Cirrhosis can lead to several serious complications including ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, portal hypertension, variceal bleeding, hepatorenal syndrome, and hepatocellular carcinoma. The document outlines the pathophysiology, clinical presentation, diagnostic approach, and treatment options for each of these common complications of cirrhosis. It provides detailed guidance on managing ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome.

1. Complication of cirrhosis
Introduction
Cirrhosis is a major cause of morbidity and mortality all over the world. The lecture is
meant to stress uponthe different types ofcomplications which may occurin the clinical
setting of cirrhosis. The complications include mainly ascites,spontaneous bacterial
peritonitis, hepatic encephalopathy, portal hypertension, variceal bleeding,and
hepatorenal syndrome.as well as hepatocellular carcinoma.
Key Outlines:
1. Ascites,
2. Spontaneous bacterial peritonitis,
3. Hepatic encephalopathy,
4. Portal hypertension,
5. Variceal bleeding
6. Hepatorenal syndrome.
7. Hepatocellular carcinoma.
8. Pathophysiology.
9. Clinical manifestations with diagnostic
approach.
Cirrhosis
Definition
• Diffuse fibrosis following hepatocyte destruction and nodular regeneration
• Multiple causes
– All liver diseases may lead to cirrhosis
• Asymptomatic (compensated)
• Symptomatic (decompensated):
Jaundice, Anorexia, Generalized weakness, Easy fatigability,
Nausea, Vomiting, Diarrhea ,,Variceal hemorrhage ,,
Ascites ,, Encephalopathy .. etc

2. Examination Findings
• Spider angiomatas
• Palmar erythema
• Gynecomastia
• Testicular atrophy
• Leuconychia
• Parotid gland hypertrophy
• Dupuytren’s contractures
• Clubbing
• Jaundice
Portal Hypertension
Increased intrahepatic vascular resistance
 Fixed component
Sinusoidal fibrosis
Compression by regenerative nodules
 Functional component
Vasoconstriction
Deficiency in intrahepatic NO
Enhanced activity of vasoconstrictors
 Portal Venous Pressure (PVP)
Normal = 5-10 mm Hg
 Hepatic Venous Pressure Gradient
(HVPG)
= portal venous pressure - hepatic venous pressure or RA pressure
Normal = 1-5 mm Hg

3. Classification
 Pre hepatic: Portal or splenic vein thrombosis
Intrahepatic
• Presinusoidal Schistosomiasis
• Sinusoidal Cirrhosis
• Postsinusoidal Veno-occlusive disease
Post hepatic Hepatic vein thrombosis
Constrictive pericarditis
Varices :
Common lethal complication 50% of patients with cirrhosis More likely to bleed
in more decompensated disease
Varices: Portosystemic Collateral Formation
• Esophageal varices
• Caput medusa
• Rectal varices
Variceal Bleed: Risk Factors
• High Gradient
• Large esophageal varices
• Endoscopic features
– red wale markings
– cherry red signs
Treatment
• Primary prophylaxis (never bled)
– If no varices: no need for nonselective B blocker
– If small varices: no long term evidence to use B blocker unless red signs
present

4. – If large varices:
• High risk patient (red wale, childs B/C): B blocker (nadolol/
propranolol) or prophylactic banding
• Low risk patients: B blocker
• Titrate B blocker to max tolerated dose
• Blood transfusion:
• Antibiotics: norfloxacin, IV cipro, ceftriaxone (probably best)
• Vasopressin, telipressin, octreotide, vapreotide x 3-5 days
– Splanchnic vasoconstriction, reduced portal flow
• EGD within 12 hours
– Banding(almost always) or sclerotherapy (rare)
• Balloon Tamponade (Blakemore / Minnesota tube) temporizing measure for
up to 24 hours
• TIPS
• Secondary prophylaxis
– All patients who have has a variceal bleed
– Combination of B Blocker and serial banding
– Continue banding (usually outpt) until varices are eradicated
Ascites
Fluid within the peritoneal cavity
Occurs in 50-60% of patients with
cirrhosis over 10-15 years
Pathophysiology
 Elevated Hydrostatic Pressure
• Cirrhosis
• Congestive heart failure
• Constrictive pericarditis
• Hepatic outflow block

5.  Decreased Oncotic Pressure
• Nephrotic syndrome
• Protein-losing enteropathy
• Malnutrition
• Cirrhosis
 Peritoneal Fluid Production > Resorption
• Infections (bacterial, tuberculosis, fungal)
• Neoplasms
CP
• Abdominal distention
• Bulging flanks
• Shifting dullness
• Fluid wave
• Fluid detected on US or CT scan
Serum-Ascites Albumin Gradient
≥1.1 caused by portal hypertension
<1.1 others e.g. -Nephrotic syndrome, TB… etc.
Treatment of Ascites
• Usually responds to Na restriction and diuretics
– When SAAG >1.1
• Dual diuretics:
– Furosemide AND Spironolactone
• Single daily dosing (40/ 100)
• Na restriction <2000mg/day
• Fluid restriction is usually NOT necessary

6. In refractory ascites…
• AVOID
– ACE inhibitors / angiotensin receptor blockers
• Blood pressure / adverse renal effects
– Propranolol
• Blood pressure / circulatory dysfunction during LVP
• Renal function
– Consider risks benefits
– NSAIDS
Large / Tense ascites
• Therapeutic paracentesis followed by diuretics / Na restriction
• 6-8 g/of albumin per liter of ascites removed
• Midodrine may be helpful
– Shown to increase BP, survival benefit
• Consideration of liver transplantation referral
Spontaneous Bacterial Peritonitis (SBP)
Infectious complications of cirrhosis
1. Spontaneous bacterial peritonitis (SBP)
2. Urinary tract infection
3. Pneumonia
4. Bacteremia
SBP 7-25% of hospitalized cirrhotics
– In-hospital mortality 20-50%
Recurrence of SBP 30-70%
Eschericia coli 43%
Miscellaneous 20%
Klebsiella pneumoniae 8%

