2.  Presented by Dr. K M J Zaki Associate Professor Department of Hepatology SOMC, Sylhet.

4.   The prevalence of HCV infection in children is low (<3%)  Most new HCV infections in children are perinataly acquired with a risk of around 5% with HCV infected mother.  The risk is increase if the mother is coinfected with HIV (20-30%).  Neither elective caesarean section nor breast feeding increase the rate of transmission. HCV Infection in Children continue

5.   Majority of children with HCV infection are clinically well with a normal or mildly elevated transaminase.  Very slowly progressive but probably irregular fibrotic process occur.  ESLD are rare.  Spontaneous HCV clearance is more in children (around 40%) than in adult (20-40%).  Spontaneous clearance may occur even after >2 years where as in adult it occurs within 6 months of acquiring infection. continue

6.   Diagnosis of perinataly acquired HCV requires positive anti HCV test after 18 months of age.  HCV PCR might not detect HCV infection at birth. PCR and liver function test might be done after the age of 2 months.  At 2 months of age if HCV RNA is negative then the test should be repeated after 15 months (in HCV positive mother). continue

7.   Treatment is like that of adult with Peg IFN & Ribavirin.  Treatment should be started if there is rapid disease progression in older than 2 years age.  Response rate is like that in adult population.  SVR( sustained virological response) is 100% in genotype 2 & 3,apporoximately 45% in genotype1.  Data and recommendations is not available regarding the use of DAA( Directly Acting Agent/Antivirals) in children.

9.   HCV infection in pregnancy is not aggressive.  Few data suggest an increase in cholestatic disease of pregnancy with HCV infection.  Due to immunosuppression there is lowering of SGPT and increase in HCV RNA conc. specially in 2 nd & 3 rd trimester.  Immediate after delivery there is rise in SGPT and decrease in HCV RNA conc. HCV infection in pregnancy continue

10.   Peg IFN / Ribavirin are contraindicated in pregnancy.  Best result of Peg IFN / Ribavirin can be achieved if treatment is given immediately after delivery.  Data regarding treatment with DAA and their recommendation is not available.

12.   HCV infection in a person may give rise to some form of renal problems (10%) -  These are : Mixed cryoglobulinaemia with mesangio capillary glomerulonephritis. Membranous glomerulonephritis. Membranoproliferative nephropathy. Alternatively if a person suffer from these renal problems,etiology like HCV should be sought out. There is increase prevalence in African-American, Asian & may occur in both naïve/Alograft kidney. HCV infection associated with Kidney Disease

13.   These HCV induced renal disease can be treated with Peg IFN & Ribavirin provided creatinine clearance is > than 50ml/ minute Ribavirin dose should be adjusted when creatinine clearance is less than 50ml/minute  Ribavirin and its metabolites are not filtered by dialysis.

14.  In other settings, a person with renal failure may become infected with HCV. This HCV infections may occur due to multiple blood transfusions or as a technical fault in haemodialysis. But data suggest that the haemodialysis machines themself do not have a significant role. It is likely that HCV transmission in dialysis principally results from breakdown of universal infection control guidelines resulting horizontal (pts to pt/ or staff to pt) transmission. HCV infection in Renal Failure continue

15.  Haemodialysis is one of the peculiar situation where HCV infection may present with negative test for anti HCV. Other situations is immunosuppression. In these situation HCV RNA test is mandatory to declare HCV infection free. Peg IFN & Ribavirin can be given to renal failure pt. but ribavirin dose adjustment is mandatory. Ribavirin either 200mg daily or 200mg thrice weekly or every alternate day.

16.  Soforbuvir, simeprevir and daclatasvir can be given to renal failure patient, but the dose should be adjusted. Soforbuvir can be given in mild and moderate renal failure. Simeprevir can be advice in mild,moderate and severe renal failure DAA in renal failure continue

17.  With this regimen treatment should be done before transplantation. After transplantation IFN is contraindicated because this may cause transplant rejection. Persistance of HCV infection following renal transplantation increase the hepatic fibrosis & deterioration of liver disease due to immunosuppression.

19.   20-40% spontaneous recovery occur following HCV acute infection in adult within 6 months.  60-80% develop chronic state. Of these chronic state 10-20% develop cirrhosis by 20-30 years,& 1-5% ultimately die due to decompansation & HCC.  Histopathology of liver infected with HCV give rise peculiar state like granuloma and fatty change in addition to hepatitis and cirrhosis. HCV infection in Cirrhotic Patient continue

20.   DAA are now the treatment of choice for compensated cirrhosis with HCV infections.  Where DAA are not available compensated cirrhosis caused by HCV infection can be treated with Peg IFN & Ribavirin.  IFN and Ribavirin regimen is contraindicated in decompensated cirrhosis where DAA are the only choice to treat HCV infection.

