Cirrhosis / Complications


    Source: MKSAP 16




    • Divide cirrhosis into compensated and decompensated
    • Decompensated --> Presence of overt clinical complications of cirrhosis
      • Ascites
      • Variceal Hemorrhage
      • Hepatic Encephalopathy

    Portal Hypertension

    • Hemodynamic alterations in portal venous blood flow.
    • Significant portal HTN when >8-10mmHg (normal 3-5 mmHg).
    • Most common cause is cirrhosis.
    • Manifestations:
      • Gastro-Esophageal Varices (30-60% of pts with cirrhosis)
      • Ascites
      • Hepatic encephalopathy
    • Gastro-Esophageal Varices
      • Can spontaneously rupture causing death.
      • Mortaliy 15% with treatment (>50% without)
    • Management:
      • Upper endoscopy required to screen for GE varices (see below)


    Gastro-Esophageal Varices

    Screening Guidelines

    • Surveillance Endoscopy Guidelines:

      First screening upper endoscopy required in all cirrhosis patients.

      • IF NO varices found:
        • Need surveillance endoscopy q2-3 years.
      • IF SMALL varices found:
        • Need q1y (annual) screening
        • Primary prophylaxis ONLY if risks of bleeding (Child's Pugh B/C OR Whale Marks on Varices)
      • IF MEDIUM or LARGE varices found:
        • IF bleed risk high ->
          • Non-selective BB or EVL
        • All others: Non-selective BB Preferred
        • (see primary prevention of bleeding section)

      EVL - Endoscopic Variceal Ligation

    Variceal Bleed - Primary Prevention

    • If LARGE varices found, pick one:
      • 1st line: Non-Selective Beta-Blocker
        • Propranolol
        • Nadolol (MOST COMMON)
      • 2nd line: Endoscopic variceal ligation (If contraindication for BB or if bleed on BB - use both)
    • DO NOT use for primary prevention:
      • Nitrates alone
      • Endoscopic sclerotherapy (complications, not used anymore)
      • Shunt therapy (TIPS or surgical) (last line)
      • Non-selective BB + nitrates.
    • Pts with BB contraindications (asthma, low BP, bradycardia) could be offered endoscopic ligation threapy.







    Starting dose of 20 mg orally twice a day

    Increase to maximally tolerated dose or until heart rate is approximately 55/min


    Ensure heart-rate goals met at each clinic visit; no need for follow-up endoscopy


    Starting dose of 40 mg orally oncea day

    Increase to maximally tolerated dose or until heart rate is approximately 55/min


    Ensure heart-rate goals met at each clinic visit; no need for follow-up endoscopy

    Endoscopic variceal ligation

    Every 2-4 weeks

    Obliterate varices

    Until variceal obliteration achieved (usually 2-4 sessions)

    Perform first surveillance endoscopy 1-3 months after obliteration, then every 6-12 months indefinitely

    Source: Garcia-Tsao G, Bosch J. Management of varices and variceal hemorrhage in cirrhosis. N Engl J Med. 2010;362(9):823-32. PMID: 20200386. Copyright 2010, Massachusetts Medical Society.


    Variceal Bleeds - ACUTE Management

    • Pick ONE from each category! (see table below)
      • Antibiotics (ceftriaxone or norfloxacin) - for acute bleeds
      • Vasoconstrictors (Octreotide)
      • Endoscopic therapy (Variceal band ligation or less commonly sclerotherapy)
    • IF bleeding not controlled:
      • Trans-Jugular TIPS procedure (porto-systemic shunt) - highly effective for bleeding.









    Intravenous 50-µg bolus, followed by infusion of 50 µg/h

    2-5 days

    Bolus can be repeated in first hour if variceal hemorrhage uncontrolled; if rebleeding occurs during therapy, consider TIPS

    Available in the United States


    2 mg given intravenously every 4 h for first 48 h, followed by 1 mg given intravenously every 4 h

    2-5 days

    If rebleeding occurs during therapy, consider TIPS

    Not available in the United States


    Intravenous 250-mg bolus, followed by infusion of 250 mg/h

    2-5 days

    Bolus can be repeated in first hour if variceal hemorrhage uncontrolled; if rebleeding occurs during therapy, consider TIPS

