vertical trans- mission only one child resulted positive when tested with PCR HCV (31). The third study conducted with 3712 pregnant women, re- sulted in 35 (0.94%) women that were anti- HCV positive and out of this number 20 women (57%) were HCV RNA positive (32). The vertical transmission rate was 5%, where only one new-born of 29 of maternal RNA HCVs positive resulted HCV RNA even after 12 months of birth that speaks for HCV per- sistent infection (32). Table 2. Hepatitis C related to pregnancy Paper Year Country Study de- sign Study sam- ple Laboratory tests Results (26) 2006 Pakistan Case con- trol 5339 Elisa HCV 119 (2%) were HCV positive (27) 1992 USA Prospective 1005 HCV anti- body 2.28% (N = 23) were HCV posi- tive (28) 1994 USA Prospective 599 Elisa HCV 4.3% were HCV positive (29) 2006 Italy Case con- trol 74 HCV RNA trans- mitting mothers and 403 HCVRNA not trans- mitting HCV RNA, ALT HCV transmission was higher in mothers with fluctuating ALT levels (31/154; 20.1%) when compared with mothers with normal ALT levels (35/292; 12%) (30) 1997 Italy Prospective 78 HCV positive Anti-HCV, HCV RNA 8 of 60 (13.3%) infants born to HCV-RNA positive mothers ac- quired HCV infection, but only 2 (3.3%) were still infected by the end of follow-up. (31) 2001 Ireland Retrospec- tive 36 women with HCV Elisa HCV. HCV RNA The 36 cases were positive Elisa and 26 (76%) were PCR positive for HCV genotype 1b. In terms of Rashiti-Bytyçi A, Ramadani N, Kalaveshi A, Muçaj S, Gashi L, Rashiti P. Hepatitis C in several risk groups: literature review (Review article). SEEJPH 2021, posted: 31 May 2021. DOI: 10.11576/see- jph-4487 P a g e 10 | 19 vertical transmission only one child resulted positive PCR HCV. (32) 1996 Germany Prospective 3712 preg- nant women Anti-HCV, HCV RNA Out of 3712 women, 35 (0.94%) were anti-HCV positive and out of this number 20 (57%) were HCV RNA positive. The vertical transmission rate was 5%. Results on HIV / HCV coinfection Regarding the relation between the HCV and HIV, a number of research papers, presented in Table 3, discussed the coinfection, while proving unfortunately that the problem is on the rise. The first study reviewed, was a pro- spective study performed in Ghana, where from 1520 HIV infected cases, HCV RNA test was performed in all HBsAG positive subjects (n=236) and a random subset of HBsAg negative subjects (n=172), which re- sulted in 4 positive cases (3 cases of genotype 2 and 1 case of genotype 1). From these four infected cases surgical procedures and blood transfusion procedure was reported as an im- portant risk factor for HCV infection (33). In 2018, a study in Spain was performed in- cluding 322 patients with Hepatocellular car- cinoma in patients with HIV/HCV coinfec- tion (34). The study aimed finding the rela- tionship between the use of antiviral agents and the risk of HCC in HIV/Hepatitis C co- infected patients. As a result, 42 (13%) of pa- tients occurred after sustained virological re- sponse. It is interesting to mention that after using direct antiviral agents in HIV/HCV co- infected patients, the frequency of hepatocel- lular carcinoma was not increased. A study conducted in Canada between 2005 and 2015, examined the relationship between HIV-seropositivity and having access to a physician for regular HCV care (35). In total, 1627 HCV-positive cases were eligible for analysis; from whom 582 (35.8%) were HIV- positive at baseline and 31 (1.9%) became HIV-positive during follow-up. Their results demonstrated a positive relationship between HIV-seropositivity and having access to a physician for regular HCV care, which is par- tially explained through increased frequency of engagement in health care (35). In 11 Eu- ropean countries, data were used for perform- ing retrospective and cross sectional study with 229 HCV / HIV cases of children and young adults (36). That resulted in 63% of cases that were infected with hepatitis C ver- tically, 7% of them were infected with hepa- titis C as nosocomial infection, 17% with drug use and 13% of them has no data about the way of infection. Study also reveals that among infected patients with hepatitis C, a high number of patients with