Acute HepatitisBy Dr Osman Bukhari

CausesCauses 1-1-ViralViral: HAV, HBV, HCV, HDV, HEV, EBV, : HAV, HBV, HCV, HDV, HEV, EBV,

CMV, HIV, Yellow feverCMV, HIV, Yellow fever

2- 2- Non viralNon viral: Toxoplasmosis, Q fever & : Toxoplasmosis, Q fever & Leptospira iclerohaemorrhagua Leptospira iclerohaemorrhagua

3-3- Alcohol Alcohol

4- 4- Drugs & poisonsDrugs & poisons : Paracetamol, Halothane, : Paracetamol, Halothane, A.T.T, CCLY, Aspirin (Reyes)A.T.T, CCLY, Aspirin (Reyes)

5-5- Metabolic Metabolic: Wilson's, alpha- one anti- trypsin : Wilson's, alpha- one anti- trypsin deficiency deficiency

6-6- Ischemic Ischemic: shock, Budd- chiari : shock, Budd- chiari

Pathology

1- Depends on the cause

2- In viral & drug hepatitis :

- Pathology throughout the liver, specially centrilobular. Lobules affected variably

- Damaged hepatocyte are swollen & granular, while dead ones are shrunken & deeply stained acidophilic

- Mononuclear cell infiltration

- Polymorph infiltration & fatty change in some cases of tetracycline & CCL4 poisoning

- Severe damage collapse of reticulin frame - Severe damage collapse of reticulin frame work ,particularly between central work ,particularly between central

veins & portal tract linking them together veins & portal tract linking them together (briding). Very severe damage massive (briding). Very severe damage massive necrosis & FHFnecrosis & FHF

- Cholestasis +_ - Cholestasis +_

Viral HepatitisViral Hepatitis Hepatitis A (HAV)Hepatitis A (HAV) 1- RNA- pecorna virus (27nm)1- RNA- pecorna virus (27nm) 2- Secreted through the bile to the 2- Secreted through the bile to the

stoolsstools 3- Most common type of viral hepatitis3- Most common type of viral hepatitis 4- Faecal- oral spread4- Faecal- oral spread 5- Over crowding & poor sanitation 5- Over crowding & poor sanitation

facilitate spreadfacilitate spread

6- No vertical spread6- No vertical spread 7- parental & sexual transmission is a rare 7- parental & sexual transmission is a rare

possibility during the transient viraemia in the possibility during the transient viraemia in the I.PI.P

8- Patients are most infectious 2-3 weeks before 8- Patients are most infectious 2-3 weeks before the onset of jaundice & 1-2 weeks after .the onset of jaundice & 1-2 weeks after .

9- I.P 2-4 weeks & mainly affect youngs9- I.P 2-4 weeks & mainly affect youngs10- No carrier state or chronic sequelae 10- No carrier state or chronic sequelae 11- Mortality < 0.5% from FHF11- Mortality < 0.5% from FHF12- Passive immunization of contact with 1g 12- Passive immunization of contact with 1g

(0.04 - 0.06 units/kg I.M) protects for 3-4 (0.04 - 0.06 units/kg I.M) protects for 3-4 monthsmonths

13-Vaccin for people traveling to endemic areas 13-Vaccin for people traveling to endemic areas & those with chronic liver disease. Single dose & those with chronic liver disease. Single dose with booster one year after protects for 10yearwith booster one year after protects for 10year

14- Diagnosis : IgM anti HAV indicate acute 14- Diagnosis : IgM anti HAV indicate acute infection (within 3months) & IgG anti HAV is infection (within 3months) & IgG anti HAV is persistent & used for epidemiology persistent & used for epidemiology 15- The virus is cultured for 15- The virus is cultured for research purposes research purposes

Hepatitis B (HBV)Hepatitis B (HBV) 1- DNA hepadna virus (42nm)1- DNA hepadna virus (42nm)

2- Has nucleocapsid core & envelope (capsule)2- Has nucleocapsid core & envelope (capsule)

3- Contains HBsAg, HBeAg, HBcAg, DNA & 3- Contains HBsAg, HBeAg, HBcAg, DNA & DNA polymerase DNA polymerase

4- Parental, sexual & vertical transmission4- Parental, sexual & vertical transmission

5- I.P 1-5 M5- I.P 1-5 M

6- Individual incubating or with clinical attack 6- Individual incubating or with clinical attack are highly infections as long as HBsAg is are highly infections as long as HBsAg is positive positive

7- Carrier rate 0.5-15%7- Carrier rate 0.5-15%

8- Chronic sequelae (chronic hepatitis, 8- Chronic sequelae (chronic hepatitis, Cirrhosis & HCC) can follow infection.Cirrhosis & HCC) can follow infection.

