INTRODUCTION — Cirrhosis represents a late stage of progressive hepatic fibrosis characterized by distortion of the hepatic architecture and the formation of regenerative nodules. It is generally considered to be irreversible in its advanced stages, at which point the only option may be liver transplantation. In earlier stages, specific treatments aimed at the underlying cause of liver disease may improve or even reverse cirrhosis.
Patients with cirrhosis are susceptible to a variety of complications, and their life expectancy can be markedly reduced. Cirrhosis accounted for approximately 49,500 deaths and was the eighth leading cause of death in the United States in 2010 . In addition, there were an estimated 19,500 deaths due to liver cancer, which often occurs in the setting of cirrhosis. Similarly, a study that used data from the National Death Index from the Centers for Disease Control and Prevention and the Rochester Epidemiology Project estimated that liver disease was responsible for 66,007 deaths in 2008, of which 18,175 were due to hepatobiliary cancer .
This topic will review the complications, general management, and prognosis of cirrhosis. An overview of the causes and diagnosis of cirrhosis is presented separately. (See "Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis".)
MAJOR COMPLICATIONS — Major complications of cirrhosis include (table 1):
●Spontaneous bacterial peritonitis
Once these complications develop, patients are considered to have decompensated cirrhosis. Multiple factors can predispose to decompensation in a patient with cirrhosis. Risk factors for decompensation include bleeding, infection, alcohol intake, medications, dehydration, and constipation [3-5]. In addition, patients with obesity are at increased risk for decompensation . Once decompensation has developed, patients should be considered for liver transplantation. (See "Liver transplantation in adults: Patient selection and pretransplantation evaluation" and "Liver transplantation in adults: Patient selection and pretransplantation evaluation", section on 'Cirrhosis'.)
Other major complications of cirrhosis include portal vein thrombosis and cardiomyopathy. However, patients with these complications alone are not considered to have decompensated cirrhosis.
This section provides an overview of the complications of cirrhosis. The individual complications are discussed in detail in their respective topic reviews.
Complications of portal hypertension — Many of the complications of cirrhosis are the result of portal hypertension (increased pressure within the portal venous system). This can lead to the formation of venous collaterals (varices) as well as circulatory, vascular, functional, and biochemical abnormalities that contribute to the pathogenesis of ascites and other complications. (See "Portal hypertension in adults" and "Pathogenesis of ascites in patients with cirrhosis", section on 'Portal hypertension'.)
Complications of portal hypertension include:
●Spontaneous bacterial peritonitis
●Portal hypertensive gastropathy
Variceal hemorrhage — Patients with variceal hemorrhage typically present with hematemesis and/or melena. It is typically treated with endoscopic variceal band ligation. Other treatments include endoscopic sclerotherapy and placement of a transjugular intrahepatic portosystemic shunt (TIPS). (See "General principles of the management of variceal hemorrhage".)
Variceal hemorrhage is associated with high mortality rates. In the past, the mortality rate of a single variceal hemorrhage was 30 percent, and only one-third of patients survived for one year [7,8]. Although survival has improved with modern techniques for controlling variceal hemorrhage, mortality rates remain high (15 to 20 percent 30-day mortality) .
Portal hypertensive gastropathy — Portal hypertensive gastropathy (congestive gastropathy), while extremely common in patients with portal hypertension, is an uncommon cause of significant bleeding in these patients. When portal hypertensive gastropathy is the sole cause of bleeding, there is diffuse mucosal oozing with no other lesions, such as varices, to account for the GI bleeding and anemia. The mucosa is friable, and bleeding presumably occurs when the ectatic vessels rupture. The severity of gastropathy is related to the level of portal pressure, the level of hepatic vascular resistance, and the degree of reduction in hepatic blood flow (See "Portal hypertensive gastropathy".)
Ascites — Ascites is the accumulation of fluid within the peritoneal cavity. It is the most common complication of cirrhosis. The first step leading to fluid retention and ultimately ascites in patients with cirrhosis is the development of portal hypertension. Patients without portal hypertension do not develop ascites or edema. Those with ascites have several circulatory, vascular, functional, and biochemical abnormalities that contribute to the pathogenesis of fluid retention. (See "Pathogenesis of ascites in patients with cirrhosis".)
