PBL: liver cirrhosis Flashcards

1
Q

What is recommend daily limit of alcohol consumption?

A

2 units for male, 1 unit for female
1 unit = 8g of pure alcohol
* 1 shot, 8 oz beer

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2
Q

Pathophysiology of alcoholic liver disease

A
  • Acetaldehyde produced from the metabolism of ethanol in the liver
  • Increased in oxidative stress to the liver –> interrupts oxidation of fatty acids –> promoting fatty acid synthesis –> steatosis
  • Toxic and structural alterations of cellular proteins –> damge to hepatocytes –> liver fibrosis

Leading to alcoholic related liver disease
* AFLD (more than 90%)
* Alcoholic hepatitis (10-35%)
* Cirrhosis (10-20%)

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3
Q

What are the clinical features of alcoholic liver disease?

A

AFLD
* Asymptomatic with abnormal liver enzymes (raised AST and ALT)
* USG shows echogenic liver

Alcoholic hepatitis
* Rapid onset of jaundice in recent heavy alcohol use
* Tender hepatomegaly
* AST elevated, AST/ALT ratio >1.5
* Significant short term mortality from sepsis and renal failure

Cirrhosis
* Stigmata of chronic liver disease e.g. palmar erythema, dupuytrens contracture, spider naevi and gynaecomastia
* Serious complications: esophageal variceal hemorrhage, ascites
* Nodular liver, sizes varies

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4
Q

Ix for alcoholic liver disease?

A
  • CBC, LT
  • USG
  • Can do transient elastography to assess extent of fibrosis
  • Glascow alcoholic hepatitis score can be used to assess the prognosis of alcoholic hepatitis
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5
Q

What is the Mx of alcoholic liver disease?

A
  • ALCHOL CESSATION
  • Nutrition (previous poor diet from heavy drinking)
  • Severe alcoholic hepatitis: Use Maddrey discriminant function to assess whether patient needs steroids/pentoxifylline
  • Liver transplantation: 6 months abstinence of alcohol beforehand (arbitrary number but used to ensure that the liver graft is not wasted if patient resumes drinking after transplantation)
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6
Q

What is the underlying cause of PSC and SS?

A

Postulated to be a mixture of autoimmune disorder/underlying inflammation and scarring of the intrahepatic and extrahepatic ducts.
In PSC the inflammation and scarring causes narrowing of the bile ducts, leading to impaired bile flow. Bile stasis precipitates infective cholangitis ultimately leading to cholestasis and liver failure.

Immune activation: 50% have elevated IgM, increased IgG fraction autoantibody, 75% have anti-Sm antibodies and 80% have pANCA
Linked with IBD (increased permeability of bacteria into the portal circulation across an inflamed colonic wall may lead to chronic or recurrent cholangitis.

SS
* Pruritis: cholestatic jaundice
* Fatigue
* RUQ discomfort
* Constitutional symptoms: fever and chills, night sweats

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7
Q

What are the blood and imaging Ix done for PSC?

A

Blood tests
* LFT: increased AST and ALT, increased ALP and GGT (but ALP predominant), conjugated bilrubin increased (as post hepatic obstruction)
* AMA: normally absent in PSC but required to help exclude primary biliary cholangitis
* Serum IgG4: marker of autoimmune pancreatitis but also elevated in PSC. IgG4 associated disease have a more rapidly progressive course and are less responsive to corticosteroids
* Autoantibodies: IgM, IgG4, Hypergammaglobulinemia, pANCA

Imaging tests
* USG abdomen: bile duct wall thickening, focal bile duct dilatation. Gallbladder wall thickening and enlargement, presence of gallstones.
* MRCP 1st line imaging modality due to non invasiveness and diagnostic accuracy
* ERCP (therapeutic + diagnostic): when MRCP contraindicated such as in implanted metal devices. Characteristic multifocal strictures that alternate with dilatation of intrahepatic or extrahepatic bile ducts resulting in beaded appearance of bile duct. Cholangiogram (In PBC the appearance will be normal)

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8
Q

MRCP and ERCP findings of primary sclerosing cholangitis?
Compare it to PBC (primary biliary cirrhosis)

A

In PBC: cholangiogram will appear normal as there is no strictures present (only microscopic level affected)

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9
Q

What are the causes of secondary sclerosing cholangitis?

