19
Infections in Cirrhosis in Critical Care
Laurel C. Preheim
Departments of Medicine, Medical Microbiology and Immunology, Creighton University School of Medicine,
University of Nebraska College of Medicine, and V.A. Medical Center, Omaha, Nebraska, U.S.A.INTRODUCTION
Cirrhosis is characterized by fibrosis of the hepatic parenchyma with regenerative nodules
surrounded by scar tissue. It can result from a variety of chronic, progressive liver diseases.
The clinical manifestations vary widely from asymptomatic disease (up to 40% of patients) to
fulminant liver failure. Cirrhosis is a major cause of morbidity worldwide. In the United States
cirrhosis has an estimated prevalence of 360 per 100,000 population and accounts for
approximately 30,000 deaths annually. The majority of cases in the United States are a result of
alcoholic liver disease or chronic infection with hepatitis B or C viruses.
Infection is a common complication of cirrhosis (reviewed in Refs. 1–4). A Danish death
registry study (5) examined long-term survival and cause-specific mortality in 10,154 patients
with cirrhosis between 1982 and 1993. The results revealed an increased risk of dying
from respiratory infection (fivefold), from tuberculosis (15-fold) and other infectious diseases
(22-fold) when compared to the general population. In a prospective study (6) 20% of cirrhotic
patients admitted to the hospital developed an infection while hospitalized. The mortality
among patients with infection was 20% compared with 4% mortality in those who remained
uninfected. Of patients admitted to the critical care unit, 41% became infected. The most
common bacterial infections seen in cirrhotic patients are urinary tract infections (12% to 29%),
spontaneous bacterial peritonitis (7% to 23%), respiratory tract infections (6% to 10%), and
primary bacteremia (4% to 11%) (7). The increased susceptibility to bacterial infections among
cirrhotic patients is related to impaired hepatocyte and phagocytic cell function as well as the
consequences of parenchymal destruction (portal hypertension, ascites, and gastroesophageal
varices).
It should be noted that the usual signs and symptoms of infection may be subtle or
absent in individuals who have advanced liver disease. Thus a high index of suspicion is
required to ensure that infections are not overlooked in this patient population, especially in
those who are hospitalized. Occasionally fever may be due to cirrhosis itself (8), but this must
be a diagnosis of exclusion made only when appropriate diagnostic tests, including cultures,
have been unrevealing.
ROLE OF THE LIVER IN HOST DEFENSE AGAINST INFECTION
The liver plays an important role in host defense against infection. Cirrhosis can adversely
affect a number of these host defenses. The mechanisms identified in human and experimental
animal studies include depression of reticuloendothelial system clearance of organisms from
the bloodstream (9); impairment of chemotaxis, phagocytosis, and intracellular killing by
polymorphonuclear leukocytes (PMNL) and monocytes (10–12); reduction in serum bacteri-
cidal activity and opsonic activity (13,14); depression of serum complement (15–17);
dysregulation of cytokine synthesis and metabolism (18), and reduced protective efficacy of
type-specific antibody (19) and granulocyte colony-stimulating factor (20).
CLASSIFICATION OF LIVER DISEASE SEVERITY
Patients who have cirrhosis are at increased risk for both community-acquired and nosocomial
infections, the majority of which are bacterial. The incidence of infection is highest for patients
with the most severe liver disease (6,21–23). Accurate assessment for risk of infection is
dependent upon proper classification of the extent of liver disease. The Child–Pugh scoring
system of liver disease severity (24) is based upon five parameters: (i) serum bilirubin,
(ii) serum albumin, (iii) prothrombin time, (iv) ascites, and (v) encephalopathy. A total score is