2-Viral_Hepatitis presentation sign and symptoms-6y.pptx

Viral hepatitis

1. Viral Hepatitis Prepared by: Dr. Ruqaya Al- Kathiry

2. Hepatitis A Common in children but often asymptomatic. ~30% of adults will have serological evidence of past infection but give no Hx of J. Causative Agent: HAV is an RNA virus. Route Of Transmission: Faecal -oral route. Vehicles Of Transmission: water & shellfish in occasional outbreaks. I.P: 2-6wks. Infectivity: excrete HAV in faeces for 2-3wks before onset of symp. & then after 2wks . Invx: The virus cannot be grown readily. Anti-HAV/HAV Ab (IgM): Dx of an ac. HAV infection present at the onset of illness & ↓ within ~3ms of recovery. Anti-HAV (IgG): Dx of previous HAV infection . It indicates immunity to HAV. Prevention & Rx: No role for antiviral drugs. Improving social conditions: overcrowding & poor sanitation. Active immunisation : an inactivated HAV vaccine protects for upto 20y if completed 2doses, 6m apart. Passive immunisation : serum IG given soon after exposure to the virus, those at particular risk: close contacts of HAV-infected pts, elderly, those with major dis., pregnant, travelers to endemic areas, in an outbreak of hepatitis (school or nursery).

3. Complications: Ac. liver failure is rare (0.1%). Chr. carrier state does not occur. Chr. infection does not occur. HAV infection in pts with CLD may cause serious or life-threatening dis. In adults, a cholestatic phase with ↑ALP levels & bilirubin may complicate infection. Hepatitis B Hepatitis B is the most common causes of CLD & HCC worldwide. ~ ⅓ of the world’s population have serological evidence of past/current infection with hepatitis B & ~350-400 million people are chr. HBsAg carriers. Ac. & chr. hepatitis B are asymptomatic. Progression to CLD depends on source & timing of infec . Chr . hepatitis → cirrhosis or HCC after decades of infect. Causative Agent: HBV is the only DNA virus. Vehicles of Transmission: Humans are the only source of infection: Vertical transmission (90%) from mother to child in perinatal period is most common cause of infection worldwide & carries the ↑risk of chr. infection & Horizontal (10%) .

4. I.P: 6wks-6ms. Invx: Serology: HBV contains 5 serological markers which are imp. in identifying infection. Hepatitis B surface antigen ( HBsAg ): Means a pt is “ making” HBV. Levels may be ↓ or very ↑. It can be ac. or chr. Appears in the blood late in the IP, but before the prodromal phase of ac. hepatitis B; may be present for a few ds only, disappearing even before J has developed, but usu. lasts for 3-4wks & can persist for up to 5ms. N.B: Persistence of HBsAg for >6ms indicates chr. infection. Anti- HBsAg ( HBsAb ): Almost always means the pt has immunity i.e.: "cured“ of previous HB infection ( with IgG HBcAb ) “vaccinated” if it is the only marker ( no IgG HBcAb ) Appears after 3-6ms & persists for many ys or permanently. Hepatitis B core antigen ( HBcAg ): HBcAg is not found in the blood only in the liver. Anti- HBcAg ( HBcAb ): It appears early & rapidly ↑ titre , which subsides gradually but then persists. IgM: rises when the HBsAg has disappeared & before HBsAb has developed= window . IgG: appears later. It is the best marker for previous exposure to HBV. Hepatitis B e antigen (HBeAg): It appears transiently at the outset of the illness.

5. Means the pt is “ highly infectious & actively making” HBV i.e. active viral replication in the liver. Its absence usu. implies ↓viral replication. Anti- HBeAg ( HBeAb ): Follows HBeAg production . Once infected, the 1 st marker detectable in the serum is the HBsAg . This is followed by the appearance of HBcAb ( lgM ). After HBsAg becomes undetectable, there is a period of wks to ms before the HBsAb becomes detectable. This is called the "window," and you must perform an HBcAb IgM test during this period to confirm ac. hepatitis B.

