ACUTE…….Hepatitis A and E ACUTE AND CHRONIC ……. Hepatitis B and C Viral Hepatitis ACUTE…….Hepatitis A and E ACUTE AND CHRONIC ……. Hepatitis B and C

HEPATITIS A VIRUS It is RNA virus . Route of transmission of HAV is the fecal-oral route, by either person-to-person contact or ingestion of contaminated food or water. Hepatitis A is acute and usually self limited and never be chronic (i.e. never more than 6 months duration). Patients with HAV infection usually present with one of the following five clinical patterns: (1) asymptomatic without jaundice, (2) symptomatic with jaundice and self-limited after approximately 8 weeks, (3) cholestatic, with jaundice lasting 10 weeks or more, (4) relapsing, with two or more bouts of acute HAV infection occurring over a 6- to 10-week period, and (5) Fulminant hepatic failure.

Prodromal symptoms in patients with acute hepatitis A include fatigue, weakness, anorexia, nausea, vomiting, and abdominal pain. Less common symptoms are fever, headache, arthralgias, myalgias, and diarrhea. Symptoms of hepatitis may last from a few days to 2 weeks and usually decrease with the onset of clinical jaundice. Right upper quadrant tenderness and mild liver enlargement are found on physical examination in 85% of patients. Complete clinical recovery is achieved in 60% of affected persons within 2 months and in almost everyone by 6 months. The overall prognosis of acute hepatitis A in otherwise healthy adults is excellent. Potentially fatal complications (e.g., FHF) develop in a few patients .

Certain populations have increased morbidity and a high risk of acute liver failure ( FHF ) from HAV infection. Among these groups are the elderly and persons with chronic liver disease and HIV infection. Bad signs include deep jaundice , prolonged PT and encephalopathy. Diagnosis of acute hepatitis A requires demonstration of IgM anti-HAV in serum. The test result is positive from the onset of symptoms and usually remains positive for approximately 4 months. Treatment is symptomatic. HAV vaccine is available for high risk non infected groups.

Groups at High Risk of Hepatitis A Virus Infection Healthy persons who travel to endemic areas, work in occupations for which the likelihood of exposure is high, are family members of infected patients, or adopt infants or children from endemic areas. Persons who have tested positive for human immunodeficiency virus. Persons with chronic liver disease. Persons with clotting factor disorders. Users of injection and noninjection illicit drugs.

HEPATITIS E VIRUS It is RNA virus . Route of transmission of HEV is the fecal-oral route, by either person-to-person contact or ingestion of contaminated food or water. Hepatitis E is acute and usually self limited and never be chronic (i.e. never more than 6 months duration). Patients with HAV infection usually present with one of the following five clinical patterns: (1) asymptomatic without jaundice, (2) symptomatic with jaundice and self-limited , (3) cholestatic, (4) relapsing, (5) Fulminant hepatic failure. Have high morbidity and mortality in pregnant woman. Diagnosis: Enzyme immunoassays (EIAs) for the detection of immunoglobulin M (IgM) and IgG antibodies to HEV. Treatment is symptomatic.

HEPATITIS B VIRUS It is DNA virus. HBV is transmitted efficiently by percutaneous and mucous membrane exposure to infectious body fluids. The virus is 100 times as infectious as human immunodeficiency virus (HIV) and 10 times as infectious as hepatitis C virus (HCV). HBeAg seropositivity indicates a higher risk of transmission. Route of transmission of HBV: sexual, vertical (from an HBV carrier mother to her neonate at delivary), needlestick exposure, injection drug use, Other less common sources of infection are household contact with an HBV carrier, hemodialysis, exposure to infected health care workers, tattooing, body piercing, artificial insemination, and receipt of blood products or organs. May be acute or chronic ( the chronic may be carrier or active. The active one may be cirrhotic or not) .

HBV carrier has often been used to refer to persons persistently infected with HBV who have normal serum aminotransferase levels. Acute hepatitis B : one of the following five clinical patterns: (1) asymptomatic without jaundice ( the usual story), (2) symptomatic with jaundice , (3) cholestatic, (4) Fulminant hepatic failure. Clinical Sequelae of Acute Hepatitis B Virus Infection: The age at which a person becomes infected with HBV is a principal determinant of the clinical outcome. HBV infection in adults with an intact immune system is likely to cause clinically apparent acute hepatitis B; only 1% to 5% of these persons become chronically infected. By contrast, as many as 95% of infected neonates become chronic HBV carriers because of immunologic tolerance to the virus.

