Chronic liver disease ppt for intense learning

1. Chronic liver disease
Waleed Al-hamoudi
Gastroentrology and hepatology unit

2. Case
 56 year old male patient presents with 3 months history of
abdominal distension and bilateral leg swelling. Over the
last 1 month he was noted to have yellow eyes. On the day
of admission he was slightly confused. He has no
comorbidities .
 PMH: Blood transfusion 30 years ago.

3. Case
 CBC: Hb 10, wbc 3.5, PLT 70.
 ALT 40, AST 85, ALP 160, BILI 42
 INR 2.1, albumin 21
 US shrunken liver

4. Cause of chronic liver disease
Viral
 Chronic hepatic disease
 hepatitis B(Hbsag) , C (hcv ab), D
 Acute, self-limited viruses
 hepatitis A, E, G, CMV, EBV

5. Causes of chronic liver disease
 Autoimmune
ANA, ASMA, Immunoglobulins (IgG,IgM,IgA)
 Cholestatic liver disease
Primary billiary cirrhosis : AMA
Primary sclerosing cholangitis : ERCP, MRCP

6. Causes of chronic liver disease
 Metabolic liver disease
*Hemochromatosis: iron studies
*Wilson disease: 24 hour urinary copper,
ceruloplasmin, K-F RINGS.
*α-1 antitrypsin: enzyme level

7. Causes of chronic liver disease
 Alcoholic liver disease: history
 Nafld: exclude other etiology.
 Budd-chiari syndrome: doppler us
 Drugs: methotrexate

8. Causes of chronic liver disease
 Congenital liver disease
 Bilharziasis: serology
 Cryptogenic cirrhosis

9. examination
&
History
 Hepatatic and cholestatic symptoms.
 Risk factors for viral hepatitis.
 Alcohol, risk factors for NAFLD.
 Complications of portal HTN: abdominal
distension, edema, confusion, gi bleed
 Family history
 Drugs
 Examination: stigmat for CLD.

10. Investigations
 Cbc (pancytopenia, thrombocytopenia)
 Liver enzymes ast>alt
 INR, Bilirubin, Albumin (child class)
 Liver imaging
 Kidney function and electrolytes
 Liver biopsy and fibroscan

12.  Interpretation
 Child Class A: 5 to 6 points
 Life expectancy: 15 to 20 years
 Abdominal surgery peri-operative mortality: 10%
 Child Class B: 7 to 9 points
 Indicated for liver transplantation evaluation
 Abdominal surgery peri-operative mortality: 30%
 Child Class C: 10 to 15 points
 Life expectancy: 1 to 3 years
 Abdominal surgery peri-operative mortality: 82%

13. Portal hypertension
 Hepatic blood flow is normally about 1500 mL/minute.
 Normal, uncorrected pressure in the portal vein ranges
from 5 to 10 mm Hg. Gradient of 2-6.
 Portal HPN present when gradient > 12 mmHg.
 Approximately 2/3 of the hepatic blood supply is provided
by portal venous blood.
 The high-pressure, well-oxygenated hepatic arterial blood
mixes completely with the low-pressure, low-oxygen-
containing, nutrient-rich portal venous blood within the
hepatic sinusoids.

14. Complications
 Ascites
 Variceal bleed
 Encephalopathy
 HCC

15. Ascites
 Ascites is of Greek derivation ("askos") and refers to a bag
or sack describes pathologic fluid accumulation within the
peritoneal cavity.
 Most patients (80%) with ascites have cirrhosis.
 The three most common causes of cirrhosis at the present
time are alcohol, chronic hepatitis B,C, and nonalcoholic
steatohepatitis (NASH) related to obesity.

18. Serum-Ascites Albumin Gradient (SAAG):
 Measuring the albumin concentration of serum and ascitic
fluid specimens and simply subtracting the ascitic fluid
value from the serum value.
 The gradient is calculated by subtraction and is not a ratio.
 If the SAAG is greater than or equal to 1.1 g/dL (11 g/L), the
patient can be diagnosed with portal hypertension with an
accuracy of approximately 97%.
 Conversely, if the SAAG is less than 1.1 g/dL (11 g/L), the
patient does not have portal hypertension with an accuracy
of approximately 97%.

19. COMPLICATIONS
 Infection
 Tense Ascites
 Pleural Effusions
 Abdominal Wall Hernias

20.  Spontaneous Bacterial Peritonitis (SBP)
(1) Positive ascitic fluid culture.
(2) An elevated ascitic fluid absolute PMN count (i.e.at least
250 cells/mm3 or wbc >500cells/mm3
(3) without evidence of an intra-abdominal surgically
treatable source of infection.