9- Patients with chronic HBV infections are 9- Patients with chronic HBV infections are most infectious when markers of cont. most infectious when markers of cont. replication are present in the blood:( HBeAg, replication are present in the blood:( HBeAg, DNA & DNA polymerase) & least infectious DNA & DNA polymerase) & least infectious when they are absent & anti HBe is positivewhen they are absent & anti HBe is positive

10- Mortality 1% with FHF10- Mortality 1% with FHF

11- Passive immunization with HBIG 11- Passive immunization with HBIG (500units for adult, 200units for (500units for adult, 200units for neonates)neonates)

12- Active immunization with vaccine 12- Active immunization with vaccine containing HBsAg for those at risk & who are containing HBsAg for those at risk & who are anti HBsAg negativeanti HBsAg negative gives 90% protection. gives 90% protection. (day 0,1month , 6months & booster every 3-5 (day 0,1month , 6months & booster every 3-5 years)years)

13- 13- People at riskPeople at risk include: I.V drugs abusers, include: I.V drugs abusers, homosexual, newborn of infected mother, homosexual, newborn of infected mother, regular sexual partener of infected person, regular sexual partener of infected person, dentists, surgeon, causality personale, in ICU, dentists, surgeon, causality personale, in ICU, patients & staff in haemodialysis units, patients & staff in haemodialysis units, endoscopy units, liver units, oncology units & endoscopy units, liver units, oncology units & labs stafflabs staff

14- Viral markers14- Viral markers - HBsAg: acute or chronic hepatitis or - HBsAg: acute or chronic hepatitis or

carrier state carrier state - HBeAg: Persistant replication (highly - HBeAg: Persistant replication (highly

infectious)infectious) - HBV DNA: viral replication- HBV DNA: viral replication - Anti HBsAg: immunity from previous - Anti HBsAg: immunity from previous

exposure or vaccineexposure or vaccine - Anti HBeAg: seroconversion- Anti HBeAg: seroconversion - Anti HBc IgM: acute infection- Anti HBc IgM: acute infection - Anti HBc IgG: previous exposure - Anti HBc IgG: previous exposure

Hepatitis D (HDV)Hepatitis D (HDV) 1- Incomplete RNA virus (35nm)1- Incomplete RNA virus (35nm) 2- Can not replicate by it's own & has no independent 2- Can not replicate by it's own & has no independent

existanceexistance 3- It occur either as super infection to HBV or as 3- It occur either as super infection to HBV or as co-infectionco-infection 4- Similar mode of transmission to HBV specially in 4- Similar mode of transmission to HBV specially in

I.V drug abusers I.V drug abusers 5- I.P (6-9W)5- I.P (6-9W)

6- Diagnosed by detecting IgM anti HDV or by HDV 6- Diagnosed by detecting IgM anti HDV or by HDV

RNA in the serumRNA in the serum

7-Fulminant hepatitis & chronic liver disease 7-Fulminant hepatitis & chronic liver disease can followcan follow

Hepatitis C (HCV)Hepatitis C (HCV) 1- RNA flaviurus (30-38nm)1- RNA flaviurus (30-38nm)

2- Causes chronic liver disease & HCC2- Causes chronic liver disease & HCC

3- Most pts never suffer acute infection3- Most pts never suffer acute infection

4- Parental mode of transmission specially in 4- Parental mode of transmission specially in I.V abusers (90%) & sexual transmission is I.V abusers (90%) & sexual transmission is possible but uncommon. Vertical transmission possible but uncommon. Vertical transmission can occurcan occur

5- I.P (2-26weeks)5- I.P (2-26weeks)

6- Diagnosis by detection of HCV RNA by 6- Diagnosis by detection of HCV RNA by PCR & detection of HCV antibodiesPCR & detection of HCV antibodies

7- Mortality < 1%7- Mortality < 1%

8- Carrier rate varies from 0.2% in Europe , 6% 8- Carrier rate varies from 0.2% in Europe , 6% in Africa & 19% in Egypt in Africa & 19% in Egypt

Hepatitis E(HEV)Hepatitis E(HEV) 1- Prevalent in countries with poor sanitation 1- Prevalent in countries with poor sanitation

and causes water born epidemics and causes water born epidemics

2- RNA calici virus(27nm)2- RNA calici virus(27nm)

3- transmission is faecal oral3- transmission is faecal oral

4- Similar clinical picture to HAV4- Similar clinical picture to HAV

5- No carrier state & no chronic sequelae5- No carrier state & no chronic sequelae

6- Diagnosis by detection of HEV RNA by 6- Diagnosis by detection of HEV RNA by PCR & by detection of IgG & IgM anti HEV PCR & by detection of IgG & IgM anti HEV by Eliza by Eliza

