Hepatocellular carcinoma in Wilson's disease. Case report and review of the literature.

A 33-year-old man with Wilson's disease developed hemoptysis and radiographic evidence of nodular pulmonary infiltrates. A premortem diagnosis of hepatocellular carcinoma was made on the basis of alpha-naphthylannidase stains of pulmonary tissue obtained by open lung biopsy. We review all previous cases of Wilson's disease with this unusual complication and discuss the role of copper in hepatic oncogenesis as well as the alpha-naphthylannidase stain for the diagnosis of hepatocellular carcinoma.

Should we routinely perform liver biopsy in suspected alcoholic liver disease?

The traditional arguments for routinely performing liver biopsy in patients with suspected alcoholic liver disease are examined. These arguments may not withstand critical scrutiny and, in most substances, clinical diagnosis may suffice.

Distal splenorenal vs. portal-systemic shunts after hemorrhage from varices: a randomized controlled trial.

Between 1975 and 1983, 303 cirrhotic patients with endoscopically proven major variceal hemorrhage were admitted to the participating hospitals of the Boston-New Haven Collaborative Liver Group. Of these, 274 were evaluated for admission to a prospective, randomized controlled trial comparing portal-systemic shunts with distal splenorenal shunts. The criteria for inclusion were as follows: (i) a portohepatic pressure gradient greater than or equal to 12 mmHg; (ii) angiographic evidence of antegrade portal venous flow; (iii) angiographic demonstration that the inferior vena cava and portal, splenic and left renal veins were anatomically suitable for either a portal-systemic or distal splenorenal shunt, and (iv) the patient was a reasonable operative risk. Eighty-one patients from the six participating hospitals fulfilled the criteria and consented to participate. Thirty-eight patients were randomly assigned to have portal-systemic shunt and 43 to have distal splenorenal shunt. After a follow-up period of 11 years (mean = 3.5 years for all patients), survival was found to be similar in the two groups of patients. The 30-day operative mortality was 13% for the portal-systemic shunt group and 9% for the distal splenorenal shunt patients. Late mortality was 55% for the portal-systemic shunt and 37% for the distal splenorenal shunt group. Total mortality was 68% for the portal-systemic shunt and 46% for the distal splenorenal shunt group. None of these differences is statistically significant. In those patients who survived greater than 30 days after surgery, recurrent variceal hemorrhage occurred in four (12%) in the portal-systemic shunt group compared to seven in the distal splenorenal shunt group (18%) (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Portal pressure, presence of gastroesophageal varices and variceal bleeding.

This study was performed to examine the relationships between portal pressure measurements and the presence of esophagogastric varices, the size of varices and the occurrence of hemorrhage from varices in 93 patients with alcoholic cirrhosis, using standardized measurements of portal pressure by hepatic vein catheterization. The mean hepatic vein pressure gradient (HVPG) was significantly higher in 49 patients who had bled from varices than in 44 cirrhotic patients who had not (20.4 +/- 5.1 vs. 16.0 +/- 5.2; p less than 0.001). None of the 49 patients who had bled from varices had an HVPG less than 12 mm Hg. Among the 87 patients who had been examined by endoscopy for varices, all 72 with varices had an HVPG greater than 12 mm Hg. Six of 15 cirrhotic patients without varices had HVPG less than 12 mm Hg. The mean HVPG in the 15 patients without varices (15.1 +/- 6.8 mm Hg) was lower than the 72 patients with varices (19.3 +/- 4.8 mm Hg; p less than 0.01). Of the 72 patients with varices, 40 had large varices, 28 had small varices, and in four patients variceal size could not be assessed adequately. The mean HVPG was similar in the patients with large or small varices (19.8 +/- 4.8 vs. 18.3 +/- 5.0 mm Hg; p greater than 0.10). There was a positive relationship between the presence of large varices and the occurrence of bleeding from varices.(ABSTRACT TRUNCATED AT 250 WORDS)

The pharmacologic treatment of portal hypertension.

