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HEPATITIS C

HEPATITIS C. DR OKEKE F.I. INTRODUCTION EPIDEMIOLOGY PATHOGENESIS CLINICAL FEATURES DIAGNOSIS TREATMENT CONCLUSION. INTRODUCTION. Hepatitis C virus (HCV) is an RNA virus known to infect humans and chimpanzees, causing similar disease in these 2 species.

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HEPATITIS C

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  1. HEPATITIS C DR OKEKE F.I

  2. INTRODUCTION • EPIDEMIOLOGY • PATHOGENESIS • CLINICAL FEATURES • DIAGNOSIS • TREATMENT • CONCLUSION

  3. INTRODUCTION • Hepatitis C virus (HCV) is an RNA virus known to infect humans and chimpanzees, causing similar disease in these 2 species. • Is an infectious disease affecting primarily the liver. It is 4 times more infectious than HIV

  4. 80% of cases of acute HCV infection will progress to chronic HCV, 20 to 25 % will progress to cirrhosis and 1 to 4% to hepatocellular carcinoma. • Hepatitis C accounts for 40% of CLD and is the most frequent indication for liver transplantation.

  5. Harvey Alter discovered the virus in the mid 1970s and initially called it ”non-A, non-B hepatitis (NANBH)”, • In 1987, Drs Michael Houghton & D.W. Bradley identified it by molecular cloning and in 1988, Dr Alter confirmed it was the NANBH. April 1989, HCV discovery was published. • In 2000, Drs. Alter and Houghton were honored with the Lasker Award for Clinical Medical Research

  6. Discovery of Hepatitis C 4/22/2011 ICVH Baltimore 2011

  7. The hepatitis C virus (HCV) is a small, measures (40-60nm) enveloped, single-stranded, positive-sense 9600-nucleotide RNA virus. It is the only member of the Hepacivirus genus in the family Flaviviridae. • The HCV genome contains a single, large open reading frame (gene) that codes for approx 3000 amino acid polypeptide which is cleaved after translation into 10 viral proteins.

  8. Pic of genome

  9. EPIDEMIOLOGY • HCV Infection occurs throughout the world, and up until the introduction of anti-HCV screening tests for blood donors, introduced in 1990/1991 in Europe and the United States, it has represented the major cause of transfusion-associated hepatitis. • The WHO estimates that 3% (170 million) of the world's population are chronically infected with HCV.

  10. HCV: A Global Health Problem 170 Million Carriers Worldwide, 3 - 4 MM new cases/year 3% of World Population EAST MEDITERRANEAN 20M WEST EUROPE 9 M CANADA 300,000 FAR EAST ASIA 60 M U.S.A. 4 M SOUTH EAST ASIA 30 M AFRICA 32 M SOUTH AMERICA 10 M AUSTRALIA 0.2 M SOURCE, WHO 1999

  11. HEPATITIS C AROUND THE WORLD

  12. Worldwide Prevalence Hepatitis C Virus Infection Reprinted from Cohen J. Science. 1999;285:26.

  13. In the United States, about 2% of people have hepatitis C,with the number of new cases per year stabilized at 17,000 since 2007. The number of deaths from hepatitis C has increased to 15,800 in 2008and by 2007 had overtaken HIV/AIDS as a cause of death in the USA. This mortality rate is expected to increase, as those infected by transfusion before HCV testing become apparent

  14. The prevalence is reported to be highest (>10 -20%) in Egypt • The prevalence is higher (>2%) in several countries in Latin America, Eastern Europe, and the former Soviet Union, and certain countries in Africa, the Middle East, and South Asia;

  15. Sub-Saharan Africa is of great interest because it is reported to have the highest HCV prevalence rate (5.3%), and a concurrent HIV epidemic • The Central African Region has an estimated prevalence of 6%, West Africa has an estimated prevalence of 2.4%, and South and East Africa with the lowest estimated prevalence of 1.6%.

  16. In Nigeria, a study done by OS Ejiofor et al over a period of 12 months from January to December 2009 showed that the prevalence of hepatitis C virus infection is increasing in Nigeria, ranging from 4.7-5% in Ilorin, to 5.3-6.6% in Enugu, to 11% in Ibadan and 20% in Benin.

