cirrhosis
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Introduction
A condition of the liver characterized by parenchymal necrosis, regenerating nodules, & fibrosis.
Etiology
- alcohol abuse
- infectious etiologies
- metabolic disorders
- biliary cirrhosis:
- pharmacologic agents
- toxins: carbon tetrachloride
- malnutrition
- gastroplasty
- jejunoileal bypass
- cardiac
Epidemiology
- 12th leading cause of mortality among adults USA
- 5th leading cause of death in adults 45-54 years USA
- cirrhosis-related deaths increased by 3.4% annually from 2009-2016[26]
Clinical manifestations
- easy bruising
- fatigue, malaise
- weight loss
- clubbing
- gynecomastia
- hepatomegaly
- palpable liver
- end stage, the liver is often small & hard
- jaundice
- parotid gland enlargement
- muscle wasting
- testicular atrophy
- cutaneous stigmata
- palmar erythema
- spider angioma
- loss of fingernail lunulae
- dilated abdominal veins
- stigmata of portal hypertension
- abdominal collateral veins (caput medusae)
- ascites: bloody ascites fluid suggests carcinoma
- encephalopathy
- esophageal varices
- hemorrhoids
- splenomegaly; palpable spleen
- central nervous system stigmata
- impaired mental status (hepatic encephalopathy)
- confusion or agitation
- hyperreflexia
- asterixis
- abdominal bruit or friction rub suggests carcinoma
- signs & symptoms of primary etiology of cirrhosis
Diagnostic criteria
- small non-palpable liver
- splenomegaly
- spider telangiectasias (spider angioma)
- hepatic synthetic dysfunction
- pancytopenia
- RUQ abdominal ultrasound findings[35]
Laboratory
- general
- serum albumin is generally diminished
- serum transaminases (serum AST, serum ALT)
- serum alkaline phosphatase
- serum bilirubin
- serum globulin
- serum 5'nucleotidase
- coagulopathy occurs when cirrhosis is advanced
- prothrombin time (PT is generally prolonged as a result of dysfibrinogenemia
- activated partial thromboplastin time (aPTT) is prolonged
- thrombin time (TT) is prolonged
- factor V in plasma is low, factor VII in plasma is low
- factor VIII in plasma is high (synthesized by vascular endothelium & cleared by liver)
- D-dimer in plasma may be elevated (cleared by liver)
- plasma fibrinogen is low
- complete blood count (CBC)
- thrombocytopenia due to splenomegaly
- platelet count does not predict risk of unprovoked bleeding[23]
- increased bleeding time greater than expected from degree of thrombocytopenia
- serum alpha-fetoprotein (hepatocellular carcinoma screen)
- every 6 months
- especially useful in viral hepatitis-related cirrhosis[17]
- serum alpha-fetoprotein unnecessary with transient elastography[35]
- ascites fluid analysis
- [[[A13149|serum albumin]]] - [[[A13231|ascitic fluid]] albumin] > 1.1
- tests for specific etiologies
- liver biopsy
- see ARUP consult[8]
Diagnostic procedures
- upper GI endoscopy (all patients)
- assess for presence of esophageal varices
- endoscopic variceal ligation[2]
- surveillance upper GI endoscopy
- every 3 years for compensated cirrhosis without varices
- every year for compensated cirrhosis with small varices
- every 2 years for chronic hepatitis, alcohol use, NAFLD with elevated serum ALT or other liver injury
- paracentesis of ascites*
- calculate serum to ascites albumin gradient
- neutrophil count > 250/uL spontaneous bacterial peritonitis
* paracentesis takes priority over upper GI endoscopy if no GI bleeding & new onset ascites, especially with evidence of acute renal failure[35]
Radiology
- abdominal CT
- radiodensity of hepatic parenchyma
- contrast studies can highlight vascular lesions
- 4 phase CT: lesions > 1 cm that enhance in the arterial phase with washout of contrast in the venous phase confirm a diagnosis of hepatocellular cardinoma (not biopsy needed)[2]
- abdominal ultrasound (see hepatobiliary ultrasonography)
- high mean flow velocity through hepatic artery predicts poor response to beta-blocker therapy[5]
- screen for hepatocellular carcinoma every 6 months[2]
- if positive, gadolinium contrast MRI (rather than liver biopsy)[2]
- assess for ascites
- hepatic transient elastography (Fibroscan)
- estimates risk for portal hypertension & esophageal varices (see management)[35]
- 1st priority after abdominal ultrasound[35]
- magnetic resonance imaging
- delineates vascular lesion
- double contrast material-enhanced MRI may identify fibrosis[5]
- differentiation of regenerating nodules in cirrhosis from hepatocellular carcinoma