Ascites is typically treated with a combination of diuretics and sodium restriction, though some patients require repeated therapeutic paracenteses or TIPS placement. Among patients with refractory ascites or spontaneous bacterial peritonitis, the use of nonselective beta blockers may be associated with increased mortality [10,11]. This may occur because failure to maintain an adequate mean arterial blood pressure is strongly correlated with survival in patients with advanced cirrhosis. (See "Ascites in adults with cirrhosis: Initial therapy" and "Ascites in adults with cirrhosis: Diuretic-resistant ascites", section on 'Discontinuing beta blockers' and 'Decompensated cirrhosis' below and "Spontaneous bacterial peritonitis in adults: Treatment and prophylaxis", section on 'Discontinue nonselective beta blockers'.)
Spontaneous bacterial peritonitis — Spontaneous bacterial peritonitis (SBP) is an infection of preexisting ascitic fluid without evidence for an intra-abdominal secondary source, such as a perforated viscus. SBP is almost always seen in the setting of end-stage liver disease. Clinical manifestations of SBP include fever, abdominal pain, abdominal tenderness, and altered mental status. Some patients are asymptomatic and present with only mild laboratory abnormalities. (See "Spontaneous bacterial peritonitis in adults: Clinical manifestations".)
The index of suspicion for SBP must be high with a low threshold for diagnostic paracentesis. The diagnosis is established by a positive ascitic fluid bacterial culture and/or an elevated ascitic fluid absolute polymorphonuclear leukocyte count (≥250 cells/mm3). Without early antibiotic treatment, mortality is high. (See "Spontaneous bacterial peritonitis in adults: Diagnosis" and "Spontaneous bacterial peritonitis in adults: Treatment and prophylaxis".)
Hepatorenal syndrome — Hepatorenal syndrome refers to the development of renal failure in a patient who has advanced liver disease due to cirrhosis, severe alcoholic hepatitis, acute liver failure, or less often, a metastatic tumor. Rather than being a new disease, hepatorenal syndrome usually represents the end-stage of a sequence of reductions in renal perfusion induced by increasingly severe hepatic injury. Arterial vasodilatation in the splanchnic circulation, which is triggered by portal hypertension, appears to play a central role in the hemodynamic changes and the decline in renal function in hepatorenal syndrome. The initial reductions in glomerular filtration rate are often masked clinically since associated decreases in muscle mass and hepatic urea production minimize elevations in the plasma creatinine concentration and blood urea nitrogen. (See "Hepatorenal syndrome", section on 'Pathogenesis'.)
Hepatorenal syndrome is characterized by a generally benign urine sediment, a very low rate of sodium excretion, and a progressive rise in the plasma creatinine concentration. There is some confusion regarding the presence or absence of oliguria. The percentage of patients with oliguria depends upon the cut-off for defining oliguria. If the cutoff is 400 mL/day, only 44 percent of patients are oliguric. If 500 mL/day is used, approximately two-thirds are oliguric. (See "Hepatorenal syndrome", section on 'Clinical presentation'.)
The diagnosis is one of exclusion, being made when other causes of renal dysfunction have been excluded. In particular, volume depletion (as with overly rapid diuresis) can mimic all of the findings of hepatorenal syndrome. The prognosis is poor unless hepatic function improves or a liver transplantation is performed. (See "Hepatorenal syndrome", section on 'Diagnosis' and "Hepatorenal syndrome", section on 'Treatment'.)
Hepatic hydrothorax — Hepatic hydrothorax is defined as the presence of a pleural effusion in a patient with cirrhosis and no evidence of underlying cardiopulmonary disease. It results from the movement of ascitic fluid into the pleural space through defects in the diaphragm, and it is usually right-sided. (See "Hepatic hydrothorax".)
The treatment for hepatic hydrothorax includes diuretics and sodium restriction. Patients who do not respond to conservative therapy may require repeated therapeutic thoracenteses or TIPS. The most important aspect of management is evaluation for liver transplantation (algorithm 1). Chest tubes should not be placed in patients with hepatic hydrothorax. Placement of chest tubes in this setting can result in massive protein and electrolyte depletion, infection, renal failure, and bleeding.
Hepatopulmonary syndrome — Hepatopulmonary syndrome (HPS) is defined by the following triad (see "Hepatopulmonary syndrome in adults: Prevalence, causes, clinical manifestations, and diagnosis"):
●Increased alveolar-arterial gradient while breathing room air
●Evidence for intrapulmonary vascular abnormalities, referred to as intrapulmonary vascular dilatations
Estimates of the prevalence of HPS among patients with chronic liver disease range from 4 to 47 percent, depending on the diagnostic criteria and methods used. Even in those without HPS, mild hypoxemia is common and is presumably caused by ascites, with resulting diaphragmatic elevation and ventilation/perfusion mismatch. There are no effective medical therapies for HPS. Liver transplantation offers the most promise for successful treatment. (See "Hepatopulmonary syndrome in adults: Natural history, treatment, and outcomes".)
