Antonio Cipolla

Alpha interferon treatment may prevent hepatocellular carcinoma in HCV-related liver cirrhosis

BACKGROUND/AIMS The aims of alpha-interferon treatment for chronic viral liver infections are clearance of the virus and healing of the disease. Hepatocellular carcinoma is a complication of viral cirrhosis; but it is not yet known whether treatment of viral cirrhosis with alpha-interferon prevents this complication. METHODS The incidence and the risk (Cox regression analysis) of developing hepatocellular carcinoma were calculated in 347 patients with hepatic cirrhosis; 227 (34 hepatitis B virus and 193 hepatitis C virus related) were treated with alpha-interferon and 120 (28 hepatitis B virus and 92 hepatitis C virus) did not receive this treatment, in order to evaluate the efficacy of alpha-interferon in the prevention of hepatocellular carcinoma. In all patients, the cirrhosis was well compensated (Child A). RESULTS Over mean follow-up periods of 49 months for hepatitis B virus and 32 months for hepatitis C virus, 20/347 patients (6/62 hepatitis B virus and 14/285 hepatitis C virus) developed hepatocellular carcinoma. The risk of developing this tumor was significantly greater in males (p < 0.007) and in patients not treated with alpha-interferon (p < 0.01). The Relative Risk of developing hepatocellular carcinoma increased significantly (p < 0.0002) with each passing year. In patients with hepatic cirrhosis secondary to hepatitis B virus infections, the risk did not seem to be modified by alpha-interferon treatment, even though a greater, but not significant risk (Relative Risk = 4.9; p = 0.3) was calculated for untreated patients; in contrast, in hepatitis C virus-related cirrhosis, this risk was reduced by a factor of 4.0 (p = 0.04). The tumor developed only in non-responder patients regardless of virus type. After adjustment for confounding factors (sex, age, alcohol consumption, cigarette smoking), a statistically significant (p < 0.025) effect of interferon treatment in preventing hepatocellular carcinoma was still demonstrated when responders were matched with controls, but not when responders were compared with non-responders. CONCLUSIONS These results show that, in addition to its ability to halt the progression of viral-induced liver disease, alpha-interferon is also of benefit in patients with hepatitis C virus cirrhosis who respond to this treatment by lowering their risk of developing hepatocellular carcinoma.

Tumor M2-Pyruvate Kinase, a New Metabolic Marker for Pancreatic Cancer

An isoenzyme of pyruvate kinase (Tu M2-PK) is overexpressed by tumor cells and can be measured in blood by a specific immunoenzymatic assay. Our objective was to investigate the diagnostic value of Tu M2-PK in comparison with that of CA 19-9 in pancreatic cancer. We studied 265 subjects: 60 with histologically confirmed pancreatic cancer, 43 with benign pancreatic diseases (acute and chronic pancreatitis), 5 with benign cystic neoplasms of the pancreas, 9 with neuroendocrine tumors, 77 with other abdominal malignancies, 47 with benign digestive diseases, and 24 healthy controls. Levels of plasma Tu M2-PK and serum CA 19-9 were determined by commercially available specific immunoassays. The diagnostic sensitivity and specificity of Tu M2-PK for pancreatic cancer were 85 and 41%, respectively, while those of CA 19-9 were 75 and 81%. The combination of the two tests significantly increased sensitivity (97%) but lowered specificity (38%). In discriminating between pancreatic cancer and acute or chronic pancreatitis, Tu M2-PK turned out to be less accurate than CA 19-9. In patients without pancreatic tumor, cholestasis appeared not to affect the values of Tu M2-PK, while CA 19-9 was found to be significantly higher. Tu M2-PK was also abnormally high in the majority of patients with other digestive malignancies or neuroendocrine tumors. The results demonstrate that Tu M2-PK has a satisfactory sensitivity but a poor specificity in the diagnosis of pancreatic cancer. Used together with CA 19-9, the sensitivity increases considerably.

BIOAVAILABILITY STUDY OF A NEW, SINKING, ENTERIC-COATED URSODEOXYCHOLIC ACID FORMULATION

A new enteric-coated ursodeoxycholic acid (UDCA) formulation which sinks in the stomach and releases the drug only at a pH > or = 6.5 was developed. In 12 healthy subjects we measured, using a specific enzyme immunoassay, the serum levels of UDCA after a single oral dose of 450 mg of UDCA in three different formulations; enteric coated sinking tablet, stomach-floating enteric coated hard gelatin capsule and conventional gelatin capsule. The drug was given after a meal. Results are expressed as mean +/- SD. The area under the curve [AUC, mumol l-1 (8 h)] following oral administration of enteric-coated, sinking UDCA (39.0 +/- 8.5) was significantly higher than that obtained after both conventional UDCA (30.5 +/- 4.9) and floating enteric coated UDCA (29.3 +/- 3.4). Moreover, the maximum UDCA serum concentration (Cmax) was significantly higher with the enteric coated sinking UDCA formulation when compared to the other two formulations, while the time of maximum UDCA serum concentration (tmax) occurred later. These results may be explained by the hypothesis that the sinking tablet is expelled in the latter phase of gastric emptying along with the solid content. It therefore reaches the intestine at the highest alkalization phase caused by sustained biliary and pancreatic secretions. When released, the protonated insoluble UDCA is promptly solubilized by the alkaline pH thus giving a higher UDCA concentration gradient which facilitates its passive absorption. On the other hand, the floating capsule reaches the intestine too early, still in presence of an acidic pH; and in this condition UDCA is almost insoluble and consequently may be malabsorbed.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of chronic sporadic-type non-A, non-B hepatitis with lymphoblastoid interferon: Gamma GT levels predictive for response

