Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 16-11: Cirrhosis + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Result of injury that leads to both fibrosis and regenerating nodules May be reversible if cause is removed The clinical features result from hepatic cell dysfunction, portosystemic shunting, and portal hypertension +++ General Considerations ++ The most common histologic classification of cirrhosis is micronodular, macronodular, and mixed forms Each form may be seen at different stages of the disease Risk factors Chronic viral hepatitis Alcohol Drug toxicity Autoimmune and metabolic liver diseases, including nonalcoholic fatty liver disease Miscellaneous disorders Gluten enteropathy appears to be associated with an increased risk of cirrhosis Many patients have more than one risk factor (eg, chronic hepatitis and alcohol use) and likely a genetic predisposition Three clinical stages Compensated Compensated with varices Decompensated (ascites, variceal bleeding, encephalopathy, or jaundice) Acute-on-chronic liver failure Should be diagnosed in a patient with chronic cirrhosis and acute decompensation, which is defined as New or worsening ascites Gastrointestinal hemorrhage, including variceal hemorrhage Overt hepatic encephalopathy Worsening nonobstructive jaundice Bacterial infection associated with another organ failure Precipitating factors include Infections Hemodynamic instability Heavy alcohol use Drug hepatotoxicity +++ Micronodular cirrhosis ++ Regenerating nodules are < 1 mm Typical of alcoholic liver disease (Laennec cirrhosis) +++ Macronodular cirrhosis ++ Characterized by larger nodules, up to several centimeters in diameter, which may contain central veins Corresponds to postnecrotic (posthepatitic) cirrhosis; but may not always follow identifiable episodes of massive necrosis and stromal collapse +++ Demographics ++ Eleventh leading cause of death globally Eighth leading cause of death in the United States with a prevalence rate of 0.27% Mexican Americans and African Americans have a higher frequency of cirrhosis than whites because of a higher rate of risk factors + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Can be asymptomatic for long periods Symptoms may be insidious or, less often, abrupt Fatigue, disturbed sleep, muscle cramps, anorexia, and weight loss are common Nausea and occasional vomiting Reduced muscle strength and exercise capacity Jaundice—usually not an initial sign—is mild at first, increasing in severity Abdominal pain from hepatic enlargement and stretching of Glisson capsule or from ascites Hematemesis is the presenting symptom in 15–25% Fever Present in up to 35% Usually reflects associated alcoholic hepatitis, spontaneous bacterial peritonitis, or intercurrent infection Amenorrhea in women Erectile dysfunction, loss of libido, sterility, and gynecomastia in men In 70% of cases, the liver is enlarged and firm with a palpable sharp or nodular edge; the left lobe may predominate Splenomegaly occurs in 35–50% Ascites, pleural effusions, peripheral edema, and ecchymoses are late findings Relative adrenal insufficiency appears common in advanced cirrhosis, even in absence of sepsis +++ Encephalopathy ++ Characterized by Day–night reversal Asterixis Tremor Dysarthria Delirium Drowsiness Coma Occurs late except when precipitated by an acute hepatocellular insult or an episode of gastrointestinal bleeding or infection +++ Skin ++ Spider telangiectasias on the upper half of the body Palmar erythema, Dupuytren contractures Glossitis and cheilosis from vitamin deficiencies are common Dilated superficial veins of the abdomen and thorax that fill from below when compressed +++ Differential Diagnosis ++ Chronic viral hepatitis Alcoholism Nonalcoholic fatty liver disease Cryptogenic cirrhosis Hemochromatosis Alpha-1-antiprotease deficiency Wilson disease Gluten enteropathy Primary biliary cholangitis Secondary biliary cirrhosis Chronic obstruction due to stone, stricture, neoplasm Heart failure or constrictive pericarditis Hereditary hemorrhagic telangiectasia + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ Laboratory abnormalities are either absent or minimal in early or compensated cirrhosis Anemia Usually macrocytic, from suppression of erythropoiesis by alcohol, and folate deficiency; normocytic, from hemolysis, acute blood loss from the GI tract; and microcytic, from hypersplenism, chronic blood loss from the GI tract White blood cell count May be low, reflecting hypersplenism May be high, suggesting infection Thrombocytopenia is secondary to Alcoholic marrow suppression Sepsis Folate deficiency Splenic sequestration Prolongation of the prothrombin time from reduced levels of clotting factors Modest elevations of serum