IR Acute Hepatitis B

Intern Report
January 17, 17 2011
Bryan A. Smith
Jim Woodruff, MD

Case
• 68yo M presents with jaundice and decreased
appetite x 1 mo. mo
Questions?

More Info
• Began g feeling g sick 1 mo ago g after being g treated with
cipro for UTI
• Described symptoms of fever, chills, night sweats,
llethargy, h decreased d dappetite, ddark kcolored l durine and d
light stools
• One week previous, previous presented to OSH for laser
procedure to relieve prostate obstruction. Since then
has had bladder incontinence, dark red urine, clay
colored stools
• Patient reports weight loss of 10lbs in 1 mo

• PMHx
– PProstate t t ca‐ s/p / XRT
– Islet cell tumor of pancreas s/p
resection ‘06
– HTN
– BPH
– DM‐ insulin dependent
• PSHx
• Distal pancreatectomy/
splenectomy ’06‐ lymph nodes
neg, surgical margins free of dx.
• NKDA
• FHX
– noncontributory
Case (cont)
• Social
– Li Lives with ith wife if
– Retired, once worked in
pharmaceutical sales
– +tob‐ 25 pack‐years, social EtOH,
no illi illicits i
• Meds
– Enalapril 20mg BID
– Nifedipine p 90mg g dailyy
– Sildenafil 100mg daily
– Flomax 0.4mg daily
– Finasteride 5mg daily
– Glipizide 10mg daily
– Lantus

Differential?

Classification of Jaundice
UUnconjugated j t dHHyperbilirubinemia bili bi i CConjugated j t dHHyperbilirubinemia bili bi i
• Increased bilirubin production • Biliary Obstruction
– Extravascular hemolysis
– Et Extravasation ti of f bl blood d iinto t
tissues
– Intravascular hemolysis
– Dyserythropoiesis
y y p
• Impaired Hepatic Uptake
– Heart Failure
– Portosystemic Shunts
– Drugs
– Gilbert’s Syndrome
• Impaired conjugation
– Cil Crigler‐Najjar Njj SSyndrome d
– Gilbert’s Syndrome
– Hyperthyroidism
– Liver dx‐ dx chronic hepatitis,
advanced cirrhosis, Wilson’s
disease
– Choledocholithiasis
– Intrinsic and Extrinsic tumors
– Primary Sclerosing Cholangitis
– AIDS cholangiopathy
– Acute/ chronic pancreatitis
– SStrictures‐ i s/pprocedures
/ d
– Parasitic infection
• Intrahepatic cholestasis
– Viral Hepatitis
– Alcoholic hepatitis
– Nonalcoholic steatohepatitis
– Primary biliary cirrhosis
– Drugs/ toxins
– Sepsis
– Infiltrative dx (amyloid, lymphoma, sarcoid,
TB)
– ESLD
• Hepatocellular Injury

Physical Exam
• Vitals: T: 37.4 P: 72 R: 18 BP: 158/74 O2sat: 97%RA
• GEN: NAD, well nourished
• HEENT: Scleral icterus, sublingual jaundice, moist mucus
membranes membranes, no oropharyngeal erythema/ exudate exudate, no LAD LAD,
no JVD
• CV: S1, S2, no MRG, RRR, PMI 5th ICS
• PULM: CTAB, normal respiratory effort
• GI: RUQ and epigastric mild TTP, soft, non‐distended, no
appreciable appecabeoga organomegaly, o egay, no o spider sp de angiomas a go as
• Neuro: A & O x 3, CN II‐XII intact, no asterixis
• Extremities: 2+ pulses, warm, well perfused, no LE edema

Evaluation of Jaundice
• 80% daily bilirubin
production from hemoglobin
• Normal serum concentration
of bilirubin < 1mg/dL g/
• Clinician cannot detect
jaundice until bilirubin >
2.0mg/dL
• Jaundice seen best in ocular
conjunctiva and in oral
mucus membranes (under
tongue, hard palate), and in
the skin.

Wh What labs lb would ld you lik like to order?
d ?

133 101 13
3.8 22 1.0
Labs and Studies
166
8.0
2.1
28 2.8
11.9
92 9.2 278 UA UA‐ + leuk esterase
33.1
N‐ 71
LL‐ 14
M‐ 15
MCV‐ 86.2
MCH MCH‐ 31
MCHC‐ 36.0
+ nitrite
2+ protein
3+ blood
3+ bilirubin
E‐ 0 RDW‐ 21.8 ‐ glucose
B‐0
trace ketones
PT‐ 17.8
INR‐ 1.4
7.1 2.9
21.0 16.4 / 4.6
994 1153
218
GGT‐ 351
Lipase‐ 47
Ammonia‐ 96

Wh What else l would ld you lik like to order?
d ?

• RUQ U/S
Additional Studies
– Partially distended gallbladder with gallbladder
wall thickness thickness. Sludge and gallstones within the
gallbladder noted.
– No hepatic vein thrombosis, no hepatomegaly, no
Budd‐Chiari syndrome

OSH workup arrives..
• CT abdomen/ pelvis w/ contrast‐ contrast
– s/p splenectomy and post op changes in uper abd
with clips in area of pancreas pancreas. No residual masses masses.
Thickening of gallbladder wall, may be 2/2 ascites.
No free air, no bowel obstruction.