  17. Has 6 distinct major genotypes and over 50 subtypes within genotypes (quasispecies). • Worldwide, 1 is more common and accounts for 70% in the USA • Genotypes 1-3 are widely distributed globally, with genotypes 1a and 1 b accounting for 60% of infections worldwide. Genotype 4 is characteristic for the Middle East, Egypt and Central Africa. Genotype 5 is almost exclusively found in South Africa. Genotype 6 in Hong kong.

  18. 2 5 1 4 3 6 HCV Genotypes and Subtypes Developed countries Americas + Western Europe South Africa Middle East North Africa IVDU Asia Simmonds P, Journal of Hepatology, 1999

  19. AGE: occurs in all ages. Mostly 25- 40yrs • 1988-1994 =30-40yrs • 1999- 2000 = 40 – 49 yrs • 1995 > =55 -64 yrs • Despite an 80% reduction in new infections, prevalence in the various populations was sustained by an aging cohort that acquired their infections 2 to 3 decades earlier .

  20. In a retrospective study done in Nnewi by Odenigbo et al in 2011 to determine Prevalence Of Antibodies To Hepatitis C Virus In Blood Donors In Nnewi (2005- 2009) • The prevalence of HCV antibodies was found to be 2.0%. The age group 21-30 years was found to be the lowest risk group (1.4% seroprevalence). Seroprevalence increased after the age of 30 years, though not linearly, with the highest rate (3.2%) recorded in the 31-40 years and 51-70 years age groups -

  21. Chukwurah et al studied the prevalence of the antibodies to Hepatitis C Virus (anti-HCV) in 1280 blood donors at UNTH Enugu in 2004 showed that 97 (7.6%) of the blood donors were positive for the anti-HCV.

  22. A similar study done by Udeze et al in Ibadan in 2007 showed that 16 (8%) of the donors had antibodies to HCV and highest prevalence was amongst blood donors of the age range 30-39 years. (16.5%). • In 2009, another study was done over a 6mth period in 507 prospective blood donors in UCH by Afolabi et al

  23. 1.4% were positive for anti-HCV. HCV prevalence was highest among age group of 26 – 35. • The rates were lower than the previous studies in Nigeria • perhaps this is due to the public enlightenment on transmissible transfusion infections.

  24. Obienu et al in 2011 tried to determine the prevalence of anti-HCV and risk factors associated with HCV infection in Nigerians. • The seroprevalence of anti-HCV was 4.7%. Among the risk factors evaluated, none was found to be significantly associated with anti-HCV seropositivity.

  25. Risk Factors Associated With Acquiring HCV Infection • Transfusion (blood, pooled clotting factors) • Transplant from infectious donor • Injecting drug use • Occupational blood exposure (needle sticks) • Birth to an infected mother • Infected sex partner • Multiple heterosexual partners • Unknown (20%)

  26. Intravenous drug users(even one-time use Transfusions of blood or blood products before 1992 Current recipients of multiple blood transfusions Hemophiliacs given clotting factors Sexual partners of intravenous drug users Intranasal cocaine users Tattooing or body piercings Long-term hemodialysis History of imprisonment High risk sexual contact, patients with multiple sexual partners Occupational exposure to blood or blood products Receiving an organ, graft, or tissue transplant from an HCV-positive donor Health-care workers exposed to needle-stick and sharp injuries Patients with sexually transmitted diseases, HIV, HBV HIGH RISK INDIVIDUALS

  27. PATHOGENESIS • Study of Infection, Replication and Release Difficult: • Lack of reliable culture system • Does not integrate into host genome • Low number of circulating virions

  28. Binding and Entry • Unknown at this time • Guesses: • E2 binds to CD81 on liver • Envelope protein binds to CD81 large extracellular loop • E2 binds to LDLR • Envelope coated with LDL during secretion?

  29. Evasion of Immune Response • HCV is RNA virus: mutates quickly • E1, E2 in hypervariable region – changes often • NS5A inhibits PKR(phosphorylasekinase receptor) • PKR is effector of host antiviral defense pathway: represses translation by phosphorylating eIF2 • NS5A has other activities as well: less understood

  30. cytokines in the Th2 phenotypes are profibrotic and lead to the development of chronic infection. • A dominant CD4 Th2 response with a weak CD8 gamma-interferon response may lead to rapid fibrosis. • Thl cytokines are anti-fibrotic and thus a dominant CD4 Thl and CD8 cytolytic response may cause less fibrosis. • Variability may be related to the genetic phenotype; persistence of HCV infection has been shown to be associated with HLA-DRBl*0701 and DRB4*0101..

