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cirrhosis

A condition of the liver characterized by parenchymal necrosis, regenerating nodules, & fibrosis. Etiology: 1) alcohol abuse 2) infectious etiologies a) viral hepatitis: hepatitis B, hepatitis C, hepatitis D b) schistosomiasis c) tertiary syphilis 3) metabolic disorders a) alpha-1 antitrypsin deficiency b) hemochromatosis c) Wilson's disease 4) biliary cirrhosis: a) primary biliary cirrhosis b) secondary biliary cirrhosis - primary sclerosing cholangitis 5) pharmacologic agents a) amiodarone b) isoniazid c) methotrexate d) methyldopa e) oral contraceptives 6) toxins: carbon tetrachloride 7) malnutrition a) gastroplasty b) jejunoileal bypass 8) cardiac a) right-sided heart failure b) tricuspid insufficiency Epidemiology: 1) 12th leading cause of mortality among adults USA 2) 5th leading cause of death in adults 45-54 years USA 3) cirrhosis-related deaths increased by 3.4% annually from 2009-2016 [26] Clinical manifestations: 1) easy bruising 2) fatigue, malaise 3) weight loss 4) clubbing 5) gynecomastia 6) hepatomegaly a) palpable liver b) end stage, the liver is often small & hard 7) jaundice 8) parotid gland enlargement 9) muscle wasting 10) testicular atrophy 11) cutaneous stigmata a) palmar erythema b) spider angioma c) loss of fingernail lunulae d) dilated abdominal veins 12) stigmata of portal hypertension a) abdominal collateral veins (caput medusae) b) ascites: bloody ascites fluid suggests carcinoma c) encephalopathy d) esophageal varices e) hemorrhoids f) splenomegaly; palpable spleen 13) central nervous system stigmata a) impaired mental status (hepatic encephalopathy) b) confusion or agitation c) hyperreflexia d) asterixis 14) abdominal bruit or friction rub suggests carcinoma 15) signs & symptoms of primary etiology of cirrhosis a) arthropathy b) dermatitis c) Dupuytren's contracture d) dysrhythmia e) ecchymosis f) glossitis g) hyperpigmentation h) Kayser-Fleischer ring i) neurologic abnormality j) xanthelasma k) xanthoma Diagnostic criteria: - small non-palpable liver - splenomegaly - spider telangiectasias (spider angioma) - hepatic synthetic dysfunction - pancytopenia - RUQ abdominal ultrasound findings [35] Laboratory: 1) 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 (INR 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) - anemia [42] - thrombocytopenia due to splenomegaly - platelet count does not predict risk of unprovoked bleeding [23] - increased bleeding time greater than expected from degree of thrombocytopenia - ammonia in plasma [42] - 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 - [serum albumin] - [ascitic fluid albumin] > 1.1 2) tests for specific etiologies a) alpha-1 antitrypsin deficiency - serum alpha-1 antitrypsin - blood group P1 typing b) hemochromatosis - serum iron - serum ferritin - total iron binding capacity - transferrin saturation c) primary biliary cirrhosis - anti-mitochondrial antibodies - antinuclear antibodies d) viral hepatitis - hepatitis serology - hepatitis A serology - hepatitis B serology - hepatitis C serology - hepatitis D serology e) Wilson's disease - serum ceruloplasmin - serum copper, urine copper 3) liver biopsy 4) see ARUP consult [8] Special laboratory: - 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: 1) abdominal CT a) radiodensity of hepatic parenchyma b) contrast studies can highlight vascular lesions c) 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] 2) abdominal ultrasound (see hepatobiliary ultrasonography) a) high mean flow velocity through hepatic artery predicts poor response to beta-blocker therapy [5] b) screen for hepatocellular carcinoma every 6 months [2] - if positive, gadolinium contrast MRI (rather than liver biopsy) [2] c) assess for ascites 3) hepatic transient elastography (Fibroscan) - estimates risk for portal hypertension & esophageal varices (see management) [35] - 1st priority after abdominal ultrasound [35] 4) magnetic resonance imaging a) delineates vascular lesion b) double contrast material-enhanced MRI may identify fibrosis [5] c) differentiation of regenerating nodules in cirrhosis from hepatocellular carcinoma d) gadolinium-contrast MRI suffcient for diagnosis of hepatocellular carcinoma; biopsy not needed [2] 5) cholangiography for primary sclerosing cholangitis 6) bone mineral density: risk for osteoporosis, especially if taking glucocorticoids [2] prior to liver transplantation [2] Complications: 1) ascites (most common) 50% of patients within 10 years [2] 2) hepatic encephalopathy - covert hepatic encephalopathy [42] - prevalence increases with worsening cirrhosis - 29%, 46%, & 62% for Child-Pugh class A, B, & C cirrhosis, respectively - most common in patients with cirrhosis due to - alcohol (46%) or viral hepatitis (41%) - least common in patients with cirrhosis due to - metabolic dysfunction-associated steatotic liver disease (35%) - autoimmune liver disease (27%) - associated with laboratory markers of cirrhosis severity, but none predictive [42] 3) predisposition to infection a) bacterial peritonitis b) recurring bacterial cholangitis c) common pathogens 1] bacteria a] Streptococcus