7. Streptococcus pneumoniae 8%
Group D stretocococcus 8%
Alpha-hemolytic streptococcus 5%
Miscellaneous Enterobacteriaceae 3%
Tap all patients admitted to hospital or for any reason rub you the wrong way…
• Diagnosis:
– Culture NOT needed (but send it anyways)
– PMN >250cells/mm3
• Treatment:
– 3rd gen cephalosporin i.e. cefotaxime 2g q8
– Albumin 1.5g/kg day 1 and 1.0 g/kg day 3
• Cr >1, BUN >30, or bilirubin >4
SBP : prevention
• GIT bleed and cirrhosis
– Ceftriaxone or Norfolk x 7 days
• If prior episode of SBP, long term prophylaxis
– Daily Norfloxacin or Bactrim
Hepatic Encephalopathy
Reversible alteration in the
neuropsychiatric function
• Due to shunting of neurotoxic
nitrogenous products
• Lack of hepatic detoxification
• 10-50% of cirrhotics
• 40% survival 1 year after 1st episode
• 15% survival 3 years after 1st episode
• Disturbance in diurnal sleep pattern
precedes neurologic signs
• 15-30% have abnormal NCT or abnormal EEG without overt encephalopathy

8. Treatment
• Lactulose
– First line
– 2-3 softBM/ day
• Rifaximin
– Reduced ammonia
producing bacteria
Long Term Management of HE
• After initial HE event
– Usually on therapy indefinitely or until liver transplant
– Long term use of lactulose and or rifaximin
• High protein diet is OK (and preferred in cirrhosis)
• Patients with HE should NOT undergo TIPS if possible
Hepatorenal Syndrome
Pathophysiology
• Occurs in setting of cirrhosis and
ascites
• Severe renal arterial vasoconstriction
• Compromised glomerular filtration
rate
• Normal kidney structure
• Advanced liver disease:
cirrhosis, alcoholic hepatitits,
fulminant hepatitis
• Sometimes precipitated by overdiuresis, GI bleed, use of
nephrotoxic agents

9. Clinical Features
• Ascites • Oliguria
• Hypotension •Jaundice
Course
• Typically death within weeks
• HRS Type 1
• Rapidly progressive
• Precipitating event frequent, esp SBP
• Very short survival
• HRS Type 2
• Slow onset of moderate renal insufficiency
• Poor response to diuretics (refractory ascites)
• Longer survival
 Diagnostic Criteria
1. Cirrhosis with ascites
2. Serum CR >1.5 mg/dL
3. No improvement in serum CR after at least 2 days of diuretic withdrawal &
volume expansion with albumin (max 100g/day)
4. Absence of shock
5. No current or recent nephrotoxic drugs
6. Absence of parenchymal kidney disease
Treatment
 Treatment principles
 Treat the underlying precipitant promptly
 More quickly addressed the more likely to have improvement in HRS
 Have a high suspicion for an occult precipitating event in any liver patient
who has ARF

10. - Even with removal of the precipitant, HRS may be irreversible
1. Renal vasodilators
2. Systemic vasoconstrictors
3. TIPS
4. Dialysis
5. Transplantation
Hepatocellular Carcinoma
• Seen in cirrhosis
– Exception: HBV (can be noncirrhotic)
• Diagnosis by US, CT scan, MRI
– Histology is not essential
• Alpha-fetoprotein level may be elevated
• Surveillance
– Screen all patients with cirrhosis for HCC
• Up to 8% risk of HCC/year
– Also male HBV carriers >40 and female HBV >50 (even if they don’t
have cirrhosis)
 Diagnosis
• Usually with imaging, histology used less often
• If lesion seen on u/s> 1cm then follow up with CT or MR
• If hyper vascular lesion that washes out on portal venous phase then dx
with HCC

11. Treatment of HCC
1. Resection
Less commonly used
Noncirrhotic or very well compensated
Well preserved synthetic function (INR near normal)
Normal bilirubin
Low portal pressure
Possibly for noncirrhotic HBV patient.
2. Liver transpantation
3. Systemic
– Sorafenib
Last resort
4.Local ablation
– Alcohol injection
• Only in smaller tumors
• Not used very often
– Radiofrequency ablation
• Better for larger tumors
– May use as a bridge to liver
transplantation
• Transarterial Chemoebolization
(TACE)
– Non curative
– Nonsurgical patients
– Large multifocal HCC
– No vascular invasion
– No extrahepatic spread

12. 5.Liver transplantation
– Curative approach
– Milan Criteria
• 1 tumor <5cm
• Up to 3 tumors <3cm
• No vascular / extrahepatic spread
Conclusions
• The transition from compensated cirrhosis to decompensated cirrhosis
carries a significant change in mortality
• Clinical diagnosis is important
• Simultaneous compications may (and usually arise)
References:
 Kumar and Clark's Clinical Medicine.
 USMLE CK book
 Macleod's clinical examination.
 Davidson's principles of clinical practice.
 medicinenet.com
 webmd.com

13. Supervisedby : Tropical Medicine
Department
Prepared by:
Eslam Emad Awesh