Portopulmonary hypertension — Portal hypertension-associated pulmonary hypertension (portopulmonary hypertension) refers to the presence of pulmonary hypertension in patients with portal hypertension. The prevalence in patients with cirrhosis is approximately 2 percent . Neither the prevalence nor the severity of portopulmonary hypertension appears to correlate with the degree of portal hypertension . (See "Portopulmonary hypertension".)
Patients with portopulmonary hypertension may present with fatigue, dyspnea, peripheral edema, chest pain, and syncope. The diagnosis may be suggested by echocardiography and confirmed by right heart catheterization. Patients with moderate to severe portopulmonary hypertension are difficult to treat with medical therapy, and the perioperative mortality with liver transplantation is high.
Cirrhotic cardiomyopathy — Up to 50 percent of patients with advanced cirrhosis have features of cardiac dysfunction. The term "cirrhotic cardiomyopathy" has been used to describe such patients, who are characterized as having normal to increased cardiac output and contractility at rest, but a blunted response to pharmacologic, physiologic, or pathologic stress . Patients may also have electrophysiologic abnormalities. It is thought to be related to both portal hypertension and cirrhosis. Cardiomyopathy can occur from any cause of cirrhosis, although patients with alcoholism or hemochromatosis may have additional contributing causes to cardiac dysfunction. (See "Definition and classification of the cardiomyopathies", section on 'Cirrhotic cardiomyopathy' and "Causes and pathophysiology of high-output heart failure", section on 'Cirrhosis'.)
Hepatic encephalopathy — Hepatic encephalopathy describes the spectrum of potentially reversible neuropsychiatric abnormalities seen in patients with liver dysfunction. Disturbance in the diurnal sleep pattern (insomnia and hypersomnia) is a common early feature that typically precedes overt neurologic signs (figure 1 and figure 2). More advanced neurologic features include the presence of asterixis, hyperactive deep tendon reflexes, and, less commonly, transient decerebrate posturing. (See "Hepatic encephalopathy in adults: Clinical manifestations and diagnosis".)
Treatments for hepatic encephalopathy include addressing any predisposing conditions (eg, infection or gastrointestinal bleeding), synthetic disaccharides (eg, lactulose), and nonabsorbable antibiotics (eg, rifaximin). (See "Hepatic encephalopathy in adults: Treatment".)
Hepatocellular carcinoma — Patients with cirrhosis have a markedly increased risk of developing hepatocellular carcinoma (HCC). Patients with most forms of chronic hepatitis are not at an increased risk until cirrhosis develops. Exceptions to this rule are patients with chronic hepatitis B virus infection, who can develop HCC in the absence of cirrhosis. (See "Epidemiology and etiologic associations of hepatocellular carcinoma" and "Prevention of hepatocellular carcinoma and recommendations for surveillance in adults with chronic liver disease".)
Certain causes of cirrhosis appear to have a relatively increased risk for HCC. Patients with cirrhosis from hepatitis B, hepatitis C, nonalcoholic steatohepatitis, and hemochromatosis are at the highest risk, while those with cirrhosis from autoimmune hepatitis and Wilson disease appear to have a lower risk. (See "Epidemiology and etiologic associations of hepatocellular carcinoma", section on 'Chronic hepatitis and cirrhosis'.)
Because of the large functional reserve of the liver, patients with HCC are frequently asymptomatic early in its course, and the diagnosis is often delayed. Decompensation in a patient with previously compensated cirrhosis should raise the clinical suspicion that HCC has developed. Other common signs and symptoms of HCC are usually related to mass effect from the tumor and include pain, early satiety, obstructive jaundice, and a palpable mass. HCCs can rupture, causing hemoperitoneum. Paraneoplastic manifestations include erythrocytosis, hypercalcemia, hypoglycemia, and diarrhea. (See "Clinical features and diagnosis of primary hepatocellular carcinoma".)
The diagnosis of HCC may be suggested by marked elevations of serum alpha-fetoprotein (AFP) or by characteristic radiographic findings. Elevated AFP is not specific for HCC since it can also be seen in patients with acute or chronic hepatitis, gonadal tumors, and pregnancy. However, rising serum AFP levels in a patient with cirrhosis should raise clinical suspicion for HCC. However, a significant proportion of patients with HCC have normal AFP levels, especially when the tumor is small. As a result, a normal AFP does not preclude a diagnosis. (See "Clinical features and diagnosis of primary hepatocellular carcinoma".)
