JC68 (Medicine) - Cirrhosis Complications Flashcards
Causes of liver cirrhosis
Common: Chronic viral hepatitis: Chronic hepatitis B (>60%) Alcoholic liver disease Non-alcoholic fatty liver disease Cryptogenic (15%)
Other:
Autoimmune causes: PSC, autoimmune hepatitis
Metabolic causes: Wilson’s disease, Haemochromatosis
Biliary obstruction: Primary biliary cholangitis, Secondary biliary cirrhosis
Vascular causes: Veno-occlusive disease, Cardiac cirrhosis
List 6 major complications of cirrhosis
Ascites and Spontaneous Bacterial Peritonitis
Hepatorenal syndrome
Variceal bleeding
Encephalopathy
HCC
Pathophysiology of liver cirrhosis
Liver injury results in cytokine production by Kupffer cells and hepatocytes → activates stellate cells in space of Disse
Stellate cells transform into myofibroblast-like cell upon activation, producing
→ Collagen → fibrosis
→ Pro-inflammatory cytokines → hepatocyte damage
→ MMPs → break down normal ECM and replace with scar tissue
Autocrine loops: activated stellate cells produce TGF-β, PDGF and ROS that perpetuates its own activation
Result: progressive hepatic fibrosis with widespread hepatocyte loss and persistent chronic inflammation
S/S of hepatic insufficiency due to liver cirrhosis
Jaundice
Ankle edema, leukonychia - Hypoalbuminaemia
Easy bruising, purpura - Coagulopathy, Thrombocytopenia
Confusion, Flapping tremor - Hepatic encephalopathy
S/S of portal hypertension due to liver cirrhosis
Splenomegaly, Pancytopenia - Easy bruising, anaemic S/S, frequent infection
Caput medusae, Variceal bleeding - UGIB due to portosystemic shunts
Ascites, SBP, hepatic hydrothorax - Splanchnic vasodilation, arterial underfilling and Na retention
Oligoura, Hepatorenal syndrome - vasocontriction from RAAS activation due to arterial underfilling
Endocrine changes associated with liver cirrhosis
Male hypogonadism: due to primary gonad injury or HPG axis suppression
- Testicular atrophy, impotence, infertility, low libido
Feminization, Gynaecomastia: due to increase androgen production and convertion to estradiol
- Gynaecomastia, Inversion of male pubic hair pattern, loss of axillary and pubic hair
Female hypogonadism
- Breast atrophy, Anovulation, Amenorrhea, Low libido
Vascular lesions caused by liver cirrhosis
Pathogenesis
Ddx for each lesion
Spider naevus
Palmar erythema
Due to ↑oestradiol: testosterone ratio
≥3 spider naevi significant, seen mainly in SVC drainage area (i.e. above nipple line)
D/dx for spiders: pregnancy, RA, scleroderma
D/dx for palmar erythema: pregnancy, RA, hyperthyroidism, haem malignancies
S/S cholestasis due to liver cirrhosis
Xanthelasma, Xanthomas
Due to hypercholesterolaemia from impaired biliary cholesterol excretion
Pruritus, Scratch marks
Due to impaired bile acid excretion leading to skin accumulation and pruritus
Differentiate chronic liver failure and liver decompensation
Liver decompensation occurs when metabolic capacity of the liver is exceeded
characterized by development of encephalopathy and ascites
Pathogenesis of ascites due to liver cirrhosis
Cirrhosis leads to portal hypertension
> > Increase portosystemic shunt and vasodilator release»_space; Splanchnic vasodilation (Low pressure due to dilatation, not truly hypovolemia)
> > Decrease total systemic vascular resistance»_space; systemic arterial underfilling (body reacts to apparent hypovolemia, retains water and salt in response)
Results:
Increase RAAS/ SNS for renal tubular reabsorption of sodium - sodium retention, ascites, edema
Increase Vasopressin to reabsorb water in DCT - dilutional hypoNatremia
Lower systemic vasodilator/ Increase local vasoconstriction - Renal vasoconstriction and hypoperfusion, hepatorenal syndrome
Ascites Ddx
Common:
- Malignancy: Primary peritoneal mesothelioma, Peritoneal metastasis, eg. Ca stomach
- Liver cirrhosis and Portal hypertension
- Cardiac failure
- Iatrogenic due to CAPD
Others:
- Hypoalbuminemia: liver decompensation, Nephrotic syndrome, Protein-losing enteropathy, Severe malnutrition
- Peritonitis: pancreatitis, Tuberculous peritonitis
- Hemoperitoneum