21.  The spontaneous bacterial peritonitis occur only in the
setting of severe liver disease.
 chronic (cirrhosis), but may be acute (fulminant hepatic
failure) or subacute (alcoholic hepatitis).
 Cirrhosis of all causes can be complicated by spontaneous
ascitic fluid infection.
 Essentially all patients with SBP have Child-Pugh class B or
C cirrhosis,ascites a prerequisite to the development of
SBP.

22.  currently available evidence suggests that the spontaneous
forms of ascitic fluid infection are the result of overgrowth
of a specific organism in the gut, "translocation" of that
microbe from the gut to mesenteric lymph nodes, and
resulting spontaneous bacteremia and subsequent
colonization of susceptible ascitic fluid.
 Low-protein ascitic fluid (e.g., <1 g/dL [10 g/L]) is
particularly susceptible to SBP.
 SBP are symptomatic at the time the infection is
diagnosed, the symptoms and signs of infection are often
subtle, such as a slight change in mental status.

23.  Fully 98% of causative organisms were susceptible to
cefotaxime, which did not result in superinfection or
nephrotoxicity.
 Cefotaxime or a similar third-generation cephalosporin
appears to be the treatment of choice for suspected SBP.
 IV albumin (1.5 g/kg body weight at the time the infection
is detected and 1.0 g/kg on day 3) in combination with
cefotaxime has been shown in a large randomized trial to
reduce the risk of renal failure and improve survival.

24.  Paracentesis should be repeated after 48 hours of
treatment if the course is atypical.
 < 5% of patients die of infection if appropriate antibiotics
are administered.
 Norfloxacin 400 mg/day orally has been reported to reduce
the risk of SBP in inpatients with low-protein ascites and
patients with prior SBP.
 Norfloxacin 400 mg orally twice daily for 7 days helps
prevent infection in patients with variceal hemorrhage,
however, oral antibiotics do not prolong survival and do
select for resistant organisms in the gut flora, which can
subsequently cause spontaneous ascitic infection.

25. Tense Ascites
 Requires urgent therapeutic paracentesis.
 Total paracentesis," even more than 20 L, has recently been
demonstrated to be safe, improves venous return and
hemodynamics. The myth of paracentesis-related
hemodynamic disasters was based on observations in
small numbers of patients.

26. Pleural Effusions:
 Unilateral and right-sided but occasionally may be bilateral
and larger on the right side than the left.
 A large effusion in a patient with cirrhotic ascites is
referred to as hepatic hydrothorax.
 Hepatic hydrothorax have been shown to have a small
defect in the right hemidiaphragm, With large
diaphragmatic defects, ascites may be undetectable.
 The most common symptom is shortness of breath

27.  The analysis of uncomplicated hepatic hydrothorax fluid is
similar to that of ascites.
 Rx of hepatic hydrothorax has been difficult until the
availability of transjugular intrahepatic portosystemic
stent shunts (TIPS)
 Chest tube insertion and sclerosis of the pleurae with
tetracycline.
 Sodium restriction and use of diuretics constitute the
safest and most effective first-line therapy of hepatic
hydrothorax.
 TIPS has been reported to be successful and is reasonable
second-line treatment.

28.  Determine the precipitating cause of ascites formation
(e.g., dietary indiscretion or noncompliance with diuretics
or saline iv).
 The dietary Na restriction for inpatients and outpatients is
2 grams (88 mmol) per day.
 No fluid restriction unless low Na
 Although it is traditional to order bed rest, there are no
controlled trials to support this practice, strict bed rest is
unnecessary and may lead to decubitus ulcers in these
emaciated pts.

29. Diuretics :
 spironolactone and furosemide together on the first
hospital day in initial doses of 100 mg and 40 mg,
respectively, each taken once in the morning.
 If the combination of spironolactone 100 mg/day (or 10
mg/day of amiloride) and furosemide 40 mg/day orally is
ineffective in increasing urinary sodium or decreasing body
weight, the doses of both drugs should be increased
simultaneously.

30.  The ratio of spironolactone and furosemide can be
adjusted to correct abnormal serum potassium levels.
Occasionally.
 When combined with a sodium-restricted diet in a study of
almost 4000 patients, the regimen of spironolactone and
furosemide has been demonstrated to achieve successful
diuresis in more than 90% of cirrhotic patients.
 IV diuretics cause acute decreases in the GFR in cirrhotic
patients with ascites and should be avoided.

31.  Once the edema has resolved, a reasonable maximum
weight loss is probably 0.5 kg/day.
 Encephalopathy, a serum sodium concentration less than
120 mmol/L despite fluid restriction, or a serum creatinine
level greater than 2.0 mg/dL (180 μmol/L) should result in
cessation of diuretics and reassessment of the situation.
 NSAID should be avoided in cirrhotic ascites as they inhibit
diuresis, may promote renal failure, and cause
gastrointestinal bleeding.

