Hcv Lecture

‫بسم ال الرحمن الرحيم‬

Chronic Hepatitis C Dr : Walid

El Sherbiny

Tropical Medicine Mansoura University

Incidence Hepatitis C infect 200 million people worldwide HCV is a major Epidemic problem in Egypt. Many data suggest that the Overall incidence in Egypt is 15% of population. The highest prevalence in Northern Delta 28% The lowest prevalence in Cairo and Alexandria 9% and 6 % respectively.

Virology Single stranded, enveloped RNA virus. There are 6 genotypes: 1 in USA . 2,3 in Europe & 4 in Egypt Genotypes 2 &3 has the best response to Interferon Therapy Genotypes 1 & 4 has the least response to interferon therapy

Pathology Ranges from minimal periportal lymphocytic inflammation to active hepatitis with bridging fibrosis, hepatocyte necrosis and frank cirrhosis. Activity / Fibrosis score Steatosis, lymphoid aggregates and bile duct damage are frequently found in the liver biopsy in patient with HCV infection

Methods Of Transmission 1-Iatrogenic medical and dental procedure (most important) 2-Injection drug use 3-Blood transfusion and organ transplantation 4-Occupational exposure to blood (Medical and paramedical) 5-Sexual and perinatal exposure (probably low) - The campaign of treatment of Bilharziasis using Tartar Emetics with same needle used for all patients Play an important role in transmission of HCV

Clinical Manifestations Chronic hepatitis C means HCV infection for more than 6 months. Usually asymptomatic, accidentally discovered but it may be presented with Fatigue, weight loss, muscle pain, intermittent low grade fever and flu like symptoms or GIT symptoms. Hepatitis C (PCR) is detectable in the blood within 1 to 3 weeks after infection, and antibodies to the virus within 3 to 12 weeks

Extra-hepatic manifestations Pathogenesis a- Mediators of autoimmunity b- Immune complex formation c- Virus invasion and replication

Includes:

1- Strongly associated

1-Mixed cryoglobulinemia 2-Membrenoproliferative glomerulonephritis 3-Porphyria cutenea tarda 4-Sjogren syndrome 5-Lymphoproliferative disorders 6-Leukocytoclastic vasculitis

2- Possibly associated        

1-Lichen planus 2-Autoimmune thrombocytopenia 3-Thyroid disease 4-Type 2 diabetes 5-Corneal ulcers (Mooren ulcers) 6-Pulmonary fibrosis 7-Systemic vasculitis (polyarteritis nodosa 8-Arthralgia, myalgia, polyarthritis

Vasculitis

Vetiligo

Psoriasis

Psoriasis

Pyoderma Gangrenosum (early lesion with necrotic centre)

Pyoderma Gangrenosum

Pyoderma Gangrenosum

Systemic Lupus Erythematosus

Sjogren’s Syndrome

Idiopathic pulmonary fibrosis

Prevention 1-Avoid sharing drug needles 2-Avoid unsanitary tattooing, Acupuncture and body piercing 3-Avoid needle stick injury, sharing personal items such as razors, nail clippers and teeth brush 4-Use latex condoms correctly in those with multiple sexual partners 5-Screening of blood & blood products for viral markers 6-Strilization No vaccine available to protect against

Treatment Standard treatment is a combination of Pegylated Interferon and Ribavirin. All patients with measurable level of HCV RNA and liver biopsy shows bridging fibrosis along with at least with moderate inflammation and necrosis should be considered potential candidate for therapy. In the absence of contraindications, treatment is recommended because patients are at risk of developing liver cirrhosis and Hepatocellular

Investigations before INF 1-Anti HCV antibody & HB markers 2-CBC 3-Liver function tests 4-Quantitaive PCR 5-Pregnancy test 6-Serum T.S.H 7-Serum alfa feto protein 8-Autoimmune markers 9-IHA for Bilharziasis 10-Random blood sugar and creatinine 11-ECG 12-Fundus Examination 13-Abdominal U/S 14-Liver Biopsy 15-Upper GIT endoscopy (in patients with portal

Pegylated Interferon Attachment of polyethylene glycol to a protein (pegylation) reduces its rate Of absorption following subcutaneous injection, reduces renal clearance and decrease immunogenicity of protein with resulting

Duration of Therapy Differs according to genotype. For Genotypes 2 & 3 require 24 weeks of Peg INF. alfa + ribavirin 800 mg/d while Genotypes 1 & 4 require 48 weeks of INF alfa + ribavirin 1000-1200 mg/d. Failure to decrease the viral load by 2 Logs after 12 w. of treatment is highly predictive of failure of treatment in naïve patient who has genotype 1

Time to Do PCR -Basal PCR (before start of treatment) -After 4 weeks (Quantitative), if responder (Super response) -After 12 weeks (Quantitative): If responder (early virologic response) then continue, if Non responder stop -After 24 w. (Qualitative), if Non responder stop. -After 48 weeks (Qualitative, if responder it is end treatment response.

Predictor of Non response To HCV treatment: 1-Infection with Genotype 1 2-High viral load (800,000 IU/ml) 3-Advanced fibrosis stage 5 or cirrhosis stage 6 4-High body mass index 5-age more than 40 years 6-African American race 7-Coinfection HIV with HCV

Absolute contraindications to hepatitis C therapy - Active psychiatric illnesses, such as major depression, schizophrenia, or bipolar disorder that is not controlled - Having undergone renal, heart, or lung transplant - autoimmune hepatitis - Untreated hyperthyroidism - Pregnancy OR Breast feeding

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Severe concurrent disease: severe uncontrolled hypertension, heart failure, considerable coronary artery disease, poorly controlled diabetes mellitus, severe chronic obstructive pulmonary disease

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Known hypersensitivity to INF or Ribavirin

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Inability to practice birth control

Relative contraindications: a- pancytopenia b- Seizure disorders

Adverse effects of Hepatitis c therapy:

1-Flu like symptoms 2-Neutropenia and Thrombocytopenia 3-Depression and Psychosis 4-HTN and Diabetes 5- thyroid 6-fall of hair 7-With Ribavirin, the most prominent side effect is heamolysis while the most serious is teratogenicity

Two forms of contraceptions must be used during therapy and for 6 months following treatment cessation. Anemia associated with IFN/RBV therapy is treated by Epotein alfa once weekly S.C. with OR without reduction of Ribavirin dose Leucopenia is treated with granulocyte stimulating factor s.c.

Experimental treatment: 1-Viramidine is a prodrug of the Ribavirin that has better targeting of the liver (Phase 3 trials). It will be used in conjunction with interferon as an alternative to Ribavirin 2-Protease inhibitors (VX 950) Known as Telaprevir is currently in Phase 3 trials