Transcript Slide 1 - Baylor College of Medicine

GI Grand Rounds
Johanna Chan
Gastroenterology Fellow
Baylor College of Medicine
6/27/13
No conflicts of interest
No financial disclosures
HPI
• RFC: abnormal liver function tests
• 39yo transvestite man with DM1, frequent
hospitalizations for DKA
• Admitted to hospital 4/4/13 with DKA
• ALT 765, AST 629, total bilirubin 0.5, alk phos
229, albumin 3.4
• No documented hypotension, no available INR,
no other specific GI symptoms
• Referred to GI clinic for follow up of LFTs
Past Medical History
• DM1, diagnosed in his 20s
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poorly controlled (Hgb A1c 13.7%)
frequent hospitalizations for DKA
complicated by peripheral neuropathy
chronic early satiety and nausea (?gastroparesis)
• HTN
• HLD
• Hypothyroid
Medications
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Insulin
Gabapentin
Enalapril
Esomeprazole 20 mg PO daily
Simvastatin 40 mg PO QHS (stopped after
4/2013)
• Levothyroxine 100 mcg PO daily
• Tylenol 500 mg PO BID (stopped after 4/2013)
• No herbs or supplements
HPI continued
• Presents to GI clinic approximately 6 weeks
post-hospitalization
• Malaise, poor appetite, nausea, vomiting of clear
yellow emesis, early satiety
• Clearly now markedly jaundiced, scleral icterus
• No abdominal pain, change in stools
• 60 lb unintentional weight loss over the past 10
years
Other history
• Family history
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Mother DM2
Brother DM1, HTN, HLD
No rheumatologic or other autoimmune disease
No family history of liver disease
• Social history
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Complete EtOH abstinence
No history of IVDA or tobacco
No blood transfusions or tattoos
Unprotected sex (MSM)
“Black market” hormone injections, Mexico, 1990s
Exam
• T 98.2, BP 113/72, HR 85, RR 12, O2 sat 99% RA
• 5’8”, 189 lbs
• Gen: markedly jaundiced, AAOx4, NAD,
groomed casually in women’s clothing
• HEENT: marked scleral icterus
• Neck: supple, no LAD
• CV: RRR no m/r/g
• Chest: no spider angiomata, no gynecomastia
• Lungs: CTAB no wheezes/rales/rhonchi
• Abd: S/NT/ND, NABS, no fluid wave
• Ext: no edema
Available labs
HIV negative
HAV IgM negative
HBsAg positive (negative in 2008)
HBcAb IgM positive (negative in 2008)
HBV DNA PCR 108,000,000
HBV DNA log 10 8.04
HCV IgG negative
Labs in clinic
137
100
15
200
4.1
27
0.9
13
4.8
38.2
68% PMNs
Total protein 7.1
Albumin 3.3
Total bili 8.8
ALT 2143
AST 1302
Alk phos 193
144
MCV 89
INR 1.1
PTT 39.9
TSH 3.02
HCV DNA PCR negative
HDV Ab negative
LFT trend
4/5
4/22
5/14
T prot
5.6
6.9
7.1
Albumin
2.7
3.4
3.3
ALT
765
947
2143
AST
629
727
1302
Alk phos
229
317
193
T bili
0.5
1.4
8.8
D bili
0.3
1
6.6
INR
--
--
1.1
Imaging
• RUQ U/S: mild hepatomegaly (17cm at right
mid-clavicular line) with normal echogenicity,
smooth contour; small sludge, CBD 0.3cm
Management?
LFT trend
4/5
4/22
5/14
5/20
5/28
T prot
5.6
6.9
7.1
7.4
7.1
Albumin
2.7
3.4
3.3
3.4
3.6
ALT
765
947
2143
1083
334
AST
629
727
1302
493
30
Alk phos
229
317
193
199
137
T bili
0.5
1.4
8.8
3.9
0.2
D bili
0.3
1
6.6
3
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INR
--
--
1.1
1.0
1.0
HBV DNA
108
million
95,500
8190
HBV DNA
log 10
8.04
4.98
3.91
Clinical questions
• Who is getting acute HBV in the U.S.?
• What is severe acute HBV?
• How and when should we treat severe acute
HBV?
Acute HBV demographics
• Acute HBV incidence has declined 82% since
1990
• 8.5 cases per 100,000 in 1990
• 1.5 cases per 100,000 in 2007 (the lowest rate
ever recorded)
• Declines in all age groups, but especially in
children <15 yrs, attributable to vaccination
(national vaccination strategy implemented in
1991)
Daniels et al. MMWR Surveill Summ.