The aim of this study was to evaluate the efficacy of human lymphoblastoid interferon-α treatment in chronic sporadic-type non-A, non-B hepatitis. We also aimed to determine if histological or liver function data could predict either response or relapse. Sixty patients with chronic sporadic-type non-A, non-B hepatitis were randomized in two groups of 30. One group was treated with interferon-α (3 MU thrice weekly) for one year; the other group was untreated controls. The treated group was followed for another year after interferon withdrawal. Liver function tests were performed during treatment. Liver biopsy was carried out before and a year after randomization. We evaluated rate of response [normalization of alanine aminotransferase (ALT) levels for at least three consecutive months] and rate of relapse (ALT rebound after therapy suspension). We also looked at possible predictive factors for response and relapse. In the treatment group the rate of response was 55% (16/29). No control patient exhibited ALT normalization. Among the responders, 31% (5/16) relapsed after interferon withdrawal. Low gamma GT and female sex are positive predictive factors of response (P<0.01 andP<0.02 respectively). Presence of portal and periportal inflammation at the second liver biopsy was correlated with relapse (P<0.05). In conclusion, human lyphoblastoid interferon-α treatment for one year is beneficial in patients suffering from chronic sporadic-type non-A, non-B hepatitis. Low pretreatment gamma GT levels and female sex are positive predictors of response in this patient population. Low degrees of portal and periportal inflammation, posttreatment, predict maintenance of response.

Ursodeoxycholic acid administration on bile acid metabolism in patients with early stages of primary biliary cirrhosis.

Ursodeoxycholic acid has been proposed for the treatment of primary biliary cirrhosis. The aim of this study was to evaluate the effect of ursodeoxycholic acid administration on bile acid metabolism in patients with early-stage primary biliary cirrhosis. Biliary bile acid composition, primary bile acid pool sizes, synthesis, and fractional turnover rate were measured before and after four weeks of ursodeoxycholic acid administration (600 mg/day) in nine patients with biopsy-proven primary biliary cirrhosis (stages I-III). Molar percentages of chenodeoxycholic, cholic, and deoxycholic acids in bile were significantly decreased by ursodeoxycholic acid administration, while its biliary concentration increased to 34.2% at the end of the same four-week period. The cholic and chenodeoxycholic acid pools decreased, although not significantly, while the deoxycholic acid pool was reduced by 60% (from 0.7±0.12 to 0.29±0.07 mmol,P<0.002). Primary bile acid synthesis was slightly increased, and fractional turnover rate was significantly increased. The conversion rate of cholic to deoxycholic acid was measured and found to be significantly increased (P<0.05) after ursodeoxycholic acid administration; however, serum levels of both free and conjugated deoxycholic acid were significantly decreased (from 23.2±9.7 to 3.8±1.9 μmol/liter,P<0.001). We conclude that in patients with primary biliary cirrhosis, ursodeoxycholic acid administration replaces endogenous bile acids in the enterophepatic circulation by increasing bile acid fractional turnover rate without significant increments of their hepatic synthesis.

Effect of rifaximin and paromomycin in the treatment of portal-systemic encephalopathy

Abstract Portal-systemic encephalopathy, a condition caused by liver failure, often complicates hepatic cirrhosis. Its pathogenesis is unknown, although hyperammonemia is thought to play an important role. Non-absorbable antibiotics have been used to treat hepatic encephalopathy because of their ability to reduce intestinal flora and thereby decrease the intestinal production of ammonia. We compared the effectiveness of rifaximin, a new non-absorbable antibiotic, with that of paromomycin. Thirty cirrhotic patients (20 men and 10 women, aged 39 to 75 years) suffering from portal-systemic encephalopathy with hyperammonemia were selected by Conns grading. Fifteen patients were randomly assigned to treatment with paromomycin (1,500 mg/day), and the other 15 received rifaximin (1,200 mg/day) for 10 days. Before, after 5 days, and after 10 days of treatment, we evaluated blood ammonia levels and each patients signs and symptoms according to Conns grading. Baseline ammonia levels and the degree of hepatic encephalopathy were positively correlated ( r = .65; P P P

Persistent elevation of serum CA 19-9 with no evidence of malignant disease.

