Approach to Jaundice with

Altered Liver Function Tests..!

DR PANKAJ INGALE
MD , DNB (GASTROENTEROLOGY)
Consultant Gastroenterologist

AMRAVATI INSTITUTE OF GASTROENTEROLOGY

A complete solution for Liver and GI health care
 Talk outline
• Brief understanding of liver tests

• Examples of diseases with altered liver tests

• Discussion / queries
 Liver Function Tests
• AST - Aspartate aminotransferase (0- 35 IU/L)-SGOT

• ALT -Alanine Aminotransferase (0-45 IU/L)-SGPT

• ALP - Alkaline Phosphatase (30-120 IU/L)

• GGT - Gamma-Glutaryl Transferase (0-30 IU/L)

• BILIRUBIN

• TOTAL PROTEIN, ALBUMIN, GLOBULIN

• PROTHROMBIN TIME /INR

• Serum Ammonia
• LDH
• Platelet count
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Markers of Cholestasis

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 Importance of liver function tests
• Acute / Recent vs. Chronic liver disease

• Hepatocellular vs. Cholestatic injury

• Etiology of liver disease (ALD, viral…)

• Severity of liver disease (cirrhotic –

compensated vs. decompensated)
 Facts to consider while interpreting
altered AST/ALT
• Always to be assessed in conjunction with a thorough
history and clinical examination

• History – prodrome features, alcohol intake, drug history,

travel history

• Family history

• Trend of enzyme elevation/ drop &

ratio of ALT/AST are important to consider various
etiology
 Signs of Liver Dysfunction
• Clinical : Palmar erythema, spider nevi, small
liver span, Big spleen, ascites, hepatic
encephalopathy

• Imaging : Nodular liver edges, portal

hypertension

• Endoscopy : varices, hypertensive gastropathy

 The Enzymes - ALT/AST
Alanine Transaminase (ALT)
SGPT
- Hepatocytes
- Very specific marker of
hepatocellular injury
-Longer half life than AST
-Levels fluctuate during the day
-NORMAL RANGE
MALE – 30 U/L
FEMALE – 19 U/L
- AASLD
Aspartate Transaminase (AST)
SGOT
- Two isoenzymes
mitochondrial isoenzyme –
hepatocytes
cytosolic isoenzyme skeletal
muscle, cardiac muscle,kidney
tissue.
-Rise in conjunction with ALT to
indicate hepatocellular injury
 Approach to Raised Transaminases
Marked Elevations Moderate Elevations Mild persistent Elevation
> 2000 250-1000 < 250
> 15 folds 5-15 folds ≤ 5 folds

Acute Viral Hepatitis NAFLD

Any
Drug / Toxin induced Autoimmune hepatitis Alcohol use

Ischemic liver injury Chronic hepatitis B Chronic hepatitis B/C

( shock) Infection

Wilson disease
Cirrhosis
Vascular Liver diseases Drug induced Neoplasms
 PT - INR
Most Important Test for Liver assessment
Prothrombin Time / INR

If PT/INR is normal,
what ever may be ALT/AST
Hepatocellular reserve is well preserved
 The enzymes
• Alkaline phosphatase (ALP)
- Group of enzymes (isoenzymes can be measured
- Biliary epithelium,bone,placenta,kidneys,gut
- Higher values in children
• Gamma-Glutamyl Transpeptidase(GGT)
- Liver and other viscera
- Main role is to help interpret ALP

• ALP >> GGT = Bone disease, pregnancy

• GGT >> ALP = alcohol,medications
 Bilirubin
• With elevated liver enzymes,
Reflective of liver disease or biliary obstruction

• Without elevated liver enzymes

Hemolysis
Gilbert’s syndrome
Severe liver disease
 An Approach to Jaundice
• Is it isolated elevation of serum bilirubin ?

• If so, is the ↑unconjugated or conjugated fraction?

• Is it accompanied by other liver test abnormalities ?

• Is the disorder hepatocellular or cholestatic?

• If cholestatic, is it intra- or extrahepatic?