Additional Labs
• Blood cx‐ negative • Hepatitis Panel
• Urine cx‐ negative
• AAnti‐mitochondrial ti it h d i l ab b ‐

Hepatitis B
• Affects 1.25 million people in the US and 350‐400 million worldwide
• After WHO recommended hep B vaccine included in infant immunization in 1992,
incidence has dropped from 252,000 to 51,000 cases annually in the US
• 0.1 ‐ 0.2% carriers in low prevalence areas‐ U.S., Canada, Western Europe
• 10‐20% carriers in high prevalence areas‐ southeast Asia, China, sub‐Saharan Africa
• In low prevalent areas, most acute HBV infections occur during adolescence or
early adulthood due to risky behavior
• In high prevalent areas, perinatal transmission results in chronic infection in 90%

Risk Factors
• High Prevalent Areas‐ Perinatal transmission most
common and vertical transmission as high as 90%
• Intermediate Prevalence Areas‐ common age 1‐5
– Horizontal transmission common via breaks in skin and
mucous membranes, close body contact
• Low prevalence areas‐ most common age 25‐44
– SSexual liintercourse t with ith iinfected f t diindividual di id l
• Heterosexual transmission‐39%
• MSM‐ 24%
– IV ddrug use‐ 16%
– Others‐ accupuncture, tattoo, body piercings
– Blood transfusion‐ risk 1:63,000

• Belongs to
hepadnavirus family
• Genome‐ Genome relaxed
partially dsDNA
replicates by reverse
transcriptase
Hepatitis B Virus
• Comprised of envelope of viral encoded proteins
(HBsAg) and core of nucleocapsid protein (HbcAg),
viral genome, DNA polymerase protein

Acute Hepatitis B
• Exposure‐ HBV enters bloodstream, circulates to liver
• Incubation period‐ Pt is asymptomatic, normal liver transaminases
– HBV replicates within hepatocytes, immune response initiated, HBV DNA rises
– May last 1‐6mo, with avg duration of 60 days
• Prodrome‐ non‐specific symptoms of anorexia, malaise, nausea, vomiting, abd pain
• Acute phase‐ 70% have subclinical hepatitis, while 30% develop icteric hepatitis
– Avg time from infection to jaundice 90 days.
– Labs reveal elevations in AST and ALT up to 1000‐2000 IU/L, with ALT>AST
• Resolution‐ Associated with decline in liver transaminases and symptomatic resolution
– Transaminases normalize within 2‐8 weeks
– Among those who recover, virus cleared by antiviral antibodies and cytotoxic T lymphs
– Resolution associated with elimination of virus and appearance of anti‐ HBs, conferring
lifelong immunity from re‐infection

Serologic Markers
• HBsAg‐ serologic hallmark of infection (acute and chronic)
– Detectable after 4‐10wk incubation period before symptoms and rise in ALT
– Typically becomes undetectable after 4‐6mo
– Persistence >6mo implies chronic hep B
• Anti‐HBs‐ Follows disappearance of HBsAg and persists for life
– May not be detectable during window period for few weeks –months during which
no HBsAg or anti‐HBs are detectable
• HBcAg‐ intracellular antigen expressed in hepatocytes but not expressed in serum
– Can be detected by immunohistochmical staining of liver histological specimens
• IgM anti‐HBc‐ shortly follows HBsAg positivity
– Positive during window period‐ HBsAg undetectable and anti‐HBs may not be positive
– Indication of acute HBV infection
– May remain detectable up to two years after acute infection
– May also be positive in exacerbations of chronic HBV
• IgG anti‐HBc‐ persists for life in pt with acute or chronic HBV infection

Serologic Markers (cont)
• HBeAg‐ protein marker indicating HBV replication and infectivity
– Associated with high levels of HBV DNA in serum and high rates of
transmission from carrier mothers to babies
– HBeAg seroconversion to anti‐Hbe occurs early in acute HBV, typically
before HBsAg seroconversion to anti anti‐ HBs
– Seroconversion may take months to years in pt with chronic HBV but
indicates decrease of serum HBV DNA and remission
• HBV DNA
– Most assays use real time PCR, reporting in IU/mL
– Recovery from acute hepatitis accompanied by disappearance of HBV
DNA in i serum
– Low levels HBV DNA detectable in the blood for many years

Acute Hepatitis B Treatment
• Treatment for acute HBV mainly supportive‐ progression to fulminant hepatic
failure

Over course of admission…
• Pt spiked daily fevers to 38.9 thought to be 2/2 hep B. Blood
cultures lt remained i dnegative, ti no other th source of f acute t infection. i f ti On O
ceftriaxone x 3 days for UTI.
• Symptomatic improvement‐ abdominal pain resolved, nausea
resolved resolved, pt able to tolerate PO
• Total bilirubin trended from 21.0 19.1, ALT 1153 1060, AST
994 916
• GI consult‐ consult no additional w/u indicated, follow up as outpatient
with symptomatic management for acute hepatitis B
• Surgery consult signed off
• UTI‐ pt p ggiven 3 days y of ceftriaxone and d/cwoabx /
• Source of infection remained unclear‐ pt denies any risky sexual
behavior, IVDU, recent blood transfusions, etc.

2 week follow up
• Total bilirubin: 21.0 7.4
• ALT 1153: 144
• AST: 994 71
• Albumin: 2.9 3.5
• HHepatitis titi B viral i llload: d 282199 247
• Still admits to dark urine and some fatigue but
abd bd pain i resolved l dand d feeling f li much h better btt
• Regular follow up per GI

Take Home Points
• Most acute Hepatitis p B infections are self‐limiting g and
will resolve with symptomatic management in 6mo 6
• Active infections need follow up in clinic to trend
transaminases, bilirubin, and serology
• Pts should refrain from sexual activity until they
develop anti‐HBs, which may take up to 6mo
• Those with chronic hepatitis B have increased risk of
developing cirrhosis and hepatocellular carcinoma

Thanks!
Questions?