Hepatitis G (HGV)Hepatitis G (HGV) 1- Parental mode of transmission1- Parental mode of transmission

2-No evidence that it causes liver disease2-No evidence that it causes liver disease

Clinical picture of viral hepatitisClinical picture of viral hepatitis 1- Prodromal symptoms preceed clinical 1- Prodromal symptoms preceed clinical

Jaundice by 1-2 WJaundice by 1-2 W

2- Hepatomegaly which is tender2- Hepatomegaly which is tender

3- Rarely spleenomegaly & lymphoadenopathy3- Rarely spleenomegaly & lymphoadenopathy

in children in children

4- Arthralgia, vasculitis, rash, myocarditis and 4- Arthralgia, vasculitis, rash, myocarditis and G.N specially with HBVG.N specially with HBV

5- Yellow sclerae & dark urine. 5- Yellow sclerae & dark urine. 6- Pale stool with cholastasis 6- Pale stool with cholastasis

7- Most (95%) recover in 3-6 W7- Most (95%) recover in 3-6 W

8- Few relapse8- Few relapse

9- An icteric hepatitis occur in 65%9- An icteric hepatitis occur in 65%

10- Massive hepatic necrosis occur in 1% 10- Massive hepatic necrosis occur in 1% causing F.H.Fcausing F.H.F

InvestigationsInvestigations

1- High ALT & AST(> 400U/L)1- High ALT & AST(> 400U/L)

2- High Serum bilirubin2- High Serum bilirubin

3- ALP rarely > 250U/L except in cholastasis3- ALP rarely > 250U/L except in cholastasis

4- Normal serum alb4- Normal serum alb

5- Prolong PT5- Prolong PT

6- Bilirubinuria. 6- Bilirubinuria.

7- Normal or low TWC with lymphsytosis 7- Normal or low TWC with lymphsytosis

8- Viral markers8- Viral markers

9- Mild proteinuria 9- Mild proteinuria

Complications Complications

1- F.H.F1- F.H.F

2- Relapsing hepatitis (biochem. OR clinical)2- Relapsing hepatitis (biochem. OR clinical)

3- Cholestasis3- Cholestasis

4- Post-hepatic syndrome4- Post-hepatic syndrome

5- Unconjugated hyperbilirubinaemia (Gilbert)5- Unconjugated hyperbilirubinaemia (Gilbert)

6- A plastic anaemia (HAV, HCV, HEV)6- A plastic anaemia (HAV, HCV, HEV)

7- Connective tissue disease7- Connective tissue disease

8- G.N & renal failure 8- G.N & renal failure

9- H.Sch. purpura 9- H.Sch. purpura

10- Papular acrodermatitis10- Papular acrodermatitis

11- Chronic hepatitis, liver cirrhosis and HCC 11- Chronic hepatitis, liver cirrhosis and HCC wz HBV &HCV. wz HBV &HCV.

ManagementManagement

1- No specific treatment for acute hepatitis1- No specific treatment for acute hepatitis

2- Bed rest for elderly patients, pregnant ladies 2- Bed rest for elderly patients, pregnant ladies and patient with chronic liver diseaseand patient with chronic liver disease

3- Good diet with vitamins supplements3- Good diet with vitamins supplements

4- Admit severe cases to guard against FHF4- Admit severe cases to guard against FHF

5- Avoid alcohol & sedatives 5- Avoid alcohol & sedatives

6- Avoid fatty meals6- Avoid fatty meals

7- Antiviral (Ribavirin) and alpha interferon7- Antiviral (Ribavirin) and alpha interferon

8- Reassurance for post-hepatic syndrome 8- Reassurance for post-hepatic syndrome

PrognosisPrognosis

1- Mortality 0.5% in patients under 40 years 1- Mortality 0.5% in patients under 40 years and up to 3% in those over 60%and up to 3% in those over 60%

2- Mortality more with co-existing serous 2- Mortality more with co-existing serous diseasedisease

3- 90-95% will have full recovery & 5-10% 3- 90-95% will have full recovery & 5-10% develop chronic infectiondevelop chronic infection

4- Maternal to child infection at birth lead to 4- Maternal to child infection at birth lead to chronic infection in 95% & recovery is rarechronic infection in 95% & recovery is rare

5- Chronic infection is common with immuno-5- Chronic infection is common with immuno-deficiency deficiency

6- Recovery in HBV occur in 6M. with 6- Recovery in HBV occur in 6M. with appearance of anti-bodies to viral agentsappearance of anti-bodies to viral agents

7- Persistence of HBc Ag beyond 6M indicate 7- Persistence of HBc Ag beyond 6M indicate chronic infectionchronic infection