14
SB > 1.0 mg

15
If Conj Sr Bil is increased

16
Hepatocellular Pattern

17
Approach to Abnormal Liver
Tests
• Decide on the pattern
• Assess liver function
• Old liver tests
• Imaging
• Ask abt
New – pain, systemic illness, viral prodrome
Old – Viral, autoimmune, metabolic
Always - Alcohol, medications, toxins,
risk factors for viral hepatitis
 Acute abnormalities
• With abdominal pain
Gall stones, CBD stones, Viral Hepatitis

• Without abdominal pain

Viral hepatitis, Medications, Toxins

• With systemic illness

Ischemic hepatitis
Sepsis-cholestasis
 Case 1
75 yr Mrs S,
C/O dyspepsia and “back “ pain
Background hx:
Type 2 Diabetes mellitus
Subclinical Hypothyroidism
Clinical examination :
Mild pedal oedema
Rest unremarkable

Routine investigations along with Liver Tests (Liver Profile)

 Basic investigations
Liver Tests :
CBC – •Albumin 4.3 (3.4-4.8) mg/dL
HB – 11 g%
•Total Bilirubin 1.0 mg/dL
PCV -30
TLC – NORMAL •Alkaline Phosphatase 67 (35 -104)
PLATELET – 1.1 L IU/L

•GGT 93 (5 – 36) IU/L

REST - NORMAL
•Alanaine transaminase (ALT) 40 (6
– 31) IU/L
 Further investigation
• HBs Ag – Negative

• Anti HCV antibody - Negative

• Autoimmune liver panel ( ANA,SMA,LKM 1,AMA) – Negative

 USG abdomen :
Liver: coarse echo-texture, surface nodularity,
No focal lesion, Bile ducts not dilated, portal vein 12 mm,
Spleen – 10 cm

Cirrhosis of liver
 Liver tests – in cirrhosis
• AST/ALT – not very informative, may be slightly elevated

• AST : ALT ratio >1

• Bilirubin – not very informative, may be slightly raised

• Albumin – Low levels are sensitive to detect cirrhosis

• Albumin : Globulin Ratio REVERSAL

• PT INR – May be elevated, suggestive of decompensated cirrhosis

• Platelet count – low platelet count is directly related to severity of

portal hypertension
 Case 2
18 yrs Girl ALT – 2400 ↑↑↑
Febrile illness x 2 days AST – 2100 ↑↑↑
ALP – 300 IU
Nausea, vomiting
Anorexia BILIRUBIN
Yellowish discoloration of TOTAL - 4 mg/dl ↑
urine, eyes, skin DIRECT - 3 mg/dl ↑
O/E
PROTEIN ALBUMIN – 3.5 mg/dl
icteric
GLOBULIN- 3.2 mg/dl
vitals - stable
liver + tender PT / INR – 14/14 1.01
CBC – NORMAL
USG – MILD HEPATOMEGALY

Acute Viral hepatitis Anti HAV IgM Positive

 Case 3
• 42 year man • ALT – 48
• Excessive alcohol • AST – 217
• Noticed by drinking • ALP – 192
buddy to be jaundiced • GGT – 96
• INR -2.3
• Low grade fever • ALBUMIN – 2.1
• PLATELTS – 87 K
 Case 3
• Old Liver Tests – Elevated GGT; rest normal

• USG – Mild Hepatomegaly

• AST: ALT Ratio - > 2

• Discriminant function (DF) of Maddrey

4.6 x (PT  test - control)) + S.Bilirubin in mg/d ; IF > 32

• Platelet count – LOW --in favour of cirrhosis/PHT

• Diagnosis – Alcoholic Hepatitis complicating cirrhosis

 Case 4
• 49 year old female • Bil 1.1
• Healthy • ALT 381 ↑↑
• Routine check up • AST 184 ↑
• ALP 64
• GGT 14

• ALBUMIN,INR - normal
• PLATELET - NORMAL
 Case 4
• Old liver tests
- infrequent
- Bil, ALP, GGT –Normal
- ALT and AST fluctuates from normal to 300s

• No drug history
• Autoimmune markers negative
• HBV HBsAg Positive
Anti HBeAg Antibody Positive
HBV DNA PCR – 10,00,000 copies

• HCV Antibody – Negative

• ARFI - 2.12

• Diagnosis : Chronic Hepatitis B with Cirrhosis

• Progress - Commenced on Entecavir,

- Liver tests , DNA Normalised
 Case 5
• • Bilirubin – 7 Direct – 5
78 years lady
• ALT 68
• Severe abdominal pain • AST 65
• ALP 357
• Fever with chills • GGT 350
• Past h/o one episode of • INR NORMAL
right upper quadrant
• Diagnosis- extra-hepatic
pain biliary obstruction due to
• Preveous normal LTs choledocholithiasis

• USG : Gall stones • ERCP, Sphincterotomy, Stone

extraction
 Take home message
• Jaundice is important sign which needs
evaluation.
• A good clinical history and physical
examination are often rewarding.
• If a systematic approach is adopted the cause
is often apparent.
• A specialist opinion should be sought when
appropriate.
THANK YOU…..!
 Case 8
• 45 yrs male • Bil Total 18
• HT, DM Direct 15
• Painless jaundice x 9 • ALT 111
months • AST 139
• Pruritus • ALP 740
• Weight loss • GGT 320
• Intermittent episodes of
abdominal pain, fever • Albumin 2.2
with chills, worsening of
jaundice
• Reduced Night vision
 Case 8
• Old liver tests
Bil / ALT / AST - normal
ALP - 200-450 > 3 yrs
GGT - 200-400 > 3 YRS