2009 May 22;58(3):1-27.
Acute HBV demographics
• In 2007, 4,519 acute symptomatic cases reported
(43,000 additional new infections,
asymptomatic)
• Risk factors for infection: 38% multiple sex
partners, 11% MSM, 6% sexual contact with a
person known to have hepatitis B. IVDU
reported for 15% of persons.
• 2007 reports: 76% had jaundice, 40% were
hospitalized, and 2% died.
Daniels et al. MMWR Surveill Summ.
2009 May 22;58(3):1-27.
Acute HBV incidence
Daniels et al. MMWR Surveill Summ.
2009 May 22;58(3):1-27.
Acute HBV incidence
Daniels et al. MMWR Surveill Summ.
2009 May 22;58(3):1-27.
Acute HBV incidence
Daniels et al. MMWR Surveill Summ.
2009 May 22;58(3):1-27.
Management of severe acute HBV
Typical acute HBV clearance
Tillman et al. Liver Int. 2012
Apr;32(4):544-53.
Acute hepatitis B
• In approximately 1% of cases, acute HBV
progresses to liver failure with need for
transplantation
Treatment with lamivudine for
severe acute HBV
• Large series of 37 patients (multicenter)
• Definition of severe acute hepatitis:
▫ Bilirubin >=10 mg/dl
▫ INR > 1.6
▫ Presence of hepatic encephalopathy
• Transplant-free survival with lamivudine for
severe/acute to fulminant hepatitis B was 78.3%
(29 of 37 patients) compared with 21.6% of
historic controls (p < 0.001).
Tillman HL et al. J Viral Hepat 2006;
13:256-63.
Treatment with newer antivirals
for acute HBV
• Prospective study, 6 patients in Germany with
HBV-related acute liver failure
• Entecavir 1 mg/day within 1-18 days of
admission, continued for at least 3 months
• Normalization of INR, ALT, and bilirubin within
3 months
• 1 patient went on to develop chronic hepatitis B
Jochum C et al. Digestion 2009; 80:23540.
Risk of increasing chronicity with
treating acute HBV
• 57 patients hospitalized with acute HBV
acquired in adulthood in Japan
• 7 of 57 patients developed persistence (HBsAg
positive 6 months after index hospitalization)
• 6 of the 7 received prednisolone or glycyrrhizin
during acute illness, 1 did not
• Infection persisted in 86% of patients who
received treatment vs. 2% of patients who did
not (p = 0.01)
Kobayashi M et al. J Med Virol 2002;
68:522-8.
Take home points
• Fortunately, frequency of severe acute to
fulminant liver failure in acute HBV is low
• For acute severe to fulminant HBV-related liver
failure, lamivudine has shown benefits in
transplant-free survival
• Small case series promising for entecavir in the
setting of acute severe to fulminant HBV-related
liver failure
References
• Daniels D, Grtydal S, Wasley A; Centers for Disease Control and Prevention.
Surveillance for acute viral hepatitis – United States, 2007. MMWR
Surveill Summ. 2009 May 22;58(3):1-27.
• De Socio GV et al. Severe acute hepatitis B treated with entecavir. Mediterr
J hematol Infect Dis. 2011;3(1):32011010.
• Jochum C et al. Hepatitis B-associated acute liver failure: immediate
treatment with entecavir inhibits hepatitis B virus replication and
potentially its sequelae. Digestion 2009; 80:235-40.
• Kobayashi M et al. Viral genotypes and resonse to interferon in patients
with acute prolonged hepatitis B virus infection of adulthood in Japan. J
Med Virol 2002; 68:522-8.
• Kumar M et al. A randomized controlled trial of lamivudine to treat acute
hepatitis B. Hepatology. 2007 Jan; 45(1):97-101.
References continued
• Tillman HL, Zachou K, Dalekos GN. Management of severe acute to
fulminant hepatitis B: to treat or not to treat or when to treat? Liver Int.
2012 Apr;32(4):544-53.
• Tillman HL et al. Safety and efficacy of lamivudine in patients with severe
acute or fulminant hepatitis B, a multicenter experience. J Viral Hepat
2006; 13:256-63.
• Yu JW et al. The study of efficacy of lamivudine in patients with severe
acute hepatitis B. Dig Dis Sci. 2010 Mar; 55(3):775-83.
• Yu JW et al. Lamivudine treatment is associated with improved survival in
fulminant hepatitis B. Liver Int 2011; 31:499-506.
Questions?