This describes liver diseases in an easy and understandable manner

1. Hepatology for Primary
Practitioners

2. Liver biochemistry
Profile
• Bilirubin
• Serum Aminotransferases
• Alkaline Phosphatase
• Prothrombin time
• INR
• Albumin

3. Uses of LFT
• Identifies presence of liver disease
• Type of liver disease-
• Primary hepatocellular
• Cholestatic
• Mixed
• Gauge severity and progression of liver disease
• Monitor therapy response
• Serial LFTs can identify particular cause of disease

4. Bilirubin
• Normal values of total serum bilirubin is less
than 1.0- 1.5 mg/dl (95% - 0.2-0.9)
• Indirect fraction normal values- 0.8-1.2 mg/dl
• Upper limit of normal for the Direct acting
fraction is 30%
• If direct fraction is <15%, bilirubin is entirely
indirect.

5. • Hyperbilirubinemia may result from
– overproduction of bilirubin through excessive
breakdown of hemoglobin;
– impaired hepatocellular uptake,
– conjugation, or excretion of bilirubin;
– or regurgitation of unconjugated and conjugated
bilirubin from damaged hepatocytes or bile ducts.

6. Isolated hyperbilirubinemia
cause Mechanism
Indirect hyperbilirubinemia
Hemolytic disorders
inherited
Red cell enzyme defects (G6PD DEF)
Sickle cell disease
Spherocytosis and elliptocytosis Over production of
Acquired bilirubin
Drugs and toxins
Hypersplenism
Immune mediated/ PNH/ Traumatic

7. Ineffective erythropoiesis
Cobalamine def
Folate def
Profound iron def
Thalassemia
Drugs – rifampicin/probenecid Impaired hepatocellular uptake
Inherited conditions
Crigler- Najjar type 1 and 2/ Gilbert’s
syn
Impaired conjugation of bilirubin
Hematoma Overproduction of bilirubin
DIRECT HYPERBILIRUBINEMIA
Inherited conditions
Dubin- Johnson Syndrome Impaired conjugation of bilirubin
Rotor’s Syndrome

8. • Bile duct obstruction
• Hepatitis
• Cirrhosis
• Medications/Toxins
• Primary biliary cirrhosis
• Primary sclerosing cholangitis
• Sepsis
• Total parenteral nutrition
• Isolated
• Dubin-Johnson syndrome
• Rotor syndrome
Intrahepatic cholestasis
of pregnancy
Benign recurrent
cholestasis
Vanishing bile duct
syndromes

10. Alkaline Phosphatase
• The term alkaline phosphatase applies to a group of
isoenzymes distributed widely throughout the body.
• The isoenzymes of greatest clinical importance in
adults are in the liver and bone
• Other isoenzymes originate from the placenta, small
intestine, and kidneys.
• In liver, alkaline phosphatase is found on the
canalicular membrane of hepatocytes;
• Alkaline phosphatase has a serum half-life of
approximately seven days

11. • AP elevation upto 3 times ULN
• > 3 times ULN
•Nonspecific
•Occurs in all types of liver disorders
•Viral hepatitis
•Cirrhosis
•Infiltrative diseases of the liver
•CHF etc
•Cholestatic disorders Extrahepatic
Intrahepatic
•Infiltrative disorders
•Mets
Elevation of Alkaline Phosphatase

13. Albumin
• Accounts for 75% of the plasma colloid oncotic pressure .
• Average adult produces approximately 15 g/day.
• The half-life of albumin is 14 to 21 days
• Not useful in acute liver injury.
• Levels < 3 g/dL suspect chronic injury.
• Excellent marker of hepatic synthetic function in patients with CLD and
cirrhosis
• Differential diagnosis of serum hypoalbuminemia,
– hepatocellular dysfunction,
– malnutrition,
– protein-losing enteropathy or
– nephrotic syndrome,
– chronic systemic inflammatory conditions, and hormonal imbalances

14. Prothrombin Time
• Clotting - end result of a complex series of
enzymatic reactions involving clotting factors
• All the factors are produced in liver except factor
VIII- produced by vascular endothelial cells.
• P.T is a measure of the rate at which prothrombin
is converted to thrombin,
• Reflects the extrinsic pathway of coagulation.
• Factors involved in the synthesis of prothrombin
include II, V, VII, and X.

15. INR
• Used to express the degree of anticoagulation on
warfarin therapy.
• Standardizes prothrombin time measurement
according to the characteristics of the
thromboplastin reagent used in a particular lab.
• The initial measurement is expressed as an
international sensitivity index (ISI), which is then
used in calculating the INR

16. • Causes of prolonged P.T
– hepatic dysfunction,
– congenital deficiency of clotting factors,
– vitamin K deficiency (vitamin K is required for normal
functioning of factors II, VII, IX, and X)
– disseminated intravascular coagulation (DIC).
• DIC identified by measuring a factor VIII level in
serum.
• Vitamin K deficiency -subcutaneous administration of
vit K (e.g., 10 mg) leads to improvement in P.T by
30%.