progressive liver disease was present, so it suggests the importance of improving monitoring proce- dures and offering earlier HCV proper treat- ment (36). A study in 9 emergency units in England, in 2014, during “Going Viral” cam- paign, 7807 patients were tested (37). That resulted in 39 HCV infected persons (15 newly diagnosed), 17 HIV infected persons (six newly diagnosed), and 15 HBV infected persons (11 newly diagnosed). It also re- vealed that those aged 25–54 years had the highest prevalence: 2.46% for HCV, 1.36% for HIV and 1.09% for HBV. Another study performed with 4950 participants in some re- gions in China resulted with HIV and HCV prevalence of Yanyuan county were 0.06% and 0.15%, respectively. HCV prevalence of Muli county was 0.06% HCV and none was found to be HIV positive (38). Another im- portant finding from this survey was that HIV epidemics has not spread from high risk groups to the general population. A systematic review and meta-analyses of 10 studies (39), 2382 infants, were included in Rashiti-Bytyçi A, Ramadani N, Kalaveshi A, Muçaj S, Gashi L, Rashiti P. Hepatitis C in several risk groups: literature review (Review article). SEEJPH 2021, posted: 31 May 2021. DOI: 10.11576/see- jph-4487 P a g e 11 | 19 an analysis of HCV-infected mothers (de- fined by anti-HCV and antibody assays) with and without concomitant HIV infection. The risk estimate of HCV vertical transmission was 2.82 from anti-HCV positive/HIV posi- tive co-infected mothers compared with anti- HCV positive/ HIV negative mothers. This finding revealed that the risk of HCV vertical transmission is higher in infants born to HIV co-infected mothers. Rashiti-Bytyçi A, Ramadani N, Kalaveshi A, Muçaj S, Gashi L, Rashiti P. Hepatitis C in several risk groups: literature review (Review article). SEEJPH 2021, posted: 31 May 2021. DOI: 10.11576/see- jph-4487 P a g e 12 | 19 Table 3. HIV – HCV coinfection Paper Year Country Study design Study sample Laboratory tests Results (33) 2014 Ghana Prospective study From 1520 infected HIV, all HBsAg-positive subjects (n = 236) and a random subset of HBsAg-negative subject (n = 172) were screened for HCV RNA HCV RNA 4 positive cases (34) 2018 Spain Prospective study 322 HCC cases in HIV/HCV co-infected pa- tients n/a After SVR 42 cases (13%) (35) 2005- 2015 Canada Prospective cohort 1627 HCV positive cases HCV RNA, HIV test 582 (35.8%) were HIV-positive at baseline; and 31 (1.9%) became HIV- positive during fol- low-up (36) 2016 11 Euro- pean countries Retrospective cross sectional 229 children and young adults with HIV/HCV HCV RNA, HIV RNA 63% of cases in- fected with hepatitis C vertically, 7% in- fected with hepatitis C as nosocomial in- fection, 17% drug use and 13% no data (37) 2014 England Prospective 9 units of emergency de- partments (7807 patients) HIVAg/Ab, HBsAg, HCV Ab 39 HCV infections (15 newly diag- nosed), 17 HIV in- fections (six newly diagnosed), and 15 HBV infections (11 newly diagnosed). (38) 2011 China Randomised prospective 4950 participant Elisa HIV, Elisa HCV HIV and HCV prev- alence of Yanyuan county were 0.06% and 0.15%, respec- tively. HCV preva- lence of Muli county was 0.06% HCV and none was found to be HIV positive (39) 2003 USA A systematic review 2382 infants from HCV in- fected mothers HIV RNA, HCV RNA Risk estimate of HCV vertical trans- mission was 2.82 from anti-HCV+/ HIV+ co-infected mothers compared with anti- HCV+/HIV-mothers (40) 2014 USA Review of rec- ommendations / / / Rashiti-Bytyçi A, Ramadani N, Kalaveshi A, Muçaj S, Gashi L, Rashiti P. Hepatitis C in several risk groups: literature review (Review article). SEEJPH 2021, posted: 31 May 2021. DOI: 10.11576/see- jph-4487 P a g e 13 | 19 Results on health workers, tattoo and pierc- ing procedures, patients of mental units / HCV Three of seven studies involved in the survey and presented in Table 4, revealed that health practitioners are the major risk group of get- ting HCV while giving care to their positive HCV patients. Study on health care profes- sionals approach to patients with hepatitis C revealed that during treatment they use stricter measures to protect themselves from infection (40). In the study, a