HEPATITIS C UPDATES Sanaa S. Said 10 th April, 2014
CONTENTS Introduction Epidemiology Transmission and Natural history Kenyan guidelines What is new? References
INTRODUCTION Hepacivirus genus, Flaviviridae family Enveloped, linear, single stranded RNA virus Accounts for 10-30% of acute viral hepatitis At least six distinct major genotypes of HCV have been identified
EPIDEMIOLOGY Approximately 185 million people worldwide are infected with HCV About 150 million are chronically infected 350,000-500,000 die from HCV complications each year 500,000 cases of HCV from improper screening of blood
AFRICA Prevalence varies between 0.6-18% Kenya prevalence in blood donors is 1.5-2.5% IVDU up to 30% HCV accounted for 2.8% of chronic liver disease in KNH (1996)
GLOBAL HCV PREVALENCE
HCV SEROPREVALENCE BY REGION
TRANSMISSION
Natural history 1. Acute infection - 80% subclinical, 10-20% symptomatic hepatitis w/jaundice* Incubation 1-5 months, mean 6-7 weeks Clearance in up to 30% 2. Chronic infection - up to 80% devp chronic hepatitis Of these 20-30% develop cirrhosis later HCC in 2-5% of cirrhotics/year
Extrahepatic syndromes Hematologic diseases- essential mixed cryoglobulinemia,.lymphoma (NHL) Renal disease MPGN Autoimmune disorders thyroiditis, Sjogren Dermatologic conditions- porphyria cutanea tarda, lichen planus Diabetes mellitus Others: cognitive dysfunction, fatigue and depression
KENYAN GUIDELINES
WHO TO SCREEN Blood donors Hemodialysis recipients and staff HCW and those exposed to blood IVDU Those with risky sexual behaviour Immunocompromised pts Accidental injuries Those with pre- existing liver ds
EVALUATION History Examination Labs - LFTs - confirm HCV infection/viral load - HCV genotype Imaging Liver biopsy Screen for other viruses
WHO TO TREAT All pts +ve for HCV with raised LFTs should be offered treatment
CONTRAINDICATIONS TO THERAPY Depression, psychosis, epilepsy Uncontrolled AI disease Pregnancy Those not willing to contraception Poorly controlled comorbids Untreated thyroid ds Low Hb, Neutr < 1500/mm3, Plt < 90,000/ mm3, creat > 1.5 times normal
TREATMENT GOALS Eradicate HCV RNA This is predicted by attainment of a sustained virological response - SVR (absence of HCV RNA by PCR 6 months after completing tx)
PREDICTORS OF Tx RESPONSE HCV genotype Baseline viral load Race Host genetic factors (IL28B) Use of combination therapy pegifn and ribavirin Treatment adherence
DRUG MANAGEMENT Peg IFN - alpha 2A, dose 180 ug SC once a week Or Peg IFN - alpha 2B, dose 1.5 ug/kg/week SC GT 1,4,5,6 adjust Ribavirin dose upto max of 1.2 gm daily for 48 weeks GT 2,3 adjust ribavirin to a lower dose of 800mg in divided doses
VIROLOGICAL Tx FOLLOW UP RVR- Rapid Virological Response HCV RNA - ve after 4wks of tx, if still ve at 12 wks called extended RVR EVR- Early Virological Response 2 Log 10 reduction in HCV RNA at 4 wks or ve at 12 weeks DVR- Delayed virological response/slow responders - HCV RNA ve at wk 24 who were not EVR EOT- End Of treatment response - - ve at end of tx
HIV AND HCV CO- INFECTION Globally, 4-5 million people infected Kenya prevalence, low (0.5-1.5%) Treatment of HCV may increase tolerability to HAART HAART responses are reduced Rapid HIV and HCV disease progression
Tx OF HIV/HCV COINFECTION Standard dual therapy: Peg IFN and RBV Response rates (40%), thus lower than in HIV - ve
Newer treatment GT 1 and 4 Telaprevir and Boceprevir incr response May be used in non responders to 1 st line tx Triple therapy
WHAT IS NEW?
sofosbuvir (400 mg daily) and ledipasvir (90 mg daily) plus ribavirin (1000 1200 mg daily) for 6 weeks or 12 weeks sofosbuvir and GS- 9669 (500 mg daily) plus ribavirin for 12 weeks.