    Not available in the United States


    Intravenous 50-µg bolus, followed by infusion of 50 µg/h

    2-5 days

    If rebleeding occurs during therapy, consider TIPS

    Not available in the United States



    Intravenously at a dose of 1 g/d

    5-7 days or until discharge

    No long-term antibiotics unless spontaneous bacterial peritonitis develops

    High probability of fluoroquinolone resistance, or both


    400 mg orally twice a day

    5-7 days or until discharge

    No long-term antibiotics unless spontaneous bacterial peritonitis develops

    Low probability of fluoroquinolone-resistant organisms

    Endoscopic therapy

    Endoscopic variceal ligation



    Until variceal obliteration achieved

    If rebleeding occurs during therapy, consider TIPS

    Requires endoscopist with special expertise

    Endoscopic variceal sclerotherapy


    Only at diagnostic endoscopy

    Continue with endoscopic variceal ligation until obliteration achieved

    Phased out (ligation is standard)

    Used when endoscopic variceal ligation not possible; requires endoscopist with special expertise


    Variceal Bleed - Secondary Prevention

    • Non-selective B-Blocker + endoscopic ligation


    Gastric Varices

    • Gastric varices: Non-selective BB and variceal band ligation not effective in patients with LARGE gastric varices.
    • IF gastric variceal bleed - treat with endoscopic banding OR sclerotherapy
      • Risk of re-bleeding is high.
      • TIPS sometimes recommended post-bleed for secondary prophylaxis.



    Hepatic Encephalopathy

    • Disturbance in CNS function caused by hepatic insufficiency and porto-systemic shunting.
      • TIPS can make this worse (increases porto-systemic shunting).
    • Increasing frequency and severity of HE ==> predicts mortality.
    • Exclude other causes of encephalopathy
    • Classification / Symptoms
      • Based on the West Haven Criteria for Classification of Hepatic Encephalopathy





        No abnormality


        Trivial lack of awareness, euphoria or anxiety, shortened attention span, impairment of addition or subtraction


        Lethargy or apathy, disorientation for time, obvious personality change, inappropriate behavior


        Somnolence to semistupor, responsive to stimuli, confused, gross disorientation, bizarre behavior



        Hepatology. 50(6). Bajaj JS, Wade JB, Sanyal AJ. Spectrum of neurocognitive impairment in cirrhosis: Implications for the assessment of hepatic encephalopathy; 2014-2021.

    • "Minimal HE" defined as cognitive dysfunction without clincal signs of overt HE.
      • Should be investigated to advise pts of driving, work performance, etc..
    • Diagnosis:
      • Exclude other causes of encephalopathy.
        • Exclude DIMS metabolic, infections, medications, and structural lesions.
      • Serum ammonia levels do not correlate with stage
        • Can be helpful for initial evaluation of unexplained confusion in pts without hx of liver disease.
    • Precipitating factors:
      • Portosystemic shunts can trigger encephalopathy (TIPS or spontaneous detected on imaging)
      • GE Hemorrhage
      • Infection
      • Electrolyte disturbances
      • Vascular volume (Over diuresed?)
      • Medications (sedatives, opioids)
      • Constipation
      • Superimposed acute liver injury
        • EtOH hepatitis, hypotension, portal vein thrombosis, surgery
    • Management:
      • Treat precipitating factors
      • Must reduce excess nitrogen in gut.
        • First line: Lactulose (non-absorbable disaccharide, reduces absorption of nitrogen)
          • Target 3-4 BM/day, if more, reduce dose/frequency.
          • (Do not have lactulase, causes malabsorption, colonic bacteria convert to hydrogen, which complexes with ammonia causing it to be excreted and not absorbed)
        • Oral Antibiotics (neomycin, rifaximin) (rarely used) reduce colonic bacteria (less ammonia)
          • Careful with long-term use (neomycin - ototoxicity, nephrotoxicity).
          • Reduced exacerbations by 60% (rifaximin vs. placebo).
        • Dietary protein restriction = NOT RECOMMENDED
          • Studies: increases mortality!


    Hepatorenal Syndrome

    • Renal vasoconstriction --> severe reduction in GFR (no histolic abmoralities).
      • Often renal-angiotensin system activated causing vasoconstriction (alteration in splanchnic circulation)
    • Two types:
      • Type I - Rapidly progressive reduction in GFR
      • Type II - Not rapidly progressing (often associated refractory ascites)
      • See below for criteria for diagnosis


    Type I Hepatorenal Syndrome Definition:

    • Doubling of serum creatinine to > 2.5 mg/dL (221 umol/L) in < 2 weeks
    • 50% reduction of the initial 24-hour CrCl to <20 mL/min/1.73 m2 in < 2 weeks


    Type II Hepatorenal Syndrome Definition:

    • Creatinine > 1.5 mg/dL (132.6 umol/L)
      + No other explanation; need to r/o other conditions
    • Diagnosis:
      • Diagnostic Criteria for HRS:

        • Increase in serum creatinine to > 1.5g/dL (132 umol/L)
        • Lack of response to albumin challenge (1 g/kg/day x2 days)
        • Absence of reversible causes of AKI:
          • shock
          • Nephrotoxic drugs
          • Active urine sediment
          • Proteinuria >500 mg/d
          • U/S evidence of parenchymal renal disease or obstruction
    • Treatment:
      • Terlipressin (vasopressin-like, Unavailable in US)
        • Reverses Type I and Type II HRS.  
      • IV Albumin
        • RCT evidence: Shown to improve serum creatinine and Urine output for T1 HRS.
      • Liver Transplant +/- Renal Transplant --> most effective.
      • Others:
        • Ocreatide + mitodrine + albumin
          • Reported to help HRS, but concern about mitodrine availability 
        • Octreotide monotherapy --> NO BENEFIT
      • Bottom Line:
        • Hydrate and use albumin.

    Hepatopulmonary Syndrome

    • Aka HPS
    • Defect in arterial oxygenation induced by pulmonary vascular dilatation (compared to HRS --> renal vasoconstriction) in setting of cirrhosis and portal HTN.
      • Causes physiologic shunt through the lung.
    • 5-30% in pts with cirrhosis.
    • Clincal Features:
      • Hypoxemia in cirrhosis in absence of other causes (hepatic hydrothorax, thromboembolic disease).
      • Exam: clubbing, cyanosis
    • Diagnosis:
      • ABG: Hypoxemia
      • Transthoracic Cardiac Echo (MOST effective screening/diagnostic tool)
        • Microbubble visualization within the left atrium after three to six cardiac cycles is diagnostic for HPS. (See physiologic shunt)
    • Management:
      • No effective medical therapies for HPS!!!
      • Liver Transplant!
        • PaO2 ≤ 60 mm Hg considered high-priority candidates.


    Portopulmonary Hypertension

    • aka POPH.  Characterized by coexisting primary portal hypertension with pulmonary HTN.
    • Presence of pulmonary HTN in liver disease is 4-10%.
    • Clinical Features:
      • Asymptomatic or have progressive dyspnea.
    • Diagnosis:
      • Estimated RVSP ≥ 50mmHg on TTE
      • Confirmed by R-heart catheterization. (mPAP ≥ 25 mmHg, pulm. vascular resistance of ≥ 240 dynes/s/cm-5, and PA occlusion pressure < 15 mmHg.)
    • Management:
      • Poor prognosis, esp if mPAP > 35 mmHg.
      • No RCT for medical therapy.
        • but: IV epoprostenol, oral sildenafil, and bosentan used with variable success. (same as primary pulmonary HTN)
      • 5-year survival of untreated 15% --> 65% (with med. treatment).
      • Liver Transplant:
        • PA pressurs > 35-50 mmHg --> not transplant candidates, high risk of perioperative death.


    Fulminant Hepatic Failure


    • Fulminant Hepatic Failure Defined:

      • Hepatic encephalopathy in the setting of jaundice without pre-existing liver disease.
    • (Note: Liver injury is just elevation of enzymes or jaundice with absence liver failure)
    • Classified as # of weaks post-jaundice that encephalopathy develops:
      • Hyperacute (within 1 week) - BEST prognosis
      • Acute ( 1-4 weeks)
      • Subacute (4-12 weeks)
    • Hyperacute has the best prognosis.
    • Causes:
      • Drugs
      • Viruses
      • Other
    • Drugs:

      • **Acetaminophen**
        (MOST COMMON)
      • Isoniazid
      • Sulfonamides
      • Tetracycline
      • MDMA (“ecstasy”)
      • NSAIDs
      • Herbal remedies
        (black cohosh, chaparral)
      • Cocaine


      • Hepatitis A, B, E
      • Herpes simplex virus
      • Cytomegalovirus
      • Epstein-Barr virus
      • Parvovirus B19
      • Varicella zoster virus


      • Amanita phalloides
        (mushroom intoxication)
        (Use Penicillin G)
      • Bacillus cereus
      • Budd-Chiari syndrome
      • Acute fatty liver of pregnancy
      • HELLP syndrome
      • Autoimmune hepatitis
    • Most common is Acetaminophen ( Initiate NAC protocol ASAP!)
    • Management:
      • IMMEDIATE referral to a transplant center for intense monitoring and consideration of transplant.
        • Regardless of cause
      • Get U/S to r/o dilatation (if dilated --> stat ERCP)
      • Transplant: Only treatment that improves survival.
      • Recently: NAC for mushroom toxicity (in addition to acetaminophen).
      • Supportive care while transfering:
        • Hypoglycemia
        • Infection
        • Cerebral edema** - Altered LOC --> measure ICP with invasive monitoring.
          • Most patients die from cerebral edema, be careful!
          • Use mannitol (not in renal disease), or hypothermia
        • Coagulopathy - measured by prothrombin time
          • (only transfuse FFP only if bleeding or procedure planned)