Surgical procedures that lower portal pressure, such as portacaval shunts, prevent variceal hemorrhage. Portal hypertension is the result of increased flow and increased resistance in the portal system. Pharmacologic therapy is aimed at altering these factors by the use of vasoconstrictors to reduce flow and vasodilators to decrease resistance. The current status of pharmacologic agents to achieve these effects is reviewed.

Comparison of dietary protein with an oral, branched chain-enriched amino acid supplement in chronic portal-systemic encephalopathy: a randomized controlled trial.

A randomized study was conducted in 37 hospitalized patients at six cooperating hospitals in which protein-intolerant cirrhotic patients were fed increasing amounts of either dietary protein or a branched-chain enriched amino acid solution (BCAA) until they attained an intake of 80 gm protein per day or equivalent or until they developed stage 2 encephalopathy. All patients initially received 20 gm of dietary protein for 1 week, after which 20 gm of protein or BCAA were added weekly. Nitrogen balance improved from negative to positive in all patients in whom it was measured and increased equally in both groups. Seven of the 20 patients in the protein group and 1 of 17 in the BCAA group developed encephalopathy of stage 2 or greater (p less than 0.05). Changes in each component of the portal-systemic encephalopathy syndrome were compared, and differences were statistically significant for mental status grade (p less than 0.01), asterixis (p less than 0.05), Portal-systemic encephalopathy index (p less than 0.01), but insignificant for Number Connection Test, EEG or ammonia. Plasma amino acid profiles showed an increase in BCAA in the study group. Thus, oral BCAA supplements appear to induce positive nitrogen balance to approximately the same degree as an equivalent amount of dietary protein without inducing encephalopathy as frequently.

Problems in the imaging diagnosis of hepatoma.

Two problem cases in the imaging diagnosis of hepatoma are reported. In both, a defect on the standard liver scan showed preferential gallium uptake. Ultrasound findings for a mass lesion were inconsistently present or absent. However, in the given clinical setting, a diagnosis of hepatoma was made. The microscopic changes suggested that the poor ultrasound demonstration of the tumors was due to marked fibrosis of the liver both outside and inside the tumor.

Distal splenorenal shunt vs. portal-systemic shunt: current status of a controlled trial.

A prospective controlled comparison of portal-systemic (PSS) and distal splenorenal shunts (DSRS) in cirrhotic patients who had survived hemorrhage from esophagogastric varices was undertaken 5 yr ago at five hospitals by the Boston-New Haven Collaborative Liver Group. The clinical and endoscopic criteria for massive hemorrhage were satisfied in 155 patients. Thirty-four patients were excluded, primarily because of uncontrolled hemorrhage. Thirty-four were rejected because the were poor operative risks and 21 because they did not satisfy criteria. Thirteen patients refused to participate; the remaining 53 were randomized; 29 to receive PSS and 24, DSRS. The two groups were similar in clinical, laboratory, and manometric characteristics. The DSRS group was older and tended to have had more previous hemorrhages. Followup ranged from 1 to 56 months (mean 21). After PSS, which was performed by 10 different surgeons, 6 patients died during the hospital admission (21%) compared to 2 after DSRS (12%). There were 6 late deaths in the PSS group and 4 in the DSRS group. Portal-systemic encephalopathy occurred in 5 of the 23 survivors of PSS (23%), and in 6 of the 19 who survived DSRS (32%. Two patients in the PSS group bled (9%), 1 after thrombosis and 1 after stenosis of the shunt. Three patients in the DSRS group bled (16%) and all had thrombosis of the shunt. PSS was associated with an unexplained but inordinately high operative mortality. Although the DSRS was accomplished with an acceptably low operative mortality, it was associated with frequent portal-systemic encephalopathy, shunt occlusion, and recurrent hemorrhage. Similar incidences of portal-systemic encephalopathy, shunt occlusion, and recurrent hemorrhage were observed in the PSS group. More patients and longer followup are necessary to determine which of these portal decompressive procedures is superior.