- gadolinium-contrast MRI suffcient for diagnosis of hepatocellular carcinoma; biopsy not needed [2]
- cholangiography for primary sclerosing cholangitis
- bone mineral density: risk for osteoporosis, especially if taking glucocorticoids[2] prior to liver transplantation[2]
Complications
- ascites (most common) 50% of patients within 10 years[2]
- hepatic encephalopathy
- predisposition to infection
- bacterial peritonitis
- recurring bacterial cholangitis
- common pathogens
- proton pump inhibitors increase risk[16]
- prophylaxis for spontaneous bacterial peritonitis may result in selection of resistant pathogens[16]
- sepsis & septic shock[11]
- esophageal varices & variceal hemorrhage
- hepatic failure
- acute-on-chronic liver failure[14]
- jaundice
- ascites
- hepatoma, hepatocellular carcinoma
- cumulative 5-year risk of hepatocellular carcinoma in patients with alcoholic cirrhosis is 1%, accounting for < 3% of deaths[9]
- 80% of hepatocellular carcinomas occur in patients with cirrhosis[2]
- hepatorenal syndrome
- some degree of functional renal impairment occurs in 1/2 of patients with cirrhosis & ascites[6]
- use 25% albumin (Albuminar) for acute renal failure[2]
- hepatopulmonary syndrome[2]
- portopulmonary syndrome[2]
- hepatic osteodystrophy[7], osteoporosis[2][28]
- portal vein thrombosis[2]
- increased risk of stroke (2-fold)
- increased risk especially hemorrhagic stroke[22]
Management
- general: supportive therapy
- prevention & treatment of hepatic encephalopathy
- esophageal varices
- screening with PillCam, endoscopy
- if liver stiffness is >= 25 kPa on hepatic transient elastography (Fibroscan), prophylaxis for esophageal varices with non-selective beta-blocker[35]
- treatment of portal hypertension with non-selective beta-blocker:
- IV albumin of no benefit[33]
- IV octreotide if variceal hemorrhage is suspected, preferably before endoscopy, continued for 2-5 days to prevent rebleeding[40]
- antibiotic prophylaxis for GI bleed[24]
- reduces incidence of infections
- improves control of bleeding & survival
- initiate on presentation of bleeding
- continue for up to 7 days
- ceftriaxone 1g QD vs norfloxacin 400 mg BID[24]
- treatment of ascites
- low-sodium diet
- spironolactone with or without furosemide
- discontinue ACE inhibitor & ARBs in the absence of hypertension
- compensatory upregulation of renin-angiotensin system supports blood pressure & renal function[2]
- antibiotic prophylaxis for bacterial peritonitis
- hospitalized with gastrointestinal bleeding[3][24]
- hospitalized, ascitic fluid protein < 1.0 g/dL[2]
- ceftriaxone vs fluoroquinolone for 7 days
- ceftriaxone 1g QD
- norfloxacin 400 mg PO BID
- high-risk patients with cirrhosis & ascites may not benefit from antibiotic prophylaxis to prevent spontaneous bacterial peritonitis[32]
- IV albumin useful for anti-inflammatory effects[33]
- early paracentesis[31]
- volume expansion with albumin 8 g/L if > 5 L of ascitic fluid removed[24]
- albumin may be appropriate if lesser amounts of ascitic fluid removed
- decompensated cirrhosis (worsening ascites)
- fluid restriction is not recommended in patients with cirrhosis & ascites[38]
- dietary sodium restriction & diuresis for transudative pleural effusion
- early treatment of sepsis
- use broad spectrum antibiotics
- use combination therapy[11]
- allopurinol 300 mg/day may reduce bacterial translocation & inflammation & thus reduce recurrence of infectious complications[39]
- coagulopathy of liver disease[30]
- do not routinely correct thrombocytopenia & coagulopathy for low-risk procedures such as band ligation of varices, paracentesis, & thoracentesis
- for active bleeding & to minimize bleeding in high-risk procedures:
- platelet count target of > 50,000/uL
- plasma fibrinogen target > 120 mg/dL
- level < 100 mg/dL associated with increased risk of bleeding[35]
- cryoprecipitate for hypofibrinogenemia[2]
- thromboelastography
- Less reliance on INR as a measure of hemostasis
- use of platelets & fresh frozen plasma, can lead to infectious, transfusion-related, & immunologic complications
- tranexamic acid in patients with persistent bleeding from mucosal oozing or puncture wound[30]
- desmopressin in patients with renal failure[30]
- anticoagulation considerations:
- symptomatic deep venous thrombosis (DVT) or portal vein thrombosis, systemic heparin infusion is recommended
- treatment of incidental portal vein thrombosis should be considered in transplantation candidates, as extensive thrombosis could impact surgical candidacy.