A
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10
Q

Complications of PSC?

A
  • Liver cirrhosis complications
  • Acute kidney injury: bile cast nephropathy
  • Hepatic osteodystrophy
  • Cholangiocarcinoma
  • Colorectal cancer
  • Hepatocellular carcinoma
  • Gallbladder carcinoma
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11
Q

In patient with PSC with declining renal function how do you manage?

A
  • Take off all renal toxic medications (Steroids etc)
  • Hydration
  • Rule out obstruction (causing hydronephrosis) by abd USG
  • Rule out UTI by urine dipstick
  • RFT should have already been done (may have underlying bile cast nephropathy)
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12
Q

What is the mechanism of bile cast nephropathy?

A

cholemic nephropathy
* Direct bile acid/bilirubin toxicity. Excessive serum/urine bile acid and bilirubin can cause direct bile salt induced tubular toxicity. Bile acids/bilirubin also promotes tubulointerstitial inflammation. Bile casts associated with intratubular obstruction
* 2nd hit in patients with other pathology. Acute decompensated liver cirrhosis. Haemodynamic AKI, HRS is exacerbated by bile acid/bilirubin.
Prerenal AKI and ischemic/nephrotoxic ATI/ATN also worsened by excessive urinary bile acids.

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13
Q

What is Tx for bile cast nephropathy?

A

Does not require renal biopsy for dx (as making a dx will not change treatment)

Principle of treatment: treating the underlying cause of hyperbilirubinemia to prevent kidney injury
* ERCP, tumor resection, PTBD
* Extracorporeal therapies such as haemodialysis and plasma exchange are the other treatment options
Biologics: living liver cells
Non biologic: artificial membranes and absorbents (i.e. plasmapharesis and albumin dialysis)

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14
Q

Mx of PSC?
FU of predisposing conditions?

A
  • Cholangioplasty of dominant strictures is difficult and not commonly done as there is no dominant strictures
  • UDCA (limited evidence)
  • Fat soluble vitamin suppleemnt
  • Pregabalin for pruritis
  • Long term prophylactic antibiotics for patients with recurrent cholangitis
  • Definitive treatment: orthotropic liver transplantation

FU
* IBD/colorectal cancer: ileocolonoscopy
* Cholangiocarcinom and gallbladder carcinoma: abd USG annually
* Progression of liver disease: LFT, clotting profile, fibrosis staging with transient elastography, screening for fat soluble vitamins (ADEK) deficiencies

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15
Q

Mechanism of ascites in liver cirrhosis?
Appearance of fluid?

A

Cirrhosis –> portal hypertension causing splanchnic arterial vasodilation. Decreased total systemic vascular resistance –> arterial underfilling. Decreased effective arterial blood volume –> stimulate neurohormonal systems –> increased RAAS –> increased renal tubular absorption of Na –> Na retention –> ascites, edema

Appearance of peritoneal fluid
* Straw (normal)
* Blood stained (rule out traumatic tap by 3 bottle test (uniformly blood stain) or allow to stand (xanthochromia)
* Chylous

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16
Q

What is the Mx of ascites?

A

In every patient a diagnostic paracentesis done to exclude SBP –> 1st step
* WBC/DC
* Protein level, glucose, malignant cytology (less useful)

SAAG: >11g/dL matches portal hypertension
Other ix: USG abd, AFP (for HCC)

Mx
* Low salt diet (0.5-2g/day), fluid retention (0.8-1L/day)
* Distal loop diuretics, K+ sparing e.g. spironolactone

17
Q

How to make dx of SBP?

