A comparison of Doppler flowmetry with conventional assessment of acute changes in hepatic blood flow.

The validity and clinical relevance of Doppler flowmetry in measuring changes in regional blood flow are uncertain. In the present study we compared changes induced ketanserin in regional splanchnic blood flow as measured by Doppler flowmetry with changes in conventionally measured systemic and in hepatic haemodynamic indices estimated pharmacokinetically using indocyanine green. Fourteen patients with alcoholic cirrhosis and portal hypertension were evaluated. On multivariate analyses, significant associations were noted for only three indices: changes in estimated hepatic blood flow were predicted jointly by changes in flow in the main and right portal veins and hepatic artery (R2 = 0.80); changes in intrahepatic shunting (indocyanine green extraction) were predicted by changes in flow in the main and right portal veins (R2 = 0.55); and changes in sinusoidal perfusion (indocyanine green clearance) were significantly predicted by changes in main portal vein flow alone (R2 = 0.76). These data support the validity of Doppler flowmetry in quantifying change in regional blood flow, but highlight the limitations in its clinical application and interpretation. The association of changes in main portal vein flow with changes in sinusoidal perfusion has clinical potential but requires confirmation using other modulating drugs.

Change in serum hyaluronan: a simple index of short-term drug-induced changes in hepatic sinusoidal perfusion.

BACKGROUND: Hyaluronan is an endogenous polysaccharide whose clearance from the plasma is predominantly by liver sinusoidal cells and is sinusoidal flow dependent. This study was designed to determine if a change in serum hyaluronan might reliably reflect short-term drug-induced changes in sinusoidal perfusion. METHODS: Hemodynamic changes following an oral dose of ketanserin were compared with changes in serum hyaluronan levels in 12 patients with alcoholic liver disease and portal hypertension. Indices determined comprised heart rate, mean arterial pressure (MAP), cardiac output (CO), systemic vascular resistance, hepatic venous pressure gradient (HVPG), indocyanine green (ICG) clearance and extraction, and total hepatic blood flow. Measurements were made in a basal state 1 hour after ketanserin ingestion and expressed as a ratio of values post- to pre-ketanserin administration. RESULTS: Ketanserin had variable effects comprising both increases and decreases in all indices. On univariate and multivariate analysis, changes in serum hyaluronan concentration (1.05 +/- 0.13, mean +/- SD) significantly correlated with only one index: changes in ICG clearance (0.93 +/- 0.17, r = -0.65, P = 0.02). CONCLUSIONS: Changes in serum hyaluronan levels reflect short-term drug-induced changes in sinusoidal perfusion in patients with alcoholic liver disease and portal hypertension. Serial measurement of serum hyaluronan levels may offer a simple method of screening vasoactive drugs for their short-term effects on sinusoidal perfusion.

Hemodynamic and liver function predictors of serum hyaluronan in alcoholic liver disease.

To define hepatic predictors of serum hyaluronan in patients with chronic liver disease, 62 patients with alcoholic liver disease were evaluated. In group 1, 30 patients had concurrent assessment of serum hyaluronan, liver function tests, Pugh grade and hemodynamic indices. A second, overlapping group of 42 patients (group 2) also had antipyrine clearance measured but without hemodynamic assessment. All but six patients had elevated serum hyaluronan levels. In both groups, serum hyaluronan levels differed between Pugh grades and, in each group, was significantly greater in Pugh grade C compared with those in Pugh grade A (p less than 0.05, Kruskal-Wallis test). When analyzed by correlation, serum hyaluronan was significantly associated with several indices in group 1, but on multivariate linear regression only three statistically independent predictors of serum hyaluronan were identified: serum albumin (p = 0.008), indocyanine green clearance (p = 0.024) and indocyanine green extraction (p = 0.036). The overall R2 for these correlates was 65%. In the second group, antipyrine clearance was not significantly associated with serum hyaluronan (r = 0.29, p = 0.06), but other associations were similar to the first group. On multivariate analysis, only serum albumin predicted serum hyaluronan (p less than 0.001; R2 = 43%). In conclusion, indices of hepatocyte synthetic function, sinusoidal blood flow and degree of intrahepatic shunting are independent predictors of serum hyaluronan in alcoholic liver disease. These data show the unique nature of serum hyaluronan and suggest its potential application to the assessment of acute hemodynamic changes in patients with liver disease.

"Open-access" endoscopy for general practitioners. Experience of a private gastrointestinal clinic.