- for portal vein thrombosis therapy, LMW heparin, direct-acting anticoagulants, & warfarin are recommended.
- once anticoagulation for portal vein thrombosis is started, 6-month follow-up imaging is recommended to assess efficacy[3]
- screen for hepatocellular carcinoma
- ultrasound every 6 months[2]
- serum alpha-fetoprotein every 6 months
- unnecessary with ultrasound[35]
- hospital readmission is common
- 37% within 1 month[7]
- careful discharge planning can diminish rates of rehospitalization
- common reasons for rehospitalization
- avoid proton pump inhibitors in patients with decompensated cirrhosis
- increased risk of hepatic encephalopathy & bacterial peritonitis[16][21]
- H2 receptor antagonists appear to be safe alternative[10]
- avoid NSAIDs[24]
- pain management in hospitalized patients
- low dose IV hydromorphone or low-dose IV fentanyl safest options[34]
- management of specific etiologies
- alcoholic liver disease: abstinence from alcohol
- alpha-1 antitrypsin deficiency:
- liver transplantation is curative
- hemochromatosis
- phlebotomy for removal of iron
- chelation therapy
- primary biliary cirrhosis
- ursodeoxycholic acid (ursodiol [Actigall])
- liver transplantation is curative
- secondary biliary cirrhosis
- relief of biliary obstruction by ERCP or surgery
- Wilson's disease
- penicillamine (Cuprimine)
- trientine
- zinc sulfate
- liver transplantation is curative
- surgery[27]
- surgery & anesthesia are risk factors for fulminant hepatic failure
- surgeries closest to the liver are highest surgical risk[27]
- cholecystectomy & cardiothoracic procedures with highest risk
- avoid elective surgery in patients with Child's class C cirrhosis
- avoid surgery in patients with Child-Pugh score > 10 or MELD score > 20
- avoid abdominal surgery in patients with uncontrolled ascites
- do not place transjugular intrahepatic portosystemic shunt (TIPS) prior to surgery in patients with portal hypertension[27]
- platelet count > 50,000/uL probably good idea, but not evidence-based
- postoperative management
- monitor renal function, fluid balance
- use lower doses of opiates, only short-acting benzodiazepines, avoid NSAIDs
- avoid constipation[27]
- referral for liver transplantation
- abstinence for alcohol or other drug abuse
- hepatic encelphalopathy
- complications from ascites
- variceal bleeding
- model for end-stage liver disease score of >= 15[2]
- MELD-sodium score predicts 3-month mortality & is used for allocation of liver tranplantation[2]
- decompensated cirrhosis
- preventive medicine
- vaccinations:
- screen for osteoporosis, treat with bisphophonate[2][28]
- patient education
More general terms
More specific terms
- alcoholic cirrhosis
- alpha-1 antitrypsin deficiency
- biliary cirrhosis
- Cruveilhier-Baumgarten syndrome
- cryptogenic cirrhosis
- familial cirrhosis & hepatitis
- hemochromatosis
- North American Indian childhood cirrhosis (NAIC)
Additional terms
- bacterial peritonitis (BP)
- Child-Pugh classification of cirrhosis
- coagulopathy of liver disease
- hematologic complications of hepatocellular failure
- hepatic encephalopathy
- hepatitis
- hepatobiliary ultrasonography
- liver transplantation
References
- ↑ Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 374-75
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 2.24 2.25 2.26 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia. 1998, 2006, 2009, 2012, 2015, 2018, 2021.