32. Refractory Ascites :
 ascites unresponsive to a Na-restricted diet and high-dose
diuretic treatment, which may be manifested by minimal or
no wt. loss despite diuretics or the development of
complications of diuretics.
 < 10% of patients with cirrhotic ascites are refractory to
standard medical therapy.
 Viable options for patients refractory to routine medical
therapy include liver transplantation, serial therapeutic
paracenteses, TIPS, and peritoneovenous shunts.

33. Varices

34. Portal
pressure
Resistance to
portal flow
Cirrhosis
Splanchnic
arteriolar
resistance
Portal blood
inflow
Varices
SUMMARY OF THE PATHOGENESIS OF PORTAL HYPERTENSION

35. Small varices Large varices
No varices
7-8%/year 7-8%/year
Varices Increase in Diameter
Progressively
Merli et al. J Hepatol 2003;38:266
VARICES INCREASE IN DIAMETER PROGRESSIVELY

36. Prevalence and Size of Esophageal Varices
in Patients with Newly-Diagnosed Cirrhosis
%
Patients
with varices
100
60
40
20
0
Overall
n=494
Child A
n=346
Child B
n=114
80
Child C
n=34
Large
Medium
Small
Pagliaro et al., In: Portal Hypertension: Pathophysiology and Management, 1994: 72
PREVALENCE AND SIZE OF ESOPHAGEAL VARICES IN PATIENTS WITH NEWLY DIAGNOSED CIRRHOSIS

37. Predictors of hemorrhage:

Variceal size

Red signs

Child B/C
NIEC. N Engl J Med 1988; 319:983
Variceal hemorrhage Varix with red signs
PROGNOSTIC INDICATORS OF FIRST VARICEAL HEMORRHAGE

38. Non-Selective Beta-Blockers Prevent
First Variceal Hemorrhage
Bleeding rate Control Beta-blocker Absolute
rate
(~2 year) difference
All varices 25% 15% -10%
(11 trials) (n=600) (n=590) (-16 to -5)
Large varices 30% 14% -16%
(8 trials) (n=411) (n=400) (-24 to -8)
Small varices 7% 2% -5%
(3 trials) (n=100) (n=91) (-11 to 2)
D’Amico et al., Sem Liv Dis 1999; 19:475
NON-SELECTIVE BETA-BLOCKERS PREVENT FIRST VARICEAL HEMORRHAGE

39. Other treatment options
 Band ligation
 Sclerotherapy
 TIPPS insertion
 Shunt surgery
 Transplantation

40. Acute Variceal Bleed
 ABC!!!
 Octreotide
 PPI
 *** Antibiotics ***
 Cefotaxime or Norfloxacin
 Keep Hb 80-100 g/L

41. Prophylactic Antibiotics Improve Outcomes in
Cirrhotic Patients with GI Hemorrhage
Control Antibiotic Absolute
rate
(n=270) (n=264) difference
(95% CI)
Infection 45% 14% -32%
(-42 to –23)
SBP / Bacteremia 27% 8% -18%
(-26 to –11)
Death 24% 15% -9%
(-15 to –3)
Bernard et al., Hepatology 1999; 29:1655
PROPHYLACTIC ANTIBIOTICS IMPROVE OUTCOMES IN CIRRHOTIC PATIENTS WITH GI HEMORRHAGE

42. Encephalopathy
 Grade 0 – Asymptomatic
 Can Dx with neuropsychiatry testing/trail test
 Grade 1 – Sleep/wake reversal
 Grade 2 – Fairly confused
 Grade 3 – Awfully confused/obtunded
 Grade 4 - Comatose

43. Encephalopathy
Precipitants :
 GIB
 Constipation
 Medications
 Infections
 Fever
 High protein intake
 Dehydration
 Hypotention
 Electrolyte disturbance
 Others

44. Encephalopathy Management
 Diet
 NO PROTEIN RESTRICTION!!
 1.6 g/kg/day protein
 If refractory encephalopathy:
 Restrict aromatic amino acids (animal protein)
 Liberal branched-chain amino acids (plant)
 Leucine, isoleucine, valine

45. Encephalopathy Management
 Lactulose
 Titrate to 2-4 BM/day
 Antibiotics
 Flagyl, Neomycin

46. Hepatocellular Carcinoma
recommendations
U/S abdomen, alpha-fetoprotein q6months
All cirrhotic patients
Early detection is associated with better outcome

47. Questions......