aspartate aminotransferase (AST) and alkaline phosphatase and progressive elevation of serum bilirubin Serum albumin is low Gamma-globulin levels are increased and may be as high as in autoimmune hepatitis Vitamin D deficiency has been reported in 91% of patients with cirrhosis Patients with alcoholic cirrhosis may have elevated serum cardiac troponin I and B-type natriuretic peptide levels Combinations of tests (eg, AST and platelet count) are under study for predicting cirrhosis in patients with chronic liver diseases such as chronic hepatitis C See Ascites; or Peritonitis, Spontaneous Bacterial +++ Imaging Studies ++ Ultrasonography Can assess liver size and detect ascites or hepatic nodules, including small hepatocellular carcinomas Together with Doppler studies, may establish patency of the splenic, portal, and hepatic veins Hepatic nodules can be characterized by contrast-enhanced CT or MRI Nodules suspicious for malignancy may be biopsied under ultrasound or CT guidance +++ Diagnostic Procedures ++ Esophagogastroduodenoscopy confirms the presence of varices and detects specific causes of bleeding Liver biopsy may be performed by Laparoscopy Transjugular or endoscopic ultrasonographic approach in patients with coagulopathy and ascites Wedged hepatic vein pressure measurement may establish the presence and cause of portal hypertension + Treatment Download Section PDF Listen +++ +++ Medications +++ Ascites and edema ++ Restrict sodium intake to 400–800 mg/day Restrict fluid intake (800–1000 mL/day) for hyponatremia (sodium < 125 mEq/L) Ascites may rapidly decrease on bed rest and dietary sodium restriction alone Use spironolactone (usually with furosemide) if there is no response to salt restriction The initial dose of spironolactone is 100 mg daily orally Dose may be increased by 100 mg every 3–5 days (up to a maximal conventional daily dose of 400 mg/day, though higher doses have been used) until diuresis is achieved, typically preceded by a rise in the urinary sodium concentration Monitor for hyperkalemia Substitute amiloride, 5–10 mg daily orally, if painful gynecomastia develops from spironolactone Diuresis can be augmented with the addition of furosemide, 40–160 mg daily orally. Monitor blood pressure, urinary output, mental status, and serum electrolytes, especially potassium +++ Anemia ++ Iron deficiency anemia: ferrous sulfate, 0.3 g enteric-coated tablets, three times daily orally after meals Macrocytic anemia associated with alcoholism: folic acid, 1 mg once daily orally Packed red blood cell transfusions may be necessary to replace blood loss from variceal, other GI hemorrhage +++ Hemorrhagic tendency ++ Treat severe hypoprothrombinemia with vitamin K (eg, phytonadione, 5 mg once daily orally or subcutaneously) If this treatment is ineffective, use large volumes of fresh frozen plasma. Because the effect is transient, plasma infusions are indicated only for active bleeding or before an invasive procedure Use of recombinant factor VII may be an alternative +++ Surgery ++ Liver transplantation is indicated in selected cases of irreversible, progressive liver disease Absolute contraindications include Malignancy (except small hepatocellular carcinomas in a cirrhotic liver) Sepsis Advanced cardiopulmonary disease (except hepatopulmonary syndrome) +++ Therapeutic Procedures ++ Abstinence from alcohol is most important Diet Should have adequate calories (20–40 kcal/kg /day body weight per day depending on the patient's body mass index and the presence or absence of malnutrition) Should include protein 1.2–1.5 g/kg/day depending on the presence or absence of malnutrition) and, if there is fluid retention, sodium restriction For hepatic encephalopathy, protein intake should be reduced to 60–80 g/day Vitamin supplementation is desirable L-carnitine, 300 mg orally four times a day, may help muscle cramps Patients should receive following vaccines HAV, HBV Pneumococcal Influenza (yearly) The goal of weight loss with ascites without associated peripheral edema should not exceed 0.5–0.7 kg/day Large-volume paracentesis (> 5 L) is effective in patients with Massive ascites and respiratory compromise Ascites refractory to diuretics Intolerable diuretic side effects Transjugular intrahepatic portosystemic shunt (TIPS) In refractory ascites, reduces ascites recurrence and the risk of hepatorenal syndrome Preferred to peritoneovenous shunts because of the high rate of its associated complications Increases the risk of hepatic encephalopathy compared with repeated large-volume paracentesis + Outcome Download Section PDF Listen +++ +++ Complications ++ Upper GI tract bleeding may occur from Varices Portal hypertensive gastropathy Gastroduodenal ulcer Portal vein thrombosis, which also