Infectious Complications in Critically Ill Liver Failure Patients

Amanda Cheung, MD; Sajal Tanna, MD, MPH; Michael G. Ison, MD, MS


Semin Respir Crit Care Med. 2018;39(5):578-587. 

In This Article

Abstract and Introduction


Infections remain a leading cause of morbidity and mortality among patients with liver failure. A number of factors, including relative immune dysfunction and systemic inflammation, bacterial translocation, gut dysbiosis, small intestine bacterial overgrowth, altered bile acid pools, and changes in pH due to acid suppression, contribute to the high rates of infection in this population. Though a range of infections can complicate the course of cirrhotic patients, spontaneous bacterial peritonitis (SBP), cholangitis, and cholecystitis in addition to other infections (i.e. pneumonia, urinary tract infection, bacteremia, and Clostridioides difficile colitis) are more common in this population and will be reviewed in this article. Preventative strategies are directed at minimizing the risk of SBP through the use of targeted antimicrobial prophylaxis. Lastly, the critically ill cirrhotic patient may present with an acute need for liver transplantation. Thus, careful assessment for ongoing infection should be performed and treated to optimize outcomes of transplant, if needed.


Though acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are two distinct entities with differing precipitants and underlying pathophysiology, both have significant short-term mortality rates without liver transplantation.[1] Despite these differences, infections have been implicated in the development of both ALF and ACLF. ALF is defined as acute liver injury with coagulopathy and altered mentation in patients without cirrhosis or other preexisting liver diseases except for Wilson disease, vertically acquired hepatitis B, or autoimmune hepatitis.[2] ACLF is defined as acute hepatic decompensation and at least one extrahepatic organ failure in patients with underlying chronic liver disease.[3,4] Mortality rates in ACLF patients increase incrementally with the number of organ failures,[3] with 28- and 90-day mortality rates of up to 91.8 and 98.8%, respectively, when three or more organs are involved.[5] The health care burden of ACLF is significant in the United States, costing $1.7 billion per year in 2011, with a 50% in-hospital mortality rate.[6]

Though acetaminophen overdose and idiosyncratic drug reactions are the leading causes of ALF in the United States and Western Europe, viral hepatitides, particularly hepatitis B and E, remain the most common causes of ALF in the developing world.[7] Hepatitis B may be because of new exposure or reactivation, which may occur in the setting of immunosuppression and chemotherapeutic agents or superinfection with hepatitis D virus. ALF due to hepatitis E occurs more commonly in endemic regions, particularly in pregnant and immunocompromised patients including those with underlying chronic liver disease or solid organ transplants.[8] Although hepatitis A infection is common worldwide, resulting ALF is uncommon. Additional but less common viral causes of ALF include cytomegalovirus, herpes simplex virus, varicella zoster virus, Epstein–Barr virus, parvovirus, and human herpesvirus 6.[2]

Precipitants of ACLF vary depending on the region of the world studied, and a significant portion may not have an identifiable cause. In Asia-based studies, the leading causes are reactivation of hepatitis B and bacterial infection.[9] The most common precipitating events of ACLF in Western countries are bacterial infection and alcoholic hepatitis.[3] Patients with cirrhosis have higher rates of infection, and those with infections have a significantly greater mortality rate.[10–12] These observed rates of infection in cirrhotic patients may be because of suppressed or dysfunctional immune responses and bacterial translocation alongside gut dysbiosis and portosystemic shunting.[13,14] Additionally, patients with cirrhosis have higher baseline levels of endotoxins and cytokines.[15,16] An increased or chronic inflammatory response may ultimately lead to paradoxical immune suppression and an increased risk of secondary infections.[17]