A

Diagnostic paracentesis: either WBC >500 or PMN >250/mm3

Tx
* Broad spectrum 3rd gen cephalosporin

Lifelong selective intestinal decontamination (prophylactic antibiotic) with norfloxacin/levofloxacin (quinoloen) after SBP episode. Highly active against gram-ve bacilli

18
Q

How to mx suspected variceal bleeding?

A

CBC, type and screen, clotting factors
OGD (rule out other causes of bleeding in cirrhotic patients e.g. portal hypertensive gastropathy (usually occult/mild bleeding), generalized bleeding tendency (clotting factor deficicency, thrombocytopenia), others e.g. mallory weiss syndrome)

Nil by mouth, resuscitation, urgent OGD
* Terlipressin (vasoactive agent) 2mg IV bolus q4h (Look for peripheral digital ischemia: toes and fingers. Headache, chest pain.. Or octreotide/somatostatin.
* Prophylactic antibiotics (prevent sepsis): IV ciprofloxacin 400mg BD (patients with preserved liver function), or IV ceftriaxone 1g/day (patients with advanced cirrhosis or known quinolone resistance), or IV ertapenem 1g/day (patients with recent ESBL-enterobacteriaceae infection)
* OGD management: esophageal band ligation for esophageal varices. Tissue glue (cryanoacrylate) injection for gastric varices. Vasoactive agents initiated within 30 min after confirmation of variceal bleeding if not given prior to endoscopy.
* PPI given for 2 weeks
* Prevention of rebleeding: EVL combined with a non selective BB (propranolol, carvedilol –> titrated up starting with a low dose up till 25% reduction in resting HR but not lower than 55 beats/min)

If uncontrolled bleeding: repeated endoscopy
Refer to emergency surgery (portosystemic shunting: TIPS)

19
Q

What is the pathogenesis of hepatorenal syndrome?
What are the precipitating factors?
What is the classification?

A

Renal failure in patients with severe liver disease in absence of any pahtological cauases for development of renal failure (dx of exclusion): r/o hypovolemia, sepsis, nephrotic drugs, parenchymal renal disease
Pathogenesis: reduced renal perfusion due to renal vasoconstriction triggered by RAAS activation as a result of splanchnic vasodilation
Precipitating factors: sepsis esp SBP, UGIB, severe alcoholic hepatitis

Clinical presentation: oliguria (<500ml/day): no proteinuria, haematuria

Classification
type 1: at least 2x increase in creatinine to a level of >221mmol/L over <2 weeks
Type 2: less severe than type 1, associated with refractory ascites

20
Q

What is the pathogenesis of hepatic encephalopathy?

A
  • Increased ammnia in blood: decreased hepatic ammonia detoxificiation into urea due to impaired liver function. Portosystemic shunting in which blood from GIT bypass the liver and flow directly into the systemic circulation
  • Ammonia crosses BBB and enters the brain tissues. Increased intracellular osmolarity in astrocytes (resulting from metabolism of ammonia in astrocytes into glutamine) leading to astrocyte swelling and damage and subsequently cerebral edema. Ammonia induced oxidative stress also promotes astrocyte swelling. Neurotoxic efect on brian tissue leads to neuroinflammation and altered neurotransmission affecting consiousness and behaviour
21
Q

Precipitating factors for HE

A

Increased nitrogenous products
* Infection/sepsis
* GI bleeding
* Renal failure
* Transfusion
* Constipation
* Consumed a lot of protein
Hypovolemia
* GI bleeding
* Over diuresis
* Excess paracentesis with inadequate albumin replacement
* Diarrhea, vomiting
Additional factors in cirrhotic patients
* Alcohol
* Electrolyte imbalance
* Procedures: TIPS
* Acid base imbalance

22
Q

Management of biochemical abnormalities in liver cirrhosis?

