Diagnosis and Management of Cirrhosis and Its Complications: A Review

Abstract

Importance: Cirrhosis affects approximately 2.2 million adults in the US. From 2010 to 2021, the annual age-adjusted mortality of cirrhosis increased from 14.9 per 100 000 to 21.9 per 100 000 people.

Observations: The most common causes of cirrhosis in the US, which can overlap, include alcohol use disorder (approximately 45% of all cases of cirrhosis), nonalcoholic fatty liver disease (26%), and hepatitis C (41%). Patients with cirrhosis experience symptoms including muscle cramps (approximately 64% prevalence), pruritus (39%), poor-quality sleep (63%), and sexual dysfunction (53%). Cirrhosis can be diagnosed by liver biopsy but may also be diagnosed noninvasively. Elastography, a noninvasive assessment of liver stiffness measured in kilopascals, can typically confirm cirrhosis at levels of 15 kPa or greater. Approximately 40% of people with cirrhosis are diagnosed when they present with complications such as hepatic encephalopathy or ascites. The median survival time following onset of hepatic encephalopathy and ascites is 0.92 and 1.1 years, respectively. Among people with ascites, the annual incidence of spontaneous bacterial peritonitis is 11% and of hepatorenal syndrome is 8%; the latter is associated with a median survival of less than 2 weeks. Approximately 1% to 4% of patients with cirrhosis develop hepatocellular carcinoma each year, which is associated with a 5-year survival of approximately 20%. In a 3-year randomized clinical trial of 201 patients with portal hypertension, nonselective β-blockers (carvedilol or propranolol) reduced the risk of decompensation or death compared with placebo (16% vs 27%). Compared with sequential initiation, combination aldosterone antagonist and loop diuretics were more likely to resolve ascites (76% vs 56%) with lower rates of hyperkalemia (4% vs 18%). In meta-analyses of randomized trials, lactulose was associated with reduced mortality relative to placebo (8.5% vs 14%) in randomized trials involving 705 patients and reduced risk of recurrent overt hepatic encephalopathy (25.5% vs 46.8%) in randomized trials involving 1415 patients. In a randomized clinical trial of 300 patients, terlipressin improved the rate of reversal of hepatorenal syndrome from 39% to 18%. Trials addressing symptoms of cirrhosis have demonstrated efficacy for hydroxyzine in improving sleep dysfunction, pickle brine and taurine for reducing muscle cramps, and tadalafil for improving sexual dysfunction in men.

Conclusions and relevance: Approximately 2.2 million US adults have cirrhosis. Many symptoms, such as muscle cramps, poor-quality sleep, pruritus, and sexual dysfunction, are common and treatable. First-line therapies include carvedilol or propranolol to prevent variceal bleeding, lactulose for hepatic encephalopathy, combination aldosterone antagonists and loop diuretics for ascites, and terlipressin for hepatorenal syndrome.

Figure 1.. Impact of Portal Hypertension and Hepatic Insufficiency on Cirrhosis Pathophysiology

Cirrhosis leads to intrahepatic resistance, which causes portal hypertension and, at later stages, hepatic insufficiency, which disrupts the liver’s normal metabolic functions. Together these features cause gut-barrier disruption and portosystemic shunting, resulting in the multisystem complications of cirrhosis, eg, hepatic encephalopathy, sarcopenia, ascites, and kidney injury.

Figure 2.. Noninvasive Diagnosis and Risk Stratification of Patients at Risk for Cirrhosis

The presence of cirrhosis is associated with an increased risk of complications such as liver cancer and decompensation including ascites, hepatic encephalopathy, and variceal hemorrhage. It is important to evaluate for the presence of cirrhosis in people with risk factors or any diagnosed chronic liver disease. While physical examination findings may be suggestive, it is recommended to stratify risk for all using the FIB-4 followed by elastography for at-risk patients. After identifying patients with cirrhosis, optimal care may involve referral to a hepatologist, liver cancer screening, and consideration of endoscopy for varices screening and/or initiation of nonselective β-blockers. BMI indicates body mass index. ^a Terry nails identified by white discoloration, absent lunula, and dark pink tips. ^b Biopsy is of highest value when the diagnosis of the underlying liver disease is unclear or noninvasive tests yield indeterminate or discordant results. The role of biopsy is also based on patient preference and clinical context.

Figure 3.. Natural History of Cirrhosis, Its Complications, and Modifiable Factors

The consequences of cirrhosis are depicted on a timeline from the development of compensated cirrhosis to death or transplant. Biomarkers associated with lower risk of decompensation and death are shown in green; those of indeterminate significance in yellow, and biomarkers and events associated with a higher risk of decompensation and death in red; disease-modifying measures and interventions are shown in blue. The liver stiffness measures are shown in kilopascals and are derived from vibration-controlled transient elastography. ^a Ten to 19 kPa denotes intermediate risk, 15 kPa is the threshold for assuming cirrhosis, 20 kPA is high risk, and 25 kPa is highest risk and assumes clinical portal hypertension.