Cirrhosis in adults: Overview of complications, general management, and prognosis

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. According to the Centers for Disease Control and Prevention (CDC), cirrhosis accounted for approximately 52,600 deaths and was the eighth leading cause of death in the United States in 2023 [1]. In addition, there were an estimated 12,700 deaths due to liver cancer, which often occurs in the setting of cirrhosis. Mortality rates related to cirrhosis have been rising and are estimated at 21.7 per 100,000 individuals in the United States [2].

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):

●Variceal hemorrhage

●Ascites

●Spontaneous bacterial peritonitis

●Hepatic encephalopathy

●Hepatocellular carcinoma

●Hepatorenal syndrome

●Hepatopulmonary syndrome

Once these complications develop, patients are considered to have decompensated cirrhosis. Multiple factors can predispose to decompensation in a patient with cirrhosis. The most important risk factor is the development of portal hypertension and uncontrolled chronic liver disease, particularly alcohol use and viral hepatitis. Beyond that, exposures that increase the short-term risk of decompensation include medications, infection, and surgery or trauma [3-5]. In addition, patients with obesity are at increased risk for decompensation [6]. 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. 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:

●Ascites

●Hepatic encephalopathy

●Variceal hemorrhage

●Spontaneous bacterial peritonitis

●Hepatorenal syndrome

●Portal hypertensive gastropathy

●Hepatic hydrothorax

●Hepatopulmonary syndrome

●Portopulmonary hypertension

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 placement of a transjugular intrahepatic portosystemic shunt (TIPS). (See "Overview of the management of patients with variceal bleeding".)

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) for patients with previously decompensated cirrhosis but can be as low as 0 percent for previously compensated patients [2,9].

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 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. 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, although some patients require repeated therapeutic paracenteses or TIPS placement. The most severe complications of ascites are infection and hepatorenal syndrome, the latter of which is more likely to develop in patients with low mean arterial pressures, and efforts to avoid reducing kidney perfusion in this population are needed. (See "Ascites in adults with cirrhosis: Initial therapy" and "Ascites in adults with cirrhosis: Diuretic-resistant ascites" and 'Decompensated cirrhosis' below.)

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.

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/microL). 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 kidney failure in a patient with ascites who has advanced liver disease due to cirrhosis, severe alcohol-associated 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 kidney perfusion induced by increasingly severe liver injury. It does not occur in patients without ascites. 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 kidney 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: Clinical presentation and diagnosis", 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 on 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: Clinical presentation and diagnosis", section on 'Clinical presentation'.)

Among patients with cirrhosis and ascites who are hospitalized with kidney injury, about one in four cases are due to hepatorenal syndrome [10]. The diagnosis is one of exclusion, being made when other causes of kidney injury 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 liver function improves or the patient undergoes liver transplantation. (See "Hepatorenal syndrome: Clinical presentation and diagnosis", section on 'Diagnosis' and "Hepatorenal syndrome: Treatment and prognosis".)

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. 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, kidney 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"):

●Liver disease

●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 cirrhosis range based on the biases of the studied sample. The prevalence is 0.45 percent among all patients with cirrhosis and higher among patients with decompensated cirrhosis [11], whereas the prevalence is 5 to 30 percent among patients awaiting liver transplantation. 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 [12]. Neither the prevalence nor the severity of portopulmonary hypertension appears to correlate with the degree of portal hypertension [12]. (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.

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) and loss of balance and falls are common early features 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 and, rarely, older patients with metabolic dysfunction-associated steatotic liver disease (MASLD), who can develop HCC in the absence of cirrhosis. (See "Epidemiology and risk factors for hepatocellular carcinoma" and "Surveillance for hepatocellular carcinoma in adults".)

Certain causes of cirrhosis appear to have a relatively increased risk for HCC. Patients with cirrhosis from hepatitis B, hepatitis C, 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 risk factors for hepatocellular carcinoma", section on '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 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 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. (See "Recent portal vein thrombosis in adults: Clinical features, diagnosis, and management" and "Chronic portal vein thrombosis in adults: Clinical features, diagnosis, and management".)

GENERAL MANAGEMENT — 

The goals of managing patients with cirrhosis include:

●Slowing or reversing progression of liver disease

●Preventing superimposed insults to the liver

●Identifying medications that require dose adjustments or should be avoided entirely (see "Overview of medication adjustments for adult patients with cirrhosis")

●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 disease progression — Although cirrhosis is generally considered to be irreversible in its advanced stages, the exact point at which it becomes irreversible is unclear [13,14]. 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 cirrhosis should be instituted.

As examples:

●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 SVR [15]. (See "Patient evaluation and selection for antiviral therapy for chronic hepatitis C virus infection", section on 'Benefits of treatment'.)

●Abstinence from alcohol substantially improves survival in alcohol-related cirrhosis. (See "Management of alcohol-associated steatosis and alcohol-associated cirrhosis".)