A
  • HypoNa. Hypovolemic –> fluid replacement. Hypervolemic (i.e. fluid retention) –> diuretics
  • Coagulopathy (Platelet/PT): usually no Mx needed baseline –> interventions considered when underoing invasive procedures. Balance between risk of transfusiosn and procedure. Options: TPO-R agonist, FFP, cryoprecipitate, platelet transfusion
  • Anemia: ix and Mx per cause of GIB accordingly: highly suggestive of variceal bleeding

Tolvapatan not in HK

23
Q

Therapy of uncomplicated and refractory ascites?

A
  • Sodim restriction
  • Diuretics: MRA (spironolactone/eplerenone), loop diuretics (furosmide)

If diuretics resistant or diuretic intractable ascites –> refractory ascites
* Paracentesis and albumin infusion to replace the fluid and protein loss
* CART: ascites fluid filtered, concentrated to reinfuse the proteins
* If resistant to paracentesis/CART –> peritoneovenous shunting (PVS)/ TIPS

If resistant to both PVS and TIPS –> liver transplantation

24
Q

What are the indications for SBP prophylaxis?
What antibiotic choice?

A

Indications
* Previous SBP
* Recent/current upper GI bleed

Choice
* Oral ciprofloxacin/cotrimoxazole
* If advanced cirrhosis and hospitalized: IV ceftriaxone

25
Q

What are the indications for liver transplantation?

A
  1. Acute liver failure: West haven grading of HE, Kings college criteria
  2. Liver cirrhosis with decompensation
  3. Hepatic malignancy: UCSF criteria
  4. Non cirrhotic metabolic/other disease
26
Q

What is the definition of acute liver failure?
When should they be referred for potential liver transplantation?

A

Abnormal liver synthetic function (INR>1.5) and development of hepatic encephalopathy within 26 weeks of onset of illness without history of liver disease

These patients should be referred early to avoid delay in workup for potential liver transplantation if they have any of the following criteria
* Those with rising INR (>2.0)
* Evidence of early hepatic encephalopathy

Clinical presentation and radiological findings of subacteu liver failure may mimic cirrhosis

Specific exceptions
* De novo autoimmune hepatitis
* Budd-Chiari syndrome
* Wilsons disease

26
Q

What is the grading of hepatic encephalopathy?

A
27
Q

What is the Kings criteria for transplantation?

A
28
Q

Indications for liver transplantation in liver cirrhosis with decompensation

A
  • Child’s Pugh score >9 (grade C) / MELD ≥15
  • Variceal bleeding uncontrolled endoscopically/surgical shunting
  • Diuretic-resistant/refractory ascites
  • Spontaneous bacterial peritonitis
  • Chronic or recurrent encephalopathy
  • Hepatorenal syndrome
  • Intractable pruritus
  • Hepatocellular carcinoma
29
Q

Indications for liver transplantation in hepatic malignancy?

A
30
Q

What are non cirrhotic metabolic/other liver diseases that are indicated for liver transplatantation

A
  • Familial amyloidotic polyneuropathy (FAP)
  • Biliary atresia
  • Polycystic liver (+/- kidney) disease
  • Budd-Chiari syndrome
  • Glycogen storage disease
  • Crigler-Najjar Disease
  • Hyperoxaluria
  • Tyrosinemia
31
Q

What are absolute + relative contraindications for liver transplantation?

A

Absolute contraindications
* Active substance abuse
* HIV infection
* Extrahepatic malignancy
* Uncontrolled sepsis
* Uncontrolled/limiting medical comorbidities
* Severe pulmonary hypertension
* Mean PAP ≥45mmHg

Relative contraindications
* Advanced age ≥65 years
* Portal vein and SMV thrombosis
* Poor psychosocial support
* Poor medical compliance
* Extrahepatic sepsis
* Alcohol abstinence <6 months
* Moderate pulmonary hypertension (≥35mmHg and <45 mmHg)