questionnaire was sent to 3675 health professionals and in the end 1347 completed questionnaires were taken for analysis. As a final result, the study suggests that focusing education strategies on changing health practitioners’ attitudes to- ward people with hepatitis C, injecting drug users, and infection control guidelines rather than concentrating solely on medical infor- mation might ultimately improve patient care. Another study conducted in USA, re- vealed that HIV and HCV infection was transmitted to health care workers from nurs- ing home patients, when they dealt with these infections through non-intact skin exposure. In these cases, the infection may have been prevented by consistent, unfailing use of bar- rier preventive measures (41). In Italy the re- search that was performed in 9 haemodialysis centres with 1002 patients for detecting in- fection with hepatitis B, Hepatitis C and HIV, resulted with prevalence of HBsAg in pa- tients of 5.1%; HCV antibody 39.4%; anti- bodies to HIV 0.1%. Another important re- sult in this study emphasized that health pro- fessionals in haemodialytic centres has 4000 and 8000 times lower for HIV than for hepa- titis B and hepatitis C, respectively (42). Re- garding the relation of HCV with mental ill- ness, in the review are included two studies. The first study, with 293 veterans with HCV positive, resulted with 93% of the partici- pants had at least one psychiatric problem and 73% had more than 2 mental disorders (43). The authors concluded that the routine screening for underlying psychiatric and sub- stance use disorders and early treatment in- tervention before initiating antiviral therapy is essential. Another study with 931 patients with mental illness, revealed that among this group there is a high number of infected per- sons with HIV, hepatitis B and hepatitis C - 3.1% with HIV, 23.4% cases with hepatitis B and 19.6% cases with HCV (44). A big problem, authors found, is the large number of undetected cases with hepatitis C, and de- lay in detection is related to treatment delay and also might be a source of infection to oth- ers. Regarding the relation of HCV and tat- tooing or piercing procedures, two studies are included. The first study, of 10 case-control studies, 6 reported no increased risk of HCV infection from tattooing when they controlled for injected drug use and other risk behav- iours, and 2 studies reported a 2–3 times higher risk for HCV infection when the tattoo was received in nonprofessional settings (45). Another study about knowledge of tat- too practitioners about HCV and transmis- sion revealed that from 35 employees, 34 were aware of guidelines and body piercing (46). The average number of piercing proce- dures during the week was 5.5. Study showed that body-piercing practitioners had inade- quate training, and lacked knowledge and un- derstanding of HCV transmission, infection control, and universal precautions. As a con- clusion health care practitioners are in high risk for getting HCV infection from infected patients, so they should stricter measures. Also it was identified high rate of HCV infec- tion among patient with mental health dis- eases, and large number of undetected cases, that is a sign for occurring epidemics inside mental health wards. Another conclusion re- lated to piercing and tattoo procedures re- vealed that risk of HCV infection is signifi- cant among risk groups. Also lack of knowledge about HCV transmission among Rashiti-Bytyçi A, Ramadani N, Kalaveshi A, Muçaj S, Gashi L, Rashiti P. Hepatitis C in several risk groups: literature review (Review article). SEEJPH 2021, posted: 31 May 2021. DOI: 10.11576/see- jph-4487 P a g e 14 | 19 body piercing and tattoo practitioners could be a risk factor on rise. Table 4. Hepatitis C related to health care practitioners, mental disease patients, tattoo and piercing procedures Paper Study group Year Country Study design Results (41) Health profes- sionals 2006 Australia Analytic cross sectional study Focusing education strategies on changing health practitioners’ atti- tudes toward people with hepatitis C, injecting drug users, and infec- tion control guidelines (42) Health profes- sionals 