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all types of hepatitis


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HEPATITIS Presented by: Disha Patel M.Pharm sem-2 C.P

What Is Hepatitis?:

What Is Hepatitis ? Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ . It can be caused by viruses→ hepatitis A hepatitis B hepatitis C hepatitis D hepatitis E hepatitis G medications→methyldopa /isoniazid Hepatitis A & E having no chances of chronicity & liver cancer while hepatits B, C & D having chances of chronicity & liver cancer.

Table 24.12:

Table 24.12

Sign & symptoms of hepatitis:

Sign & symptoms of hepatitis DARK URINE Abdominal discomfort R ight upper abdominal pain Jaundice Fever Nausea Anorexia Diaherrea Fatigue Hepatomegalin Elevated level of bilirubin

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HEPATITIS TRANSMISSION A Close personal contact Contaminated food, water Blood exposure (rare) B 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. C Percutaneous IV drugs Transfusion, transplant from infected donor Therapeutic (contaminated equipment, unsafe injection practices) Occupational (needle stick) Per mucosal, Perinatal, Sexual D Percutanous-injecting drug use Permucosal- sex contact E Consumption of faecally contaminated drinking water has given rise to epidemic cases, Ingestion of raw or uncooked shellfish has been the source of sporadic cases in endemic areas G blood and blood products and Sexual contact IV drug abuse and other parenteral ways of infection,tattooing transmission from infected mother to a child during the birth possibility of transmission via saliva

Hepatitis A:

Hepatitis A HAV infection is one of the most frequently reported vaccine preventable diseases. HAV does not cause chronic hepatitis and only rarely causes fulminant hepatitis. HAV occurs throughout the world and is endemic in countries with poor hygiene and sanitation. Pathophysiology The natural history of the infection is divided into three stages : Incubation, Acute hepatitis, and Convalescence

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Incubation begins after parenteral or oral inoculation with the virus HAV replication occurs & antigens are found in hepatocyte cytoplasm Largest concentration of viral particles are found in stool specimens during the 1 to 2 weeks During the incubation stage, the host is asymptomatic Acute hepatitis begins with a preicteric phase (before the onset of jaundice) acute anicteric hepatitis

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Hepatocyte destruction to produce significant liver dysfunction characterized by interruption of bilirubin metabolism and flow acute icteric hepatitis Most patients with either acute anicteric or icteric hepatitis go through the convalescence stage IgM anti-HAV usually is detectable 5 to 10 days before symptoms appear. After 2 to 6 months, the IgM antibodies are replaced with IgG antibodies, which usually persist throughout life and confer immunity to HAV.

Diagnosis of HAV:

Diagnosis of HAV Acute infection is diagnosed & Past Infection i.e. immunity is determined by the detection of HAV- IgM & HAV- IgG in serum by EIA . Direct Detection –PCR of faeces . Mild elevations of serum bilirubin γ –globulin ALT and AST values (about twice than normal). Normal values AST > M:8-46 IU/L, F:7-34 IU/L ALT > M:9-69 IU/L, F:3-33 IU/L

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Treatment of HAV A single 0.02-mL/kg dose of Ig is adequate for short trips (less than 3 months), but 0.06 mL/kg dose for every 5 months is necessary for longer visits.


HEPATITIS B HBV structure:

HBV is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma.:

HBV is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Pathophysiology : HBV ↓invade into Human body ↓by Skin & mucosa ↓via Blood flow ↓enter into organs like Liver, pancreas, bileduct , vessels, WBC, bone marrow , glomerular basement membrans . HBcAg,HBsAg,HBeAg and HLA-Ⅰ ↓ appear on infected liver cells. ↓ recognized by CTL simultaneously ↓lead to cytolysis of liver cells

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Acute hepatitis B infection 3-5% of adult acquired infections Liver failure Hepatocellular carcinoma Chronic HBV infection 95% of infant acquired infections Chronic hepatitis Cirrhosis Liver transplant Death Death 12-25% in 5 years 20-23% in 5 years 6-15% in 5 years Possible Outcomes of HBV Infection

Diagnosis of HBV:

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

Treatment of HBV:

Treatment of HBV Interferon - alpha-interferon 2b (original) alpha-interferon 2a (newer, claims to be more efficacious and efficient) Lamivudine – 100mg/day. a nucleoside analogue reverse transcriptase inhibitor. Well tolerated but problem is the rapid emergence of drug resistance. Adefovir –10mg/day. less likely to develop resistance than Lamivudine and may be used to treat Lamivudine resistance HBV . However more expensive and toxic Entecavir –0.5mg/day. most powerful antiviral. Successful response to treatment will result in the disappearance of HBsAg , HBV-DNA .


Cont.. Hepatitis B Immunoglobulin – HBIg is particular effective within 48 hours of the incident. Hepatitis B immune globulin (HBIG) is produced from plasma that contains high titers of antibody against HBsAg . It is used to provide passive immunity against hepatitis B infection. HBIG (0.06 mL/kg for adults and children) should be administered by IM injection. Newborns of hepatitis B surface antigen positive mothers should receive HBIG 0.5 mL IM within 12 hours of birth. The most common adverse reactions of HBIG are local pain, swelling, and erythema at the injection site. Allergic reactions, body and joint pain, muscle cramps, malaise, and fever have also been reported.

