JOURNAL PRESENTATION

The New England Journal of Medicine

Case Records of the Massachusetts General Hospital

An 18-Year-Old Woman
with Acute Liver Failure
Presentor :-
Dr.PRAJIT MAZUMDAR
JRA3 Medicine
RIMS Ranchi
Case 2-2017:

An 18-Year-Old Woman
with Acute Liver Failure

Kristian R. Olson, M.D., Amir H. Davarpanah, M.D.,

Esperance A. Schaefer, M.D., M.P.H., Nahel Elias, M.D.,
and Joseph Misdraji, M.D.
 PRESENTATION OF THE PATIENT
day1….

An 18-year-old woman was seen in the emergency department of

this hospital 11 weeks after the birth of her first child because of
acute liver failure.

The patient had been well until 1 week before this presentation,
when rhinorrhea , sore throat, and cough developed. On the fourth
day of illness, she was seen in an urgent care clinic because of
worsening cough, wheezing, and dyspnea.

Bronchitis was diagnosed, and promethazine–dextromethorphan

syrup and a 5-day course of oral azithromycin were prescribed. The
patient returned home.
 Day3…..
• Over the next 3 days, abdominal discomfort, nausea,
vomiting.
• Vaginal bleeding developed.
• The patient also noted progressive yellowing of her
skin and eyes.
• She recalled that during the past several days,
her gums had bleed easily when she brushed her teeth
and her urine had been tea-colored.
• Eleven weeks earlier she had given birth to her first
child.
 FINDINGS ON EXAMINATION
On assessment in local hospital , the patient had jaundice and
diaphoresis . She appeared fatigued.

The pulse was 120 beats per minute, the blood pressure 102/76 mm
Hg, the respiratory rate 22 breaths per minute, and the oxygen
saturation 100% while she was breathing ambient air.

There was tenderness in the right upper quadrant. The capillary blood
glucose level was 121 mg per deciliter (6.7 mmol per liter), and an
electrocardiogram showed sinus tachycardia.

Intravenous fluids and supplemental oxygen (through a nasal cannula

at a rate of 2 liters per minute) were administered, and the patient
was transported to the emergency department of
another hospital for better management.
On arrival at the other hospital, the patient reported abdominal pain,
which she rated at 10 on a scale of 0 to 10, with 10 indicating the most
severe pain.
The temperature was 37.0°C, the pulse 88 beats per minute, the blood
pressure 107/42 mm Hg, the respiratory rate 24 breaths per minute, and
the oxygen saturation 100% while she was breathing ambient air.

The abdomen was soft, with tenderness on the right side due to tender
hepatomegaly, and there was trace edema of the legs.
The results of the rest of SYSTEMIC examination were otherwise
unchanged.

The blood carbon dioxide level was

21 mmol per liter (reference range- 24 to 34), and
the blood glucose level was 104 mg per deciliter
(5.8 mmol per liter; reference range, 70 to 100 mg
per deciliter [3.9 to 5.6 mmol per liter]).

The anion gap and blood levels of sodium, potassium,

and chloride were normal, as were the results of
renal-function, magnesium, glucose, amylase, lipase,
and fibrinogen which were also normal
 INVESTIGATIONS
HAEMOGLOBIN 7.9 g/dl
TOTAL LEUCOCYE COUNT 11,100cells/cumm
PLATLET COUNT 1.75 LAC
MEAN CORPUSCULAR 81 fl
VOLUME(MCV)
MEAN CORPUSCULAR 26.7 pg
HAEMOGLOBIN(MCH)
MCHC 33.1 g/dl
HAEMATOCRIT 0.32%
 PBS
• SCHISTIOCYTES WERE SEEN….
 INVESTIGATIONS ……

Examination of a peripheral blood

smear revealed SCHISTIOCYTES.

Testing for urinary human

chorionic gonadotropin was negative.

A serum viral profile screen was negative, and a urine

toxicology screen was negative for all other analytes.