BACKGROUND Serum CA 19-9 is the mainstay marker for the diagnosis of biliopancreatic malignancies, though a persistent elevation can also be observed in various benign diseases. AIMS In this study, a marked increase of serum CA 19-9 was seen in 10 patients who had no evidence of malignant disease. The possible causes of this finding are discussed. PATIENTS Nine women and one man were studied, whose admitting diagnoses were as follows: pulmonary fibrosis in two, diabetes in two, non-ulcer dyspepsia in two, obesity in one, acute diarrhoea in one, colon diverticula in one and gastric ulcer in one. METHODS Routine blood tests, tumour marker determinations, imaging studies and endoscopy were carried out at admission. RESULTS Serum CA 19-9 levels ranged from 112 to 1338 IU/ml (mean 517 IU/ml). Abdominal ultrasonography, CT-scan, upper gastrointestinal X-ray series and gastrointestinal endoscopies were negative for malignancy. During the follow-up period (range 2-7 years) serum CA 19-9 values were persistently elevated in all patients. CONCLUSIONS Our study shows that persistent and significant elevation of serum CA 19-9 can be found in non-malignant and non-cholestatic disease.

Serum CA 242: the search for a valid marker of pancreatic cancer.

Abstract Many efforts have been made to find valuable serum tumour markers which help the diagnosis of pancreatic cancer. In the present study we investigated the diagnostic value of CA 242 in comparison with two other routinely used tumour markers (CA 19–9 and CA 50). Two-hundred and seventy six subjects were enrolled in this study: 46 patients with pancreatic cancer preoperatively, 53 with chronic pancreatitis, 28 with acute pancreatitis, 49 with other malignancies, 50 with miscellaneous non-neoplastic digestive diseases, and 50 healthy subjects. CA 242 was determined in serum by means of a two-step fluoroimmunometric assay. Sensitivities of CA 242, CA 19–9 and CA 50 for pancreatic cancer when all patients were considered were 41.3%, 54.3% and 47.8%, respectively (95% specificity level). No significant improvement was achieved by combination of CA 242 with CA 19–9 and/or CA 50. Cholestasis affected serum levels of CA 242 in patients without pancreatic cancer, but not in those with this tumour. The metastatic stage of pancreatic cancer appeared to influence the levels of CA 242. In conclusion, CA 242 serum assay does not seem to improve diagnostic accuracy for pancreatic cancer compared to CA 19–9 and CA 50.

Primary MALT-lymphoma of the papilla of vater

Gastrointe stinal primary lymphomas originating from mucosa-associated lymphoid tissue (MALT) have been reported with increasing frequency (1± 5). This is mainly due to an improve ment in the histological recognition of the tumor, even if a real increase in the incide nce of this disease has also been ascertained (3). The stomach is the most frequent site of this tumor and a relationship with Helicobacter pylori (Hp) infection has been documented (6 ± 8). Other sites of the gut involve d are, in decreasing order of frequency, the ileocecal tract, colon, rectum, duodenum, and esophagus (5). A primary MALT lymphoma arising from the papilla of Vater is exceptional and, to the best of our knowle dge, it has been described in only two patients: in one , the tumor was removed surgically by Whipple ’s procedure , while in the other, a spontaneous and stable regression occurred (9, 10) . We report here a case of primary MALT lymphoma of the papilla which regressed after chemotherapy without need for surgical or endoscopic resection.

Determination of fecal fat concentration by near infrared spectrometry for the screening of pancreatic steatorrhea

SummaryConclusionsNear infrared reflectance analysis (NIRA) is a useful test for diagnosing fat malabsorption. Three-day stool collection and determination of fecal fat output are recommended. The measurement of fat concentration on spot samples may be of some use only in screening malabsorption of pancreatic origin; moreover, it does not discriminate between steatorrhea resulting from pancreatic insufficiency and that caused by gastrointestinal disorders.BackgroundNIRA has been proposed as an accurate method for the determination of fecal fat excretion. The aim of this study was to ascertain whether utilization of this technique to measure fat concentration in spot samples of feces is useful in screening for malabsorption.MethodsTwenty-five patients with chronic pancreatic disease and 95 with other digestive disorders were studied. In all patients, fecal fat assay with NIRA was performed on three different samples from each daily stool collection for 3 d. In 14 patients with pancreatic disease and 21 with gastrointestinal disorders, a colorimetric assay for fecal fat was performed for comparison.ResultsWhen mean 3-d or daily fat fecal output were considered, a strict linear relationship was found between NIRA and the colorimetric method (r=0.97 and 0.94, respectively). Using fat concentration, the two tests correlated less well (r=0.74). Fat concentration was significantly higher in pancreatic than in nonpancreatic steatorrhea, even though values overlapped widely, and thus discrimination was not possible. The diagnostic efficiency of fat concentration for pancreatic and nonpancreatic steatorrhea was 72 and 61%, respectively.