Viral hepatitis. Wei-Min Ke Department of Infectious Diseases Sun Yat-sen University Mar.13, 2009, Friday, Session 8~9 Classroom 503 Mar.20, 2008, Friday, Session 8~9 Classroom 503. Ⅰ. Outline ⒈Definition Viral hepatitis is one group infectious diseases of liver lesions
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Department of Infectious Diseases
Sun Yat-sen University
Mar.13, 2009, Friday, Session 8~9 Classroom 503
Mar.20, 2008, Friday, Session 8~9 Classroom 503
The manifestations of viral hepatitis are similar,
include fatigue, anorexia, hepatomegaly and abnormal liver functions;
jaundice only in some patients.
Fatigue Anorexia Hepatomegaly Jaundice
and mainly transmitted by fecal-oral route.
But hepatitis B, C and D can be responsible to acute or chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC).
Acute hepatits Chronic hepatitis Cirrhosis HCC
Hepatitis B, C and D are often transmitted by parenteral transmission,
The pathogens of viral hepatitis only are hepatitis viruses included hepatitis A, B, C, D, and E.
From now on pathogenesis of hepatitis G, transfusion transmitted virus (TTV), Sen virus (SENV) has not been demonstrated to be causative of the liver diseases.
Hepatitis A virus particles
Hepatitis A virus (HAV) found in feces is helpful to confirm the HAV present infection and infectivity.
But hepatitis A virus infection is no chronic carrier state.
Hepatitis B virus
The viral genome consists of partially double-stranded DNA, 3.2 kb in length,
The S gene has three start codons and is capable of producing three different sizes of HBsAg (small, medium, and large S).
Hepatitis B virus (HBV) consists of three antigen and antibody systems.
HCV originally was identified by molecular clone techniques in 1989.
HCV circulates as a double-shelled enveloped virus, 30 to 60 nm in diameter.
Hepatitis C virus
which is about 9.4 kb in length,
contains a single, large open-reading frame,
encodes a large polyprotein,
post-translationally modified into three structural and several nonstructural polypeptides.
The structural proteins include two highly variable envelope antigens (E1 and E2) and a relatively conserved nucleocapsid protein (C).
Hepatitis D virus
The viral genome is 7.2~7.6 kb in length and encodes three open-reading frames,
the first (ORF1) for the nonstructural proteins responsible for viral replication,
the second (ORF2) for the capsid protein (HEV antigen),
and the third (ORF3) for a short protein of unknown function.
Hepatitis E virus
China is the high prevalent region of viral hepatitis and anti-HAV-IgG positive rate is about 80%.
There are 350 million of HBsAg carriers around the world, about 120 million in our country.
The current infections of HCV are 170 million around the world, about 30 million in our country.
Prevalent rates of hepatitis D and E in population are about 1% and 17% in our country, respectively.
⑴ Sources of infection in hepatitis A
Consumption of shellfish from contaminated waterways is a well-known but uncommon source of hepatitis A.
⑴ Sources of infection in hepatitis B
Hepatitis B is spread predominantly by the parenteral route or by intimate person contact.
Investigations of the source of hepatitis B reveal that most adult cases are due to sexual or parenteral contact.
intimate person contact
Blood transfusion and plasma products are now rarely infections for hepatitis B because of the institution of routine screening of blood donations for HBsAg and anti-HBc.
Maternal-infant spread of hepatitis B is another important mode of transmission not only in endemic areas of the world, but also in the country among immigrants from the endemic areas.
Routine screening of pregnant women and prophylaxis of newborns are now recommended.
Intrafamilial spread of hepatitis B also can occur, although the mode of spread in this situation is not well defined.
Human without anti-HBs is susceptible to hepatitis B virus.
⑵ Routes of transmission in hepatitis C
Hepatitis C is spread predominantly by the parenteral route.
At highest risk are injection drug users and persons with multiple parenteral exposures.
Sexual transmission of hepatitis C occurs but is not common.
Maternal-infant spread occurs in about 5% of cases, usually to infants whose mothers have high levels of HCV RNA in serum.
Other potential sources of HCV are needlestick accidents.
Since the introduction of routine screening of blood for anti-HCV, post-transfusion hepatitis C has become rare.
Humans are susceptible to HCV generally,
no protective immunity to in different species after infection.
⒋ Hepatitis D
Hepatitis D is linked to hepatitis B, and consequently its epidemiology is similar.
HDV can be spread by the parenteral route and sexually.
⑴ Sources of infection in hepatitis E
The source of infection only is acute case of hepatitis E.
⑵ Route of transmission in hepatitis E
HEV is spread by the fecal-oral route, and most cases can be traced to exposure to contaminated water under poor sanitary conditions .
Large outbreaks have been described from India, Pakistan, China, Northern and central Africa, and Central American.
119,000 of patients with hepatitis E were reported in south region of Xinjian in 1986 to 1988 due to contaminated source.
Covert infection is common in children and clinical infection is often in adult.
Mechanisms of viral persistence and of hepatocellular injury in patients with chronic HCV infection are poorly understood.
In generally, viral infection can produce cellular injury by direct cytopathogenicity and indirect immune-mediated injury.
⒌Pathogenesis of Hepatitis E
Acidophilic body formation
According to liver biopsy sections:
Fibrin morphometrical measurements in fibrosis S1, S2, S3, S4 are 8.3%, 11.4%, 14.9%, 20.7% respectively.