Portal vein thrombosis — Portal vein thrombosis can develop in patients with cirrhosis and contribute to the development of portal hypertension. In patients with cirrhosis, the pathogenesis is likely related to unbalanced hemostasis and slowing of portal flow. Treatment often involves anticoagulation, though the decision to anticoagulate must take into account the patient's risk for bleeding, particularly if esophageal varices are present. (See "Epidemiology and pathogenesis of portal vein thrombosis in adults", section on 'Pathogenesis' and "Acute portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management" and "Chronic portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management".)
GENERAL MANAGEMENT — The major goals of managing patients with cirrhosis include:
●Slowing or reversing the progression of liver disease
●Preventing superimposed insults to the liver
●Managing symptoms and laboratory abnormalities
●Preventing, identifying, and treating the complications of cirrhosis
●Determining the appropriateness and optimal timing for liver transplantation
Slowing or reversing the progression of liver disease — Although cirrhosis is generally considered to be irreversible in its advanced stages, the exact point at which it becomes irreversible is unclear [14,15]. Some chronic liver diseases respond to treatment even when the liver disease has progressed to cirrhosis. Thus, specific therapies directed against the underlying cause of the cirrhosis should be instituted.
●Patients with hepatitis C and advanced fibrosis or cirrhosis who achieve a sustained virologic response (SVR) with antiviral treatment have a lower risk of liver-related mortality compared with patients who do not achieve an SVR . (See "Patient evaluation and selection for antiviral therapy for chronic hepatitis C virus infection", section on 'Bridging fibrosis and compensated cirrhosis'.)
●Abstinence from alcohol substantially improves survival in alcoholic cirrhosis. (See "Prognosis and management of alcoholic fatty liver disease and alcoholic cirrhosis", section on 'Abstinence'.)
●Successful treatment of chronic viral hepatitis can improve long-term outcomes and may affect fibrosis. In a study of 91 patients with chronic hepatitis C and significant fibrosis based on liver elastography, patients who achieved a sustained virologic response had a significant decrease in liver stiffness (and thus presumably fibrosis) 24 weeks after the end of treatment . (See "Noninvasive assessment of hepatic fibrosis: Ultrasound-based elastography".)
Preventing superimposed insults to the liver
Vaccinations — Vaccination against hepatitis A and B for those who are not already immune can help prevent superimposed insults to the liver. Other vaccinations, such a yearly influenza vaccination, are also recommended (figure 3). (See "Immunizations for patients with chronic liver disease".)
Avoidance of hepatotoxins — Patients with cirrhosis should avoid medications, supplements, and other substances that are commonly associated with liver injury. This includes abused substances, such as alcohol, over-the-counter medications (such as nonsteroidal anti-inflammatory drugs), prescribed drugs with hepatotoxic side effects, and certain herbal remedies. (See "Drug-induced liver injury" and "Hepatotoxicity due to herbal medications and dietary supplements".)
Medication adjustments — Patients with cirrhosis are at increased risk of adverse events with many medications because of impaired hepatic metabolism or renal excretion. Many medications require dose adjustments or should be avoided entirely (table 3 and table 2) .
Issues related to the use of pain medications in patients with cirrhosis are discussed in detail elsewhere. (See "Management of pain in patients with advanced chronic liver disease or cirrhosis".)
Management of symptoms and laboratory abnormalities
Muscle cramps — Patients with cirrhosis may experience muscle cramps, which can be severe [19-22]. The cause is incompletely understood, although they may be related to a reduction in effective circulating plasma volume, nerve dysfunction, and alterations in energy metabolism . If other disorders are excluded, treatments that may be helpful include quinine sulfate, branched-chain amino acids, taurine, zinc repletion (for patients with low levels), and correction of electrolytes. We prefer quinine sulfate if patients are able to obtain it (200 to 300 mg at bedtime). (See "Nocturnal leg cramps", section on 'Causes and pathogenesis'.)
In patients suspected of having muscle cramps related to cirrhosis, other causes of pain should be excluded. Muscle cramping related to cirrhosis is often spontaneous, chronic, and nocturnal. If there is new onset of persistent pain, other disorders such as rhabdomyolysis, myositis, or acute kidney injury should be considered.
Quinine sulfate has been found to be beneficial for the treatment of muscle cramps in patients with cirrhosis, but it is no longer available through pharmacies for treatment of cramps because of side effects including arrhythmias and thrombocytopenia [24,25]. However, it is available through some online retailers. In a meta-analysis that included 409 patients who completed participation in randomized trials, tinnitus was the only side effect that occurred more often with quinine than with placebo. Quinine sulfate may act by reducing the excitability of the motor nerve . Note that quinine sulfate is not the same as quinidine sulfate (the latter being an antiarrhythmic drug). (See "Nocturnal leg cramps", section on 'Management'.)
