Dr – Shahrokh Ezatzadegan نفرولوژیست Dr – Ramin Radmehr پزشک دیالیز

 viral infection in CKD  Hepatitis A  Hepatitis B  Hepatitis C  Hepatitis D  HIV

 Reduced response to vaccination because of the general suppression of the immune system associated with uremia.  A lower antibody titer and an inability to maintain adequate antibody titers over time.

 Hepatitis means inflammation of the liver › Hepat (liver) + itis (inflammation)= Hepatitis  Viral hepatitis means there is a specific virus that is causing your liver to inflame (swell or become larger than normal)

5 types: A : fecal-oral transmission B : sexual fluids & blood to blood C : blood to blood D : travels with B E : fecal–oral transmission Vaccine Preventable

Source of virus fecesblood/ blood-derived body fluids blood/ blood-derived body fluids blood/ blood-derived body fluids feces Route of transmission fecal-oralpercutaneous permucosal percutaneous permucosal percutaneous permucosal fecal-oral Chronic infection noyes no Preventionpre/post- exposure immunization pre/post- exposure immunization blood donor screening; risk behavior modification pre/post- exposure immunization; risk behavior ensure safe drinking water Type of Hepatitis ABCDE

 Naked RNA virus  Related to enteroviruses, formerly known as enterovirus 72, now put in its own family: heptovirus  One stable serotype only  Difficult to grow in cell culture: primary marmoset cell culture and also in vivo in chimpanzees and marmosets  4 genotypes exist, but in practice most of them are group 1

Incubation period:Average 30 days Range days Jaundice by 14 yrs, 70%-80% Complications: Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis Chronic sequelae:None Hepatitis A - Clinical Features

 Double stranded DNA virus,the + strand not complete  Complete Dane particle 42 nm, 28 nm electron dense core, containing HBcAg and HBeAg. The coat and the 22 nm free particles contain HBsAg  The HBcAg is of a single serotype

 - In the majority of dialysis patients, testing for HBsAg is sufficient for the diagnosis of HBV infection.  - Screening: periodically (usually every 3-6 months)

 Incubation period:Average days Range days  Clinical illness (jaundice):<5 yrs, <10% 5 yrs, 30%-50%  Acute case-fatality rate:0.5%-1%  Chronic infection:<5 yrs, 30%-90% 5 yrs, 2%-10%  Premature mortality from chronic liver disease:15%-25% Hepatitis B - Clinical Features

1. Chronic Persistent Hepatitis - asymptomatic 2.Chronic Active Hepatitis - symptomatic exacerbations of hepatitis 3. Cirrhosis of Liver 4. Hepatocellular Carcinoma

HighModerate Low/Not Detectable bloodsemenurine serumvaginal fluidfeces wound exudatessalivasweat tears breastmilk Concentration of Hepatitis B Virus in Various Body Fluids

 Sexual - sex workers and homosexuals are particular at risk.  Parenteral - IVDA, Health Workers are at increased risk.  Perinatal - Mothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not. Perinatal transmission is the main means of transmission in high prevalence populations. Hepatitis B Virus Modes of Transmission

 A battery of serological tests are used for the diagnosis of acute and chronic hepatitis B infection.  HBsAg - used as a general marker of infection.  HBsAb - used to document recovery and/or immunity to HBV infection.  anti-HBc IgM - marker of acute infection.  anti-HBcIgG - past or chronic infection.  HBeAg - indicates active replication of virus and therefore infectiveness.  Anti-Hbe - virus no longer replicating. However, the patient can still be positive for HBsAg which is made by integrated HBV.  HBV-DNA - indicates active replication of virus, more accurate than HBeAg especially in cases of escape mutants. Used mainly for monitoring response to therapy.

