Minimal Hepatic Encephalopathy.

Minimal hepatic encephalopathy (MHE) is a pervasive frequent complication of cirrhosis of any etiology. The diagnosis of MHE is difficult as the standard neurologic examination is essentially within normal limits. None of the symptoms and signs of overt HE is present in a patient with MHE, such as confusion, disorientation, or asterixis. Progress has been made in diagnostic tools for detection of attention and cognitive deficits at the point of care of MHE. The development of MHE significantly impacts quality of life and activities of daily life in affected patients including driving motor vehicles and machine operation.

Acute liver failure.

Acute liver failure is a rare but often catastrophic illness affecting the liver and multiple organ systems. Patients with acute liver failure require a multidisciplinary approach for adequate management. With improved critical care and the availability of liver transplantation, survival has significantly improved. Hepatic encephalopathy, cerebral edema and infections are the most common complications of acute liver failure. The evaluation requires a diligent search for a specific etiology of the liver failure, since certain causes may respond well to specific pharmacological therapies. Acetaminophen and non-acetaminophen drug-induced hepatotoxicity account for more than 50% of cases of acute liver failure. Assessment of prognosis frequently (at least on a daily basis) by using various prognostic tools, allows the treating team to decide whether or not to proceed with urgent liver transplantation. Artificial liver support devices are still in evaluation and not ready for use in clinical practice. While it is determined whether or not there is sufficient hepatic regeneration, the care of the patient with acute liver failure revolves around managing the dysfunction of multiple extra hepatic systems.

Management of autoimmune and cholestatic liver disorders.

The management of autoimmune and cholestatic liver disorders is a challenging area of hepatology. Autoimmune and cholestatic liver diseases represent a comparatively small proportion of hepatobiliary disorders, yet their appropriate management is of critical importance for patient survival. In this article, management strategies are discussed, including the indications and expectations of pharmacologic therapy, endoscopic approaches, and the role of liver transplantation.

Coagulopathy of acute liver failure.

Coagulopathy is an essential component of the acute liver failure (ALF) syndrome and reflects the central role of liver function in hemostasis. ALF is a syndrome characterized by the development of hepatic encephalopathy and coagulopathy within 24 weeks of the onset of acute liver disease. Coagulopathy in this setting is a useful prognostic tool in ALF and a dynamic indicator of the hepatic function. If severe, it can be associated with bleeding and is commonly a major obstacle to the performance of invasive procedures in patients with ALF. This review focuses on the epidemiology, pathophysiology, presentation, evaluation, and management of coagulopathy in ALF.

Hepatic encephalopathy.

Hepatic encephalopathy (HE) is a syndrome of neuropsychiatric dysfunction caused by portosystemic venous shunting, with or without intrinsic liver disease. Patients with hepatic encephalopathy often present with the onset of mental status changes ranging from subtle psychologic abnormalities to profound coma. Several hypotheses have been proposed to explain the mental impairment associated with portosystemic shunting and liver disease. Clinicians diagnosing HE frequently have the opportunity to intervene and reverse severe HE, even hepatic coma. The recent advances in understanding and management of HE are the subject of this article.

The hepatorenal syndrome.

The onset of renal failure in a patient with cirrhosis or acute liver failure is alarming because it raises the possibility of the hepatorenal syndrome (HRS). Periodic surveillance of renal function is helpful in patients with severe liver disease to detect HRS early and to help correct reversible contributing factors. Once established, HRS responds relatively poorly to medical management, although recent advances have brought hope for an improved prognosis. In this article the diagnosis, pathophysiology, and management of HRS are discussed in detail, with an emphasis on recent diagnostic and therapeutic advances.

The coagulopathy of acute liver failure and implications for intracranial pressure monitoring.

INTRODUCTION: The development of coagulopathy in acute liver failure (ALF) is universal. The severity of the coagulopathy is often assessed by determination of the prothrombin time and International Normalized Ratio (INR). DISCUSSION: In more than 1,000 ALF cases, the severity of the coagulopathy was moderate in 81% (INR 1.5-5.0), severe in 14% (INR 5.0-10.0), and very severe in 5% (INR > 10.0). Certain etiologies were associated with more severe coagulopathy, whereas ALF caused by fatty liver of pregnancy had the least severe coagulopathy. METHODS: Management consisted of transfusions of FFP in 92%. Overall, FFP administered during the first week of admission amounted to 13.7 +/- 15 units. RESULTS: Patients who received an ICP monitor had significantly more FFP transfused than those managed without ICP monitor (22.7 +/- 2.4 vs. 12.3 +/- 0.8 units FFP; P < 0.001). Only a minority of patients developed gastrointestinal bleeding or had an intracranial pressure monitor installed. CONCLUSION: Further research is necessary to explore the reasons clinicians transfuse ALF patients with large amounts of FFP in the absence of active bleeding or invasive procedures.