Other treatments have shown some benefit in small studies. These include branched-chain amino acids (4 g granules three times daily) [26,27], taurine (3 g once daily) [28,29], and vitamin E (200 mg three times daily) . Branched-chain amino acids and taurine are thought to act by correcting alterations in energy metabolism, and vitamin E is thought to decrease circulating free radicals within cells. Correcting electrolyte abnormalities is often recommended, though it is not known whether it improves symptoms .
Zinc has been used in the past and may be beneficial in patients with low zinc levels, though its role as a therapeutic agent remains unclear [23,31]. When used, it has been given as 220 mg twice daily. Magnesium supplementation has not specifically been studied in patients with liver disease, but it does not appear to be beneficial in patients with skeletal muscle cramps in general .
One suggested approach to treatment is :
●Confirm the muscle cramps are related to cirrhosis
●Check electrolyte levels and replete if low
●Treat with branched-chain amino acids if symptoms persist
●Treat with taurine if symptoms persist
●Treat with vitamin E if symptoms persist
Our approach is to treat with quinine sulfate if patients can obtain it. If not, we believe the above approach is a reasonable alternative.
Umbilical hernias — Umbilical hernias pose a management dilemma in patients with cirrhosis, since they often develop in patients with severe liver disease and ascites who are at high risk of complications with surgical repair . Successful management using a variety of minimally invasive surgical techniques has been reported [34-38]. However, clinical experience has tempered our enthusiasm for elective surgical repair. We have witnessed an unacceptably high complication and recurrence rate in our patients referred for elective repair . Liver transplantation surgeons prefer to repair hernias at the time of transplantation and not before because many have observed high postoperative morbidity and mortality when repair was performed before the transplantation.
We have adopted the following approach to managing umbilical hernias in patients with cirrhosis:
●Most patients with ruptured or incarcerated hernias are referred for immediate repair. However, if incarceration is detected early, it can sometimes be reduced.
●Patients with symptomatic hernias or those with marked thinning of the skin overlying the hernia sac (a sign of impending rupture), especially if there is weeping of fluid or an eschar on the apex of the hernia, are referred for elective repair.
●Patients with asymptomatic hernias are managed conservatively, with surgical correction of the hernia performed at the time of liver transplantation. The cornerstone of conservative management in asymptomatic patients with umbilical hernias is aggressive management of ascites. Elastic/Velcro abdominal binders can also help reduce pain and minimize further enlargement of the hernia. (See "Ascites in adults with cirrhosis: Initial therapy" and "Ascites in adults with cirrhosis: Diuretic-resistant ascites".)
Hyponatremia — Hyponatremia is a common problem in patients with advanced cirrhosis. The pathogenesis of hyponatremia is directly related to the hemodynamic changes and secondary neurohumoral adaptations that occur in the setting of cirrhosis, resulting in an impaired ability to excrete ingested water. The severity of the hyponatremia is related to the severity of the cirrhosis. The management of hyponatremia is discussed elsewhere. (See "Hyponatremia in patients with cirrhosis", section on 'Treatment'.)
Thrombocytopenia or elevated INR — Patients with cirrhosis frequently have low platelet counts and elevated international normalized ratios (INRs). Because the liver makes coagulation factors as well as anticoagulant proteins, liver disease can lead to a hypocoagulable state or a hypercoagulable state. The relative balance or imbalance of these factors is not reflected in conventional indices of coagulation, such as the prothrombin time, activated partial thromboplastin time, or INR. (See "Hemostatic abnormalities in patients with liver disease", section on 'Effects of hepatic dysfunction'.)
Patients typically only need treatment for thrombocytopenia if an invasive procedure that is at moderate or high risk for bleeding is planned, or in the setting of active bleeding. It is reasonable to aim for platelet counts of at least 50,000/microL during moderate-risk procedures  or interventions and platelet counts closer to 100,000/microL in high-risk situations or in the presence of active bleeding . (See "Hemostatic abnormalities in patients with liver disease", section on 'Invasive procedure'.)
Because conventional indices of coagulation are not helpful in determining a patient's bleeding risk, patients who require an invasive procedure that is at moderate or high risk for bleeding or who have active bleeding may need additional testing, such as a determination of fibrinogen levels, thromboelastography, or thromboelastometry to guide management. While plasma is commonly given to patients with chronic liver disease and an elevated INR, plasma infusion may have adverse effects on portal vein pressures and collateral vessel flow. In addition, the traditional dose of two units of plasma is unlikely to significantly alter coagulation factor levels. (See "Clinical use of plasma components", section on 'Plasma products' and "Hemostatic abnormalities in patients with liver disease", section on 'Common clinical problems'.)