Clinical Sequelae of Chronic Hepatitis B Virus Infection: Chronic hepatitis B develops in 2% to 5% of persons who acquire HBV infection in adulthood. Progressive liver disease (including cirrhosis and HCC) can be expected to develop in one quarter to one third of people who acquire infection in the first few years of life. An estimated 15% to 25% of patients ultimately die of liver-related causes, with the greatest risk in male . The presence of active viral replication and long-standing necroinflammatory liver disease caused by HBV strongly influences the rate of progression to cirrhosis. Cirrhosis is associated with decreased survival and an increased frequency of HCC.

DIAGNOSIS HBsAg = infection ( presence of virus) HBsAb = previous infection in past or previous vaccination. HBcAb IgM type = acute infection ( c = core) HBcAb IgG type = chronic infection HBeAg +ve = more viral replication and more infectivity while HBeAg –ve = less repliction and less infectivity. PCR viral load( HBV DNA level ) = viral activity, active virus if more than 2000 IU/ML AND carrier inactive virus if less than 2000 IU/ML . Liver enzymes : increased ALT = INDICATOR of necoinflammation of the liver. Liver biopsy in selected case of chronic HBV Liver ultrasound and liver fibroscan to evalute the liver Virus genotypes ( from A to H ) : The worst is genotype D.

TREATMENT by antiviral drugs indicated in any chronic active HBV ( active mean PCR more than 2000 IU/ ML ) WITH increased ALT . The drugs either 1- pegylated interferon alpha ( which is used in non cirrhotic HB patient and in non genotype D ) and it is given by subcutaneous injection . OR 2- oral antiviral (Nucleoside and Nucleotide Analogs ) : The best are either entecavir or tenofovir, they are preferable in cirrhotic patient and in genotype D in whome peginterferon alpha not to be used. They are also can be used in chronic non cirrhotic patient. Prevention : Immunoprophylaxis against HBV is of two types: passive immunization using HBIG and active immunization using inactive HBsAg. Active immunization gives long-term immunity, whereas passive immunization confers only immediate and short-lived protection.

Hepatitis B Immunoglobulin: HBIG is prepared from plasma that is known to contain high titers of anti-HBs. Numerous clinical trials have established the efficacy of HBIG in preventing HBV infection in high-risk persons, such as hemodialysis patients, sexual partners of patients with hepatitis B, and newborn infants of HBsAg-positive mothers. Hepatitis B Vaccine : The vaccines typically achieve an anti-HBs titer greater than 100 mIU/mL. Antibody titers greater than 100 mIU/mL confer 100% protection against HBV infection, and a lower antibody titer (up to 10 mIU/mL) is seroprotective in most instances. It is given in 3 doses ( at 0,1,6 monthes intervals )  High-Risk Groups for Whom Hepatitis B Virus (HBV) Vaccination Should Be Considered :    Heath care workers, Hemodialysis patients, Household contacts and sexual partners of HBV carriers or patients with acute hepatitis B, Injection drug use,  International travelers to areas endemic for HBV who may have intimate contact with the local population or take part in medical activities,  Men who have sex with men,  Patients who are likely to require multiple transfusions with blood or blood products, Patients with chronic liver disease (other than chronic hepatitis B), Potential organ transplant recipients, Public safety workers with likelihood of exposure to blood,  Sexually active heterosexual men and women, if they have more than one partner,  Staff and clients of institutions for developmentally disabled. Postexposure to HBV to a known HBsAg-positive source OR PERINATAL exposure: should received HBIG withen 12 hours and start vaccination for non vaccinated or one with unknown response to previous vaccination.

HEPATITIS D VIRUS It is RNA virus. It needs active HBV for its repliction (HDV infection becomes pathogenic only if HBV coinfection is present ). Dignosis : Anti D Ab , PCR HDV RNA . TREATMENT : PEGINTERFERON plus treatment of conifected HBV.