17. Interpretation of Hepatitis B Serology

18. Ultrasonography features of CLD
• surface nodularity: (88% sensitive, 82-95% specific)
• overall coarse and heterogeneous echotexture
• segmental hypertrophy/atrophy
– caudate width: right lobe width >0.65 (43-84% sensitive,
100% specific )
– reduction of the transverse diameter (<30 mm) of the
medial segment of the left lobe (segment IV)

19. • signs of portal hypertension
– Doppler flow changes
• portal venous system
– enlarged portal vein: >13 mm (42% sensitive, 95-100% specific 6)
– slow portal venous flow <15 cm/sec
– reversal or to-and-fro portal venous flow
– Portal Vein thrombosis
– enlarged SMV and splenic vein >10 mm
» note: this should be measured during deep inspiration as size
can vary.
– loss of respiratory variation in SMV and splenic vein spectral Doppler
waveforms
– recanalization and hepatofugal paraumbilical(=umbilical) venous flow
– portosystemic collaterals
• hepatic veins
– portalisation of hepatic vein waveform
• hepatic arteries
– "corkscrew" appearance
– increased velocity (compensating for decreased portal vein flow)
– splenomegaly
– ascites
– fatty change

21. Autoimmune hepatitis
Disorder of unknown etiology characterised by
• Unresolving inflammation of the liver
• Interface hepatitis
• Hypergammaglobulinemia and
• Autoantibodies

22. When to suspect Autoimmune
hepatitis
Presentation patterns-
• Acute icteric hepatitis
• Oligosymptomatic mild to moderate chronic
liver disease
• Asymptomatic, unrecognised disease
diagnosed with cryptogenic cirrhosis

23. • 50% at presentation are asymptomatic
• 1/3 of adults and 50% of children present with
cirrhosis
• Association with other autoimmune diseases
• Hashimoto’s, Graves, Vitiligo, T1 DM, IBD,
Psoriasis, SLE, Sjogrens, Sweets syndrome,
Hemolytic Anemia, Uveitis

24. Antibody Profile
• Antinuclear antibodies (ANA)
• Smooth muscle antibodies (SMA)
• Anti-LKM 1
• Atypical pANCA
• Anti-SLA
• Anti-actin
• Anti-chromatin
• Asialoglycoprotein receptor antibody
• Anti-liver cytosol type 1(anti-LC1)
• IgA antibodies to endomysium or tissue
transglutaminase

25. Simplified IAIHG Criteria

26. Wilson Disease
 First described in 1912 by Kinnear Wilson
 Progressive lenticular degeneration, a familial nervous system
disease associated with cirrhosis of liver
 Autosomal recessive, consanguinity important.
 Incidence 1 in 30,000 to 40,000.
 Heterozygous carrier state 1 in 90 persons.
 Age of onset of symptoms 5 to 35.
 The WD gene,ATP7B on long arm of chr13q14.21

27. When to suspect Wilson Disease

28. HEPATIC
• Hepatitis
(chronic/acute)
• Cirrhosis
• Isolated Splenomegaly
• Liver failure
• Asym Transaminitis
• Gallstones
NEUROLOGIC
• Tremor
• Dysarthria & Dystonia
• Coordination defects
• Writing difficulties
• Choreiform movements
• Ataxic gait
PSYCHIATRIC
 Organic dementia
 Neuroses
 Schizophrenia
 Bipolar disorder
 Antisocial behavior
 Alcoholism
OTHER
 Hemolytic anemia
 Fanconi’s syndrome
 Nephrolithiasis
 Hypo-parathyroidism
 Amenhorrhoea/Testicular
problems/Infertility
 Arthritis & Rhabdomyolysis
 Cardiomyopathy & Pancreatitis
 Hyperpigmentation

29. • Does not interfere with
vision.
KAYSER FLEISCHER RING
Copper deposition in
descement’s membrane of
cornea seen on slit lamp
examination
.
Patients with exclusively hepatic
involvement have KF rings in 30
– 50% cases, while with
neurological/psychiatric

30. Tests for Wilson Disease
Diagnostic test Diagnostic values
• Serum ceruloplasmin
• Hepatic copper
concentration
• 24 hour urine copper
excretion
• KF ring
• Genotyping
• Haplotype analysis
• <20mg/dl
• >250micrograms/gm dry wt
• >100microgram/24 hr
• Present
• Identification of two disease
causing mutations in ATP7B
• Presence of markers on both
chromosomes.