Previous authors have questioned the value of an "open-access" upper gastrointestinal endoscopy service, its increased usage and its low useful diagnostic yield. We have analysed the results of 8270 consecutive endoscopies that were performed in one private outpatient gastrointestinal clinic from 1977 to 1984. Of these, 1409 endoscopies were performed as part of an open-access service for referring doctors. The remainder were performed after referral for a gastrointestinal consultation. No deaths or major complications occurred in either group. A steady increase in referrals to both groups was noted over the years, with an increasing proportion of normal results. A positive endoscopic finding was found significantly more frequently in the open-access group (61%) compared with those patients that were referred for a gastrointestinal consultation (52.6%). Individual endoscopists varied significantly in their tendency to report mucosal inflammatory lesions. We believe that outpatient open-access endoscopy that is performed by experienced clinicians with trained staff and appropriate facilities is a safe and acceptable alternative to barium meal examinations.

Transjugular liver biopsy: a review of 461 biopsies.

Transjugular liver biopsy was performed in a large series of patients for whom routine percutaneous biopsy was contraindicated; most of the patients had severe liver disease associated with coagulopathies or massive ascites. Of the 461 biopsies performed over a 7-year period, adequate specimens for histologic diagnosis were obtained in 425; in 14 (3.3%), the biopsy provided a false-negative result. Minor complications such as neck pain, hematoma at the puncture site, or pyrexia occurred in 79 patients (17.1%). Serious complications were encountered in six patients (1.3%) (two with cardiac arrhythmias; four with intraperitoneal hemorrhage following capsular perforation), with an overall mortality rate for the series of 0.22%. Modification of the technique--taking the biopsy with the catheter positioned centrally rather than wedged peripherally--has reduced the occurrence of capsular perforation without affecting the success rate. Transjugular liver biopsy is a valuable technique that provides diagnostic information in a high proportion of cases in which conventional percutaneous biopsy is contraindicated.

Alcohol-induced hepatomegaly: pathogenesis and role in the production of portal hypertension.

Hepatomegaly after chronic alcohol consumption results from an increase in cell size and not in cell number. About 50--60% of the increase in liver weight is accounted for by an increase in intracellular water, while extracellular water remains constant. Therefore, a substantial reduction in the ratio of extracellular to intracellular water occurs. Intracellular potassium can osmotically account for 40--50% of the excess water retained in the hepatocytes. It is proposed that an increase in hepatocyte size after chronic alcohol consumption compresses vascular-sinusoidal pathways. This results, after a threshold in cell size is exceeded, in increased intrahepatic and portal pressure. Possible factors responsible for the threshold are proposed. By applying the concept that animal cells act as osmometers, a new in vitro model has been developed to study the relationship between cell enlargement and portal pressure. In this model, the existence of a threshold and the generation of portal hypertension associated with hepatocyte enlargement have been demonstrated. In humans with alcoholic liver disease, a threshold in hepatocyte size enlargement (1600--1700 micrometer 2) before pressures were increased was also observed. In these patients, a strong correlation was also found between hepatocyte size and intrahepatic pressure. The same correlation occurs regardless of the presence or absence of cirrhosis, therefore suggesting that a major determinant of portal hypertension in cirrhosis is cell size and not the existence of nodules of fibrous septa. The higher portal pressures found in cirrhotics may be explained by the fact that these patients have larger hepatocytes.

Treatment of alcohol-related liver disease with (+)-cyanidanol-3: a randomised double-blind trial.

A randomised double-blind trial of (+)-cyanidanol-3(Catechin), 2 g/day versus placebo, was carried out in 40 patients with pre-cirrhotic alcohol-related liver disease over a three month period. Twenty received the active drug and 20 placebo; one non-compliant patient in the treatment group was withdrawn. Forty-one per cent (16/39) abstained from alcohol and showed significant improvements (P < 0.005) in mean values for serum aspartate transaminase, serum gamma glutamyl transpeptidase, and mean corpuscular volume. Ten of the 16 showed overall histological improvement on liver biopsy. Fifty-nine pr cent (23/39) continued to drink, though significantly reducing their mean daily alcohol intake (P < 0.001). No significant changes occurred in this group in mean serum enzyme values, though the mean value for mean corpuscular volume improved significantly (P < 0.01) and 16 of the 23 showed overall histological improvement. Changes occurred irrespective of treatment with Catechin which suggests that, over a three month period, this drug did not influence the course of alcohol-related liver disease.