Rare:
- Myxedema
- Urological injury
- Abdominal pregnancy
S/S ascites
Asymptomatic: if mild (<1L)
Progressive abdominal distension ± abdominal discomfort
Pressure symptoms:
→ Shortness of breath due to pressure on diaphragm
→ Early satiety due to pressure on stomach
P/E findings:
□ Shifting dullness if >1L
□ Fluid thrill if ascites is marked
□ Features of ↑intra-abdominal pressure: bulging flanks, everted umbilicus, herniae, abdominal striae, divarication of recti, scrotal oedema
Ascites
Diagnostic methods
Imaging:
- USG (1st line): free intraperitoneal fluid (hypoechoic) ± other features of portal HTN
- CT/MRI (2nd line)
Diagnostic Paracentesis
- percutaneous, USG-guided, typically at LLQ
Diagnostic paracentesis
- Indication
- Technique
- All useful exams and differentials
□ Indication: ALL new-onset ascites
□ Technique: percutaneous, USG-guided, typically at LLQ
Appearance:
→ Clear or straw-coloured: uncomplicated cirrhotic ascites
→ Turbid or cloudy: infection
→ Milky (chylous): hyperlipidaemia, TB peritonitis, malignancy (due to lymphatic obstruction)
→ Pink or bloody: traumatic tap, bleeding tendency or malignant ascites
Serum-ascites albumin gradient (SAAG) = serum [Alb] – ascites [Alb]
→ >11g/L → portal hypertension, i.e. cirrhosis, HF, PVT
→ <11g/L → exudative, i.e. malignant, infection, nephrotic syndrome
Cell count and differential:
→ WBC ≥500/mm3 and PMN >250/mm3 diagnostic of SBP
Microbiology:
→ Gram stain and culture
→ AFB smear, culture, ADA
(Cytology for malignant cell, Protein/glucose levels are NOT USEFUL)
Ascites
Management options for mild and severe ascites
General:
- Bedrest - ↓RAAS activity and ↑renal blood flow
- Dietary sodium restriction - 2g/day
- Fluid restriction - 1-1.5L/day for dilutional hypoNa
- Management of underlying liver disease, esp alcohol abstinence
- Avoid drugs affecting renal blood flow to prevent hepatorenal syndrome
Severe:
- Therapeutic paracentesis
- Diuretic therapy
Ascites Diuretic therapy
- Target weight loss
- Types, typical regimen
Target: 1kg/day weight loss
Regimen: PO spironolactone ± furosemide
Types:
K+-sparing diuretics:
→ Spironolactone (Aldactone A)
→ Amiloride (ENaC blocker)
Loop diuretics: alone or add-on K+ sparing diuretics
→ Furosemide (Lasix)
→ Bumetanide (Burinex)
Side effects of diuretic therapy for ascites
Indications to stop diuretic therapy
Spironolactone: hyperkalaemia and tender gynaecomastia in male
Amiloride (ENaC blocker): hyperK, NO gynaecomastia
Furosemide (Lasix): IV injection precipitate acute renal failure
STOP all diuretics if Na <120, progressive renal failure, ↑HE, incapacitating muscle cramps
→ Monitor K: stop Lasix if <3mmol/L, stop spironolactone if >6mmol/L
Therapeutic paracentesis
- Indications
- Target fluid extraction
- Concurrent therapies
indicated for tense or diuretic-resistant ascites, with peripheral edema present
Target: large volume (4-6L) taps
Concurrent Albumin infusion: 6-8g per L fluid removed for large volume taps (≥5L)
Therapeutic paracentesis
- Complications and precautions
Bleeding from puncture site: prevented by FFP and/or platelet concentrate
Sepsis: exclude SBP before paracentesis
Caecal perforation with Rt-sided punctures → should puncture at LLQ (Lt McBurnley’s point)
Renal impairment (may in turn precipitate hepatic encephalopathy) → caution in those with ↓BP + ↑serum Cr, monitor vitals during paracentesis
Second-line treatment options for refractory ascites
Oral midodrine: vasopressor increase renal Na excretion
TIPS to treat portal hypertension
Liver transplant for decompensated cirrhosis
Peritoneo-venous shunt for palliation
Spontaneous bacterial peritonitis
- Definition
- Complications
Ascitic fluid infection without an evident intra-abdominal surgically treatable source
Complications:
bacteremia, shock and multiorgan failure
Differentiate different forms of infected ascites
- Mono-microbial bacterascites
- Culture positive for one organism
- Normal PMN count - Culture-negative Neutrocytic Ascites
- Culture negative
- High PMN count without alternative causes
- Early SBP - SBP
