Douglas R. LaBrecque

Hepatocellular carcinoma (HCC): a global perspective

Peter Ferenci (chair) (Austria) Michael Fried (Switzerland) Douglas Labrecque (USA) J. Bruix (Spain) M. Sherman (Canada) M. Omata (Japan) J. Heathcote (Canada) T. Piratsivuth (Thailand) Mike Kew (South Africa) Jesse A. Otegbayo (Nigeria) S.S. Zheng (China) S. Sarin (India) S. Hamid (Pakistan) Salma Barakat Modawi (Sudan) Wolfgang Fleig (Germany) Suliman Fedail (Sudan) Alan Thomson (Canada) Aamir Khan (Pakistan) Peter Malfertheiner (Germany) George Lau (Hong Kong) F.J. Carillo (Brazil) Justus Krabshuis (France) Anton Le Mair (The Netherlands)

Lipogranulomas and gold in the liver in rheumatoid arthritis.

Liver biopsies have been performed routinely as part of a protocol to evaluate methotrexate therapy in severe rheumatoid arthritis. All patients in the study had failed standard medical therapy, including gold treatment. Twenty-three of 41 patients (56%) had well-formed lipogranulomas (LGs) in the lobules, compared with an incidence of –5% in our general biopsy population. Twenty-seven of 41 patients (66%) had a unique pigment in their livers. In 20 of these, the pigment was in LGs; in the seven patients with pigment not associated with lobular LG, it was found in lipid droplets in portal triads. The pigment varied from irregular pale brown granules slightly larger than those of hemosiderin, to smaller black round granules. Lipogranuloma associated pigment of this type is an unusual finding, reminiscent of argyria. There was a variable appearance upon polarization, the black granules at times being strikingly refractile. There was a positive correlation between the prominence of LG and the quantity of pigment. The pigment resembled that described with gold deposition in other tissues. Radiographic microanalysis of both brown and black granules was performed in three cases. Characteristic spectra (energy-dispersive spectroscopy) demonstrated the presence of gold in each case. Silver was not identified. The high incidence of LG may reflect the frequent administration of gold in an oily vehicle. Gold may remain trapped in the liver for a prolonged time. Thus far, we have not detected any adverse effect from the presence of LG-associated gold.

Successful Treatment of Hepatic Venocclusive Disease in a Bone Marrow Transplant Patient With Side-to-Side Portacaval Shunt

Hepatic venocclusive disease developed in a 14-yr-old white girl after allogenic bone marrow transplantation from an HLA-identical sibling donor. Clinical diagnosis of venocclusive disease was based on the development of ascites, hepatomegaly, and jaundice 3 wk after transplantation. Current treatment of hepatic venocclusive disease is ineffective. The pathophysiology of the hepatic lesion suggests that construction of a side-to-side portacaval shunt should be beneficial in relieving the ascites and preventing further hepatic damage. Because the ascites was refractory to medical therapy and she was clinically deteriorating, a side-to-side portacaval shunt was performed. Histologic examination of a liver biopsy specimen obtained at surgery documented the presence of venocclusive disease. Postoperatively, the patient diuresed and returned to her baseline weight. One year after surgery the patient was doing well, her weight was stable, and she was being maintained on salt restriction alone. While the resolution of ascites and improvement of hepatic function in our patient after side-to-side portacaval shunt does not guarantee that such an approach will be uniformly successful, it should serve to encourage others to consider such therapy for this frequently devastating complication of chemoradiation therapy.

The evolving nature of “infantile obstructive cholangiopathy”

We report four patients with neonatal conjugated hyperbilirubinemia in whom the nature of the disease varied from that predicted by the initial diagnostic work-up. In two the initial liver biopsy showed paucity of the intrahepatic bile ducts; one cleared her conjugated hyperbilirubinemia and appeared normal at 3 years, but the other proved to have extrahepatic biliary atresia. The initial liver biopsy in two additional patients showed bile duct proliferation; both patients had a paucity of intrahepatic bile ducts later in the course of their disease. These cases illustrate the necessity of carefully following patients with neonatal conjugated hyperbilirubinemia to be certain that their courses continue to conform to the original diagnoses.

Serial Bilirubin Determinations as a Prognostic Marker in Clinical Infections

Patients with documented serious infection and total bilirubin values of greater than 2 mg/dl were surveyed for serial changes in bilirubin and other laboratory and clinical features. Of 19 patients studied, 12 (Group A) had persisting or increasing hyperbilirubinemia, and 7 (Group B) had decline in bilirubin after infection onset. None demonstrated marked changes in other liver tests. Only one patient had infection directly involving the hepatobiliary system. There were no significant differences between the two groups with respect to underlying illnesses, active hepatobiliary diseases, pathogens, bacteremia, or administration of cholestatic drugs. All Group A patients died because of uncontrolled infections, whereas all Group B patients survived with resolution of infection (p less than .001). Ten of 15 patients with available preinfection liver tests demonstrated serial bilirubin increases without marked changes in other liver tests prior to clinical recognition of infection. These findings demonstrate that hyperbilirubinemia disproportionate to increases in other tests may manifest before recognition of infection and that persistent or progressive hyperbilirubinemia is indicative of ongoing active infection.