• PT/INR 19/14/1.8
 Case 8
• CT abdomen – Normal study, mild thickening
around CBD

• USG – Diffuse liver process, Gall stones,

Splenomegaly
MRCP
ERCP
 Case
28 y/o male, asymptomatic, BMI 27.7,

ALT (GPT) 132

AST (GOT) 51
ALP 66
GGT 95
Bilirubin 0.6
Albumin 4.3
P.T 1.1
globulin N

CBC N

Cholesterol 277 (LDL-C 170)

TG 304
 Differential diagnosis
• Fatty liver or NASH (non alcoholic steatohepatitis)
(DM II, HLP, obesity, insulin resistance)
• Chronic viral hepatitis (HBV, HCV)

• Alcoholic liver disease (AST>ALT, MCV , GGT )

•
• Autoimmune hepatitis (ANA, ASMA, LKM-1)

• Wilson’s disease (age < 55) (hemochromatosis, A1AT)

• Drug induced liver injury

• Celiac disease, Addison.

 Case
48 y/o male, asymptomatic, BMI 36

ALT (GPT) 100

AST (GOT) 125
ALP 66
GGT 95
Bilirubin 0.6
Albumin 3.7
P.T 1.1
Globulin 4.0
PLT 138000
Cholesterol 277 (LDL-C 170)
TG 304
 Case
61 y/o male, asymptomatic, BMI 27.7,
IHD (PTCA + stent RCA), HTN, US: “fatty liver”

ALT (GPT) 87
AST (GOT) 51
ALP 66
GGT
bilirubin
95
0.6
Statins?
albumin 4.3
P.T 1.1
globulin N
CBC N
Cholesterol 277 (LDL-C 170)
TG 304
 After 12 weeks of Rx with statins

• ALT (GPT) 220

AST (GOT) 110
• ALP 100
• GGT 95
• bilirubin 1.0
• albumin 4.3
• Cholesterol 210 (LDL-C 123)
• TG 220
 Continued treatment
3. Fulminant
ALT hepatitis

2. Chronic
liver
disease
5 ULN
1. Adaptation
1 ULN

DRUG
 Liver biopsy Findings in Abnormal LFTs

Skelly et al:
• 354 Asymptomatic patients
• Transaminases persistently 2X normal
• No risk factors for liver disease
• Alcohol intake < 21 units/week
• Viral and autoimmune markers negative
• Iron studies normal

Skelly et al. J Hepatol 2001; 35: 195-294

 Liver biopsy Findings in Abnormal LFTs
Skelly et al. J Hepatol 2001

• 6% Normal
• 26% Fibrosis
• 6% Cirrhosis
• 34% NASH (11% of which had bridging
fibrosis and 8% cirrhosis)
• 32% Simple Fatty Liver
• 18% Alteration in Management
• 3 Families entered into screening
programmes
Other Liver biopsy Findings in Abnormal
LFTs Skelly et al. J Hepatol 2001
• Cryptogenic hepatitis 9%
• Drug induced 7.6%
• Alcoholic liver disease 2.8%
• Autoimmune hepatitis 1.9%
• PBC 1.4%
• PSC 1.1%
• Granulomatous disease 1.75%
• Haemochromatosis 1%
• Amyloid 0.3%
• Glycogen storage disease 0.31%
LIVER BIOPSY FOR SERONEGATIVE ALT < 2X NORMAL

• N = 249, mean age 58, etoh < 25 units per

week, 9% diabetes, 24% BMI > 27
• ALT 51-99 (over 6 m)

• 72% NAFLD
• 10% Normal histologically
• Others: Granulomatous liver disease 4%,
• Autoimmune 2.7%, cryptogenic hepatitis 2.5%,
• ALD 1.4%, metabolic 2.1%, biliary 1.8%

Ryder et al BASL 2003

 LIVER BIOPSY FOR SERONEGATIVE ALT < 2X
NORMAL
Of those with NAFLD:
• 56% had simple steatosis
• 44% inflammation and/or fibrosis

Risk of Severe Fibrotic Disease associated with:

• BMI >27
• Gamma GT > 2x normal

Ryder et al BASL 2003

 Abnormal LFTs - Conclusions

• Many abnormal LFTs will return to normal

spontaneously
• An important minority of patients with
abnormal LFTs will have important
diagnoses, including communicable and
potentially life threatening diseases
• Investigation requires clinical assessment
and should be timely and pragmatic