hepatitis c and tuberculosis

Tumelo Roestoff FCP(SA)Fellow of Gastroenterology

Charlotte Maxeke Johannesburg Academic Hospital

is there a link between the two entities?

>10% 2.5–10% 1–2.5%

WHO. Wkly Epidemiol Rec 2002; 77: 41

Epidemiology

Impact of hepatitis C infection on TB treatment

1) normal liver chemistry before starting anti-tuberculosis treatment;

2) the patient was receiving INH, RMP or PZA alone or in combination for at least 5 days before the development of abnormal liver chemistry;

3) an increase in ALT and/or AST to ⩾3 times the upper limit of normal (ULN) with symptoms, or an increase in ALT and/or AST to ⩾5 times the ULN without symptoms;

4) no other apparent cause for the elevation of liver chemistry, such as excessive alcohol intake; and

5) removal of the medications re- sulted in a normalisation or at least a 50% improve- ment of the abnormal liver chemistry.

Definition of DIH (DILI)

“Co-infection with HBV was not associated with a higher rate of hepatitis but was associated with later onset (102 ± 68.7 vs. 37.0 ± 31.9 days, P = 0.01), higher peak alanine amino- transferase level and slower recovery (55.5 ± 62.9 vs. 15.4 ± 10.8 days, P = 0.01).”

JY chien et al. Int J tuberc lung disease, 2010; 14(5): 616 - 621

AM J RESPIR CRIT CARE MED 1998;157:1871–1876.

• 6 patients relapsed with reintroduction of TB treatment

• 2 were excluded because of HIV co-infection

• 4 patients consented to interferon alpha 2a therapy– This allowed succesful re-introduction of TB

therapy and completion of treatment– Variable response in terms of Hep C viral

loads, but no SVR attained in any of the patients

UNGO J.R et al, AM J RESPIR CRIT CARE MED 1998;157:1871–1876.

Impact of TB on Hepatitis C therapy

Respiratory: Bronchitis (≥1% to ≤5%), epistaxis (≥1% to ≤5%), nasal congestion (≥1% to ≤5%), nasopharyngitis (≥1% to ≤5%), pharyngolaryngeal pain (≥1% to ≤5%), rhinitis (≥1% to ≤5%), sinus congestion (≥1% to ≤5%), throat sore (≥1% to ≤5%), upper respiratory infection (≥1% to ≤5%), pneumonia (HIV-HCV coinfection: ≥1% to ≤3%)

UPTODATEPegylated Interferon alpha 2a and Ribavarin

Adverse reactions significant ( 1 – 10%)

Warnings/PrecautionsDisease related concerns:

Infectious disorders: Interferon therapy may cause or aggravate fatal or life-threatening infectious disorders; discontinue if signs and symptoms occur. Investigate the etiology of any persistent fever during therapy.

• Numbers are not overwhelming – controversial as to whether treatment can result in TB infection

• Mostly case reports • One study looking at HepC and HIV co-

infected population

• Adverse effects in treatment

Reactivation?

Scandinavian journal of infectious diseases; 2006

• 62yr old gentleman

• Developed cough and haemoptysis 7months into therapy with Pegylated Interferon and Ribavarin

• CT chest suggestive and Montoux was positive,

• bronchoscopy and sputum– both smear positive and MTB was cultured

• CD4+ depletion to below 290 and abnormal CD4+:CD8+ ratios

• Patient was smear positive for a total of 13 weeks on treatment

• Subsequent normalisation of CD4+ count with TB treatment

J Formos Med Assoc 2009;108(9):746–750]

• 55yr old Taiwanese lady• Type 2 Diabetes Mellitus• HepC genotype 2a/2c• Cirrhosis on liver biopsy• Symptoms began 8 weeks in to

therapy with combination pegylated interferon alpha 2a and Ribavarin

Complication of therapy?

- controversial

n = 97

TB complicating Hep C therapy in the HIV

population

Clinical Infectious Diseases 2009;48:e82–5

• Retrospective observational study• 3 hospitals in Madrid Spain• Interferon based therapy for HepC

between 1996 and 2007• HIV and Hep C con-infected patients

Results:• 570 patients• 4 developed TB during therapy

Key points:

• All therapy was discontinued upon diagnosis of TB

• Diagnosis was severely delayed – Clinical features were attributed to the

side effects of therapy

conclusion• Hepatitis C is a risk factor for TB DILI• It appears to be responsible for cases

of reactivation of latent TB–May influence clinical practice

• It does rarely complicate interferon based HepC therapy in the low incidence areas of the world

• ?treatment impact in high TB incidence areas such as Sub-Saharan africa.

Thank you