6. PCR: measures HBV-DNA levels in peripheral blood by direct assessment of: Viral loads : Active viral replication ( HBsAg & HBeAg +ve) = >105 copies/ mL. ↓viral replication ( HBsAg -ve & HbeAb +ve) = < 105 copies/ mL. It is imp. in monitoring antiviral Rx & identifying pts with pre-core mutants. Genotype: Specific HBV genotypes (A–H) can be identified. Genotype A responds better to pegylated IFN alfa , compared to genotypes C & D.

7. Management: Goals of Rx: * HBeAg seroconversion *↓HBV-DNA * NL LFTs . Indications for Rx: ↑viral load with active hepatitis (↑S. transaminases ± inflam . & fibrosis by histology). 2 different types of drug are used to Rx hepatitis B: Direct-acting nucleoside/nucleotide antiviral agents: mainstay of Rx given orally: Lamivudine , Telbivudine & Adefovir : (susceptible to viral resistance). Entecavir & tenofovir : 1 st line agents (less antiviral resistance). Interferon- alfa (IFN): In pts with ↓viral load & S. transaminases >2x upper NL. C/Is: cirrhosis as it may ↑S. transaminases & ppt. liver failure. S.Es: common ; fatigue , depression, irritability, B.M suppression, AI thyroid dis. Acute Hepatitis B: Rx is supportive. No definitive evidence that antiviral Rx ↓ severity or duration of ac. hepatitis B. Prognosis of ac. HBV: 90-95% = full recovery 5-10% = Chr. hepatitis carrier B ( for life or later recovery) common in immunodeficient individuals (Down’s syndrome or HIV). < 1% = FHF HBV & HDV co-infection, haemochromatosis , AIDS/HIV, alcohol cause more aggressive dis., worsen course & response to Rx.

8. Chronic Hepatitis B: A liver biopsy is usu. required to confirm the Dx of chr. hepatitis B. Rxs are still limited, as no drug is able to eradicate HB infection completely ( HBsAg -ve). Developing chr. HBV is inversely related to age. It occurs in: 90% of infants infected at birth 25-50% in children age 1-5 ys 5% in older children & adults There are 2 types of hepatitis B carrier states: Chronic Inactive Hepatitis B: Most are asymp . (with NL liver enz .) but can develop severe exacerbations if they become immunocompromised. Develop cirrhosis (15-20%) & HCC (20%) only after >5-20 ys . Passive immunisation : I.M hyperimmune serum globulin (HBIG) prepared from blood containing anti-HBs given within 24hrs to 1wk, of exposure to infected blood (e.g. needle stick injury, contamination of cuts or mucous mm). Active-passive immunisation : Vaccine with HBIG. Neonates born to HB-infected mothers should be vaccinated at birth & given HBIG. Hepatitis B serology should then be checked at 12ms of age. Chronic Active Hepatitis B: Rx is recommended for those with HBV DNA >20,000 & ALT >2x upper NL : Started immediately for HBeAg -ve. Delayed 3-6ms for newly Dx HBeAg +ve pts to see if seroconversion takes place.

9. The presence of cirrhosis requires less HBV DNA to initiate Rx. Treat: Compensated cirrhosis when HBV DNA >2,000 Decompensated cirrhosis when HBV DNA >200 Liver Transplantation: It is the only Rx for end-stage liver disease (5yr SR=80%). The HBV recurs in the transplanted liver, but an antiviral Rx program can help. Prevention: HBV-DNA can be found in saliva, urine, semen & vaginal secretions. HBV is about 10x infectious >HCV, which is about 10x infectious >HIV. Active immunisation : A recombinant hepatitis B vaccine containing HBsAg ( Engerix ) is capable of producing 95% of NL individuals. It should be offered to those at special risk of infection who are not already immune. N.B: It is ineffective in those already infected by HBV. Hepatitis D (Delta virus) Causative Agent: HDV is an RNA-defective virus that requires HBV for replication. Sources & Modes of Spread: as HBV Superinfection in chr. carriers of HBV → ac. hepatitis → spontaneous recovery. Chr. infection with HBV & HDV → rapidly progressive chr. hepatitis → cirrhosis. Route Of Transmission: In endemic areas: close personal contact & vertical

