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The Patient with Hepatic Encephalopathy
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The Case: A 54-year-old male comes to your office accompanied by his wife for follow-up evaluation after a recent hospital discharge for an acute exacerbation of hepatic encephalopathy, with no known trigger. He has had two additional episodes in the past 2 years. The patient has a medical history of alcoholic liver disease with cirrhosis, esophageal varices, and ascites. Present medications include: lactulose, spironolactone, propranolol, and lactulose.
Physical exam is remarkable for the presence of bilateral palmar erythema, spider angiomas, ascites, and splenomegaly. His wife states that he has chronic anxiety, a shortened attention span, and is no longer capable of balancing his checkbook.
Key Supporting Information
Important goals of therapy for patients with cirrhosis are symptom management and preventing cirrhosis-related complications. Patients with cirrhosis are susceptible to a wide variety of complications, and their life expectancy can be markedly reduced, accounting for approximately 49,500 deaths. As of 2010, cirrhosis is the eighth leading cause of death in the United States.
Cirrhotic liver damage may lead to secondary complications such as portal hypertension, esophageal variceal bleeding, spontaneous bacterial peritonitis, and hepatic encephalopathy (HE). Screening for and management of these complications incurs substantial health care costs. Thus, determining the most beneficial treatment strategies that improve overall quality of life is essential.
The gut-liver axis is now being viewed as a key pathophysiological mechanism leading to complications of cirrhosis. Physicians should be aware of evidence-based medicine regarding how this axis may influence the development of these complications in order to apply this information to practice and improve patient health.
Malnutrition and poor nutritional status in cirrhotic patients is associated with a worse prognosis. Therefore, early intervention to correct nutrient deficiency can prolong life expectancy, improve quality of life, reduce complications, and increase the probability of successful transplantation.
Complications of cirrhosis place an enormous toll on both the patient and the health care system. Applying quality measures and addressing specific clinical variables may improve health-related quality of life while reducing the burden of the disease and re-hospitalization rates.
The breakdown of gut-liver axis equilibrium plays a central role in the development of immune disorders involving the small bowel and liver. The gut-liver axis in cirrhosis and portal hypertension is gaining increasing attention as a key pathophysiological mechanism responsible for progression of liver failure and development of complications such as spontaneous infections, HE, and hepatocellular carcinoma.
Bacterial overgrowth is common in cirrhosis. Bacterial translocation is thought to cause spontaneous bacterial peritonitis. Bacterial infection is one of the most frequent complications in cirrhosis and results in high mortality rates. Patients with cirrhosis have altered and impaired immunity, which favors bacterial translocation. Lipopolysaccharide (LPS), a component of the gram negative bacterial cell wall, also translocates into the bloodstream through permeable tight junctions of the gut. This is thought to be one possible trigger of splanchnic vasodilation in the hyperdynamic circulatory state of portal hypertension.
HE represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic liver disease and/or portosystemic shunting of blood flow, manifesting with progressive deterioration of the superior neurological functions. The frequency of HE is unrelated to the etiology of cirrhosis. However, increased severity and frequency of encephalopathic episodes are associated with an increased risk of death. The 1-year mortality of cirrhotic patients with HE is very high, approaching 60% to 80% in recent studies.
The West Haven criteria classify HE into 5 stages (0-V). Stage 0 applies to those with no detectable abnormalities. Stage I is classified by anxiety, lack of awareness, decreased attention span, and impaired addition or subtraction. Stage II is characterized by personality changes, inappropriate behavior, loss of time orientation, and lethargy. Stage III patients are confused, with gross disorientation and bizarre behavior, confusion, and somnolence. Stage IV is coma. Serum ammonia levels may be helpful in evaluating unexplained confusion in patients with chronic liver disease, but do not correlate with the stage of HE.
The pathophysiology of this disease is complex, as it involves overproduction and reduced metabolism of various neurotoxins, particularly ammonia. Management of HE is diversified and requires several steps: elimination of precipitating factors, removal of toxins, proper nutritional support, modulation of resident fecal flora, and down regulation of systemic and gut-derived inflammation. Bajaj et al concluded that cirrhosis, especially when complicated with HE, is associated with significant alterations in the stool microbiome compared with healthy individuals. Specific bacterial families (Alcaligeneceae, Porphyromonadaceae, Enterobacteriaceae) are strongly associated with cognition and inflammation in HE.
Antibiotics and nonselective -blockers (NSBB) intercept the gut-liver axis and each drug has proven efficacy in clinical trials. There is an increasing body of evidence supporting improved outcome with expanded use of NSBB and antibiotic therapy beyond current indications.
Little is known about the physiological impact the microbiota has on host health, an area which has recently been described as “one of the hottest areas in medicine.” The mechanisms through which microbiota exert beneficial or detrimental influences remain largely undefined, but include elaboration of signaling molecules and recognition of bacterial epitopes by both intestinal epithelial and mucosal immune cells.
Forthcoming evidence that intestinal microbiome abnormalities may play a pivotal role in both intestinal and liver disorders should prompt researchers to investigate to improve the knowledge of the interaction between infection and autoimmunity. Being aware of the advances in modeling and analysis of gut microbiota will further physicians’ knowledge of their role in health and disease, and allow for customization of existing and future therapeutic and prophylactic modalities.
Given the liver’s multiple synthetic, regulatory, and detoxifying functions, one of the characteristics accompanying severe hepatocellular dysfunction is the presence of malnutrition. In cirrhotic patients, poor nutritional status is a major risk factor for mortality. Independent of the etiology for the cirrhotic liver, poor nutritional status is associated with a worse prognosis and therefore early intervention to correct nutrient deficiency can prolong life expectancy, improve quality of life, reduce complications, and increase the probability of successful transplantation.
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Learning Objectives
Upon successful completion of this educational activity, participants should be better able to assess hepatic encephalopathy.
Overview
Author(s)/Faculty: Ronald A. Codario, MD, FACP, FNLA, RPVI, CHCP Source: Healio Gastroenterology Education Lab Type: Monograph Articles/Items: 4 Release Date: 9/15/2015 Expiration Date: 9/15/2016 Credit Type: CME Number of Credits: 0.25 Cost: Free Provider: Vindico Medical Education
CME Information
Provider Statement: This continuing medical education activity is provided by Vindico Medical Education. Support Statement: No commercial support for this activity. Target Audience: The target audience for this activity is gastroenterologists and other health care professionals with an interest in the treatment of patients with gastroenterological disorders.