Viral hepatitis

Pharmacotherapeutics of viral hepatitis

1. Dr . V. S. Swathi Assistant professor Viral Hepatitis

2. Definition Viral hepatitis is an inflammation that causes liver inflammation and damage by hepatitis virus A, B, C, D and E.

3. Epidemiology Globally around 2.3 billion people of the world are infected with one or more of the hepatitis virus and results around 1.4 million deaths In India: Chronic HBV infection accounts for 40-50% of hepatocellular carcinoma Chronic HBV infection accounts for 20-30% of cirrhosis Chronic HCV infection accounts for 12-32% of hepatocellular carcinoma Chronic HCV infection accounts for 12-20% of cirrhosis

4. Types Hepatitis A - It is caused by Hepatitis A Virus (HAV), self limiting, and leads to acute infection and mainly transmitted by contaminated food and water Hepatitis B - It is caused by Hepatitis B Virus (HBV), severe, and leads to chronic infection and mainly transmitted by injectables Hepatitis C - It is caused by Hepatitis C Virus (HCV), severe, and leads to chronic infection, mainly transmitted by injectables Hepatitis D - It is caused by Hepatitis D Virus (HDV), commonly occurs in patients with Hepatitis B, causes chronic infection and mainly transmitted by injectables Hepatitis E - It is caused by Hepatitis E Virus (HEV), self limiting, and causes acute infection and mainly transmitted by contaminated food and water

5. Risk factors Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E Poor sanitation Lack of safe water Living in a household with an infected person Sex with hepatitis affected partner Use of recreational drugs Patients undergoing blood transfusion and dialysis Infants Children Injectable drug users Patients undergoing blood transfusion and dialysis Injectable drug users Intranasal drug users Patients undergoing blood transfusion and dialysis People live in closed settings Sex with hepatitis affected partner Children born to mother infected with HCV People who have tattoos/ piercings Injectable drug users Chronic HBV carriers People who are not immune to HBV vaccine Sex with hepatitis affected partner Poor sanitation Ingestion of undercooked meat Injectable drug users Patients undergoing blood transfusion and dialysis Children born to mother infected with hepatitis

6. Etiology Hepatitis A- It is caused by Hepatitis A Virus (HAV) Hepatitis B- It is caused by Hepatitis B Virus (HBV) Hepatitis C- It is caused by Hepatitis C Virus (HCV) Hepatitis D- It is caused by Hepatitis D Virus (HDV) Hepatitis E- It is caused by Hepatitis E Virus (HEV)

7. Pathogenesis of Hepatitis A and E

8. Pathogenesis of Hepatitis B,C and D

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10. Clinical Presentation Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E Acute failure Anorexia Nausea Fatigue Malaise Vomiting Fever Head ache Right upper quadrant abdominal pain Dark urination Alcoholic stools Pruritis Chronic failure Fatigue Anxiety Anorexia Malaise Ascites Jaundice Variceal bleeding Hyper excitability Impaired mentation Confusion Obtundation Coma Chronic failure Fatigue Anxiety Anorexia Malaise Ascites Jaundice Abdominal pain Dark urine Advanced stage Spider nevi Splenomegalay Palmar erythema Testicular atrophy Caput medusae Chronic failure Jaundice Abdominal pain Vomiting Loss of appetite Dark urine Fatigue Acute failure Anorexia Mild fever Abdominal pain Itching Skin rash Joint pain Jaundice Hepatomegaly

11. Spider nevi

12. Caput medusae

13. Complications Acute / Sub acute hepatic necrosis Chronic hepatitis Cirrhosis Hepatic failure Hepatocellular carcinoma Glomerulonephritis Cryoglobulinemia Hepatic encephalopathy Portal hypertension Porphyria HIV infection

14. Diagnosis Physical examination Liver function tests Anti HAV testing HBSAg testing Anti HCV testing Anti HDV testing Anti HEV testing Liver biopsy Ultrasound of liver

15. Non Pharmacological Treatment Hepatitis vaccination for Hepatitis A, B and E Immunoglobulin treatment Counselling about risk factors and transmission Stopping of alcohol Stopping of smoking Physical exercise Liver transplantation

16. Treatment Algorithm Hepatitis A Vaccination Immunoglobulins Symptomatic treatment Hepatitis B Interferons Pegylated interferons Entecavir Tenofavir Adenovir Lamivudine Telbivudine

17. Hepatitis C Type Without Cirrhosis With Cirrhosis Genotype 1a and 1b Daclatasavir+ Sofosbuvir for 12 weeks Daclatasavir+ Sofosbuvir+ Ribavirin for 24 weeks Simeprevir + Sofosbuvir for 12 weeks Simeprevir + Sofosbuvir+ Ribavirin for 24 weeks Genotype 2 Daclatasavir+ Sofosbuvir for 12 weeks Daclatasavir+ Sofosbuvir+ Ribavirin for 24 weeks Genotype 3 Daclatasavir+ Sofosbuvir for 12 weeks Daclatasavir+ Sofosbuvir+ Ribavirin for 24 weeks Daclatasavir+ Ribavirin+ PEG interferon for 12 weeks Daclatasavir+ Ribavirin+ PEG interferon for 12 weeks

18. Hepatitis D PEG INF for 48 weeks Liver transplantation in case of fulminant hepatitis and end stage liver disease Hepatitis E Vaccination Symptomatic treatment Ribavirin in case of immunosupressed people

19. Drugs used in treatment of viral hepatitis Drug Category Mode of action Dose Adverse affects IG Immunoglobulin Produces passive immunity 0.02ml/kg -IM Head ache Erythema Myalgia Malaise Injection site reactions Pegylated interferon Immunomodulator Enhances activity of phagocytic activity of macrophages and cytotoxic activity of lymphocytes for target cells 180mcg-SC-once weekly for 24-48- weeks Fatigue Headache Fever Myalgia Influenza like illness Entecavir Nucleoside reverse transcriptase inhibitor Inhibit viral replication 0.5-1mg- PO-OD Fatigue Head ache Dizziness Nausea Diarrhoea

20. Tenofavir Nucleoside reverse transcriptase inhibitor Inhibit viral replication 300mg-PO-OD Asthenia Diarrhoea Nausea Pain Anorexia Lamivudine Nucleoside reverse transcriptase inhibitor Inhibit viral replication 100mg-PO-OD Diarrhoea Cough Fever Joint pain Pancreatitis Telbivudine Nucleoside reverse transcriptase inhibitor Inhibit viral replication 600mg-PO-OD Fatigue Headache Cough Diarrhoea Abdominal pain

21. Daclatasavir HCV NS5A inhibitor Inhibit viral replication 60mg-PO-OD Headache Nausea Fatigue Diarrhoea Elevation of lipase levels Sofosbuvir HCV NS5B inhibitor Inhibit viral replication 400mg-PO-OD Fatigue Headache Nausea Fatigue Insomnia Simeprevir HCV protease inhibitor Inhibit viral replication 150mg-PO-OD Photosensitivity Hyperbilirubenemia Pruritis Dyspnoea Myalgia Ribavirin Synthetic nucleoside analog of ribofuranose Inhibit viral protein synthesis 800-1000mg/day-BD Fatigue Headache Myalgia Haemolysis Rigors

22. Resources https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418070/ http://www.ijmm.org/article.asp?issn=0255-0857;year=2018;volume=36;issue=2;spage=217;epage=223;aulast=Sarkar https://www.ncbi.nlm.nih.gov/pubmed/29798951 https://doi.org/10.1111/jvh.12870 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719604/