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

Hepatitis C Virus Infection In

Special Situation

Presented by

Dr. K M J ZakiAssociate Professor

Department of HepatologySOMC , Sylhet.

HCV Infection in Children

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

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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

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).

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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.

HCV infection in pregnancy

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 2nd & 3rd trimester.

Immediate after delivery there is rise in SGPT and decrease in HCV RNA conc.

HCV infection in pregnancy

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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.

HCV infection associated with Kidney Disease

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

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.

• 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

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• 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.

• 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

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• 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.

HCV infection in Cirrhotic Patient

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

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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.

Liver transplantation

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

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.

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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

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Low serum HCV RNA < 400000 IU/ml)Genotype 2 and 3

Viral Factors

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.

HCV infection in Thalassaemia &

Haemophilia

• 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

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• 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.

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• 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

• 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.

HIV / HCV co-infection

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

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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

Anti retroviral neive HIV / HCV co-infected

patients with a CD4 count 100-350/mm3 should received HAART prior to HCV treatment.

HIV / HCV co-infected patients with advanced HIV disease (CD4 count <100/mm3 should receive HAART first & HCV treatment delayed until immune function is improved preferably to a CD4 count >200/mm3

HIV / HCV co infected patients with CD4 count >350/mm3 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

HBV / HCV co-infection

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

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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)

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