    Liver Transplantation

    • Indications:
      • Fulminant hepatic failure, decompensated cirrhosis
      • HCC within the "Milan" criteria --> one tumor ≤ 5cm or ≤ 3 tumors each ≤ 3cm
    • Decompensated cirrhosis: Ascites, hepatic encephalopathy, jaundice, portal HTN- related bleeding --> consider liver transplant. 
    • One year survival post-transplant: 80-90%.
    • Pre-transplant workup:
      • R/O contraindications to liver transplant:
      • Contraindications to liver transplant:

        • Severe cardiac and pulmonary disease
        • Cholangiocarcinoma (with exception of clinical protocols)
        • Hepatocellular carcinoma exceeding Milan criteria limits
        • Active alcohol or substance abuse
        • Extrahepatic malignancy
        • Systemic infections without adequate treatment
        • Morbid obesity
        • Inability to comply with pre- and posttransplant regimens
        • AIDS (HIV infection is a contraindication at some transplant centers)
        • Advanced age (relative contraindication)


    Hepatocellular Carcinoma


    Health Maintenance in Cirrhosis

    Metabolic Bone Disease

    • Osteoporosis, osteopenia, osteomalacia. (50% of cirrhotics)
      • Often Due to: Poor nutrition, EtOH, hypogonadism.
    • Spinal fractuers are often a concern (often asymptomatic)
    • BMD screen for all patients with cirrhosis and risk factors (Poor nutrition, Alcohol use, hypogonadism)

      • In the absence of osteoporisis, DEXA surveillance testing q2-3y


    • Management
      • Weight bearing exercises
      • Pharmacologic therapy
        • Calcium, Vitamin D for osteopenia + osteoporosis
        • Oral bisphosphonates or raloxafine (No studies on safety on cirrhosis, but tolerated well)
        • IV bisphosphonates for pts with large varices, or recent esophageal banding.
      • Hypogonadism can be treated with transdermal testosterone (there is a theoretical risk of HCC)


    • Ruotine immunizations considered safe
    • BUT AVOID live attenuated vaccines
    • Required:
      • Annual influenza
      • Pneumococcal q5y
      • Tetanus toxoid q10y
      • Hep A and B vaccines are safe and highly recommended!
        • (90-99% response rates)
        • Booster to HepB may be need if lost titre
        • MUST test for prev. exposure to Hep A and B (natural titres may be sufficient)


    Medications to Avoid

    • Caution due to potential of adverse events.
    • Regular NSAIDs and ASA should be avoided in:
      • Esophageal Varices (risk of ulceration)
      • Ascites (risk of renal injury)
    • Acetaminophen
      • Safe and better alternative to NSAIDS, unless patient drinks EtOH!
    • Taramadol --> no risk.
    • Benzodiazepines metabolized in liver (diazepam, chlordiazepoxide)
      • Can accumulate + sedate.
      • Use lorazepam, oxazepam instead!
    • Opioids --> Use with caution, REDUCE dose, PROLONG intervals.
    • ZolpidemZopiclone --> Unknown, but commonly used in compensated cirrhosis.
    • Antibiotics ass'd with drug-induced liver injury (Amox-Cav, Isoniazid) --> AVOID!
    • FluoroquinolonesCephalosporins --> SAFE!
    • TMP-SMX --> rarely ass'd w/ cholestasis, but useful.
    • Statins --> SAFE! Do not increase risk of hepatotoxicity (monitor liver enzymes!)
    • Diabetes --> Oral hypoglycemic agents are OK!



    • Cirrhosis is a catabolic state, many at risk of protein-calorie malnutrition --> further wasting.
      • Gastric accommodation is impaired --> early satiety and poor intake.
    • Management:
      • Smaller portions, 4-6x/day, allows daily carolic req'ts to be met.
      • Enteral supplements (high-calorie, low-volume products) if needed.
      • Snack pre-bedtime can blunt the catabolic response (intensifies overnight)
      • Check serum levels of fat-soluble vitamins (ADE) and zinc, replace orally if needed.
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