hcv lecture
TRANSCRIPT
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الرحيم الرحمن الله الرحيم بسم الرحمن الله بسم
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Chronic Hepatitis C Chronic Hepatitis C
Dr : Dr : Walid El - Walid El - SherbinySherbiny
Tropical Medicine Tropical Medicine Mansoura UniversityMansoura University
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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.
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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
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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
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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
- Bad sterilization procedures in hospitals is very important source of infection
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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 (up to 1 y).
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Extra-hepatic manifestationsPathogenesis 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 7-Neuropathy
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2- Possibly associated2- Possibly associated
1-Lichen planus1-Lichen planus 2-Autoimmune thrombocytopenia2-Autoimmune thrombocytopenia 3-Thyroid disease3-Thyroid disease 4-Type 2 diabetes4-Type 2 diabetes 5-Corneal ulcers (Mooren ulcers)5-Corneal ulcers (Mooren ulcers) 6-Pulmonary fibrosis6-Pulmonary fibrosis 7-Systemic vasculitis (polyarteritis 7-Systemic vasculitis (polyarteritis
nodosa nodosa 8-Arthralgia, myalgia, polyarthritis 8-Arthralgia, myalgia, polyarthritis
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VasculitisVasculitis
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VetiligoVetiligo
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PsoriasisPsoriasis
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PsoriasisPsoriasis
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Pyoderma Gangrenosum (early Pyoderma Gangrenosum (early lesion with necrotic centre)lesion with necrotic centre)
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Pyoderma Pyoderma GangrenosumGangrenosum
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Pyoderma Pyoderma GangrenosumGangrenosum
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Systemic Lupus ErythematosusSystemic Lupus Erythematosus
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Sjogren’s SyndromeSjogren’s Syndrome
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Idiopathic pulmonary fibrosis
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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 contracting HCV
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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 carcinoma
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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 hypertension)
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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
increasing in half life of interferon.
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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
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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.-SVR (sustained virologic response): –ve Qualitative PCR 6 months after end treatment
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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 64-High body mass index5-age more than 40 years6-African American race7-Coinfection HIV with HCV
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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 concurrent disease:
severe uncontrolled hypertension, heart severe uncontrolled hypertension, heart failure, failure, considerable coronary artery considerable coronary artery disease, poorly disease, poorly controlled diabetes controlled diabetes mellitus, severe chronic mellitus, severe chronic obstructive obstructive pulmonary disease pulmonary disease
Known hypersensitivity to INF or RibavirinKnown hypersensitivity to INF or Ribavirin
Inability to practice birth controlInability to practice birth control
Relative contraindications:Relative contraindications:
a- a- pancytopeniapancytopenia
b- b- Seizure disordersSeizure disorders
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Adverse effects of Hepatitis c therapy:
1-Flu like symptoms2-Neutropenia and
Thrombocytopenia3-Depression and Psychosis4-HTN and Diabetes5- thyroid6-fall of hair7-With Ribavirin, the most
prominent side effect is heamolysis while the most serious is teratogenicity
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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.
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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
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