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Background: Dobutamine stress echocardiography (DSE) is frequently used in the evaluation of cardiac risk prior to orthotopic liver transplantation (OLT). In the general cardiac population, an inducible left ventricular outflow tract gradient (LVOT Delta) during DSE has variable prognostic importance. The purpose of this study was to determine the prevalence and clinical significance of LVOT Delta in patients undergoing OLT during DSE., Methods: Consecutive medical records of 106 patients who had undergone OLT at our institution from January 1997 until January 2002 were retrospectively analyzed and divided into two groups based on the presence (Group I, LVOT Delta >36 mmHg) or absence (Group II, LVOT Delta< or = 36 mmHg) of a significant LVOT Delta measured during DSE. We determined any outcome differences between these two groups with regard to intraoperative hypotension, cardiac mortality, length of hospital stay, graft function, and renal function post-OLT., Results: Forty-six patients had an LVOT Delta > 36 mmHg (Group I) and 60 patients had LVOT Delta< or = 36 mmHg (Group II). Baseline demographics were similar in both groups. There was no significant overall difference in cardiac mortality between Group I versus Group II patients (0 versus 1 patient, respectively, P=0.57). Intraoperative hypotension occurred in 4 patients in Group I versus 0 patient in Group II (P=0.03). Length of stay, graft function, and postoperative renal function were similar in both groups., Conclusion: A significant LVOT Delta >36 mmHg is a frequent finding occurring in 46/106 (43%) of patients who have DSE pre-OLT. Intraoperative hypotension is associated with patients having an LVOT Delta. However, post-OLT patients with significant LVOT Delta have a similar in-hospital outcome compared to patients without significant LVOT Delta.

Background: Retroviruses have been implicated in the aetiology of various autoimmune diseases. We used immunoblots as a surrogate test to find out whether retroviruses play a part in the development of primary biliary cirrhosis., Methods: We did western blot tests for HIV-1 and the human intracisternal A-type particle (HIAP), on serum samples from 77 patients with primary biliary cirrhosis, 126 patients with chronic liver disease, 48 patients with systemic lupus erythematosus, and 25 healthy volunteers., Findings: HIV-1 p24 gag seroreactivity was found in 27 (35%) of 77 patients with primary biliary cirrhosis, 14 (29%) of 48 patients with systemic lupus erythematosus, 14 (50%) of 28 patients with chronic viral hepatitis, and nine (39%) of 23 patients with either primary sclerosing cholangitis or biliary atresia, compared with only one (4%) of 24 patients with alcohol-related liver disease or alpha1-antitrypsin-deficiency liver disease, and only one (4%) of 25 healthy volunteers (p=0.003). Western blot reactivity to more than two HIAP proteins was found in 37 (51%) of patients with primary biliary cirrhosis, in 28 (58%) of patients with systemic lupus erythematosus, in 15 (20%) of patients with chronic viral hepatitis, and in four (17%) of those with other biliary diseases. None of the 23 patients with either alcohol-related liver disease or alpha1-antitrypsin deficiency, and only one of the healthy controls showed the same reactivity to HIAP proteins (p<0.0001). Our results showed a strong association between HIAP seroreactivity and the detection of autoantibodies to double-stranded DNA. HIAP seroreactivity was also strongly associated with the detection of mitochondrial, nuclear, and extractable nuclear antigens., Interpretation: The HIV-1 and HIAP antibody reactivity found in patients with primary biliary cirrhosis and other biliary disorders may be attributable either to an autoimmune response to antigenically related cellular proteins or to an immune response to uncharacterised viral proteins that share antigenic determinants with these retroviruses.

As part of an effort to examine the relationship between chemosensory disturbance and oral chemistry, we analyzed expired lung air samples from a series of 24 patients with liver disease and 24 healthy controls using gas chromatography-mass spectrometry. Compared to samples from controls, lung air from patients with liver disease contained unusually high levels of limonene, a monoterpene that is a major component of the essential oil of citrus fruits (0.1 vs 7.0 micrograms/20 liters for controls and patients). Only half the patients showed high levels of limonene. Patients with noncholestatic liver disease were significantly more likely to have elevated lung air limonene levels than those with cholestatic liver disease (0.2 vs 13.8 micrograms/20 liters). Responses to food frequency and dietary behavior questionnaires indicated a pattern of diet selection and food preferences that were consistent with a dietary origin for the limonene in these patients.