 Vaccination - highly effective recombinant vaccines are now available. Vaccine can be given to those who are at increased risk of HBV infection such as health care workers. It is also given routinely to neonates as universal vaccination in many countries.  Hepatitis B Immunoglobulin - HBIG may be used to protect persons who are exposed to hepatitis B. It is particular efficacious within 48 hours of the incident. It may also be given to neonates who are at increased risk of contracting hepatitis B i.e. whose mothers are HBsAg and HBeAg positive.  Other measures - screening of blood donors, blood and body fluid precautions.

Initial 3 doses 1-2 months HBs ab titer > 10 IU/L Additional three-dose Ab titer falls to ≤ 10 in F/u NO YES single booster dose of 40 mcg

 HIV infection does not appear to decrease the effectiveness of the hepatitis B vaccine in dialysis patients, suggesting that this vaccine should be offered to these patients.

 Machine segregation is now standard practice.  In contrast to other blood-borne infections, the circulating load of HBV can be high in HBsAg-positive individuals, and the virus can survive on environmental surface.

Pain at injection site Mild systemic complaints (fatigue, headache) Temperature >37.7 C Severe systemic reactions Adults 13%-29% 11%-17% 1% rare Infants and Children 3%-9% 0%-20% 0.4%-6% rare

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 Genome resembled that of a flavivirus positive stranded RNA genome of around 10,000 bases

Incubation period:Average 6-7 wks Range 2-26 wks Clinical illness (jaundice):30-40% (20-30%) Chronic hepatitis:70% Persistent infection:85-100% Immunity:No protective antibody Hepatitis C - Clinical Features

 The spectrum of chronic hepatitis C infection is essentially the same as chronic hepatitis B infection.  All the manifestations of chronic hepatitis B infection may be seen, albeit with a lower frequency i.e. chronic persistent hepatitis, chronic active hepatitis, cirrhosis, and hepatocellular carcinoma.

 Transfusion or transplant from infected donor  Injecting drug use  Hemodialysis (yrs on treatment)  Accidental injuries with needles/sharps  Sexual/household exposure to anti-HCV- positive contact  Multiple sex partners  Birth to HCV-infected mother Risk Factors Associated with Transmission of HCV

 Neither the CDC in the United States nor the KDIGO guidelines recommend the use of dedicated machines, patient isolation, or a ban on reuse in HD patients with HCV infection.

 HCV antibody - generally used to diagnose hepatitis C infection. Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears.  HCV-RNA - various techniques are available e.g. PCR and branched DNA. May be used to diagnose HCV infection in the acute phase. However, its main use is in monitoring the response to antiviral therapy.  HCV-antigen - an EIA for HCV antigen is available. It is used in the same capacity as HCV-RNA tests but is much easier to carry out.

 With the initiation of hemodialysis or transfer from another hemodialysis facility,; If the new hemodialysis facility has a low prevalence of HCV; HCV Ab testing with ELISA, if positive, followed by PCR should be considered. › If the new hemodialysis facility has a high prevalence of HCV: testing with PCR  PCR should be performed in patients with unexplained abnormal aminotransferase levels.  In the setting of possible nosocomial infection, PCR should be performed in all patients who may have been exposed. 30

HBsAg RNA  antigen Hepatitis D (Delta) Virus

 The delta agent is a defective virus which shows similarities with the viroids in plants.  The agent consists of a particle 35 nm in diameter consisting of the delta antigen surrounded by an outer coat of HBsAg.  The genome of the virus is very small and consists of a single-stranded RNA

 Dialysis isolation is not recommended.  Needlestick transmission — The risk of HIV seroconversion after a needlestick injury is estimated to be 3 in 1000 or 0.3 percent. › Postexposure prophylaxis with antiretroviral therapy (ART) should be offered to exposed healthcare workers. › no viral RNA was detectable in the ultrafiltrate. › HIV virus that is capable of replication is recoverable from peritoneal dialysis effluent 34

Annual vaccination with influenza virus in Adults with all stages of CKD. Kidney International Supplements (2013) 3, 91–111