Correspondingly, the liver parenchyma morphometrical measurements in fibrosis S1, S2, S3, S4 are 91.7%, 88.6%, 85.1%, 79.3% respectively.
Chronic severe form hepatitis
The average incubation periods
4 weeks(2~6weeks) in hepatitis A;
three months(1~6 months) in hepatitis B;
6 weekss (2 weeks~6 months) in hepatitis C
4~20 weeks in hepatitis D
6 weeks (2~9weeks) in hepatitis E
The onset of dark urine marks the icteric stage of illness, during which jaundice appears, and symptoms of fatigue and nausea worsen.
If jaundice is severe, stool color lightens, and pruritus may appear.
Physical examination usually shows jaundice and hepatic tenderness.
In more severe cases, hepatomegaly and splenomegaly may be present.
The symptoms and jaundice disappear gradually, and enlargement of liver and splenomegaly recover to normal.
The duration is 1 to 2 months.
⑵Anicteric form of acute hepatitis
Hepatitis D occurs in two clinical patterns, termed coinfection and superinfection.
Delta coinfection is the simultaneous occurrence of acute HDV and acute HBV infections.
It resembles acute hepatitis B but may manifest a second elevation in aminotransferase levels associated with the period of delta virus replication.
Acute delta superinfection is the occurrence of acute HDV infection in a chronic HBV carrier.
Superinfection with HDV is more frequent than coinfection and is far more likely to lead to chronic hepatitis D.
Hepatitis D trends to be more severe than hepatitis B alone
and is more likely to lead to fulminant hepatitis and more likely to cause severe chronic hepatitis and ultimately cirrhosis.
Hepatitis E is frequently cholestatic, with prominence of bilirubin and alkaline phosphatase elevations.
Hepatitis E also trends to be more severe than other forms of epidemic jaundice,
with a fatality rate of 1 to 2% and a particularly high rate of acute liver failure in pregnant women.
Decreased liver size Hepatic encephalopathy deepen jaundece
ascites lowed PTA hepatorenal syndrome
⒈ Routing blood examination
White blood cell count is normal or slight decreased, and lymphocytes are elevated in acute hepatitis; sometimes atypical lymphocytes can be seen.
But white blood cells are increased in severe form hepatitis.
Deceases of platelet, RBC and WBC can be found in cirrhosis with hypersplenism.
The detection of bilirubinuria and urobilinogen can make diagnosis of hepatitis early and help to differentialdiagnosis of jaundice.
Bilirubinuria and urobilinogen are positive in hepatic cell jaundice at the same time.
Bilirubinuria and urobilinogen are predominently increased in obstructive and hemolytic jaundice, respectively.
In chronic hepatitis, mild, moderate and severe chronic hepatitis can be classified according to the different levels of ALT, T Bilirubin, Albumin, albumin/globulin, νGlobulin, choline esterase and prothrombin activity.
⑴Serology of hepatitis A (IgM, IgG antibodies against HAV)
⑸ Serology of hepatitis E
Morphology of liver and spleen can be measured accurately.
However, these are nonspecific, and in the vast majority of cases biopsy is not indicated.
⒈ Hepatic encephalopathy
⒊ Hepatorenal syndrome
Case history, symptoms and physical examinations.
Severe chronic hepatitis can easily develop into chronic severe form hepatitis or decompensated cirrhosis.
3. Caution for hepatic decompensation particularly in patients with moderate/severe cirrhosis or severe reactivation of hepatitis.
but development of drug resistance may reverse the benefits.
2. Proven to be able to retard disease progression including reducing the risk of hepatocellular carcinoma in patient with chronic hepatitis B infection with long-term therapy.
Efficacy at one year:
1. HBV DNA suppression (<400 copies/ml):
HBeAg (+) 21%; HBeAg (-) 51%.
2. HBeAg seroconversion: 12% (29% at year 2).
3. ALT normalization:
HBeAg (+) 48%; HBeAg (-)72%.
HBeAg (+): 0% (year 1), 3% (year 2-3), 20% (year 5).
HBeAg(-): 0%, 3%, 11%, 18%, 29% (from year 1 to 5).
Side effect of adefovir:
Efficacy at one year:
1. HBV DNA suppression (<300 copies/ml):
2. HBeAg seroconversion: 22%.
3. ALT normalization:
HBeAg(+) 77%, HBeAg (-)74%.
HBeAg(+)4.4%(year 1), 21.6%(year 2);
HBeAg(-)2.7%(year 1), 8.6%(year 2).
same as that for lamivudine.
A.Oral administration has poorly absorbable antibiotics such as neomycin, norfloxacin and lactulose.
C.Administration of branched-chain amino acids can increase the ratio of plasma aromatic amino acids to branched-chain amino acids.
Fungal infections develop in up to one third of patients with severe form hepatitis. The majority of these are caused by candida albicans.
Liver transplantation has transformed the management of patients with decompensated cirrhosis and liver failure.
live attenuated hepatitis A vaccine
After accidental needle stick and of infants born to HBsAg-positive mothers, the first vaccine dose is combined with HBIG,
In any case, it is established that administration of the vaccine to individuals already infected or immune is not harmful.
hepatitis B immune globulin,HBIG