Relationships between liver biochemical test values and reported frequency of consumption of various foods were examined using a principal-component analysis of data from 42 patients with chronic liver disease. The statistical procedure identified relationships among biochemical and dietary variables. One relationship included the variables albumin, bilirubin, and frequency of intake of fruits and vegetables, starch, and meats. A relationship was also found between serum alkaline phosphatase (ALP) levels and fat/oil intake. Data from patients with primary biliary cirrhosis (PBC) and noncholestatic liver disease were compared using a correlational analysis. In patients with PBC, serum ALP levels were positively correlated with frequency of intake of fat/oil (r = 0.59, p < 0.01) and meats (r = 0.46, p < 0.05), whereas serum bilirubin (Bili) and aspartate aminotransferase (AST) levels were significantly correlated with frequency of intake of dairy products (rs = 0.48 and 0.45, ps < 0.05 for Bili and AST, respectively), meats (rs = 0.59 and 0.65, ps < 0.01), and fat/oil (r = 0.54, p < 0.02 and r = 0.48, p < 0.05). In patients with noncholestatic liver disease, Bili levels were correlated with frequency of intake of fat/oil (r = 0.58, p < 0.01), and fruits and vegetables (r = 0.68, p < 0.01). These results suggest that the degree of elevation of some liver biochemical tests in patients with liver disease may be affected by dietary intake.

We evaluated chemosensory function, food preferences, and appetite in 88 patients with liver disease including those with hepatitis, cirrhosis, primary biliary cirrhosis, and sclerosing cholangitis. Reported chemosensory disturbances were common in the patients with liver disease: over 40% reported recent taste changes, and 27% reported recent changes in smell, compared to only 6% of healthy, age- and gender-matched controls with no history of marked chemosensory malfunction. Compared to controls, a greater proportion of liver patients reported food cravings (47 vs. 17%) and food aversions (33 vs. 16%). Foods with a predominantly bitter taste were specifically less preferred in patients with liver disease compared to healthy controls. Patients were also more likely to report poor to fair appetite than controls (37 vs. 5%). Groups of patients with different types of liver pathology showed varying patterns of food preferences, suggesting that dietary recommendations to liver patients might be tailored to the altered preferences associated with a particular type of hepatic dysfunction.

Many advances have been made in the understanding, diagnosis, and management of severe complications of liver disease. The pathogenesis of hepatic encephalopathy remains a challenge. Several toxins including ammonia, mercaptans, short-chain fatty acids, benzodiazepine-like substances, GABA-like substances, and impaired glutamatergic neurotransmission are at the top of the list of candidates. Use of the benzodiazepine antagonists is an experimental but promising new therapy in patients with hepatic encephalopathy. In patients with cirrhosis, spontaneous bacterial peritonitis (SBP) remains a common and highly lethal complication. The diagnosis of SBP is based on the polymorphonuclear cell count in the ascites and confirmed by culture of ascitic fluid. Early diagnosis and aggressive treatment has reduced mortality of SBP from greater than 90 per cent to 30 to 50 per cent. The appearance of cerebral edema in severe acute hepatocellular failure is associated with high mortality and conventional neurologic signs may be unreliable indicators of brain swelling. Current management of cerebral edema in fulminant hepatocellular failure may include early placement of an extradural sensor for continuous monitoring of intracranial pressure, so that short-term measures can be instituted making later liver transplantation safer. Coagulopathy remains a serious problem in patients with liver disease. Exchange plasmapheresis is a promising short-term adjuvant therapy. However, liver transplantation should be considered the definitive treatment for fulminant hepatocellular failure. The gastroenterologist often encounters multiorgan failure in patients with severe liver disease. Liver transplantation is now an important therapeutic consideration in almost every patient with severe, irreversible liver disease. Efforts should be targeted to early diagnosis of irreversible disease and coordination of patient care with a liver transplant center.