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ 3.0 3.1 3.2 Talwalker JT & Kamath PS, Influence of recent advances in medical management on clinical outcomes of cirrhosis
- ↑ Berzigotti A et al, Primary prophylaxis with naldolol in cirrhotic patients: Doppler patterns of splanchnic hemodynamics in good & poor responders J Hepatol 2006; 44:310 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16343679 Mayo Clin Proc 80(11):1501, 2005
- ↑ 5.0 5.1 5.2 Aguirre DA, Behling CA, Alpert E, Hassanein TI, Sirlin CB. Liver fibrosis: noninvasive diagnosis with double contrast material-enhanced MR imaging. Radiology. 2006 May;239(2):425-37. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16641352
- ↑ 6.0 6.1 Montoliu S et al. Incidence and prognosis of different types of functional renal failure in cirrhotic patients with ascites. Clin Gastroenterol Hepatol 2010 Jul; 8:616. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20399905
- ↑ 7.0 7.1 7.2 7.3 Volk ML et al. Hospital readmissions among patients with decompensated cirrhosis. Am J Gastroenterol 2012 Feb; 107:247. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21931378
- ↑ 8.0 8.1 ARUP Consult: Cirrhosis The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/cirrhosis
- ↑ 9.0 9.1 Jepsen P et al. Risk for hepatocellular carcinoma in patients with alcoholic cirrhosis: A Danish nationwide cohort study. Ann Intern Med 2012 Jun 19; 156:841 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22711076
- ↑ 10.0 10.1 Bajaj JS et al Association of proton pump inhibitor therapy with spontaneous bacterial peritonitis in cirrhotic patients with ascites. Am J Gastroenterol 2009 May; 104:1130. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19337238
Bajaj JS et al. Proton pump inhibitors are associated with a high rate of serious infections in veterans with decompensated cirrhosis. Aliment Pharmacol Ther 2012 Sep 11 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22966967 <Internet> http://onlinelibrary.wiley.com/doi/10.1111/apt.12045/abstract;jsessionid=63AAEC22827345E993522335B4680B03.d02t03 - ↑ 11.0 11.1 11.2 Arabi YM et al. Antimicrobial therapeutic determinants of outcomes from septic shock among patients with cirrhosis. Hepatology 2012 Dec; 56:2305. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22753144
- ↑ O'Leary JG, Yachimski PS, Friedman LS. Surgery in the patient with liver disease. Clin Liver Dis. 2009 May;13(2):211-31. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19442915
- ↑ European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010 Sep;53(3):397-417 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20633946
- ↑ 14.0 14.1 Moreau R et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 2013 Jun; 144:1426 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23474284
- ↑ Forner A, Vilana R, Ayuso C et al Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatology. 2008 Jan;47(1):97-104. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18069697
- ↑ 16.0 16.1 16.2 16.3 O'Leary JG et al. Long-term use of antibiotics and proton pump inhibitors predict development of infections in patients with cirrhosis. Clin Gastroenterol Hepatol 2015 Apr; 13:753. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25130937
- ↑ 17.0 17.1 Chang T-S et al. Alpha-fetoprotein measurement benefits hepatocellular carcinoma surveillance in patients with cirrhosis. Am J Gastroenterol 2015 Jun; 110:836 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25869392
- ↑ Tripodi A, Primignani M, Chantarangkul V et al An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology. 2009 Dec;137(6):2105-11 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19706293
- ↑ Adams PC Evaluation of cirrhosis with an elevated ferritin. Clin Gastroenterol Hepatol. 2012 Apr;10(4):368-70 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22037432
- ↑ Ge PS, Runyon BA. Treatment of Patients with Cirrhosis N Engl J Med 2016; 375:767-777. August 25, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27557303 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMra1504367
- ↑ 21.0 21.1 21.2 Dam G, Vilstrup H, Watson H, Jepsen P. Proton pump inhibitors as a risk factor for hepatic encephalopathy and spontaneous bacterial peritonitis in patients with cirrhosis with ascites. Hepatology. 2016 Oct;64(4):1265-72. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27474889
- ↑ 22.0 22.1 Parikh NS, Navi BB, Schneider Y et al Association Between Cirrhosis and Stroke in a Nationally Representative Cohort. JAMA Neurol. Published online June 5, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28586894 <Internet> http://jamanetwork.com/journals/jamaneurology/fullarticle/2629721