8- 80% of HCV infection are chronic8- 80% of HCV infection are chronic

9- Chronic HBV & HCV remain asymptomatic 9- Chronic HBV & HCV remain asymptomatic for years, however many patients eventually for years, however many patients eventually develop cirrhosis & some progress to HCCdevelop cirrhosis & some progress to HCC

10- Combined HBV, HDV cause more 10- Combined HBV, HDV cause more aggressive disease aggressive disease

PreventionPrevention

1- Improve over crowding & sanitation (HAV)1- Improve over crowding & sanitation (HAV)

2- Active immunization & Ig. for immediate 2- Active immunization & Ig. for immediate protection after exposure for HAV.to those at protection after exposure for HAV.to those at close contacts, elderly, pregnant & other major close contacts, elderly, pregnant & other major diseasesdiseases

3- HBV vaccine to those at special risk who are 3- HBV vaccine to those at special risk who are not already immune (Anti HBs Ag negative).not already immune (Anti HBs Ag negative).

Hyper immune serum glob within 7days.after Hyper immune serum glob within 7days.after exposure to infected bloodexposure to infected blood

4- No vaccine for HCV4- No vaccine for HCV

5- Sterilization of instruments & screening of 5- Sterilization of instruments & screening of blood & blood products for transfusion.blood & blood products for transfusion.

6- Moral vaccine.6- Moral vaccine.

Acute (Fulminat) hepatic failureAcute (Fulminat) hepatic failure 1- Rare condition in which encephalopathy 1- Rare condition in which encephalopathy

result from sudden severe impairment of result from sudden severe impairment of hepatic function occurring within 2W of onset hepatic function occurring within 2W of onset of precipitating illness in the absence of pre-of precipitating illness in the absence of pre-existing liver disease existing liver disease

2- If it occur 2-12W = sub acute FHF2- If it occur 2-12W = sub acute FHF

3- Rare but 90% mortality following acute 3- Rare but 90% mortality following acute hepatitis from any causehepatitis from any cause

4- Causes include 4- Causes include - viral infection (HAV , HBV , HDV) - viral infection (HAV , HBV , HDV) - drugs (pracetamol , aspirin , halothane , - drugs (pracetamol , aspirin , halothane , ATT) ATT) - poisons (mushroom , CCL4) - poisons (mushroom , CCL4) - acute fatty liver of pregnancy - acute fatty liver of pregnancy - shock & cardiac failure - shock & cardiac failure - bud- chiari - bud- chiari syndrome - syndrome - leptospirosis leptospirosis - Wilson's disease - Wilson's disease

5-Pathologically5-Pathologically

- There is extensive liver cell necrosis with - There is extensive liver cell necrosis with severe fatty degeneration being characteristic severe fatty degeneration being characteristic of tetracycline , pregnancy & Reyes of tetracycline , pregnancy & Reyes

- There is cerebral aedema & disruption of - There is cerebral aedema & disruption of BBBBBB

6- Clinically6- Clinically

Low alertness , poor conc. , restlessness , Low alertness , poor conc. , restlessness , aggression, drowsiness , disorientation , aggression, drowsiness , disorientation , change of sleep rhythm & comachange of sleep rhythm & coma

-Slurred speech , yawning , hiccough and -Slurred speech , yawning , hiccough and seizures. seizures. - Asterixis (Flapping tremers) - Asterixis (Flapping tremers) & foeter hepaticus are other features& foeter hepaticus are other features

- Myoclonus , spalicity , decorticate rigidity - Myoclonus , spalicity , decorticate rigidity may be seenmay be seen

- Papilla edema is very late (high I.C.P)- Papilla edema is very late (high I.C.P) - Fever , vomiting , hypotension and - Fever , vomiting , hypotension and

hypoglythemia may occurhypoglythemia may occur - Jaundice & small liver size- Jaundice & small liver size - Fluid retention & spleenomegaly are - Fluid retention & spleenomegaly are

uncommonuncommon

7- Investigation7- Investigation Markedly deranged LFT , ECG ,CBC , BUN & Markedly deranged LFT , ECG ,CBC , BUN &

electrolytes , U/S ,viral markers , toxicity , electrolytes , U/S ,viral markers , toxicity , screening , Auto-antibodies , CXR , se cu & screening , Auto-antibodies , CXR , se cu & caeruloplasmincaeruloplasmin

8- Management8- Management 1- No specific treatment except liver transplant1- No specific treatment except liver transplant 2- Support life & monitor2- Support life & monitor 3- Ranitol , vitK , H2RA ,antibiotics3- Ranitol , vitK , H2RA ,antibiotics 4-Treatment of cardio-respiratory arrest & fail.4-Treatment of cardio-respiratory arrest & fail. 5- Exchange transfusion , plasmapheres & 5- Exchange transfusion , plasmapheres &

charcoal haemoperfusioncharcoal haemoperfusion