pneumonia b] Listeria monocytogenes c] Vibrio vulnificus d] Pasteurella multocida e] Yersinia enterocolitica f] Capnocytophaga 2] fungi: Zygomycetes (mucormycosis) d) proton pump inhibitors increase risk [16] e) prophylaxis for spontaneous bacterial peritonitis may result in selection of resistant pathogens [16] 4) sepsis & septic shock [11] 5) esophageal varices & variceal hemorrhage 6) hepatic failure - acute-on-chronic liver failure [14] - jaundice - ascites 7) hepatoma, hepatocellular carcinoma a) cumulative 5-year risk of hepatocellular carcinoma in patients with alcoholic cirrhosis is 1%, accounting for < 3% of deaths [9] b) 80% of hepatocellular carcinomas occur in patients with cirrhosis [2] 8) 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] 9) hepatopulmonary syndrome [2] 10) portopulmonary syndrome [2] 10) hepatic osteodystrophy [7], osteoporosis [2,28] 11) portal vein thrombosis [2] 12) increased risk of stroke (2-fold) - increased risk especially hemorrhagic stroke [22] - intracerebral hemorrhage, subarachnoid hemorrhage Management: 1) general: supportive therapy a) prevention & treatment of hepatic encephalopathy - lactulose [2] - combination of lactulose plus rifaximin improves outcomes [35,37] - avoid proton pump inhibitors in patients with ascites [21] - high-dose proton pump inhibitors are associated with higher mortality in patients with cirrhosis [41] - IV albumin of no benefit [33] - probiotics may mitigate hepatic encephalopathy [43] b) 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: - propranolol, naldolol, or carvedilol - 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] c) 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] d) 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) - long-term IV albumin may confer survival advantage [25] - IV albumin of no benefit [33] - fluid restriction is not recommended in patients with cirrhosis & ascites [38] e) dietary sodium restriction & diuresis for transudative pleural effusion f) 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] g) 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] h) screen for hepatocellular carcinoma - ultrasound every 6 months [2] - serum alpha-fetoprotein every 6 months - unnecessary with ultrasound [35] i) hospital readmission is common - 37% within 1 month [7] - careful discharge planning can diminish rates of rehospitalization - common reasons for rehospitalization - inappropriate titration of lactulose - failure to recognize hypovolemia after a change in diuretic dosage [7] j) avoid proton pump inhibitors in patients with decompensated cirrhosis - increased risk of hepatic encephalopathy & bacterial peritonitis [16,21] - high-dose proton pump inhibitors are associated with higher mortality in patients with cirrhosis [41] - H2 receptor antagonists appear to be safe alternative [10] k) avoid NSAIDs [24] l) pain management in hospitalized patients - low dose IV hydromorphone or low-dose IV fentanyl safest options [34] 2) management of specific etiologies a) alcoholic liver disease: abstinence from alcohol b) alpha-1 antitrypsin deficiency: - liver transplantation is curative c) hemochromatosis - phlebotomy for removal of iron - chelation therapy - deferoxamine (Desferal) - ascorbic acid d) primary biliary cirrhosis - ursodeoxycholic acid (ursodiol [Actigall]) - liver transplantation is curative e) secondary biliary cirrhosis - relief of biliary obstruction by ERCP or surgery f) Wilson's disease - penicillamine (Cuprimine) - trientine - zinc sulfate - liver transplantation is curative 3) 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] 4) referral for liver transplantation a) abstinence for alcohol or other drug abuse b) hepatic encelphalopathy c) complications from ascites d) variceal bleeding e) 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] e) decompensated cirrhosis - ascites, jaundice, hepatocellular carcinoma, hepatorenal syndrome, variceal hemorrhage, spontaneous bacterial peritonitis, hepatic encephalopathy [2] 5) preventive medicine a) vaccinations: - hepatitis A vaccine - hepatitis B vaccine - pneumococcal vaccination (PPSV-23 & PCV-13) - annual influenza virus vaccine - Herpes zoster vaccine - avoid live virus vaccines [2] b) screen for osteoporosis, treat with bisphophonate [2,28] 6) patient education - increased potential for drug adverse effects - avoid alcohol, opiates, NSAIDs [24] & raw shellfish [2] - appropriate nutrition needed to avoid catabolic effects of cirrhosis [2]

Interactions

disease interactions

Related

bacterial peritonitis (BP) Child-Pugh classification of cirrhosis coagulopathy of liver disease hematologic complications of hepatocellular failure hepatic encephalopathy hepatitis hepatobiliary ultrasonography liver transplantation

Specific

alcoholic cirrhosis alpha-1 antitrypsin deficiency biliary cirrhosis Cruveilhier-Baumgarten syndrome cryptogenic cirrhosis familial cirrhosis & hepatitis hemochromatosis North American Indian childhood cirrhosis (NAIC)

General

chronic liver disease hepatic fibrosis liver (hepatic) failure/insufficiency

References

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