- ↑ 23.0 23.1 Basili S, Raparelli V, Napoleone L et al. Platelet count does not predict bleeding in cirrhotic patients: Results from the PRO-LIVER Study. Am J Gastroenterol 2017 Dec 19; PMID: https://www.ncbi.nlm.nih.gov/pubmed/29257146
- ↑ 24.0 24.1 24.2 24.3 24.4 24.5 24.6 European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018 Apr 10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29653741 https://www.journal-of-hepatology.eu/article/S0168-8278(18)31966-4/fulltext
- ↑ 25.0 25.1 Caraceni P, Riggio O, Angeli P, et al. Long-term albumin administration in decompensated cirrhosis (ANSWER): An open-label randomised trial. Lancet 2018 May 31; PMID: https://www.ncbi.nlm.nih.gov/pubmed/29861076 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)30840-7/fulltext
Garcia-Tsao G. Long-term albumin in cirrhosis: Is it the ANSWER? Lancet 2018 May 31 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29861077 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)30948-6/fulltext - ↑ 26.0 26.1 Tapper EB, arikh ND. Mortality due to cirrhosis and liver cancer in the United States, 1999-2016: Observational study. BMJ 2018 Jul 18; 362:k2817 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30021785 Free PMC Article
- ↑ 27.0 27.1 27.2 27.3 27.4 Northup PG, Friedman LS, Kamath PS. AGA Clinical practice update: Surgical risk assessment and perioperative management in cirrhosis. Clin Gastroenterol Hepatol 2018 Sep 28; PMID: https://www.ncbi.nlm.nih.gov/pubmed/30273751 https://www.cghjournal.org/article/S1542-3565(18)31075-9/pdf
- ↑ 28.0 28.1 28.2 Santos LA, Romeiro FG. Diagnosis and Management of Cirrhosis-Related Osteoporosis. Biomed Res Int. 2016;2016:1423462. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27840821 Free PMC Article
- ↑ Long B, Koyfman A. The emergency medicine evaluation and management of the patient with cirrhosis. Am J Emerg Med. 2018 Apr;36(4):689-698. Epub 2017 Dec 23. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29290508
- ↑ 30.0 30.1 30.2 30.3 O'Leary JG, Greenberg CS, Patton HM, Caldwell SH. Coagulation in cirrhosis. Gastroenterology 2019 Apr 12 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30986390 https://www.gastrojournal.org/article/S0016-5085(19)35694-X/pdf
- ↑ 31.0 31.1 Rosenblatt R, Tafesh Z, Shen N et al. Early paracentesis in high-risk hospitalized patients: Time for a new quality indicator. Am J Gastroenterol 2019 Dec; 114:1863-69. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31688022 https://insights.ovid.com/crossref?an=00000434-201912000-00011
- ↑ 32.0 32.1 Komolafe O, Roberts D, Freemasn SC et al. Antibiotic prophylaxis to prevent spontaneous bacterial peritonitis in people with liver cirrhosis: A network meta-analysis. Cochrane Database Syst Rev 2020 Jan 16; 1:CD013125 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31978256 https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013125.pub2/ful
- ↑ 33.0 33.1 33.2 33.3 33.4 China L, Freemantle N, Forrest E et al. A randomized trial of albumin infusions in hospitalized patients with cirrhosis. N Engl J Med 2021 Mar 4; 384:808 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33657293 https://www.nejm.org/doi/10.1056/NEJMoa2022166
- ↑ 34.0 34.1 Klinge M, Coppler T, Liebschutz JM et al The assessment and management of pain in cirrhosis. Curr Hepatol Rep. 2018 Mar;17(1):42-51. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29552453 PMCID: PMC5849403 Free PMC article
- ↑ 35.0 35.1 35.2 35.3 35.4 35.5 35.6 35.7 35.8 35.9 NEJM Knowledge+ Gastroenterology
- ↑ de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C; Baveno VII Faculty. Baveno VII - Renewing consensus in portal hypertension. J Hepatol. 2022 Apr;76(4):959-974. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35120736 Review.
- ↑ 37.0 37.1 Sharma BC, Sharma P, Lunia MK et al A randomized, double-blind, controlled trial comparing rifaximin plus lactulose with lactulose alone in treatment of overt hepatic encephalopathy. Am J Gastroenterol. 2013 Sep;108(9):1458-63. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23877348
- ↑ 38.0 38.1 NEJM Knowledge+ Question of the Week. Oct 3, 2023 https://knowledgeplus.nejm.org/question-of-week/1681/
- ↑ 39.0 39.1 Glal KAM, El-Haggar SM, Abd-Elsalam SM et al. Allopurinol Prevents Cirrhosis-Related Complications: A Quadruple Blind Placebo- Controlled Trial. Am J Med. 2023 Oct 11:S0002-9343(23)00607-1. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37832758
- ↑ 40.0 40.1 Garcia-Tsao G et al. AGA clinical practice update on the use of vasoactive drugs and intravenous albumin in cirrhosis: Expert review. Gastroenterology 2024 Jan; 166:202. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37978969 https://www.gastrojournal.org/article/S0016-5085(23)05143-0/fulltext