To assess the risk factors, natural history, and eligibility for curative treatment of early-detected hepatocellular carcinoma (HCC), 385 hemophiliacs who were treated with blood or plasma derivates for at least 10 years and had persistently elevated aminotransferase values underwent an annual screening with an abdominal ultrasound examination and measurement of the serum alpha-fetoprotein (AFP) level. Of these, 355 had serum antibody to hepatitis C virus (anti-HCV), 29 had anti-HCV and hepatitis B surface antigen (HBsAg), and one had HBsAg alone; 141 had serum antibody to human immunodeficiency virus (anti-HIV). During 48 months of follow-up study, six patients developed HCC. All HCC patients had a HCV-related cirrhosis and had been exposed to HCV risk at a median age of 40 years. All patients had a multicentric tumor, which was not eligible for curative treatment. Univariate analysis showed age, cirrhosis, and baseline AFP levels to be significantly associated with an increased risk of HCC. By multivariate analysis, the risk of HCC was infinite in patients with cirrhosis, 31.0 for those with baseline AFP higher than 11 ng/mL, and 17.9 for those more than 45 years of age. In conclusion, the risk of cancer was greater for patients infected later in life, particularly those with cirrhosis and high AFP. Annual screening of hemophiliacs with ultrasound and AFP fails to identify potentially curable tumors because the diagnosis is made at a late stage of the disease.

AIMSTo evaluate the prevalence, the incidence and the history of cholelithiasis in liver cirrhosis.PATIENTS AND METHODSA series of 233 consecutive cirrhotic patients (193 Child A, 35 Child B and 5 Child C) were assessed for cholelithiasis by ultrasonography. Of these, 201 (those who had never had cholecystectomy) were followed-up with repeated ultrasonographies.RESULTSThe prevalence of cholelithiasis was 38% (22% gallstones and 16% previous cholecystectomies). No relationships with the usual risk factors for cholesterol gallstones, such as age, sex, body mass index, serum glucose or triglycerides, were found. On the contrary, close correlations were observed with serum albumin, bilirubin, prothrombin time and Pugh score. By multivariate analysis, only serum bilirubin was independently correlated with cholelithiasis. Histories of biliary pain were more frequent in patients with previous cholecystectomy (62% cases) than in those with gallstones (21%) and those without cholelithiasis (7%). On the contrary, complaints of dyspepsia were similar in the three groups of patients. During a mean follow-up of 34.4 +/- 0.9 months, there was a 4.9% annual rate of development of new stones in 127 patients without cholelithiasis at the first investigation. This rate is markedly higher than that reported for normal subjects in a previous survey carried out in a similar geographic area. During a mean follow-up of 31.8 +/- 1.2 months, symptoms or complications were seen in 2 out of 45 patients with initial gallstones (4.4%). The annual rate of complications was estimated to be less than 2%.CONCLUSIONSCholelithiasis is frequently associated with cirrhosis and the risk of developing new stones remains high during the natural history of the disease.

BACKGROUND & AIMS The association of liver disease with hepatitis C virus (HCV) genotypes mainly refers to patients with serious liver damage; little information is available on symptomless carriers. The aim of this study was to investigate the correlation of genotypes with clinical course, risk factors for infection, and antibody to HCV reactivity in asymptomatic subjects. METHODS One hundred nine viremic blood donors with at least 1 year of follow-up were studied; 41 underwent liver biopsy. Genotypes were determined by line-probe assay. RESULTS Genotype 1 was found in 47 (43.1%), genotype 2 in 48 (44%), genotype 3 in 8 (7.3%), genotype 4 in 2 (1.8%), and coinfections in 4 (3.7%). The relative risk (RR) for a raised pattern of alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltranspeptidase was 2.1 (confidence interval [CI], 1.4-3.2), 1.7 (CI, 1.2-2.4), and 2.8 (CI, 1.6-4.9) in subjects with genotype 1 vs. 0.4 (CI, 0.2-0.7), 0.4 (CI, 0.3-0.7), and 0.4 (CI, 0.2-0.8) in subjects with genotype 2. Chronic hepatitis was found in 68%; the RR of chronic hepatitis was similar for genotypes 1 and 2 (RR, 1.1 [CI, 0.8-1.7] vs. RR, 1.0 [CI, 0.7-1.6]). Reactivity to NS4-derived antigens was infrequent in type 2-infected subjects. CONCLUSIONS Genotype 2 was as frequent as genotype 1 but associated with less liver function impairment. The high prevalence of chronic hepatitis should be considered in counseling viremic asymptomatic donors.