Hepatitis C:

Hepatitis C Hepatitis C virus also known as Non A or Non B virus found while doing experiments on Chimpanzees. HCV has been classified into a total of six genotypes (type 1 to 6) on the basis of phylogenetic analysis. Genotype 1 and 4 has a poorer prognosis and response to interferon therapy. In chronic HVC CD4+T & CD8+T cells have been identified . Due to HCV. ↓ hepatocytic injury ↓ Produce antiviral cytokines ↓by T-lymphocytes


Pathophysiology The incubation period for HCV hepatitis ranges from 2 to 26 weeks, with a mean of 6 to 12 weeks. HCV enters in hepatocytes Uncoats virus and release genome for replication Viral genome work as templete for translation of polyprotein Non structural protein form complex with genome and formation of positive strand RNA interact with envelope and core the protein New virus synthesized

Diagnosis of HCV:

Diagnosis of HCV HCV antibody -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 . ELISA test results to be confirmed with Immunoblotting assay.

Clinical Outcome of Hepatitis C Infection:

Clinical Outcome of Hepatitis C Infection Acute Infection Fulminant < 1% Asymptomatic, anicteric 70-80% Symptomatic, icteric 20-30% Chronic infection 70-85% Death Complete Recovery 15-30% Mild hepatitis 30-50% Chronic hepatitis more severe 20-50% * Cirrhosis, irreversible 10-20% * Hepatocellular carcinoma 5-10% * Death

Treatment of HCV:

Treatment of HCV Interferon - may be considered for patients with chronic active hepatitis. The response rate is around 50% but 50% of responders will relapse upon withdrawal of treatment. Ribavirin -Dose is 800ml/kg. R ecent studies suggest that a combination of interferon and ribavirin is more effective than interferon alone . No vaccine is available for HCV infection.

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Drug Brand name Dose Action A/E Other Lamivudine Hepavud 100 mg/d Supressed HBV DNA Transient ALT elevation Resistance is produced Adefovir Adesera 10 mg/d Supressed HBV DNA Headache Abdominal pain, nephrotoxicity Effective in lamivudine resistant Entecavir Baraclude 0.5 mg/d Supressed HBV DNA Lung adenomas Lamivudine resistant 1.0 mg/d Ribavirin Cap Rebetol 800 mg/d Inhibit DNA & RNA viruse Insomnia, depression, rash, pruritus Use in hep B & hep C

Hepatitis D:

Hepatitis D Hepatitis D is caused by the virus HDV. You can only get hepatitis D if you are already infected with hepatitis B . HDV is caused by direct cytopathic effect on hepatocytes .


Pathophysiology Delta hepatitis arises in two ways :(1) coinfection and (2) superinfection In first case, HBV infection become established before HBsAg is available for the development of complete HDV virions coinfected persons can clear the viruses and recover completely Fulminant hepatitis, and rarely chronic hepatitis, may occur In superinfected individuals in most cases, there is an acceleration of hepatitis, most often to leads chronic hepatitis carrier may have been previously asymptomatic ("healthy") or may have underlying chronic hepatitis

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DIAGNOSIS : Following HBV-HDV co-infection both IgM anti-HDV and IgG anti-HDV are detectable in the serum. Following HBV-HDV super infection , chronic HDV infection with detectable HDAg usually occurs. Both IgM anti-HDV and IgG anti-HDV remain detectable .

Treatment :

Treatment Alpha-interferon (IFN) effective therapy for hepatitis D. Dose of IFN : 9 million units (MU) three times a weekly. Besides IFN, other drugs such as, acyclovir, ribavirin have been helpful. Pegylated -IFN could represent a reasonable therapeutic option in the chronic hepatitis D. Liver transplantation provides a valid option for end-stage HDV liver disease. Hepatitis D infection can also be prevented by hepatitis B vaccine .

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Hepatitis E It is caused by the virus HEV. Replicative virus has been found in the → small intestine colon lymph nodes liver of experimentally infected pigs. It causes swelling of the liver, but no long-term damage. It is Calicivirus .

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Diagnosis of HEV Acute hepatitis E is diagnosed when the presence of IgM & IgG anti-HEV is detected . Immunofluorescent antibody blocking assays to detect antibody to HEV antigen in serum and liver . Immune electron microscopy to visualize viral particles in faeces . HEV RNA can be detected in acute phase faeces by PCR.


Treatment Pegylated α- interferon can effectively treat chronic HEV infection. Ribavirin was given at 600-800 mg/day in 2 separate doses. Ribavirin inhibits the replication of HEV. After three months therapy of ribavirin HEV RNA may undetectable in serum. Anemia was the main side effect caused by ribavirin therapy.