causes varices Liver failure may be precipitated by alcoholism, surgery, and infection The risk of carcinoma of the liver is increased greatly in patients with cirrhosis Hepatic Kupffer cell (reticuloendothelial) dysfunction and decreased opsonic activity lead to an increased risk of systemic infection Osteoporosis +++ Prognosis ++ Prognostic scoring systems for cirrhosis include the Child-Pugh score (Table 16–8) and the Model for End-Stage Liver Disease (MELD) score MELD is used to determine priorities for liver transplantation In patients with a low MELD score (< 21), a low serum sodium concentration (< 130 mEq/L), an elevated hepatic venous pressure gradient, and persistent ascites predict a high mortality rate Only 50% of patients with severe hepatic dysfunction (serum albumin < 3 g/dL, bilirubin > 3 mg/dL, ascites, encephalopathy, cachexia, and upper GI bleeding) survive 6 months Long-term intravenous administration of albumin has been reported to improve 18-month survival in patients with cirrhotic ascites The risk of death is associated with Muscle wasting Age ≥ 65 years Mean arterial pressure ≤ 82 mm Hg Renal failure Cognitive dysfunction Ventilatory insufficiency Prothrombin time ≥ 16 seconds Delayed and suboptimal treatment of sepsis Secondary infections Liver transplantation has markedly improved survival, particularly for patients referred for evaluation early ++Table Graphic Jump LocationTable 16–8.Child-Pugh and Model for End-Stage Liver Disease (MELD) scoring systems for staging cirrhosis.View Table||Download (.pdf) Table 16–8. Child-Pugh and Model for End-Stage Liver Disease (MELD) scoring systems for staging cirrhosis. Child-Pugh Scoring System Parameter Numerical Score 1 2 3 Ascites None Slight Moderate to severe Encephalopathy None Slight to moderate Moderate to severe Bilirubin, mg/dL (mcmol/L) < 2.0 (34.2) 2–3 (34.2–51.3) > 3.0 (51.3) Albumin, g/dL (g/L) > 3.5 (35) 2.8–3.5 (28–35) < 2.8 (28) Prothrombin time (seconds increased) 1–3 4–6 > 6.0 Total Numerical Score and Corresponding Child-Pugh Class Score Class 5–6 A 7–9 B 10–15 C MELD Scoring System Original MELD = 11.2 loge (INR) + 3.78 loge (bilirubin [mg/dL]) + 9.57 loge (creatinine [mg/dL]) + 6.43. (Range 6–40.) The MELD-Na score was developed in 2016 by adding the serum sodium as a component: MELD-Na = MELD + (140 – Na) × (1 – 0.025 × MELD). INR, international normalized ratio. +++ When to Refer ++ For liver biopsy When the MELD score is ≥ 14 For upper endoscopy to screen for gastroesophageal varices +++ When to Admit ++ Gastrointestinal bleeding Stage 3–4 hepatic encephalopathy Worsening kidney function Severe hyponatremia Serious infection Profound hypoxia + References Download Section PDF Listen +++ + +Adebayo D et al. Refractory ascites in liver cirrhosis. Am J Gastroenterol. 2019 Jan;114(1):40–7. [PubMed: 29973706] + +Angeli P et al. News in pathophysiology, definition and classification of hepatorenal syndrome: a step beyond the International Club of Ascites (ICA) consensus document. J Hepatol. 2019 Oct;71(4):811–22. [PubMed: 31302175] + +Asrani SK et al. Burden of liver diseases in the world. J Hepatol. 2019 Jan;70(1):151–71. [PubMed: 30266282] + +Bajaj JS et al. Acute-on-chronic liver failure: getting ready for prime time? Hepatology. 2018 Oct;68(4):1621–32. [PubMed: 29689120] + +Carey EJ et al. A North American expert opinion statement on sarcopenia in liver transplantation. Hepatology. 2019 Nov;70(5):1816–29. [PubMed: 31220351] + +Carrion AF et al. Renal dysfunction in cirrhotic patients. Am J Gastroenterol. 2019 Sep;114(9):1407–10. [PubMed: 31397680] + +European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018 Aug;69(2):406–60. [PubMed: 29653741] + +European Association for the Study of the Liver. EASL Clinical Practice Guidelines on nutrition in chronic liver disease. J Hepatol. 2019 Jan;70(1):172–93. [PubMed: 30144956] + +Kaplan DE et al; VOCAL Study Group. Effects of hypercholesterolemia and statin exposure on survival in a large national cohort of patients with cirrhosis. Gastroenterology. 2019 May;156(6):1693–706. [PubMed: 30660733] + +Martin Mateos R et al. Sepsis in patients with cirrhosis awaiting liver transplantation: new trends and management. Liver Transpl. 2019 Nov;25(11):1700–9. [PubMed: 31408581] + +O'Leary JG et al. AGA Clinical Practice Update: coagulation in cirrhosis. Gastroenterology. 2019 Jul;157(1):34–43. [PubMed: 30986390] + +Simonetto DA et al. Management of sepsis in patients with cirrhosis: current evidence and practical approach. Hepatology. 2019 Jul;70(1):418–28. [PubMed: 30516866] + +Ufere NN et al. Physicians' perspectives on palliative care for patients with end-stage liver disease: a national survey study. Liver Transpl. 2019 Jun;25(6):859–69. [PubMed: 30963669]