Urinalysis revealed slightly cloudy, amber-colored urine with

a specific gravity of 1.019, a pH of 6.0, 2+ bilirubin,
2+ urobilinogen and 0 to 2 red cells per high-power field.
BILIRUBIN(T) 26.5 mg/dl
BILIRUBIN(D) 21.9 mg/dl

AST(aspartate 154 U/L

transaminase)
ALT(alanine 22 U/L
transaminase)

ALP(alkaline phosphatase) 14 U/L

GAMMA GLUTAMYL 116 (normal range-<55U/l)

TRANSPEPTIDASE(y GGT)-
PROTHROMBIN TIME(PT) 24 SEC

INTERNATIONAL 2.5
NORMALIZED RATIO
(INR)

TOTAL PROTEIN 5.2

SERUM ALBUMIN 2.2
SERUM GLOBULIN 3.1
 NON REACTIVE
HBsAG
NON REACTIVE
ANTI HCV
NON REACTIVE
IgM HAV
IgM HEV NON REACTIVE

OPTIMAL TEST NEGATIVE

DENGUE PROFILE NEGATIVE

IGM HERPES SIMPLEX(HSV) NEGATIVE

IGM LEPTOSPIRA NEGATIVE

IgM CMV(CYTOMEGALOVIRUS) NEGATIVE

A chest radiograph and
a computed tomographic (CT) scan of the head
(obtained without the administration of intravenous
contrast material) were normal.

Ultrasonography of the abdomen revealed mildly

increased hepatic parenchymal echogenicity This
finding, although nonspecific, could reflect hepatic
steatosis or diffuse parenchymal disease and no focal liver
lesions were identified.

The common bile duct was normal in diameter, with no

intrahepatic biliary ductal dilatation on USG
• Doppler ultrasonography of the abdomen revealed
persistent evidence of wall oedema and intraluminal
sludge in the gallbladder.

 Pulsed-wave Doppler ultrasonography revealed

normal arterial flow in the main hepatic artery.

There was also normal hepatopetal flow in the

portal veins and hepatofugal flow in hepatic veins
 Investigations for hemolysis….
SERUM LDH(lactatae dehydrogenase) ---344 Iu/l

RETICULOCYTE count =6 %

Corrected reticulocyte
count=(6%*0.32/0.45)=4.2%
(normal range- adults 0.5-2.5)
 UNDERLYING HEMOLYSIS
The patient described in this case had severe hemolysis
as evidenced by schistocytes on peripheral blood smear,
reticulocytosis, elevated LDH

The presence of hemolytic anemia in

conjunction with the hepatic dysfunction and
Persistent elevation of serum bilirubin and
the severity of jaundice---------

---------MADE US SUSPECT OF SOME

UNDERLYING PATHOLOGY CAUSING
HEMOLYSIS .
SICKLING TEST- NEGATIVE

G 6PD(GLUCOSE 6 11.4 u/G OF HB (NORMAL

PHOSPHATE DEHYDROGENASE) RANGE-6-18)

DIRECT AND NEGATIVE

INDIRECT
COOMBS TEST
 Acute liver failure was diagnosed
Criteria for the diagnosis include the presence of coagulopathy
(international normalized ratio [INR] >1.5), hepatic
encephalopathy, and an illness of less than 24
weeks’ duration.

This patient has evidence of

liver injury and an INR well above 1.5.

She does not have features of encephalopathy, such as altered

consciousness, compromised intellectual
functioning, tremors, or asterixis, and thus she
may meet only the criteria for acute liver injury.
However, it has been seen in young population
(having patients who are up to 21 years of age), up
to 50% of patients who present with acute liver
failure do not present with encephalopathy.

Modified criteria for the diagnosis

of acute liver failure in young patients include
evidence of acute liver injury and severe
coagulopathy
(INR >2.0) in the absence of encephalopathy.