Pharmacologic therapies that do not directly target the cause of cirrhosis have also been studied:

●Nonselective beta blockers – Nonselective beta blockers (NSBB) have been studied for preventing complications in patients with cirrhosis, but the implication for clinical practice is uncertain. In a trial including 201 patients with compensated cirrhosis and portal hypertension (ie, hepatic venous pressure gradient [HVPG] ≥10 mmHg) with a median follow-up of 37 months, patients treated with NSBB had lower rates of decompensated cirrhosis (defined by ascites, bleeding, or encephalopathy) or death compared with placebo (16 versus 27 percent; HR 0.51, 95% 0.26-0.97) [16]. Further study is needed to establish a noninvasive method for identifying patients with portal hypertension because HVPG is not routinely measured [17]. (See "Portal hypertension in adults", section on 'Noninvasive tests'.)

In addition, long-term beta blocker use may not be tolerated by some patients due to adverse effects (fatigue, dizziness). (See "Major side effects of beta blockers".)

●Other therapies – Other drug therapies (eg, lipid-lowering agents, nonabsorbable antibiotics) have been studied for preventing cirrhosis-related complications, but the therapeutic benefits have not been clearly established [18-21]. In a randomized trial comparing simvastatin plus rifaximin therapy with placebo in 237 patients with decompensated cirrhosis, simvastatin plus rifaximin did not result in significantly lower rates of cirrhosis-related complications (43 versus 46 percent), liver transplantation or death (19 versus 24 percent), or acute-on-chronic liver failure (18 versus 14 percent) [18]. While statins lower cardiovascular risk and are generally safe for patients with compensated cirrhosis and while rifaximin prevents recurrent hepatic encephalopathy, data from this trial do not support the use of a statin plus rifaximin as a general preventive strategy [22,23]. (See "Statins: Actions, side effects, and administration" and "Hepatic encephalopathy in adults: Treatment", section on 'Specific treatments'.)

Preventing superimposed insults to the liver

Vaccinations — Vaccination against hepatitis A and B virus infection for those who are not already immune can help prevent superimposed insults to the liver. Other vaccinations, such as yearly influenza vaccination, are also recommended (figure 3). (See "Immunizations for adults with chronic liver disease".)

Patients with chronic liver disease can receive the COVID-19 vaccine, and details regarding administration and efficacy of COVID-19 vaccines are presented separately. (See "COVID-19: Vaccines" and "COVID-19: Issues related to liver disease in adults", section on 'COVID-19 vaccination'.)

Avoidance of hepatotoxins — Patients with cirrhosis should avoid medications, supplements, and other substances that are commonly associated with liver injury. This includes substances, such as alcohol, hepatotoxic over-the-counter medications, prescribed drugs with hepatotoxic side effects, and certain herbal remedies. (See "Drug-induced liver injury" and "Hepatotoxicity due to herbal medications and dietary supplements" and "Adjusting pain medications in adult patients with cirrhosis".)

Medication adjustments — Patients with cirrhosis are at increased risk of adverse events with many medications because of impaired hepatic metabolism or kidney excretion. Many medications require dose adjustments or should be avoided entirely. (See "Overview of medication adjustments for adult patients with cirrhosis".)

Issues related to the use of pain medications in patients with cirrhosis are discussed in detail elsewhere. (See "Adjusting pain medications in adult patients with cirrhosis".)

Management of symptoms and laboratory abnormalities

Muscle cramps — Patients with cirrhosis may experience muscle cramps (eg, leg cramps), which can be severe [24,25]. 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 [25]. The diagnostic evaluation for patients with cirrhosis who experience leg cramps is similar to the approach for patients without cirrhosis, with the addition of routinely measuring serum electrolytes and calcium levels in patients with cirrhosis. The management of leg cramps is discussed in detail separately. (See "Nocturnal muscle cramps".)

For patients with muscle cramps who do not respond to non-pharmacologic (ie, stretching) and initial pharmacologic therapies, small studies suggested a role for other therapies such as taurine, vitamin E, or sips of pickle juice [2,25-30].

Umbilical hernias — Umbilical hernias pose a management dilemma in patients with cirrhosis, since they often develop in patients with decompensated cirrhosis and ascites who are at high risk of complications with surgical repair [31]. Successful management using a variety of minimally invasive surgical techniques has been reported [32-36]. 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 [37]. 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 decompensated 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 'Management'.)

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 'Physiologic 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 high-risk procedures (eg, ERCP with sphincterotomy, liver biopsy) [38]. (See "Hemostatic abnormalities in patients with liver disease", section on 'Invasive procedures'.)

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 cirrhosis and an elevated INR, plasma infusion may have adverse effects on portal vein pressures and collateral vessel flow. In addition, plasma transfusions are unlikely to improve hemostatic function such as thrombin generation. (See "Clinical use of plasma components", section on 'Plasma products' and "Hemostatic abnormalities in patients with liver disease", section on 'Laboratory abnormalities'.)

The management of patients with cirrhosis 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 procedures'.)

Preventing complications — We monitor patients for the development of complications, and when possible, use strategies to prevent their development.