HEPATITIS G HGV is RNA virus and is similar to HCV but only has 25 amino acids. A 34 year-old surgeon name G . Barker, who fell ill in 1966 with a non-A non-B hepatitis which at the time was thought to have been caused by a new, infectious hepatic virus . In 1995-96 the virus was identified as a distinct virus different from other human hepatitis viruses (A, B, C, D, E) and was named “GB agent” after the surgeon & then known as HGV. Three genotypes of this virus were identified by investigators and termed GB-A, GB-B and GB-C. GB-A and GB-B are likely tamarin viruses; GB-C can infect humans. It can be diagnosed only by detecting its RNA in the serum by polymerase chain reaction.


Cont … HGV is a distinct from the other hepatitis viruses. It is found in blood donor, patients on heamodialysis and as a coinfection with HIV. HGV is cleared from plasma in majority of people. Small percentage of cases have chronic HGV infection who do not develop hepatitis in also their blood is not infected with this virus. This type of patients daignosed by screening of HGV-RNA in patients serum.

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HEPATITIS PREVENTION A Vaccination Maintain good hygienic condition B Vaccination Never share drug equipment, i.e. needles, syringes Never share tooth brushes/razors or any personal hygiene articles that have blood on them (even tiny amounts) Always make sure new & sterilized equipment is being used for tattooing & piercing Make sure ink for tattooing is not being shared C No vaccine is available. Current recommendations for prevention of HCV include universal precautions for the prevention of blood-borne infections and anti-HCV screening of blood, organ, and tissue donors . Programs that focus on reducing HIV transmission are also likely to decrease transmission of HCV in high-risk groups. D There is no vaccine for Hepatitis D, but it can be prevented in persons who are not already HBV-infected by giving Hepatitis B vaccine E The only way to prevent the disease is to reduce the risk of exposure to the virus. Reducing risk of exposure means avoiding tap water when traveling internationally and practicing good hygiene and sanitation. Avoid drinking water (and beverages with ice) of unknown purity and uncooked fruit/vegetables G No vaccine available Use of disposable syringes and avoiding contaminated needles for ear piercing and tattooing are also effective measures.

Drug induced hepatitis:

Drug induced hepatitis Definition : Drug-induced hepatitis involves inflammation of the liver, caused by medication. Drug-induced hepatitis is similar to acute viral hepatitis but parenchymal destruction tends to be more extensive. Painkillers and fever reducers that contain acetaminophen are a common cause of liver inflammation . Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen, may also cause drug-induced hepatitis.


Cont … Drugs that cause ACUTE hepatitis: Acetaminophen Phenytoin Aspirin Isoniazid Diclofenac Amoxicillin / clavulanic acid Drug that cause CHRONIC hepatitis : Minocycline Nitrofurantoin Phenytoin Propylthiouracil Fenofibrate methamphetamine

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The clinical course of drug-induced hepatitis is quite variable, depending on the drug and the patient's tendency to react to the drug. For example, halothane hepatitis can range from mild to fatal as can INH -induced hepatitis. Hormonal contraception can cause structural changes in the liver. Amiodarone hepatitis can be untreatable since the long half life of the drug (up to 60 days) means that there is no effective way to stop exposure to the drug. Statins can cause elevations of liver function blood tests normally without indicating an underlying hepatitis. Lastly , human variability is such that any drug can be a cause of hepatitis.

Diagnosis :

Diagnosis Specific laboratory blood tests , such as the following: Liver function studies Cellular blood counts Bleeding times Electrolyte tests Tests for other chemicals in the body Drug screening tests Ultrasound (also called sonography ). Liver biopsy.

Tretment :

Tretment Specific treatment for drug-induced hepatitis will be determined by your doctor based on: Your age, overall health, and medical history Extent of the disease Your tolerance for specific medications, procedures, or therapies Expectations for the course of the disease

Management :

Management There is no specific treatment for drug-induced hepatitis other than discontinuing the medication that is causing the problem. People with acute hepatitis should avoid physical exertion, alcohol, paracetamol and any other hepatotoxic substances Unfortunately, other than the use of N- acetylcysteine for paracetamol hepatotoxicity, there are no specific antidotes for drug-induced liver disease . Supportive care for acute liver failure and even liver transplantation may be required . You should rest during the acute phase of drug-induced hepatitis, when the symptoms are most severe. If you have more severe nausea and vomiting, you may need to get fluids through a vein .

Prevention :

Prevention If you use over-the-counter medications containing acetaminophen (Tylenol), never use more than the recommended dose. If you drink heavily or regularly, you should avoid these medications or discuss safe doses with your health care provider . If you have liver disease, it is very important to tell your doctor about all the medicines you take. You should avoid the medications like Acetaminophen & Phenytoin.


References … Eric T. Herfindal , et al; Textbook of therapeutics; Drug & Dieses management; 8 th edition 2006; lippincott wililans & wilkins ; page no: 1331-1345 Pharmacotherapy; Joseph T. Dipiro , Robert L.Talbert , et al; 6 th edition 2005; page no: 737-756. Roger walker; Clinical Pharmacy & Therapeutics book; 3 rd edition 2004; page no: 209-228. Harsh mohan ; Textbook of Pathology; 6 th edition 2010; page no: 605-614. http:// en.wikipedia.org/wiki/Hepatitis

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