Epidemiology of HCV infection among HD pts in Iran and prevention strategies

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2 Epidemiology of HCV infection among HD pts in Iran and prevention strategies B. Einollahi Professor of Internal Medicine/Nephrology Division Baqiyatallah University of Medical Sciences 4th International Congress of Nephrology and Urology Tehran, I.R.Iran

3 The Virus Single stranded, positive sense, RNA Falviviridae family Spherical, enveloped ~ 50 nm Discovered in 1989 Six known genotypes and more than 50 subtypes (quasispecies) Choo, Science 1989;244:359-62

4 Viral hepatitis is the 7th leading cause of mortality worldwide with HCV accounting for about half of this mortality.

5 Epidemiology Estimated prevalence is 1.8% of the U.S. population Estimated 4 million people in U.S. infected with HCV; 2.7 million have chronic infection 8,000 10,000 deaths per year from HCV-related chronic liver disease A fourfold increase in the number of persons diagnosed with chronic HCV is projected from Global prevalence 170 million 5 X more prevalent than HIV Management of Hepatitis C: NIH Consensus Development Conference Statement Lauer, NEJM 2001;345:41-52

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7 Kane, Bull WHO 1999;77:801-7 HCV Global Prevalence Number-of countries by WHO Region where data are not available WHO Region Total Population (Millions) Hepatitis C prevalence Rate % Infected Population (Millions) Africa Americas Eastern Mediterranean Europe South-East Asia Western Pacific Adeel A. Butt, MD Total

8 World J Gastroenterol. 2016; 22(34):

9 The Lancet Gastroenterology & Hepatology 2017,

10 HCV Infection: Worldwide Genotype Distribution 1a, 1b 2a, 2b, 2c, 3a 1a, 1b 2a, 2b, 3a 2a 4 4 1b, 3a 1b 1b, 6 3b 1a, 1b, 2b, 3a 5a 1b, 3a Fang et al. Clin Liver Dis

11 Epidemiology of HCV in Pts on HD In US, estimated HCV prevalence of 8% - (approximately 400,000 persons on HD) HCV prevalence 5X greater in HD patients than in general US population Risk factors for HCV infection among hemodialysis patients: - Number of years on dialysis - Number of blood product transfusions - Injection drug use - History of organ transplantation Finelli L, et al. Semi Dial. 2005;18:52-61.

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13 HCV in HD pts HCV is a blood borne pathogen transmitted parenterally such as through sharing of injections and use of contaminated medical equipment. (Prati D. J. Hepat 2006; 45: ) Pts undergoing HD are at a higher risk of HCV exposure due to sharing of dialysis machines. (Sy T, Jamal MM. Int J Med Scien 2006; 3: 41-6.) It has been estimated that HD increases the odds of acquiring HCV by five folds. (Sun J, et al. Renal Fail. 2009; 31: )

14 Risk factors for HCV infection among HD pts Duration and frequency of dialysis and exposure to blood transfusions were the most commonly reported risk factors. -Goher SA, et al. Sci Med J 1998; 10: Saddik Y, El Azoni M. Sci Med J 1997; 9: Ramzi ZS, et al. Zanco J Med Sci 2010; 14:

15 Risk factors for HCV infection among HD pts In one prospective observational study conducted in three major continents, the prevalence of HCV in HD pts were higher among those who were on dialysis for longer duration, male gender, black ethnicity, concurrent illness like diabetes or hepatitis B infection, prior kidney transplant and alcohol or substance abuse. Fissell RB, et al. Kidney Int 2004; 65:

16 Prevalence of HCV infection and related risk factors among Iranian HD pts To investigate the prevalence of HCV infection in pts on HD and its associated risk factors, we conducted a prospective case series study of 838 pts on HD in Tehran, Iran. Pts were selected randomly (cluster sampling) and all were screened for anti-hcv antibodies, using ELISA 3rd generation and confirmed by using RIBA 2nd generation. We found that 111 pts (13.2%) were infected. Alavian SM, Einollahi B. NEPHROLOGY 2003;8,

17 Prevalence of HCV infection and related risk factors among Iranian HD pts By applying univariate analysis: longer duration on hemodialysis (P= 0.000), more weekly dialysis sessions (P=0.03), history of blood transfusion (P=0.03) and history of previous renal transplantation (P=0.01) were found to be associated with a higher rate of HCV infection. Alavian SM, Einollahi B. NEPHROLOGY 2003;8,

18 Prevalence of HCV infection and related risk factors among Iranian HD pts Multivariate analysis revealed that length of time on dialysis (P=0.000) and history of blood transfusion (P=0.02) were significantly associated with HCV infection. Alavian SM, Einollahi B. NEPHROLOGY 2003;8,