●General measures – General 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 over-diuresis (hepatorenal syndrome); and only using urinary catheters, mechanical ventilation, and central lines when clearly indicated (secondary infections). (See 'Major complications' above.)

●Variceal bleeding – We perform upper endoscopy in most patients with cirrhosis and clinically significant portal hypertension to evaluate for esophageal varices. Alternatively, patients estimated to have clinically significant portal hypertension based on liver stiffness measurement (LSM) by transient elastography >20 kPa or platelet count <150,000/microL can be offered nonselective beta blocker therapy instead of endoscopy. Strategies to prevent variceal bleeding and time intervals between surveillance endoscopies are discussed in detail separately. (See "Primary prevention of bleeding from esophageal varices in patients with cirrhosis".)

●Hepatocellular carcinoma – We screen patients with cirrhosis for hepatocellular carcinoma, and the approach to surveillance is discussed separately. (See "Surveillance for hepatocellular carcinoma in adults".)

●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. (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 2). (See "Hepatic encephalopathy in adults: Clinical manifestations and diagnosis" and "Hepatic encephalopathy in adults: Treatment".)

●Portal vein thrombosis – Prevention of portal vein thrombosis (PVT) in patients with cirrhosis focuses on optimizing liver function and reducing portal venous pressure. Management of PVT is discussed in detail separately. (See "Hemostatic abnormalities in patients with liver disease", section on 'Portal vein thrombosis (PVT)'.)

●Hepatorenal syndrome – Nephrotoxic agents (such as aminoglycosides) and overdiuresis should be avoided in patients with cirrhosis since they can precipitate kidney failure. (See "Hepatorenal syndrome: Clinical presentation and diagnosis".)

●Cirrhosis-associated immune deficiency – Patients with cirrhosis develop a state of immune deficiency known as cirrhosis-associated immune deficiency [39]. This condition predisposes such patients to common infections including urinary tract infections, pneumonia, and SBP. Patients are also at higher risk for other infections such as cryptococcal meningitis. In addition, patients with cirrhosis and iron overload are more susceptible to Yersinia enterocolitica and Vibrio vulnificus infections.

●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 [40]. 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 [40]. Respiratory infections were the most common (14 patients), followed by urinary tract infections (13 patients), and Clostridioides 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, kidney 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 higher. (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 [41]. 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) [41].

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 [42]. 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. Many other factors are associated with limited survival independent of MELD. These include hypotension, frailty/disability, and endocrinopathies.

Patients with decompensated cirrhosis often require liver transplantation. For those who are not candidates, palliative care can be considered for patients with predicted survival of ≤6 months. (See "Liver transplantation in adults: Patient selection and pretransplantation evaluation" and "Palliative care for patients with end-stage liver disease".)

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 3) has been used to assess the risk of non-shunt operations in patients with cirrhosis (calculator 1 and calculator 2) [43]. 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 serum albumin and bilirubin, ascites, encephalopathy, and nutritional status (table 4) [44]. 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 [45]. Other studies have validated the utility of the Child-Pugh classification for the assessment of surgical risk [46]. (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 [47,48]. Child-Pugh class is also associated with the likelihood of developing 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 [49].

MELD score — Another model to predict prognosis in patients with cirrhosis is the MELD score. It is based on bilirubin levels, creatinine, and INR (original MELD score). The MELD score has been modified over time to include sodium, albumin, and patient sex. The version of MELD used for allocation of liver transplantation is the MELD 3.0. (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 5^th to 6^th 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 10^th to 12^th 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.)

●Basics topics (see "Patient education: Cirrhosis (The Basics)" and "Patient education: Liver cancer (The Basics)")

●Beyond the Basics topics (see "Patient education: Cirrhosis (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Background – Cirrhosis represents a late stage of progressive liver 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.)

●Complications of cirrhosis – Patients with cirrhosis are susceptible to a variety of complications, and their life expectancy can be markedly reduced. Major complications of cirrhosis include (table 1) (see 'Major complications' above):

•Variceal hemorrhage

•Ascites

•Spontaneous bacterial peritonitis

•Hepatic encephalopathy

•Hepatocellular carcinoma

•Hepatorenal syndrome

•Hepatopulmonary syndrome

•Portal vein thrombosis

●Goals of management – The major goals of managing patients with cirrhosis include (see 'General management' above):

•Slowing or reversing disease progression (see 'Slowing or reversing disease progression' above).

•Preventing superimposed insults to the liver (see 'Preventing superimposed insults to the liver' above).

•Identifying medications that require dose adjustments or should be avoided entirely (see 'Medication adjustments' above and "Overview of medication adjustments for adult patients with cirrhosis").

•Managing symptoms and laboratory abnormalities (see 'Management of symptoms and laboratory abnormalities' above).

•Preventing and treating the complications of cirrhosis (see 'Preventing complications' above).

•Determining the appropriateness and optimal timing for liver transplantation (see 'Liver transplantation' above).

●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 higher. (See 'Decompensated cirrhosis' above.)