31. 9/4/2022
Drug Mode of
action
Neurological
deterioration
Side effect
D-penicillamine
Rs12.5 per 250
mg cap
10mg/k/d stat f/b
20-30mg/k/d in 2-
3 divided dosage
•Active reductive chelator
•Induces cupruria
•Tends to interfere with
pyridoxine action so
supplemented with
vitamin B6
•10%-20% during
initial phase of
treatment.
• Hypersensitivity reaction,fever, rash,
protenuria,lupus like reaction.
• Aplastic anemia, leucopenia,
thrombocytopenia, nephrotic
syndrome,hepatotoxicity.
Trientine
$18 per 250 cap
25mg/k/d in 3
divided doses 1 hr
before meal.
•General chelator
•Induces cupruria
•10-15% during initial
phase of therapy.
•No hypersensitivity reactions
•Gastritis
•Sideroblastic anemia
•protenuria

32. LIVER BIOPSY
1. 1 of above 3 abnormal
2. High suspicion and
ceruloplasmin= 20-30
mcg/dl
3. If ceruloplasmin measured
by immunologic method a is
in the normal range
PERFORM
1. Ceruloplasmin levels
2. 24 hr urinary copper
3. KF ring examination
Drugs Mode of action Neurologic
deterioration
Side effect
Zinc
( Rs50/-)
25-50mg of
elemental zinc 3
times daily 1 hr
before meals.
•Metallothionine
inducer.
•Blocks intestinal Cu
absorption.
Can occur in initial
phase of treatment.
•Mild abdominal
discomfort.
•Possible change in
immune function.
Tetrathiomolybdate
Not available in
India.
•Complexes copper
with protein.
•Detoxify copper.
•Blockage of copper
absorption.
•Reports of rare
neurologic
deterioration during
initial treatment.
•Anemia
•Neutropenia
•Hepatotoxicity

33. Alcoholic Hepatitis definitions
Definite alcoholic hepatitis:
Histological confirmation of features of alcoholic hepatitis.
Probable alcoholic hepatitis:
• Clinical diagnosis based on
• (a) heavy alcohol use for >5 years,
• (b) active alcohol use until 4 weeks prior to presentation,
• (c) sudden onset or worsening of jaundice,
• (d) AST/ALT ratio >1.5:1 with levels
Possible alcoholic hepatitis:
Clinical diagnosis uncertain due to another confounding etiology of liver
disease or unclear history on alcohol consumption
ACG CPG

34. Management AH

35. Acute Liver Failure
Requires liver failure in a previously healthy organ
Based on jaundice-encephalopathy interval, classified
as
Hyperacute- < 7 days,
Acute – 8-28 days, and
Subacute- > 28 days
O’Grady et al

36. Acute on Chronic Liver Failure
“A syndrome in patients with chronic liver disease with or without
previously diagnosed cirrhosis which is characterized by acute hepatic
decompensation resulting in liver failure (jaundice and prolongation of
prothrombin time) and one or more extrahepatic organ failures that is
associated with increased mortality within a period of 28 days and up
to 3 months from onset”
EASL- CLIF Definition

37. Child –Pugh Classification

38. Fatty Liver causes

39. NAFLD – why the concern

40. Fibroscan

41. Drugs in use for NAFLD

42. Budd Chiari Syndrome- in whom to
suspect

43. Diagnosis BCS

44. Management BCS

45. Drug Induced Liver Injury

46. Patterns of liver injury by drugs

47. When to stop offending drug

48. Liver Abscess

49. When to drain Liver Abscess
• Diagnosis is uncertain
• Lack of improvement after 48-72 hrs of Rx
• Left lobe abscess
• Rim <10 mm
• Sero negative abscess
• With impending rupture
• Size >10 cms

50. Hepatocellular Carcinoma

51. Surveillance
High risk groups-
Patients with cirrhosis
In Chronic Hepatitis B-
• Asian descent (Males more than 40y; Females more than 50y)
• African descent
• Family history of HCC
Patients with HCV with cirrhosis
Stage 4 Primary Biliary Cholangitis
Genetic hemochromatosis with cirrhosis
Alpha 1 AT Deficiency and cirrhosis

53. Methods
• Ultrasonography
• AFP testing every 6 months
Ultrasound with AFP had significantly higher
sensitivity than ultrasound alone (relative risk,
1.23; 95% CI, 1.08–1.41)
A model including sex, age, AFP-L3, AFP, and
des-γ-carboxy prothrombin (GALAD)
demonstrated sensitivity >70% for overall HCC
detection and >60% for early HCC detection.

54. Management of HCC