Pancreatic damage has been well described in HIV+ patients and can occur both for therapy and opportunistic infections, but its prevalence is not clear. The aim of our study was to evaluate the prevalence of pancreatic damage in a cohort of HIV+ hemophiliacs together with the clinical and prognostic value of the diagnostic methods commonly used. We studied 75 HIV+ patients and 26 HIV- as a control group: they were evaluated by biochemical tests, indirect pancreatic functional tests, abdominal ultrasound (US) and computed tomography (CT). No differences were observed between HIV+ and HIV- in elevation of pancreatic enzymes. Eleven patients had slight CT alterations and none had abnormal US. In HIV+ there was no relationship between enzyme elevation and CDC group, CD4+ cell count or therapy. In conclusion, pancreatic disorders have a very low prevalence in HIV+ hemophiliacs and biochemical alterations we found had a doubtful clinical significance. Lipase and isoamylase are the more reliable tests and lipase, being the cheapest and easiest to perform, has to be considered as the first test of choice for monitoring pancreatic damage in HIV+ patients.

Gallstone disease was detected in 28% of 119 patients on regular dialysis treatment. The disease was silent in 82% of the patients. Stones were radiolucent in 88% of the cases, radioopaque in 8% and mixed in 4%. Among 49 variables considered, increasing age was the only variable that correlated significantly with increasing prevalence of gallstone disease. Since no relationships were found between gallstones and age or modes of dialysis, it is conceivable that some mechanism(s) linked with the preexisting chronic nephropathy might have been involved in the development of cholelithiasis. End-stage renal disease could be another so far unrecognized risk factor for cholelithiasis.

The association between hepatocellular carcinoma (HCC) and cirrhosis provides a formidable means for prospectively studying patients who are at risk of HCC. Early diagnosis of HCC is possible not only due to knowledge of the risk factors for this tumor, but also because HCC has a very long phase of intrahepatic growth and tends to grow as a solitary mass. Early diagnosis is also possible because sensitive and relatively inexpensive diagnostic tools are available. Several prospective studies of Oriental and Western patients with cirrhosis now in progress have led to the identification of many patients with small tumors. However, in the face of this evidence that screening high-risk patients may increase the yield of subclinical small tumors, no firm conclusion has yet been reached on whether early diagnosis of HCC may also increase the number of operable patients and reduce the mortality rate for this tumor.

The effect of two different single oral doses of loxiglumide (CR 1505, CAS 107097-80-3) on gall-bladder emptying induced by a 550-cal standard mixed meal in 6 healthy volunteers was studied. Following placebo, the maximal gall-bladder emptying occurred about 90 min after the meal (minimal residual gall-bladder volume 27.4% of basal volume). Loxiglumide 400 or 800 mg dose-dependently inhibited the physiologica gall-bladder emptying. Loxiglumide plasma levels dose-dependently increased. The inhibition of gall-bladder emptying and the kinetic of loxiglumide plasma levels were temporally related. The results of the present study confirm that oral loxiglumide is a potent orally active cholecystokinin (CCK) antagonist in man and that CCK is the major physiological mediator of gallbladder emptying in response to meal.

BACKGROUND AND METHODS:Patients with cirrhosis of the liver are recognized as being at risk for hepatocellular carcinoma. The magnitude of the risk, the natural history of this disease, and the possibilities for detecting potentially curable tumors in patients in the Western world are unknown. To address these questions, we examined 447 Italian patients with well-compensated cirrhosis (which was of viral origin in 62 percent of them) from 1985 through 1990, performing serum alpha-fetoprotein assays and real-time ultrasonography every 3 to 12 months.RESULTS:Hepatocellular carcinoma was found in 30 patients (7 percent) at base line and in another 29 patients (7 percent of 417 patients free of tumor at base line) during follow-up periods averaging 33 months (range, 1 to 48). The cumulative hazard of the development of hepatocellular carcinoma during follow-up was higher among patients with persistently elevated serum alpha-fetoprotein levels (12 with tumors among 42 with such levels) than among those with fluctuating levels (11 among 82) or those with consistently normal levels (6 among 255). Only 17 patients had potentially operable tumors. The proportion of potentially operable tumors among those detected during follow-up was significantly lower than the proportion at enrollment (4 of 29 vs. 13 of 30, P = 0.027). The survival at one year of the 12 patients who underwent surgery was 67 percent, and the tumor-recurrence rate was 60 percent. Outcome was not appreciably different for the five patients who refused surgery.CONCLUSIONS:In the West, as in Asia, patients with cirrhosis of the liver are at substantial risk for hepatocellular carcinoma, with a yearly incidence rate of 3 percent. Our screening program did not appreciably increase the rate of detection of potentially curable tumors.