The management of patients with chronic liver disease who require an invasive procedure that is at moderate or high risk for bleeding, or who have active bleeding, is discussed in detail elsewhere. (See "Hemostatic abnormalities in patients with liver disease", section on 'Bleeding' and "Hemostatic abnormalities in patients with liver disease", section on 'Invasive procedure'.)
Preventing and identifying complications — Patients should be monitored for the development of complications, and when possible, steps should be taken to prevent their development. In particular, patients should be screened for esophageal varices and hepatocellular carcinoma. If varices are present, prophylactic treatment with beta blockers or esophageal variceal ligation is indicated.
Other measures to decrease the risk of complications include judicious diuresis and avoiding proton pump inhibitors in patients without clear indications for their use (spontaneous bacterial peritonitis); treating infections (spontaneous bacterial peritonitis, hepatic encephalopathy); avoiding sedatives and treating hypokalemia and hyponatremia (hepatic encephalopathy); avoiding nephrotoxic agents and aggressive diuresis (hepatorenal syndrome); and only using urinary catheters, mechanical ventilation, and central lines when clearly indicated (secondary infections). (See 'Major complications' above.)
●Variceal bleeding: All patients with cirrhosis should undergo screening for esophageal varices with upper endoscopy so that prophylactic therapy can be given to those with varices that are at increased risk for bleeding and to determine the risk of variceal hemorrhage. Prophylactic therapy most commonly involves treatment with a nonselective beta blocker or endoscopic variceal ligation, which reduces the risk of variceal bleeding. (See "Primary and pre-primary prophylaxis against variceal hemorrhage in patients with cirrhosis".)
●Hepatocellular carcinoma: Patients with cirrhosis should undergo surveillance with ultrasonography every six months. (See "Prevention of hepatocellular carcinoma and recommendations for surveillance in adults with chronic liver disease", section on 'Surveillance methods'.)
●Spontaneous bacterial peritonitis: The risk of spontaneous bacterial peritonitis (SBP) can be reduced by efforts to diurese patients since diuresis concentrates ascitic fluid, thereby raising ascitic fluid opsonic activity. Early recognition and aggressive treatment of localized infections (eg, cystitis, cellulitis) can also help to prevent bacteremia and SBP. Proton pump inhibitor use has been associated with an increased risk of SBP, so proton pump inhibitors should only be given to patients who have clear indications for their use. Finally, prophylactic antibiotics aimed at decontaminating the gut have a role in specific clinical settings. (See "Spontaneous bacterial peritonitis in adults: Treatment and prophylaxis".)
●Hepatic encephalopathy: Patients with cirrhosis should be evaluated regularly for hepatic encephalopathy, the earliest features of which can be subtle. Events that can precipitate hepatic encephalopathy include the development of variceal bleeding, infection (such as SBP), the administration of sedatives, hypokalemia, and hyponatremia, all of which should be corrected/avoided whenever possible (table 4). (See "Hepatic encephalopathy in adults: Clinical manifestations and diagnosis" and "Hepatic encephalopathy in adults: Treatment".)
●Portal vein thrombosis: Enoxaparin may be effective for preventing portal vein thrombosis (PVT) in patients with cirrhosis, though it is not used routinely. If it is to be used, we suggest eradication of varices (if present) prior to initiation of anticoagulation when possible. (See "Chronic portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management", section on 'Prevention in patients with cirrhosis' and "Primary and pre-primary prophylaxis against variceal hemorrhage in patients with cirrhosis", section on 'Endoscopic variceal ligation'.)
●Hepatorenal syndrome: Nephrotoxic agents (such as aminoglycosides) and vigorous diuresis should be avoided in patients with cirrhosis since they can precipitate renal failure. (See "Hepatorenal syndrome".)
●Secondary infections: Patients with cirrhosis who are hospitalized often acquire infections while in the hospital. Factors that have been associated with hospital-acquired secondary infections in patients with cirrhosis include the use of urinary catheters, mechanical ventilation, and the placement of central lines . Many of these interventions are performed routinely (such as placement of urinary catheters to measure urine output). However, avoiding these interventions unless they are absolutely necessary may decrease the risk of acquiring an infection while in the hospital, and it is our practice to only use these interventions when clearly indicated.