Driving with minimal hepatic encephalopathy: real world consequences?

Mounting evidence suggests that minimal hepatic encephalopathy of cirrhosis may compromise driving performance. A study now reveals that patients with minimal hepatic encephalopathy had a greater self-reported frequency of motor vehicle accidents and traffic violations. There are still numerous issues to be resolved before this increasingly recognized variant of hepatic encephalopathy can be firmly linked to hazardous driving. Minimal hepatic encephalopathy affects a substantial proportion of patients with otherwise well-compensated cirrhosis, and because therapies are effective in reversing this type of encephalopathy, its role in motor vehicle accidents deserves further attention.

Differences between Caucasian, African American, and Hispanic patients with primary biliary cirrhosis in the United States.

UNLABELLED: Primary biliary cirrhosis (PBC) is an uncommon chronic cholestatic liver disease that primarily afflicts young and middle-aged Caucasian women; there are limited data on the clinical presentation and disease severity among non-Caucasian patients with this disease. The goal of this study was to examine differences in the severity of liver disease between Caucasian and non-Caucasian patients with PBC screened for enrollment in a large national multicenter clinical trial. Demographic features, symptoms, physical findings, and laboratory tests obtained during screening were examined in 535 patients with PBC with respect to ethnicity, gender, and antimitochondrial antibody (AMA) status; 73 of 535 (13.6%) were non-Caucasian (21 were African American, and 42 were Hispanic). Non-Caucasians were more likely than Caucasians to be ineligible for participation in the clinical trial (46.5% versus 25.1%, P = 0.0001), primarily because of greater disease severity. African Americans and Hispanics were also more likely to have a lower activity level, more severe pruritus, and more advanced disease. However, the mean age, male-to-female ratio, and seroprevalence of AMA positivity were similar between the 2 groups. CONCLUSION: Liver disease severity at clinical presentation is higher among non-Caucasians than Caucasians with PBC, and this cannot be explained by demographic or serologic features alone. Possible mechanisms underlying this health discrepancy are not clear, but increased awareness of PBC as a cause of chronic cholestatic liver disease is critical in evaluating non-Caucasian patients in the United States.

Methotrexate (MTX) plus ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis.

This placebo-controlled, randomized, multicenter trial compared the effects of MTX plus UDCA to UDCA alone on the course of primary biliary cirrhosis (PBC). Two hundred and sixty five AMA positive patients without ascites, variceal bleeding, or encephalopathy; a serum bilirubin less than 3 mg/dL; serum albumin 3 g/dL or greater, who had taken UDCA 15 mg/kg daily for at least 6 months, were stratified by Ludwig's histological staging and then randomized to MTX 15 mg/m2 body surface area (maximum dose 20 mg) once a week while continuing on UDCA. The median time from randomization to closure of the study was 7.6 years (range: 4.6-8.8 years). Treatment failure was defined as death without liver transplantation; transplantation; variceal bleeding; development of ascites, encephalopathy, or varices; a doubling of serum bilirubin to 2.5 mg/dL or greater; a fall in serum albumin to 2.5 g/dL or less; histological progression by at least two stages or to cirrhosis. Patients were continued on treatment despite failure of treatment, unless transplantation ensued, drug toxicity necessitated withdrawal, or the patient developed a cancer. There were no significant differences in these parameters nor to the time of development of treatment failures observed for patients taking UDCA plus MTX, or UDCA plus placebo. The trial was conducted with a stopping rule, and was stopped early by the National Institutes of Health at the advice of our Data Safety Monitoring Board for reasons of futility. In conclusion, methotrexate when added to UDCA for a median period of 7.6 years had no effect on the course of PBC treated with UDCA alone.

Cardiovascular risk factors after liver transplantation.

1. Yearly screening of liver recipients with serum cholesterol, triglycerides, and lipoproteins, and assessment for risk factors for atherosclerotic cardiovascular disease, is an important component of comprehensive post transplant care. 2. Revised guidelines and target levels of LDL-cholesterol levels specific for moderate and high cardiovascular risk patients have been recently revised. 3. Transplant physicians should be aware of advances in the management of post transplant arterial hypertension, diabetes mellitus, obesity, and nicotine dependence.