22.   HCV related ESLD and HCC in now the leading indication for adult elective liver transplantation performed in Europe, North America and Australia.  In candidates who are serum HCV RNA positive during transplantation recurrent HCV infection of the allograft is universal following liver transplantation and probably occurs at the time of reperfusion.  Patient develop acute hepatitis. A number of patient with HCV develop severe cholestatic hepatitis may progress rapidly to graft failure and death.  In most patient graft dysfunction settle sponteneously, but spontenous viral clearance has not been observed. Liver transplantation

23.   Most patient develop chronic hepatitis C in the graft  10-30% progresses to allograft cirrhosis within 5 years.  Treatment with IFN and Ribavirin prior to transplantation is controversial. Only patient with child pugh score ≤ 7 can be treated with IFN and Ribavirin prior to transplantation.  IFN and Ribavirin should not be given in the early post transplant phage.Treatment should be considered in established recurrence (> 6 months post transplant) with severe disease.DAA are the treatment of choice. continue

24.  Age <45 year Female Non-obese Duration of infection <5 year No co infection with HBV / HIV Not immunosupressed No alcoholism Moderately ↑ ALT Normal gama glutamyl transpeptidase. Low activity score in liver biopsy No cirrhosis Liver iron low No insulin resistance Possible factors predicting a favourable response to antiviral therapy in chronic HCV infection (IFN and Ribavirin) Host Factors continue Low serum HCV RNA < 400000 IU/ml) Genotype 2 and 3 Viral Factors

25.   From this slide,we can see DM, obesity insulin registance are bad prognostic / Negative predictors for treatment of HCV infections.  Infact patient with these negative predictors who have HCV infection should receive extended doses of IFN & Ribavirin.  That is 48 weeks in genotype 2 or 3 and 72 week in genotype 1 instead of 48 weeks.

27.  Blood Transfusion is the main source of HCV transmission globally where blood is not adequately screened. Patient with transfusion dependent blood disorders are at high risk of acquiring HCV infection. HCV infection can now cause greater morbidity and mortality in these patients then the original disease. World wide carriers of haemoglobinopathies are estimated to total 269 million. Patient with haemoglobinopathies are generally infected with HCV during the first 10 years of life. HCV infection in Thalassaemia& Haemophilia continue

28.  Persistances of HCV infection is favoured by iron overload and various immune abnormalities. HCV infection and iron overload might act as synergistic risk factor for the development of cirrhosis and HCC. Patient with HCV infection may develop HCC earlier in thalassamic than without thalassamia. Treatment of this group of patient is with Peg IFN with Ribavirin. If Rivaririn is added,strong iron chelation therapy should be given. continue

29.  After bone marrow transplantation for thalassamia treatment for HCV should be considered only after patients have been off all immunosuppression therapy for 6 months and when there is no graft vs host disease or immunosuppression. Usually this patient able to discontinue immunosuppression 1 year after receiving bone marrow transplantation. continue

30.  The prevalence of HCV in patients with haemophilia has been reported to be as high as 70-95%. However the natural history of chronic HCV infection and the potential for progressive disease is similar in patients with and without haemophilia. Due to improvement in the management of haemophilia infections such as HCV and HIV have become major causes of mortality. SVR with combination therapy including Peg IFN & Ribavirin is nearly 60%. Ribavirin has potential to elevate the activity of factor VII by an unknown mechanism.

32.   Hepatitis C has a limited impact on HIV disease progression. Conversely HIV alters the natural history of hepatitis C in several important areas.  HCV transmission from pregnant mother to their baby is much higher (>2-5 times) when mother is co infected with HIV.  Progression to chronic hepatitis is increased  Levels of HCV viral load is higher. HIV / HCV co-infection continue

33.   Rates of progression to cirrhosis and ESLD are increased 2 & 6 fold respectively.  HCC occurs in much younger age.  Risk of antiretroviral related hepatotoxicity is increased upto three fold.  SVR rate is 15-20% lower when treated with Peg IFN & Ribavirin

34.   Anti retroviral neive HIV / HCV co-infected patients with a CD4 count 100-350/mm 3 should received HAART prior to HCV treatment.  HIV / HCV co-infected patients with advanced HIV disease (CD4 count 200/mm 3  HIV / HCV co infected patients with CD4 count >350/mm 3 should be considered for HCV treatment and do not require HAART.  Peg IFN & Ribavirin and triple therapy in addition with a DAA like Soforbuvir /Simeprevir is recommended. continue

36.   The prevalence of dual infection with both virus seems to be low in healthy population. 2% of anti HCV positive patient have HBsAg in their serum.  On the other hand 3-20% of HBsAg patients have anti HCV in their serum in Asia pacific region.  Probably this low prevalence is due to mutual inhibition of viral replication.  The overall dominant effect appears to be HCV suppression of HBV. HBV / HCV co-infection continue

37.   However liver disease is worsened & faster in co infection.  Risk of developing HCC is increased.  In patients who are anti HCV and HBsAg positive and HCV RNA positive Peg IFN & Ribavirin is recommended (DAA also can be given with some modification)  For patient who are HCV RNA negative with detectable HBV DNA at significant level Peg IFN or Nucleosides analogue or both can be given. (DAA are not required)

38. 