HEPATITIS C VIRUS It is RNA virus . May be acute or chronic ( the chronic may be carrier or active. The active one may be cirrhotic or not) . Modes of transmission of HCV can be divided into percutaneous (blood transfusion and needlestick inoculation) and nonpercutaneous (sexual contact and perinatal exposure). Acute hepatitis C: one of the following five clinical patterns: (1) asymptomatic without jaundice ( the usual story), (2) symptomatic with jaundice , (3) cholestatic, (4) Fulminant hepatic failure. The rate of viral persistence after acute infection ( i.e. transmitted to chronic HCV) varies, ranging from 45% to more than 90%. Age and gender clearly influence the risk of chronicity, with younger and female patients having the lowest rates of chronicity.

Serum alanine aminotransferase (ALT) levels are usually elevated in patients with chronic HCV infection. Because levels commonly fluctuate, however, as many as one half of patients may have a normal ALT level at any given time. DIAGNOSIS : 1- Anti HCV Ab ( used as screening test ) 2- PCR confirmation for infection if Anti HCV Ab +ve then PCR VIRAL LOAD . 3- HCV GENOTYPING ( from 1 to 6 ) should be done because treatment regimen depend on genotype. 4- liver fibroscan ((or liver biopsy) especially in genotype 1 and 4 .

Factors Associated with Progression of Hepatic Fibrosis and cirrhosis in Patients with Chronic HCV Infection: Age >40 years, Alcohol consumption, Hepatitis B virus coinfection, HIV coinfection, Immunosuppressed state, Insulin resistance, Obesity, Severe hepatic necroinflammation, White race, Male gender, Increased hepatic iron concentration. BUT Viral genotype and Viral load not associated with disease progression. Treatment : should be in combination therapy ( at least 2 drugs together and may be 3), the drugs used are peginterferon , ribavirin and new direct acting antiviral drugs (DAA) e.g. sofosbuvir. The best predictor of response to treatment is genotype and the rate of the initial fall in serum HCV RNA levels during treatment.

Other viral hepatitis : hepatitis G virus , EBV , cytomegalovirus , herpes virus. Bacterial hepatitis : Gram +ve and –ve , TB. Parasitic : e.g. amebiasis and schistosomiasis. Fungal : candidiasis and histoplasmosis. Liver abscess : either pyogenic or amebic.

AUTOIMMUNE HEPATITIS Autoimmune hepatitis (AIH) is a disorder of unknown cause characterized by unresolving inflammation of the liver and by the presence of interface hepatitis on histologic examination , hypergammaglobulinemia, and autoantibodies. TYPICALLY affecting young female with female to male ratio 9:1. Diagnosis requires the exclusion of other chronic liver diseases that have similar features, including Wilson disease, chronic viral hepatitis, drug-induced liver disease, nonalcoholic fatty liver disease, and the immune cholangiopathies of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC).

DIAGNOSTIC CRITERIA: elevation of the serum aminotransferase levels ( elevated AST or AST/ALK PHOSPHATASE > 3) + ELEVATERD Gamma globulin or IgG level (hyperGamma globulinemia) . Seropositivity for autoantibodies including antinuclear antibodies (ANA), smooth muscle antibodies (SMA), or antibodies to liver-kidney microsome type 1 (anti-LKM1). Exclusion of other similar disorders ( -ve AMA, normal ceruloplasmin, normal alfa 1 antitrypsin, normal s.iron,-ve HBsAg,Anti HC Ab,Anti HA Ab, alcohol intake < 25 gm/ day, -ve drugs and toxin). Interface hepatitis on histologic examination.

CLASSIFICATION: TYPE 1 AUTOIMMUNE HEPATITIS: Type 1 AIH is characterized by SMA, ANA, or both . Antibodies to actin have greater specificity, but less sensitivity, for the diagnosis of AIH than SMA. Most affected persons are young ladies. TYPE 2 AUTOIMMUNE HEPATITIS : Type 2 AIH is characterized by the expression of anti-LKM1 .Most affected persons are children (ages 2 to 14 years),

:TREATMENT REGIMENS : Steroids (prednisone), alone or at a lower dose in combination with azathioprine, is effective therapy. END POINTS : Glucocorticoid therapy is continued until remission(absence of symptoms, resolution of all laboratory indices of active inflammation, and histologic improvement to normal or minimal changes). That is occur withen 3 – 4 years in most patients. LIVER TRANSPLANTATION : Liver transplantation is effective in the treatment of decompensated AIH.