19 Prevalence of HCV infection and related risk factors among Iranian HD pts Our results suggest that Early transplantation and avoidance of blood transfusion, as much as possible, are the two most important practical interventions to reduce the HCV exposure rate in our pts on HD. Alavian SM, Einollahi B. NEPHROLOGY 2003;8,

20 Comparison of pretransplant factors between HCV-positive and HCV-negative pts Anti-HCV Ab Anti-HCV-Ab P-value Positive (n=41) negative (n=868) Duration on HD (months) 39.6± ± Retransplantation (yes/no) 9/32 (21.9%) 61/807 (7.0%) Einollahi B, et al. J Gastroenterol Hepatol. 2003;18:

21 Epidemiology of Hepatitis C in Iran Hepatitis C infection prevalence has decreased dramatically in Iranian HD population during the last decade. 14.4% in % in 2006 Alavian 2008

22 Percentage of HBS Ag and HCV Ab positive pts on HD in Iran Alavian, 2008

23 The latest incidence of HD pts with HCV Ab positive: 2018 Overall incidence: 542 pts (1.7%) Lowest incidence: 0% Highest incidence: 5.4% Unpublished data

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25 The incidence of HCV infection in dialysis patients has significantly decreased over the past few decades. This is due to the following factors: 1. Screening of blood products for HCV Ab 2. Implementation of infection control measures 3. Regular screening of HD pts for HCV 4. Reduced need for transfusion after the advent of erythropoietin

26 There has been a noticeable decrease in HCV infection among hemodialysis patients. after the introduction of regular screening for HCV and the use of erythropoietin Its incidence varies from 5% to 25% in the United States, with a prevalence of 6.8% in Europe and ranges 3.4% to 32.1% in developed countries. Molino C, et al. Int J Artif Organs. 2008;31: Terrault NA, Adey DB. Clin J Am Soc Nephrol. 2007;2:

27 Though HCV infection is a public health concern globally, the Middle East and North Africa (MENA) is the most affected region by this infection. For 2015, MENA was estimated to have the highest incidence rate of all regions at 62.5 per person-year, second largest incidence at new infections per year, highest HCV antibody prevalence at 2.3%, and largest number of chronically infected people at 15 million. Harfouche et al. Epidemiol. Infect. (2017), 145,

28 Descriptive epidemiologic syntheses, effects meta-analyses and meta-regressions, and genotype analyses were conducted. They analyzed 289 studies, including HD pts. HCV incidence ranged between 0 and 100% as seroconversion risk, and between 0 and 14.7 per 1000 person-years as incidence rate. The regional pooled mean estimate was 29.2% (95% CI: %) for HCV antibody positive prevalence and 63.0% (95% CI: %) for the viremic rate. Genotype diversity varied across countries with four genotypes documented regionally: genotype 1 (39.3%), genotype 2 (5.7%), genotype 3 (29.6%), and genotype 4 (25.4%). These findings showed that one-third of HD pts are HCV antibody positive and onefifth are chronic carriers and can transmit the infection. Harfouche et al. Epidemiol. Infect. (2017), 145,

29 Population proportion of HD in the MENA Harfouche et al. Epidemiol. Infect. (2017), 145,

30 Pooled mean estimate for HCV Ab prevalence among HD pts across countries of the MENA Harfouche et al. Epidemiol. Infect. (2017), 145,

31 The pooled mean estimate of HCV prevalence by country, by temporal duration, and for the region The country-specific mean estimate ranged from 7.3% (95% CI: %) in Lebanon to 65.5% (95% CI: %) in Egypt. HCV prevalence was 51.6% (95% CI: %) in years of publication , and decreased to 27.8% (95% CI: %) in , and 18.8% ( %) in The mean estimate for the region was 29.2 % (95% CI: %). Egypt, Syria, Saudi Arabia, Yemen, Morocco, and Qatar had a mean estimate exceeding 40%. Harfouche et al. Epidemiol. Infect. (2017), 145,

32 Pooled mean estimate for HCV viremic rate among HD pts across countries of the MENA. HCV viremic rate is the prevalence of HCV chronic infection (HCV RNA positivity) among antibody-positive persons Harfouche et al. Epidemiol. Infect. (2017), 145,

33 Frequency, distribution, and Shannon Diversity Index of HCV genotypes among HD pts across the MENA Harfouche et al. Epidemiol. Infect. (2017), 145,

34 Ghorbani NR, et al J Res Med Sci 2017;22:123.

35 Papers search and review flowchart for selection of primary study Ghorbani NR, et al J Res Med Sci 2017;22:123.

36 Prevalence of hepatitis C virus infection among HD pts according to type of kit Ghorbani NR, et al J Res Med Sci 2017;22:123.