In a study of 207 patients with cirrhosis who were admitted with or developed an infection during hospitalization, 50 (24 percent) developed a second infection during hospitalization . Respiratory infections were the most common (14 patients), followed by urinary tract infections (13 patients), and Clostridium difficile. Of the urinary tract infections, 6 (46 percent) were related to the use of bladder catheters. Other factors associated with second infections included intensive care unit admission, the use of central lines, mechanical ventilation, shock, renal replacement therapy, and hepatic encephalopathy. Overall mortality was 39 percent, but it was 48 percent for those who developed a second infection during admission.
Treatment of complications — The treatment of the complications of cirrhosis is discussed in the respective topic reviews. (See 'Major complications' above.)
Liver transplantation — Liver transplantation is the definitive treatment for patients with decompensated cirrhosis. It is important to determine whether patients may be eligible for transplantation and to refer them to a transplant center for evaluation. Several guidelines are available which help determine when referral for liver transplantation may be beneficial. The decision to proceed to liver transplantation (either cadaveric or live donor) depends upon the severity of disease, quality of life, and the absence of contraindications. (See "Liver transplantation in adults: Patient selection and pretransplantation evaluation".)
PROGNOSIS — The prognosis of cirrhosis is highly variable since it is influenced by a number of factors, including etiology, severity, presence of complications, and comorbid diseases. Once decompensation occurs (eg, the patient develops variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis), mortality rates are high. (See 'Decompensated cirrhosis' below.)
Compensated cirrhosis — Patients with cirrhosis who have not developed major complications are classified as having compensated cirrhosis. The median survival of patients with compensated cirrhosis is >12 years . Patients with varices but who have not developed variceal bleeding are considered to have compensated cirrhosis, though their prognosis is worse than that of patients who have compensated cirrhosis without varices (3.4 versus 1.0 percent one-year mortality rates) .
Decompensated cirrhosis — Patients who have developed complications of cirrhosis, such as variceal hemorrhage, ascites, spontaneous bacterial peritonitis, hepatocellular carcinoma, hepatorenal syndrome, or hepatopulmonary syndrome, are considered to have decompensated cirrhosis and have a worse prognosis than those with compensated cirrhosis. (See 'Major complications' above.)
A systematic review found that the median survival was ≤6 months in patients with decompensated cirrhosis and a Child-Pugh score ≥12 or a Model for End-stage Liver Disease (MELD) score ≥21 . In addition, patients with decompensated cirrhosis who had been hospitalized with an acute liver-related illness (eg, variceal hemorrhage or spontaneous bacterial peritonitis) had a median survival of ≤6 months if the Child-Pugh score was ≥12 or the MELD score was ≥18.
An important factor related to survival is mean arterial pressure. In a series of 139 patients with cirrhosis and ascites, a mean arterial pressure of ≤82 mmHg was an important predictor of survival . Among patients with a mean arterial pressure ≤82 mmHg, survival was 20 percent at 24 months and 0 percent at 48 months (compared with 70 and 50 percent, respectively, for patients with a mean arterial pressure >82 mmHg).
Another factor that may be associated with survival is the presence of relative adrenal insufficiency [46,47]. In a study of 143 patients who were admitted to the hospital with decompensated cirrhosis, relative adrenal insufficiency was detected in 37 patients (26 percent) . At the time of presentation, compared with patients who did not have relative adrenal insufficiency, patients with relative adrenal insufficiency had lower mean arterial pressures (76 versus 83 mmHg) and serum sodium levels (131 versus 135 mEq/L) and had higher blood urea nitrogen levels (32 versus 24 mg/dL). During three months of follow-up, patients with relative adrenal insufficiency were more likely to develop infection (41 versus 21 percent), severe sepsis (27 versus 9 percent), type 1 hepatorenal syndrome (16 versus 3 percent), and death (22 versus 7 percent). (See "Diagnosis of adrenal insufficiency in adults".)
Among patients with cirrhosis and severe septic shock, administration of hydrocortisone may improve outcomes . (See "Treatment of adrenal insufficiency in adults", section on 'Glucocorticoid regimens'.)
Other factors associated with poor survival in patients with decompensated cirrhosis included hepatopulmonary syndrome, rapidly progressive hepatorenal syndrome, and intensive care unit admission for complications of liver disease along with hypotension requiring pressor support, serum creatinine >1.5 mg/dL, or jaundice.
Patients with decompensated cirrhosis often require liver transplantation. For those who are not candidates, hospice care can be considered for patients with predicted survival of ≤6 months. (See "Liver transplantation in adults: Patient selection and pretransplantation evaluation" and "Benefits, services, and models of subspecialty palliative care".)