  31. CLINICAL FEATURES • Acute Hepatitis C occurs after an incubation period of 15 -160 days (mean of 50) • Most – asymptomatic • 10% - symptomatic – prodromal symptoms preceding onset of jaundice by 1-2 weeks, RUQ pain, proceeding to recovery phase (2-12 wks) with complete clinical and biochemical recovery in those who clear the virus

  32. Asymptomatic – 10 -15% will clear the virus while 85 – 90% will progress to the chronic state • Symptomatic – 25 – 52% will clear /48 -75% will progress • 10- 20% of those who progress will end up in cirrhosis in 10 -30 years • 7-15% of cirrhotics will develop hepatocellular carcinoma.

  33. Chronic –usually asymptomatic, anorexia, nausea, fatigue, weight loss, features of CLD, evidence of decompensation. • Factors which worsens progression includes alcohol, male sex, concomitant HBV or HIV or both, fatty liver, DM, Iron, older age, longer duration , genotype 1, advanced histologic stage and grade. • Persistence of HCV infection has been associated with HLA DRB1*0701 and DRB4*0101.

  34. Hepatitis C Progression Fibrosis & Disease Progression in Hepatitis C. Marcellin, et al. Hepatology, 2002

  35. Alcohol Are you sure he said we can only have one?

  36. RELATIONSHIP BETWEEN CIRRHOSIS AND YEARS AFTER EXPOSURE Wiley et al. Hepatology, 1998

  37. HCV Infection: Extrahepatic Manifestations • Hematologic • Mixed cryoglobulinemia • Aplastic anemia • Thrombocytopenia • • Non-Hodgkin’s b-cell lymphoma • Ocular • Corneal ulcer • Uveitis • Vascular • Necrotizing vasculitis • Polyarteritis nodosa • Dermatologic • Porphyriacutaneatarda • Lichen planus • Cutaneous necrotizing vasculitis • Neuromuscular • Weakness/myalgia • Peripheral neuropathy • Arthritis/arthralgia • Renal • Glomerulonephritis • Nephrotic syndrome • Autoimmune • Phenomena • CREST syndrome • Sjoren’s/Sicca syndrome • Endocrine • Anti-thyroid antibodies • Diabetes mellitus • Salivary • Sialadenitis Hadziyannis SJ. J Eur Acad Dermatol Venereol. 1998;10:12-21.

  38. A study done by Dr Ukonu and Uhunmwangho to determine the prevalence of hep C among lichen planus patients between Jan 2010 and Dec 2011, 720 new patients in MOPD. • The control group included patients’ relations and some dermatology patients known to have low risk of hepatitis C virus infection Result: Anti- HCV antibodies were detected in nine cases (21.4%) and one case (3.3%) in the control group. Hypertrophic variant was more prevalent.

  39. Investigations • ACUTE; HCV RNA (1-8 wks), • AntiHCV antibodies after 8weeks. • LFT:Elevated ALT, elevated bilirubin, • FBC: neutropenia, lymphopenia or relative lymphocytosis, • prolonged PT • antiLKM(anti liver/kidney microsomal) antibodies type 1.

  40. Hepatitis C Antibody (Anti-HCV) Test • EIA test for detection of hepatitis C antibodies • Sensitivity over 99% • Detection of anti-HCV following infection averages 12 weeks • Positive test usually diagnostic in patients with elevated levels of liver enzymes and presence of risk factors • False negatives in Immunosuppressed and Chronic Dialysis Patients • False positive in autoimmune hepatitis and hyperglobulinaemia. Management of Hepatitis C. NIH Consensus Statement, 2002.

  41. CHRONIC; • HCV RNA, • AntiHCV, • Elevated or normal ALT, • Liver biopsy , • HCV genotyping • Serologic testing :antinuclear antibody(41%) ,anti thyroid antibody(13%) .rheumatoid factor (38%) ,anticardiolipin antibody(27%) and anti smooth mzle antibody(9%)

  42. HCV RNA • Genotype • Viral load • These two parameters do not affect the rate of fibrosis.

  43. Liver Biopsy • May be guided by CT or ultrasound • Helps determine • Degree of disease progression • Cause of liver disease • Need for treatment / Patient Motivation • Estimate chance of response • Findings: lymphocytic infiltration ,moderate degrees of inflammation and necrosis ,portal or bridging fibrosis . Regenerative nodules in pxs with cirrhosis

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