- Culture positive
- High PMN count
Pathogenesis of SBP
- Precipitating factors
- Pathophysiology
- Bacteriology
Precipitating factors of bacteremia:
- Deficiency serum complements
- Poor reticulo-endothelial system function
- GI hemorrhage
- Invasive procedures
Consequence depends on ascitic fluid opsonic activity
→ Poor → SBP
→ Moderate → CNNA (considered an early form of SBP)
→ Good → resolution of bacterascites with macrophage clearance
□ E. coli (43%), K. pneumoniae (11%), Streptococcus spp (28%), Enterobacteriaceae (4%)
Diagnostic criteria of SBP
Diagnostic paracentesis:
→ Protein: often low → reflects ↓opsonin activity and liability to infection
→ Cell count: note that for every 250 RBC/mm3 one PMN should be subtracted
- >500 WBC/mm3 → suspicious
- >250 PMN/mm3 → diagnostic if S/S of SBP present
- >500 PMN/mm3 → diagnostic if S/S of SBP absent
→ Culture: usually Gram-negative or streptococci but may be negative (does not preclude SBP diagnosis as in CNNA)
SBP
Clinical features
13% asymptomatic
Diffuse abdominal discomfort: pain (59%), tenderness (49%)
Diarrhoea (32%) due to concomitant intestinal bacterial overgrowth
Systemic upset: fever (69%), altered mental status (54%), hypotension (21%)
Ileus (30%)
Secondary bacterial peritonitis vs SBP
How to differentiate
Secondary bacterial peritonitis:
ascitic fluid analysis showing (Runyon’s criteria)
- Total protein >10g/L
- Glucose <50mg/dL
- LDH > serum ULN
SBP
Empirical antibiotic treatment
- Drug choice
- Indications
- Timing and duration
Empirical antibiotic therapy:
→ Indications: symptomatic or ascitic fluid PMN >250/mm3
→ Choice: IV 3G cephalosporin (ceftriaxone or cefotaxime)
→ Effect: usually see exponential fall in PMN count after initiation
→ Duration: usually recommend 5-10 days of Abx, can stop if PMN ≤250 + clinical improvement
SBP
Treatment plan
- All treatment options
Discontinue β-blockers: a/w poorer outcome in SBP
Empirical antibiotic therapy - Ceftriaxone IV
Repeat paracentesis 48h later if complicated
(Albumin infusion if Hepatorenal syndrome)
SBP Prophylaxis regimen
Indication
Function
Benefits
NORFLOXACIN PROPHYLAXIS
Indication:
Cirrhosis with GI bleeding
Previous SBP, or ascitic fluid protein <1.5g/d with impaired RFT or liver failure
Function: long-term selective intestinal decontamination
Highly active vs G- bacilli but low activity vs anaerobes (hence preserves flora)
Benefits:
Incompletely absorbed by gut → ↓S/E
Rarely causes resistance
Hepatorenal syndrome
- Definition
- Prevalence
- Pathogenesis
Hepatorenal syndrome (HRS): renal failure in patients with severe liver disease in absence of any pathological cause for development of renal failure
Prevalence: ~10% of patients with advanced cirrhosis complicated by ascites
Cause: ↓renal perfusion due to RAAS/SNS activation secondary to splanchnic vasodilatation and systemic underfilling
Ddx renal failure with liver diseases
□ Hypovolaemia due to overdiuresis (commonest cause), GI bleeding
→ ALWAYS recheck meds and adjust accordingly, do NOT assume HRS
□ Sepsis due to pre-renal failure
□ Nephrotoxic drugs
□ Parenchymal renal disease
□ Hepatorenal syndrome: if unexplained by any of the above cause
Hepato-renal syndrome
- Precipitants
- Diagnostic criteria by biochemical tests
□ Clinically evident liver disease: can be both acute or chronic
□ Precipitant by an acute insult, eg. SBP, GI bleeding
Diagnostic criteria:
1. Renal impairment: progressive ↑serum Cr, serum sodium <130mEq/L
- Oliguria: usually <500mL/d
-
Intact tubular function as reflected by
- Urine Na <10mEq/L, i.e. no natriuresis
- Urine osmo > plasma osmo, i.e. no failure in concentrating urine - No proteinuria (<500mg/d) or haematuria
Hepato-renal syndrome
Clinical classifications
Type 1 HRS: ≥2× serum Cr to >221mmol/L under 2 weeks
→ A/w very poor prognosis (median survival <1mo w/o treatment)
→ Should r/o other important causes of acute renal failure
Type 2 HRS: renal impairment that is less severe than in T1HRS
→ Usually a/w diuretic-resistant ascites
Hepato-renal syndrome
How to clinically diagnose?