10. transmission. In non-endemic areas : mainly parenteral drug misuse. I.P: 4-24wks. Invx: Delta Ag appears in the blood only transiently thus Dx is by anti-HDV IgM. Simultaneous infection with HBV & HDV followed by full recovery: ↓ anti-HDV of IgM type within a few ds of onset of the illness disappearing within 2 ms. Superinfection of pts with chr. HBV infection: ↑ anti-HDV, initially IgM & later IgG. may then develop chr. infection with both viruses=anti-HDV titres plateau at ↑ levels. Management: Effective management of hepatitis B prevents hepatitis D. Suspect hepatitis D if sudden decompensation in pt with chr. hepatitis B. Hepatitis C Only 25% of ac. infections are symptomatic; identified when they develop CLD. 70-80% of ac. HCV infections become chronic. Usu. identified in asymptomatic individuals screened because they have RFs for infection (previous IVDU) or have incidentally been found to have ABNL LFT. Fatigue can complicate chr. infection & is unrelated to the degree of liver damage. Causative Agent: an RNA virus. Route Of Transmission: Needlestick transmission from an infected pt (2-6%); transplacental infection (~2%); sexual transmission (2% after 10-20ys) Invx:

11. Serology & Virology: HCV Abs: are used in Dx but may take 6-12 wks to appear in the blood following an ac. infection (needle stick injury). Hepatitis C RNA: identified in the blood as early as 2-4 wks after infection. S. hepatitis C RNA & anti-HCV Abs +ve=Active infection. Anti-HCV Abs persist in serum even after viral clearance (spontaneous or post-Rx) does not confer immunity (as does the HBV antibody to HB). Molecular analysis : There are 6 common viral genotypes, the distribution varies worldwide. Genotype has no effect on progression of liver dis. but affects response to Rx. Genotype 1 is less easy to eradicate than genotypes 2 & 3. LFT: NL/fluctuating b/w 50-200 U/L. J is rare; usu. appears in end-stage cirrhosis. S.transaminase levels in hepatitis C are a poor predictor of the degree of liver fibrosis Liver biopsy : To stage the degree of liver damage histologically , by the Metavir system. Management: Dual therapy: (was Rx of choice) S.C pegylated IFN- alfa /weekly & oral ribavirin (synthetic nucleotide analogue). S.Es of ribavirin are HA & teratogenicity . Virological relapse can occur in the 1 st 3ms after stopping Rx. Cure: loss of virus from serum 6ms after completing Rx=sustained virological response An early virological response “-ve HCV RNA in serum 1m after starting Rx” has better response to Rx & thus shorten the Rx.

12. Triple therapy: (Rx of choice) protease inh . ( telaprevir & boceprevir ) + pegylated IFN + ribavirin has SVR rates for genotype 1 similar to those in genotypes 2 & 3. Measure response to Rx by following HCV RNA: No response at 12 wks ( ↓ in HCV RNA) = discontinue Rx. Response: if genotype 1=Rx for 1 yr; if genotype 2 or 3=Rx for 6 ms. Liver Tx : when complications of cirrhosis occur. HC almost always recurs in the Tx liver in ~15% of pts within 5ys. There is no active or passive protection against HCV. Cirrhosis occurs in ~20% over 20-40 ys . RFs: ♂ , immunosuppression (co-infection with HIV), prothrombotic states & heavy alcohol. Once cirrhosis has developed, the 5-yr SR=95% & 10-yr SR=81% . ⅟ 4 with cirrhosis develop complications within 10 ys &, once arisen, the 5-yr SR=~50%. 2-5% /year will develop 1ary HCC. Hepatitis E Similar to hepatitis A, self-limiting ac. hepatitis Does not cause CLD, although some cases of immunocompromised pts have. Hepatitis E differs from hepatitis A in that infection during 3 rd trimester of preg . is associated with the development of ac. liver failure (↑MR). Causative Agent: an RNA virus . Route of Transmission: Faecal oral route due to contamination of water .

13. I.P: 2-9 wks. Invx: In ac. infection, IgM Abs to HEV are +ve. Think of hepatitis E in a traveler with ac. hepatitis & -ve HAV & HBV serology. Hepatitis G It causes < 0.5% of community-acquired hepatitis. No evidence that HGV causes CLD. Route of Transmission: bloodbome , like hepatitis B & C. There is evidence of infection in 1.5% of blood donors.

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