A controlled comparison of continuous intraarterial and intravenous infusions of vasopressin in hemorrhage from esophageal varices.

Infusions of intraarterial vasopressin (IAV) into the superior mesenteric artery have been shown to be effective in controlling hemorrhage from esophagogastric varices. Intravenous infusions of vasopressin (IVV), which can be initiated rapidly and require less sophisticated equipment and personnel, have also been reported to control variceal hemorrhage. We undertook a controlled clinical trial to compare these two routes of administration. Twenty-two cirrhotic patients with massive hemorrhage from varices were randomized to receive either IVV or IAV. Intraarterial vasopressin was begun at 0.1 U/min and increased progressively as needed to 0.2, 0.3, 0.4, and 0.5 U/min. Intravenous vasopressin was begun at 0.3 U/min and increased progressively as needed to 0.6, 0.9, 1.2, and 1.5 U/min. Hemorrhage was controlled in 5 of 10 episodes (50%) with IVV and in 6 of 12 episodes (50%) with IAV. Seven of the ten episodes treated with IVV (70%) ended fatally compared with 9 of 12 treated with IAV (75%). Side-effects and complications occurred with similar frequency in the two groups. The two routes of administration are equal in effects, side-effects, and complications. We recommend that IVV, which can be administered more easily, be given a brief therapeutic trial early in the management of hemorrhage from varices.

The Berkson bias in action.

Thirty years ago Berkson recognized that differences in selection rates of different diseases for admission to the hospital will systematically change the frequency with which those diseases co-exist in hospitalized patients from the frequency rate in the general population. Mainland subsequently demonstrated that postmortem studies systematically show a lower co-morbidity rate for any two individually lethal diseases than would be expected from the individual prevalence of these diseases. In studying the concurrence of bacterial endocarditis and cirrhosis, we examined the relationship of these diseases at autopsy where, according to this concept, we would expect a negative association. We found the frequency of bacterial endocarditis to be three times greater in cirrhotic than in non-cirrhotic patients, a statistically significant difference that was even more convincing, since a negative correlation was anticipated. In accord with the Berkson-Mainland hypothesis, however, no such association was seen between bacterial endocarditis and either emphysema or myocardial infarction, two other chronic diseases of different lethality. Similarly, glioblastoma multiforme, a brain tumor with a high mortality rate, showed a negative correlation with cirrhosis, emphysema, and myocardial infarction. A corollary of this bias-that the mean age at death should be lower in patients dying with two lethal diseases than in patients dying of either disease alone-was supported by our study. This investigation provides evidence to validate the Berkson-Mainland hypothesis, and suggests that rather than being always an adverse bias, it may be used beneficially to document the validity of the increased co-existence of diseases at autopsy.

Neomycin-sorbitol and lactulose in the treatment of acute portal-systemic encephalopathy. A controlled, double-blind clinical trial.

In a double-blind, randomized study the efficacy of lactulose was compared with neomycin-sorbitol in 45 episodes of acute nitrogenous portal-systemic encephalopathy (PSE) induced by dietary protein, azotemia, or gastrointestinal hemorrhage. All patients had underlying cirrhosis, and at the time of randomization had encephalopathy of at least grade 2 severity and arterial ammonia concentrations greater than 150 microgram/100 ml. Two thirds of the patients in each group returned to normal mental status and more than 80% in each group showed at least one grade improvement in mental state. In addition, there was equivalent improvement in asterixis, in the performance of the Number Connection Test, in the electroencephalographic pattern, and in arterial ammonia concentration. The principal difference between the two groups was a greater reduction in stool pH after lactulose therapy than after neomycin-sorbitol therapy. One patient randomized to neomycin-sorbitol had to be withdrawn from the study because of persistent vomiting related to the administration of the medication. Otherwise there were no complications attributable to therapy in either group. These data suggest that neomycin-sorbitol and lactulose are equally effective in the treatment of acute nitrogenous portal-systemic encephalopathy.