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38 An overall prevalence of 25.3% of HCV infection was reported among HD pts in the Middle-East region according to the present study. The overall prevalence of HCV infection among HD pts in Iran according to the last decade s publications was estimated as 12%. The prevalence was higher in ages 40 to 50 yrs old. Among patients who were under hemodialysis for more than 5 years the prevalence of hepatitis C was higher than those who were treated for a shorter time period.

39 Follow diagram of systematic review and searches for HCV infection prevalence among HD pts in the Middle-East countries. Ashkani-Esfahani S et al. World J Gastroenterol 2017; 23(1): 15166

40 The prevalence of HCV infection in Middle-East countries

41 Prevalence of HCV infection in Iran An overall anti-hcv antibody prevalence of less than 1% was reported in the general population of Iran. Alavian SM, et al. Arch Iranian Med 2005; 8:84-90 Liakina V, et al. J Viral Hepat 2015; 22 Suppl 4: 4-20 Taherkhani R, Farshadpour F. World J Gastroenterol 2015; 21: The most dominant genotype of HCV in Iran was subtype 1a (44.9%) followed by 3a (39.6%), and 1b (11.3%) among the general population. ( Jahanbakhsh Sefidi F, et al. Hepat Mon 2013;13: e7991.

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43 The overall estimation of HCV prevalence in Iran hemodialysis patients according to the data of 12 provinces was 13.57% (95% CI: %) with ELISA and 7.61% (95% CI: %) with the RIBA/PCR method

44 Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int Suppl 2008; 109: S1-S99 There is no need for physical isolation during dialysis or of dedicated machine utilization for infected patients to prevent HCV transmission. Given HCV incidence during the first year of dialysis, a regular (each 6 or 12 months), serological screening for HCV is recommended to dialysis patients.

45 Impact of chronic HCV on kidney function

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50 Impact of chronic HCV on survival

51 Impact of Hepatitis C Infection on Hemodialysis Patients: Increased overall risk of mortality Increased risk of cirrhosis Increased incidence of hepatocellular cancer Source: Fabrizi F, et al. J Viral Hepat. 2007;14:

52 Impact of HCV infection on survival on regular hemodialysis. Espinosa M, et al. Nephrol Dial Transplant 2001;16 (8):

53 Increased mortality of HCV-infected patients on regular dialysis is mainly attributed to cardiovascular events, which reflect the chronic endothelial damage induced by the virus. Sepsis and liver failure also contributes to the decline in patient survival. Perico N, et al. Clin J Am Soc Nephrol 2009;4(1): Balasubramanian A, et al. J Gen Virol 2005;86:

54 A meta-analysis on pts receiving maintenance HD, found that HCV-positive pts have higher mortality compared to HCV-negative pts. This study showed that liver-related death was higher than cardiovascular-related death among these groups [adjusted relative risk 3.82 (95%CI: 1.92; 7.61) vs 1.26 (95%CI: 1.10; 1.45) respectively]. Fabrizi F, et al. J Viral Hepat 2012; 19: 601-7

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56 HCV does not cross the dialysis membranes, so infection is invariably caused by inter-patient transmission, usually by the staff. Accordingly, transmission can be prevented by adequate staff training on universal dialysis wards hygiene rather than isolating infected patients. However, local regulations in certain countries impose isolation, which has been rewarded by significant reduction in transmission, expressed as a decline in the sero-conversion of HCV negative pts. Yang CS, et al. J Formos Med Assoc 2003;102(2):79 85.

57 There is no observed difference between hemodialysis and peritoneal dialysis on the survival rate of these HCV infected dialysis dependent patients. Chou CY, et al. Perit Dial Int 2010; 30: Bose B, et al. Clin J Am Soc Nephrol 2011; 6:

58 Hepatitis C and Renal Disease Hepatitis C as a Cause of Renal Disease HCV infection in pts with advanced liver failure increases risk for renal disease Chronic HCV infection associated with increased risk for RCC Chronic HCV infection accelerated renal disease in HIV-infected pts Source: (1) Ozkok A, et al. Gastroenterol. 2014;20: (2) Gordon SC, et al. Cancer Epidemiol Biomarkers Prev. 2010;19: (3) Peters L, et al. AIDS. 2012;26:

59 Conclusion HCV infection is a public health concern globally especially in HD pts. Hepatitis C infection prevalence has decreased dramatically in Iranian HD population during the last decade. Duration and frequency of dialysis, re-transplantation and exposure to blood transfusions were the most commonly reported risk factors. Chronic HCV impairs kidney function Decreased survival of HCV-infected patients on regular dialysis

60 Thank you all for your attention