TB Case Management Hepatitis

Transcription

1 TB Case Management Hepatitis Chris Keh, MD TB Controller, TB Prevention and Control Program, San Francisco Department of Public Health Assistant Clinical Professor, Division of Infectious Diseases, University of California, San Francisco PITCA, September 12, 2017

2 Disclosures None

3 Objectives List symptoms that are concerning for hepatotoxicity. Identify situations when TB medications should be held. Describe the evaluation of patient with abnormal liver enzymes. Discuss methods for restarting medications after recovery from abnormal liver enzymes.

4 INH-induced hepatitis Incidence of hepatitis in persons taking INH is lower than previously thought (0.1 to 0.15%) Hepatitis risk increases with age Uncommon in persons <20 years old Nearly 2% in persons 50 to 64 years old Risk increased with underlying liver disease or heavy alcohol consumption

5 INH-induced hepatitis Past data suggested much higher rates of hepatoxicity, but that included asymptomatic rise in transaminases. Newer data, used signs and sx to trigger lab diagnosis (AST/ALT >5x nl) Good clinical monitoring, rather than routine lab testing can produce reasonably low rates of adverse events. N=13,838 Hepatitis Age (yr) Cases/1000 < > Kopanoff, Am Rev Resp Dis 1976 US public health survey N=11,141 Hepatitis Age (yr) Cases/ Nolan CL, JAMA 1999 Seattle Public health TB clinic

6 INH Adverse Reactions Asymptomatic elevation of hepatic enzymes are more common - seen in 10%-20% of people taking INH Levels usually return to normal even when treatment is continued (and after completion of treatment)

7 The image part with relationship ID rid3 was not found in the file. Scenario A patient with Pott s disease develops fatigue and anorexia while on TB treatment. You check LFT s and AST 200, ALT 150. What do you do?

8 The image part with relationship ID rid3 was not found in the file. Drug-induced Liver Injury (DILI) Causative: PZA (1%) INH Asymptomatic elevation <5x ULN in 10-20% Clinical hepatitis, % depending on combo Fatal hepatitis <0.023% RIF rare except in combination with other drugs Asymptomatic hyperbilirubinemia (0.6%) Cholestatic pattern of hepatitis

9 DILI (management) HOLD medications for the following or any GI complaint: abdominal pain, diarrhea, fatigue, nausea/vomiting, anorexia, malaise, jaundice, dark urine. Check LFT s If LFT <5x upper limit of normal (ULN) and asymptomatic, okay to restart but may need closer monitoring. If LFT <3x ULN and symptomatic, okay to restart with supportive measures, e.g. treatment of gastritis or nausea. May need closer monitoring.

10 DILI (management) STOP medications for the following: Asymptomatic + LFT >5x upper limit of normal (ULN) Symptomatic + LFT >3x ULN Screen for hepatitis (A, B, C) or other underlying causes of liver disease (alcohol use, other hepatotoxic medications). Check INR. Determine if urgent evaluation or admission is needed (e.g. >10x ULN or any evidence of liver failure- asterixis, confusion, dehydration, coagulopathy)

11 DILI (re-challenge) Monitor LFTs weekly until 2x ULN (some programs completely normal), before re-challenging with medications. If severe TB disease, may need to start liversparing regimen. Seek consultation in re-introduction of medications Choice in med re-challenge depends on co-morbidities (cirrhosis), degree of hepatitis (mild vs severe), susceptibilities (pan-susceptible or pending), phase (initial or continuation), and most likely suspect (PZA>INH>RIF). Typically, start least suspect agent first (along w/ non-hepatotoxic meds), monitor LFTs in 3-7 days, and if remain normal then re-challenge with next agent.