2003 USA Case report HIV and HCV transmission from the patient to the HCW appears to have occurred through non-intact skin exposure (43) Health profes- sionals 1993 Italy Prospective The risk of acquiring infection was calculated to be 8000 times lower for HIV than for hepatitis C. (44) Mental health patients 2005 USA Prospective 93% of the patients had a current or past history of at least 1 psychiatric disorder, and 73% had ⩾2 disorders (45) Mental health patients 2001 USA Prospective Prevalence rates of HBV (23.4%) and HCV (19.6%) were approxi- mately 5 and 11 times the overall es- timated population rates for these in- fections, respectively (46) Tattoo and piercing proce- dures 2015 USA Meta –analyse Risk of HCV infection is significant, especially among high-risk groups (adjusted odds ratio, 2.0–3.6), when tattoos are applied in prison settings or by friends (47) Tattoo and piercing proce- dures 2003 Australia Cross - sectional survey Body piercing practitioners had in- adequate training, and lacked knowledge and understanding of HCV transmission, infection con- trol, and universal precautions Discussion As for the first part of the research on haemo- dialysis, presented in Table 1, most of the studies were of prospective nature, indicating the importance of following up the relations between the haemodialysis and HCV. Less than half of the studies had a bigger sample than 1000 patients. The timing of haemodial- ysis and the risk of infection with hepatitis C virus appear to be in the right proportion, as the years of haemodialysis increase and the risk of acquiring hepatitis C infection in- creases. The laboratory tests in almost all of the studies, included HCV antibody and/or HCV RNA but considering that HCV RNA test is more expensive, in developing coun- tries like Sudan, only the HCV antibody test Rashiti-Bytyçi A, Ramadani N, Kalaveshi A, Muçaj S, Gashi L, Rashiti P. Hepatitis C in several risk groups: literature review (Review article). SEEJPH 2021, posted: 31 May 2021. DOI: 10.11576/see- jph-4487 P a g e 15 | 19 was conducted, which can’t differentiate be- tween an active infection versus a chronic or previously acquired infection. But, still the HCV antibody test, can provide an overview of the infected population with hepatitis C. This is also confirmed by the results of three studies (9,12,17) where over 70% of HCV Ab positive cases were found to be HCV RNA positive. Generally, most of the studies sug- gest stronger preventive measures and stronger infection control strategies on hae- modialysis centres. The second part of the research, dealing with relation between hepatitis C and pregnancy, presented in Table 2, most of the studies were of prospective nature. Injections (intravenous drugs) and hospitalization were identified as most common pathways of infection of preg- nant women with HCV. Other studies fo- cused on vertical transmission, identified that new-borns were infected with HCV. These results emphasise the importance of routine screening for HCV during pregnancy. The part of the research dealing with hepatitis C and HIV co-infection, identified several publications, where most of them conducted prospective studies. The laboratory tests in- cluded HCV RNA and HIV test. Several studies call for routine screening in order to find out if they are infected but as well to of- fer earlier and proper treatment. The last part of the research included health care practitioners, mental health patients and tattoo and piercing procedures. According to the publications, health care practitioners are in high risk for getting HCV infection, from infected patients, so they should use stricter measures. Also, a high rate of HCV infection among patient with mental health diseases was observed, and large number of unde- tected cases, that is a sign for occurring epi- demics inside mental health wards. Mean- while, related to piercing and tattoo proce- dures, research revealed that risk of HCV in- fection is significant among risk groups. Also lack of knowledge about HCV transmission among body piercing and tattoo practitioners could be a risk factor on the rise. 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