Teaching clinic: 2 cases of cirrhosis HBV

Question 1

Which is the first step in the management of ascites for in-hospital patient? * Bedrest * Fluid restriction * Salt restriction * Diagnostic paracentesis * Diuretic therapy

Answer 1

• Diagnostic paracentesis (Exclude SBP)

Question 2

Ascites physical properties

Answer 2

Physical properties
* Colour
- straw
- blood-stained (3 bottle tests: uniformly blood stained
- chylous: (TB kidney) must check lipoprotein (hyperlipidemia), malignancy (gynecological/lymphoma cauasing lymphatic obstruction)
* Protein - may be as high as 40 g/L without special significance
* Rate of reabsorption - 900 ml/day (In tense ascites, may to 1.5 l/day)
* WCC < 500/mm3 (< 250 PMN)
* Malignant cells < 10% positive in malignant ascites

If CA lung pleural fluid: will have 80% chance of picking up malignant cells

Question 3

Mx of ascites

Answer 3

• Diagnostic paracentesis in every patient for white cell count
• Salt restriction (1/2-2g/day)
• Fluid restriction (0.8-1L/day)
• (a) Diuretics: spirolactone (not 1st line in other fluid retention causes such as cardiac: furosemide). K+ sparing. High incidence of gynectomastia especially in alcoholic cirrhosis. Amiloride can be used for male
  (b) Proximal loop diuretics if (a) insufficient. Bumetadine (Burinex) furosemide absorption unreliable in portal hypertension
  (c) albumin infusion (increase intravascular oncotic pressure) and IV diuretics

Oliguria: <500ml/day
Insensible water loss: 600-800ml (undetectable water loss i.e. skin and lungs)

Question 4

Complications of therapeutic paracentesis

Answer 4

• shock
• electrolyte disturbance
• uraemia
• infection (HO dirty finger)
• encephalopathy
• protein depletion

Question 5

Safety of therapeutic paracentesis?

Answer 5

Abd tap of 4-6L is safe
* With albumin infusion and/or
* If patient has peripheral edema

(1) and (2) can prevent intravascular volume depletion

NB
* Bleeding from puncture sites
* Sepsis
* Perforation of caecum with right sided punctures (sigmoid colon more mobile due to sigmoid mesentery)

Question 6

Which other physical sign is most likely to be present? * Bilateral basal crepitations * R pleural effusion * L pleural effusion * Hard nodular hepatomegaly

Answer 6

• R pleural effusion

Question 7

Answer 7

None of the above

Question 8

Effect of diuresis in SBP

Answer 8

Leads to selective condensation of ascites H2O with
* Increase in protein content
* Increase in lymphocytes because of long life span
* Constant PMN because of short lifespan
Lymphocytes: lifelong
PMN lifespan: 3-7 days

Answer 9

More ascitic protein means less opsonic activity which means more prone to SBP

Question 10

What is max tapping for pleural effusion?
AE of overtapping?

Answer 10

1L per day, if more the collapsed lung will have decreased surfactant –> will result in reexpansion pulmonary edema

Most common cause of reexpansion pulmonary edema is when there is pneumothorax with delayed admission

Question 11

SBP mechanism

Answer 11

If known cirrhotic: just describe the protein as low (<10g/L) or high

Question 12

Clinical features of SBP

Answer 12

Common: 10-20%
* P. U. O.
* Encephalopathy
* Abdominal S/S - none to marked
* Diarrhoea
* Hypothermia
* Asymptomatic
* May be fatal/recurrent

Question 13

dx of SBP

Answer 13

• WCC (do differential count) :
• > 500 WBC / mm3 suspicious
• > 250 PMN / mm3 in pts with S/S of SBP
• > 500 PMN / mm3 in asymptomatic pts
• • Culture (usually G-ve or streptococci; may be neg.): gut in origin (not likely to be anaerobic)

pH<7.3 suspicious (if blood pH not acidotic)
pH<7.15 poor prognosis
Arterial/ascitic fluid pH gradient of 0.10

Question 14

Tx of SBP

Answer 14

Broad spectrum 3rd gen cephalosporin: exponential fall in PMN count after initiation of antibiotics

Duration of treatment: 5 days
Can stop antibiotics as soon as PMN count <250/mm3

Question 15

Prevention of recurrence of SBP

Answer 15

Ofloxacin
- incompletely absorbed by gut
- highly active against gram neg bacilli
- low activity against anaerobes
- rarely causes bacterial resistance
- low side-effects

Long term use of quinolones increases the risk of ESBL enterobactericacae
Use rifaximin if quinolone resistance

Question 16

Which antibiotic well absorbed by gut and used for systemic infections, requires double dosage?

Answer 16

Metronidazole for amoebiasis

Question 17

The cause of the LFT deterioration is :
* Acute graft rejection
* Acute-on-chronic graft rejection
* CMV infection
* Post-transplant lymphoproliferative disorder
* Emergency of lamivudine resistant HBV

Answer 17

• Emergency of lamivudine resistant HBV (YMDD mutant)

Cant be graft rejection: within 1 hours
Not on chronic graft rejection
CMV would not present with hyperbilirubinemia
PTLD: EBV clonal expansion (would present with lumps and bumps)

Question 18

TDF warnings

Answer 18

• Slightly greater decrease in bone mineral density suggesting increased bone turnover
• HypoP and osteomalacia secondary to proximal renal tubulopathy can also occur

Question 19

Benefits of TAF

Answer 19

– Comparable viral suppression (HBV DNA <29 IU/mL)
– Improved rates of ALT normalization
– No resistance development
– Rates of HBeAg loss and seroconversion similar

Less toxicity: decline in hip and spine BMD with improved bone biomarkers
Well tolerated in HBeAg-ve and +ve patients
Can be used in pregnancy now (small studies)

Question 20

What is the most likely histologic finding?
* Subacute fulminant hepatitis
* Re-development of cirrhosis
* Fibrosing cholestatic hepatitis

Answer 20

ALT and AST not elevated: so not subacute fulminant hepatitis
Redevelopment of cirrhosis can occur within a year if reinfected. Cirrhosis of the liver would not lead to this degree of cholestasis (increased bilirubin)

Ans: fibrosing cholestatic hepatitis

Question 21

Features of fibrosing cholestatic hepatitis

Answer 21

Histology of explanted liver
* Prominent loss of hepatocytes
* Portal expansion by fibrosis
* Hepatocytes
- diffuse marked balloon degeration
- cholestasis excess HBsAg in cytoplasm and excess HBcAg in nuclei
- Dx - Fibrosing cholestatic hepatitis

Question 22

Pathogenesis of fibrosing cholestatic hepatitis

Answer 22

• Pathogenesis
• primary cytopathic effect of HBV dysregulation of viral transcription
• Increased HBV mRNA → viral Ag in endoplasmic reticulum → cell death
• Rapid graft failure and death
• Rapid recurrence with re-transplant

Question 23

Prevention of recurrent HBV in liver transplant

Answer 23

• Indefinite high dose HBIG – 65-80% effective
• Lamivudine – depends on rate of resistance developing
• Low dose HBIG + nucleoside analogue - >90% effective; current practice in most >90% centres

Monotherapy with entecavir/tenofovir for liver transplantation is a viable option