Predictive models — Multiple studies have attempted to predict the prognosis of patients with cirrhosis based on clinical and laboratory information. Two commonly used models are the Child-Pugh classification and MELD.
Child-Pugh classification — The Child-Pugh classification (table 5) has been used to assess the risk of non-shunt operations in patients with cirrhosis (calculator 1 and calculator 2) . It is a modification of the Child-Turcotte classification, which incorporated five variables that were designed to stratify the risk of portacaval shunt surgery in patients with cirrhosis. The variables included the serum albumin and bilirubin, ascites, encephalopathy, and nutritional status (table 6) . The Child-Pugh classification replaces nutritional status with prothrombin time. The score ranges from 5 to 15. Patients with a score of 5 or 6 have Child-Pugh class A cirrhosis (well-compensated cirrhosis), those with a score of 7 to 9 have Child-Pugh class B cirrhosis (significant functional compromise), and those with a score of 10 to 15 have Child-Pugh class C cirrhosis (decompensated cirrhosis).
In a review of 92 patients with cirrhosis who underwent abdominal surgery, the mortality rate was 10 percent for patients with Child-Pugh class A cirrhosis, 30 percent for patients with Child-Pugh class B cirrhosis, and 82 percent for patients with Child-Pugh class C cirrhosis . Other studies have validated the utility of the Child-Pugh classification for the assessment of surgical risk . (See "Assessing surgical risk in patients with liver disease".)
The Child-Pugh classification system also correlates with survival in patients not undergoing surgery; one-year survival rates for patients with Child-Pugh class A, B, and C cirrhosis are approximately 100, 80, and 45 percent, respectively [53,54]. Child-Pugh class is also associated with the likelihood of developing of complications of cirrhosis. As an example, patients with Child-Pugh class C cirrhosis are much more likely to develop variceal hemorrhage than those with Child-Pugh class A cirrhosis .
MELD score — Another model to predict prognosis in patients with cirrhosis is the MELD score. It is based upon bilirubin levels, creatinine, INR, and the etiology of cirrhosis (calculator 3 and calculator 4). The MELD score has been adopted for use in prioritizing patients awaiting liver transplantation and has an expanding role in predicting outcomes in patients with liver disease in the non-transplantation setting. In January 2016, Organ Procurement and Transplantation Network Policy 9.1 (MELD Score) was updated to include serum sodium as a factor in the calculation of the MELD score . The MELDNa score can be calculated online. (See "Model for End-stage Liver Disease (MELD)".)
WHEN TO REFER TO A SPECIALIST — Referral to a hepatologist is recommended if the patient develops decompensated cirrhosis or major complications of cirrhosis. Patients with a MELD score ≥10 should be referred to a liver transplantation center for evaluation. In addition, referral to a hepatologist should be considered if the patient requires treatment for the underlying cause of the cirrhosis (eg, hepatitis C, autoimmune hepatitis) or if the clinician managing the patient would like the assistance of a hepatologist in the patient's general management. (See "Liver transplantation in adults: Patient selection and pretransplantation evaluation", section on 'Cirrhosis'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cirrhosis".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: Cirrhosis (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Cirrhosis represents a late stage of progressive hepatic fibrosis characterized by distortion of the hepatic architecture and the formation of regenerative nodules. It is generally considered to be irreversible in its advanced stages. In earlier stages, specific treatments aimed at the underlying cause of liver disease may improve or even reverse cirrhosis. (See 'Introduction' above.)
●Patients with cirrhosis are susceptible to a variety of complications, and their life expectancy can be markedly reduced. Major complications of cirrhosis include (see 'Major complications' above):
•Spontaneous bacterial peritonitis
•Portal vein thrombosis
●The major goals of managing patients with cirrhosis include (see 'General management' above):
•Slowing or reversing the progression of liver disease (see 'Slowing or reversing the progression of liver disease' above).
•Preventing superimposed insults to the liver (see 'Preventing superimposed insults to the liver' above).
•Managing symptoms and laboratory abnormalities (see 'Management of symptoms and laboratory abnormalities' above).
•Preventing and treating the complications of cirrhosis (see 'Preventing and identifying complications' above).
•Determining the appropriateness and optimal timing for liver transplantation (see 'Liver transplantation' above).
●The prognosis of cirrhosis is highly variable since it is influenced by a number of factors, including etiology, severity, presence of complications, and comorbid diseases. Once decompensation occurs (eg, the patient develops variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis), mortality rates are high. (See 'Decompensated cirrhosis' above.)