Omeprazole heals mucosal ulcers associated with endoscopic injection sclerotherapy

Endoscopic injection sclerotherapy (EIS) is a standard and definitive therapy for bleeding esophageal varices. While the overall complication rate of the procedure is low, a substantial minority of patients treated by EIS develop refractory mucosal ulceration and/or esophageal strictures. However, despite the prophylactic use of H2 blockers and sucralfate in our EIS protocol, we observed a number of patients who developed nonhealing esophageal and/or gastroduodenal ulceration. We conducted an open trial in which we enrolled nine patients who had refractory ulcer disease. Patients that enrolled in the trial exhibited complete healing of their mucosal ulcers. These results suggest that acid is an important contributory factor in the pathogenesis and perpetuation of EIS-associated mucosal ulceration. Patients with alcohol-associated liver disease may be at increased risk for the development of EIS-associated complications.

Severe hepatic damage after acetaminophen use in psittacosis

A 63-year-old man with acute psittacosis had severe hepatic damage after ingesting about 10 g of acetaminophen over a 48 hour period. Transaminase levels showed striking elevation, with a serum glutamic-oxaloacetic transaminase level of over 15,000 IU/liter, and decreased rapidly, consistent with a toxic insult. No other etiologic agents were identified by history or serologic testing to explain this degree of damage. Liver histologic findings at autopsy showed severe central necrosis. Although psittacosis may infrequently cause a similar pattern of hepatic injury, disease of this severity has not been previously reported. It is postulated that acetaminophen may have accentuated hepatic disease produced by Chlamydia psittaci in this patient.

Liver Transplantation for Disulfiram-induced Fulminant Hepatic Failure

Disulfiram has been used as a popular adjunct in programs for alcohol rehabilitation. However, in rare cases, disulfiram has been reported to cause fulminant hepatitis. Disulfiram use and its associated complications in adolescents have received minimal attention in the literature. We report the first pediatric case of successful orthotopic liver transplantation for disulfiram-induced fulminant hepatic failure in a 16-year-old girl, who developed an idiosyncratic reaction associated with short-term, low-dose disulfiram use, as evidenced by her liver biopsy and explanted liver. This case report indicates that a high index of suspicion, and aggressive therapeutic interventions are necessary to recognize and manage disulfiram-induced fulminant hepatic failure in adolescents. Success of this case suggests that transplant centers should consider liver transplantation of an adolescent alcoholic patient with fulminant hepatic failure due to non-alcohol-related causes such as disulfiram. Orthotopic liver transplantation should be considered early in the management of disulfiram-induced fulminant hepatic failure.

Gallbladder Scalloping, Mammillated Caudate Lobe, and Inferior Vena Cava Scalloping: Three Novel Ultrasound Signs of Cirrhosis

PURPOSEnWe aimed to present three new ultrasound signs-gallbladder scalloping, mammillated caudate lobe, and inferior vena cava scalloping-and determine their accuracy in diagnosing liver cirrhosis.nnnMATERIALS AND METHODSnA total of 201 consecutive patients with a history of chronic liver disease who had undergone ultrasound imaging and liver biopsy were identified. A senior ultrasound radiologist blindly reviewed the ultrasound examinations. Specificity, sensitivity, positive predictive value, and negative predictive value of diagnosing cirrhosis were calculated for all evaluated ultrasound signs and selected combinations of signs, using the liver biopsy results as the reference standard.nnnRESULTSnOf the 201 patients, 152 (76%) had either pathology-proven cirrhosis or significant fibrosis. Caudate lobe hypertrophy was the most specific (88%) and most positive predictor (90%) for cirrhosis, whereas mammillated caudate lobe was the most sensitive (78%). Inferior vena cava scalloping was the most specific (78%) of the three proposed ultrasound signs. When signs were combined, the presence of either gallbladder scalloping or liver surface nodularity was highly sensitive for cirrhosis (87%), whereas the presence of either gallbladder scalloping or inferior vena cava scalloping with caudate lobe hypertrophy was highly specific (93%).nnnCONCLUSIONSnGallbladder scalloping, mammillated caudate lobe, and inferior vena cava scalloping are three novel signs that improve the accuracy of ultrasound in diagnosing cirrhosis.