Given this patient’s age, we would argue

that she meets the criteria for acute liver failure
On the basis of the above clinical findings and
investigations a provisional diagnosis of ACUTE
LIVER FAILURE was made which was preceded by a
viral infection of upper respiratory tract
DIFFERENTIAL DIAGNOSIS
1------Acetaminophen Exposure

Although a serum acetaminophen level was undetectable

in this patient on presentation, it is
important to maintain suspicion for either inadvertent
chronic ingestion or an acute one-time
ingestion several days before presentation.

The prevalence of postpartum depression is approximately

10%,and young age and unplanned pregnancy have
been identified as risk factors.
There is no history
of a psychiatric illness, which might suggest the
possibility of an intentional overdose.

The hallmark of liver injury in acetaminophen is markedly

elevated aminotransferase levels, which are usually
in the thousands and frequently 400 times
the upper limit of the normal range.

This biochemical feature is not consistent with this patient’s

laboratory test results.
2-----Pregnancy

During pregnancy, dilutional hypoalbuminemia

and elevation of the placental-derived alkaline
phosphatase level can lead providers to falsely
assume that the patient has liver disease.

However,the elevations of the aspartate

aminotransferase level, dearranged PT- INR, and γ-
glutamyltransferase level in this patient are uniformly
abnormal suggesting alternate diagnosis.
3----Eclampsia
Eclampsia affects 2 to 8% of pregnant women and can
occur up to 6 weeks post partum, but this patient’s
symptoms developed later around 11 weeks post partum

Furthermore, in pregnant women with eclampsia, the

aminotransferase levels are typically 10 to 20 times the upper limit
of the normal range and the bilirubin level is typically
less than 5 mg per deciliter which is not seen in this case

Also, the gamma-gluamyl transferase level in this patient

is higher than would be expected during
eclampsia.
The HELLP syndrome (hemolysis, elevated liver
•enzyme levels, and a low platelet count) occurs
in less than 1% of pregnant women, and only
one third of cases occur after delivery.

.
However,the patient’s platelet count was normal.
4-Ischemic Hepatopathy
•The Budd–Chiari syndrome, or hepatic venous
outflow obstruction, is another consideration
because the prevalence during pregnancy
and the puerperium is approximately 6.8%.

•However, acute liver failure develops in less than

5% of patients with the Budd–Chiari syndrome.

•In addition, although the aminotransferase levels

may be only moderately elevated (as in this patient),
the bilirubin level is seldom higher than 7 mg
per), whereas the bilirubin level in this patient is higher than 20 mg
per deciliter .

•This patient also had a normal vascular Doppler ultrasound

evaluation, which rules out the diagnosis of the
Budd–Chiari syndrome.
5---Viral hepatitis

Viral hepatitis is the cause of acute liver failure

in 10% of cases in developed countries.

An exacerbation of hepatopathy can occur as the result of

the relative immunosuppression associated with pregnancy.

However, this patient had negative viral serology profile.

In addition,she had no fever and few risk factors for acute

hepatitis B virus infection, and viral hepatitis
typically results in aminotransferase levels that
are more than 25 times the upper limit of the
normal range.
6---Autoimmune Hepatitis

Autoimmune hepatitis is a chronic, progressive

disorder, but it can also cause acute liver failure.

Patients with autoimmune hepatitis typically

present with nonspecific symptoms, including
fatigue, lethargy, malaise, anorexia, nausea, abdominal
pain, and itching

Symptoms may first become evident during pregnancy, and postpartum

exacerbations do occur.

However, some features of autoimmune hepatitis are absent in this

patient, including coexisting autoimmune conditions,
associated small-joint arthralgias, and the
typical pattern of markedly elevated aminotransferase
levels.

In addition, she does not have elevated

globulin levels
7----Wilson’s Disease

Wilson’s disease, also known as hepatolenticular

degeneration, is an autosomal recessive disease
characterized by impaired copper metabolism
due to a defective ATPase.

The mean age at onset ranges from 12 to 23 years, and

this patient’s age falls within that range.

Patients with Wilson’s disease may present with chronic

liver disease,acute hepatitis,acute liver failure, hemolysis,
and psychiatric or neurologic manifestations.
She underwent a slit-lamp examination, and
there was no evidence of Kayser–Fleischer
rings.