diagnosis of exclusion! – rule out
□ Pre-renal failure: over-diuresis, sepsis-related AKI
□ Renal failure: use of nephrotoxin, gloermulonephritis/renal vasculitis
□ Post-renal failure: renal stones
Hepato-renal syndrome
Treatment options + refractory treatment options
Treatment of underlying liver disease
Optimize BP to lessen arterial underfilling
→ Glypressin/terlipressin ± albumin as 1st line
→ Octreotide + midodrine ± albumin as alternative
→ Norepinephrine ± albumin: mainly in critically ill patients
Optimize renal haemodynamics:
→ Therapeutic paracentesis for tense ascites, drop BP
Therapy for refractory cases:
→ TIPS
→ Dialysis
Therapy to improve arterial underfilling in hepato-renal syndrome
MoA
Glypressin/terlipressin ± albumin as 1st line
- ADH analogues: ↑BP and renal perfusion pressure (main mechanism), ↑central blood volume and ↓SNS activation
- Albumin: to improve intravascular volume
Octreotide + midodrine ± albumin as alternative
- Octreotide: ↓endogenous vasodilator release → ↓splanchnic vasodilation
- Midodrine: systemic vasoconstrictor → ↑BP
Causes of bleeding in cirrhotic patients
Varices (50-90%): oesophageal or gastric most common, HVPG >12mmHg
Portal hypertensive gastropathy (PHG)
Peptic ulcer disease
Generalized bleeding tendency
Others, eg. Mallory-Weiss tears (in alcoholic cirrhosis)
Management plan for variceal bleeding
Shock, haemodynamic stabilization
- Monitor vitals, maintain SBP 90-100mmHg
- Volume resuscitation
- Packed cells, FFP/ platelets
Correct coagulopathy:
- Vitamin K1 replacement if cholestatic
Emergency OGD: find bleed and intervention
Manage complications e.g. HE
Variceal bleeding
Treatment options for haemostasis
- endoscopic options, medical, surgical …etc
Endoscopic treatment:
- Band ligation + Injection Sclerotherapy
- Variceal obliteration by tissue adhesive, injection of cyanoacrylate
Drug:
- Vasoconstrictors: decrease portal venous pressure
→ Terlipressin (1st line)
→ Octreotide: used if IHD
Sengstaken-Blakemore tub/ Balloon Tamponade
Emergency surgery if failed endoscopic therapy
→ Transjugular intrahepatic portosystemic shunt (TIPS)
→ Shunt surgery: portocaval shunts, splenorenal shunt
→ Non-shunt surgery: oesophageal transection, Sugiura procedure
Band ligation + Injection sclerotherapy for variceal bleed
Function
Complications
Disadvantage
Effectiveness
Function: Immediately stop bleeding + sclerotherapy to vasoconstrict bleeding vessels
Complications:
- Transient esophageal pain
- Esophageal ulcers
- Stricture
- Infections: mediastinitis, aspiration pneumonia
- Dislodge/ sloughing bands by later endoscopy
Disadvantage:
Cannot reach gastric varices
Effectiveness
- 90% acute bleed, high recurrence, 60% overall
Vasoactive drugs for variceal bleed
- Examples
- MoA of each
IV terlipressin: preferred agent (1st line)
MoA: synthetic ADH-analogue → slow, sustained release of ADH → constriction of mesenteric arterioles → ↓blood flow to gut → ↓portal venous inflow
IV octreotide: 2nd line agent, preferred in IHD/PVD
→ Pharmacology: synthetic octapeptide sharing 4AAs with somatostatin → longer half-life with ↑potency
→ MoA: action not well-defined, a/w ↓splanchnic blood flow
Prevention of Varices rebleeding
Propranolol or other B blockers
Repeated band ligation
TIPS - Transjugular Intrahepatic Portosystemic Shunt
Liver Transplant
TIPS
Procedure
Effectiveness
Transjugular intrahepatic portosystemic shunt (TIPS)
Colapinto catheter inserted transjugularly into middle hepatic vein and wedged there
advanced through liver parenchyma to Rt branch of portal vein
stent deployed to open up channel (painful)
Efficacy: achieve haemostasis in 90-100% pt
TIPS
Indication
Contraindication
Indications: → Variceal bleeding: - As definitive Tx in resistant and recurrent bleeding or acute uncontrolled bleeding - As secondary prophylaxis → Refractory ascites → Refractory hepatic hydrothorax → Budd-Chiari syndrome → Pre-transplant portal decompression
C/I:
→ Severe liver failure if not pre-transplant (risk of hepatic encephalopathy)
→ Hepatocellular carcinoma (needle tract seeding)
→ Liver abscess or cholangitis
→ DIC or severe coagulopathy
→ Cavernous transformation of portal vein (CTPA):
→ IJV, SVC, IVC thrombosis
TIPS
Acute complications
Bleeding:
- Severe/ fatal intra-abdominal bleed from liver capsule perforation or portal bifurcation
- Hemobilia, liver haematoma
Vascular:
- Thromboembolism with clot in stent
- Volume overload with HF due to rapid channeling of portal blood
- DIC
Contrast nephropathy
Sepsis
TIPS
Chronic complications
Hepatic encephalopathy
Recurrent bleeding: due to non-portal hypertensive bleed or from inadequate portal decompression
Stent stenosis or occlusion