Sofosbuvir, a nucleotide analogue inhibitor of HCV ribonucleic acid (RNA)- dependent RNA polymerase, was approved in Dec 2013. Simeprevir, a second- wave, first- generation NS3/4A protease inhibitor approved in Nov 2013. Daclatasvir, an NS5A inhibitor, is likely to be approved in August or September 2014, according to the EASL statement
HCV VACCINE
SUMMARY OF RECOMMENDATIONS WHO, APRIL 2014 1. Recommendations on screening A) screening to confirm HCV infection B) when to confirm diagnosis of chronic HCV infection
2. Recommendations on care of HCV infected A) Screening for alcohol use and counselling to reduce moderate and high levels of alcohol intake B) Assessing degree of liver fibrosis and cirrhosis In RLS use of Apri and FIB 4 scores
APRI and FIB4 APRI- AST to PLT Ratio Index AST value/ast ULN X 100 Platelet count (10 9 /L) Range 0.5-1.5 FIB 4 Age X AST Platelets 10 9 X ALT Range 1.45-3.25
3. recommendations on treatment of HCV infection A) Assessing for HCV treatment B) Treatment with pegylated interferon and ribavirin C) Treatment with telaprevir or boceprevir: given in combination with pegylated interferon and ribavirin, is suggested for genotype 1 HCV (triple therapy)
D) Treatment with sofosbuvir: in combination with ribavirin with or without pegylated interferon (depending on the HCV genotype), is recommended in genotypes 1, 2, 3 and 4 HCV E) Treatment with simeprevir: in combination with Peg IFN +RBV, recommended for persons with genotype 1b HCV infection and for persons with genotype 1a HCV infection without the Q80K polymorphism
REFERENCES Harrison s Principles of Internal Medicine, 18 th edition EMI guidelines, http://www.hpsc.ie/hpsc/a- Z/ EMIToolkit/appendices/app24.pdf Guidelines for the treatment of chronic hepatitis B and C virus in Kenya Brian J McMahon MD, Director Liver Disease and Hepatitis Program ppt presentation
The Massachussets General Hospital handbook of internal Medicine, 4 th edition WHO Guidelines for the screening, care and treatment of persons with hepatitis C infection, April 2014 Emedicine.medscape.com http://www.jwatch.org/na34064/2014/03/28/ sofosbuvir- plus- second- antiviral- hcv- genotype- 1- infection? query=topic_hepatitis#sthash.ngb0rhmm.dpuf
http://www.nytimes.com/2014/03/22/ business/lawmakers- attack- cost- of- new- hepatitis- drug.html?_r=0 http://www.aasld.org/journals/hepatology/ Pages/hcvsexualtransmission.aspx http://www.jwatch.org/ fw108238/2013/12/09/fda- approves- sofosbuvir- hepatitis- c?query=pfw
http://www.cdc.gov/features/ dshepatitisawareness/ http://www.inovio.com/products/infectious- disease- vaccines/hepatitis/ino8000hcv/
RISK FACTORS ASSOCIATED WITH PROGRESSION Heavy alcohol usage: Strongest factor Male sex Diabetes or hepatic steatosis (fat) Older age at time of infection Co- infection with HIV or HBV Not associated: Viral load Presence of Anti- HBc without HBsAg HCV genotype
VIT D AND HCV 197 HCV genotype 1 patients receiving IFN- RBV therapy; 49 healthy controls matched by age and sex 25 (OH) D levels significantly lower in HCV persons (25) vs. controls (43); p<0.001) Low levels significantly associated with: Female sex, increased liver inflammation, increased liver fibrosis and decreased rate of cure with therapy Hepatology 2010;51:1158-67
COFFEE CONSUMPTION AND HCV US NIH Trial HALT- C trial serial liver biopsies every 2 years Coffee consumption > 3 cups/day associated with: Significantly reduced fibrosis (Hepatology 2009;50:1360-9) Significantly better response to Peg IFN+RBV (Freedman Gastroenterology 2011) Quantity of coffee consumption associated with decreased risk of HCC (Hepatology 2008;48:129-36)
COUNSELLING IN HCV Abstinence from alcohol Condoms not necessary in monoinfection for steady partners: HCV difficult to transmit sexually except if HIV or other STD is present Exception: anal intercourse or during menses Don t share toothbrushes, razors or nail clippers Drink coffee if available: 3 cups/day Vitamin D in low sun areas or in persons who cover their skin
PREVALENCE OF ANTI- HCV IN IDU