HOWEVER,IT HAS BEEN SEEN THAT K-F RINGS ARE

ABSENT IN 60% OF PATIENTS WITH EXCLUSIVE
HEPATIC INVOLVEMENT AND IN PRESYMPTOMATIC
STAGE.
WILSON DISEASE WORKUP
24 HR URINARY 1419 uG/specimen <40 Ug/specimen
COPPER

SERUM 0.25 g/l 0.2-0.35 G/L

CERULOPLASMIN

HEPATIC COPPER COULD NOT BE

ESTIMATION DONE DUE TO
DEARRANGED PT-
INR
SERUM COPPER 0.96 μg per reference range,
milliliter 0.75 to
1.45 ug/ml
Our patient had-------
1. Coombs negative hemolytic
anaemia
2. Increased 24 hour urinary
copper excretion
3. Absence of K-F rings
4. Ratio of alkaline
phosphatase(ALP) to total serum
bilirubin <4
5. Ratio of SGOT/SGPT >2.2
•The patient’s age, sex, possible hemolytic
anemia, and low alkaline phosphatase level
raised strong clinical suspicion for Wilson’s
disease.

• The ratio of alkaline phosphatase to total

bilirubin was <4-----0.5 in our pt

•The ratio of aspartate aminotransferase(AST)

to alanine aminotransferase(ALT) was >2.2 --
--- 6.3 in our pt

•These findings suggest that a diagnosis of

Wilson’s disease could be made using LEIZPIGs
CRITERIA( score -3)
 PATHOGENESIS-----
It has been previously noted that viral infection or
drug toxicity may serve as a trigger for fulminant
Wilson’s disease.

In this patient, therefore, either the antecedent

UPPER RESPIRATORY TRACT INFECTION may have
played a role.

It has been postulated that an acute insult like viral

infection damages the hepatocytes in pts with
underlying silent wilsons disease ----which may release
free copper in toxic concentration----- which in turn
damages cell membrane leading to haemolysis and more
severe liver damage
Because she had intact renal function, chelation
therapy with penicillamine was initiated to promote
urinary copper excretion as a bridging measure
while she awaited transplantation

Shortly after the patient was placed on the

liver transplantation list, a donor was
identified, and the patient underwent
orthotopic liver transplantation that day.
 Diagnosis….
• From the case discussed above, an impression
can be drawn that the patient was suffering
from underlying silent Wilson’s disease (WD)
and diagnosis came into picture with viral
super infection
 FINAL DIAGNOSIS

ACUTE hepatic failure due

to Wilson’s disease
 FOLLOW UP…
• This patient received a good-quality liver donated
from a deceased 23-year-old man who had
been declared brain dead because of penetrating
head trauma and hemorrhagic shock.

We performed liver transplantation with the use of the

“piggyback” technique, in which the surgeon
performs hepatectomy with preservation of the
inferior vena cava and then performs anastomosis
to attach the donor’s suprahepatic inferior
vena cava to the recipient’s inferior vena cava at
the level of the hepatic veins.
The patient was extubated on day 1
after transplantation and transferred to the
inpatient unit the following day.

She received maintenance therapy with a

triple immunosuppression
regimen (tacrolimus, mycophenolate
mofetil, and prednisone) and was discharged
home on day 9 after transplantation.
Since the transplantation, the patient has
done well, with the exception of three episodes
of allograft dysfunction;

the first was relatively minor and occurred during an upper

respiratory tract infection,

and the second and third were

due to acute rejection during the administration
of subtherapeutic tacrolimus levels 11 and 15
months after transplantation.

The two episodes of rejection resolved after treatment with

intravenous methylprednisolone and an increase in
immunosuppression maintenance therapy.
.
The outcomes associated with liver transplantation
for acute liver failure induced by Wilson’s disease
are excellent, if transplantation is performed
prior to neurologic deterioration
ECG -1
CHAPMAN SIGN
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WELLEN SIGN
THANK YOU