[Costal osteolytic lesions and multiple hepatic neoformations in a patient with inflammatory pseudotumor]. / Lesioni litiche costali e neoformazioni epatiche multiple in un caso di pseudotumore infiammatorio.

Inflammatory pseudotumor is a rare disease, that is regarded as a benign reactive inflammatory process, although its etiology and pathogenesis are still unknown. The liver is one of the organs most frequently involved, but inflammatory pseudotumors have been reported in many other sites in the body. Inflammatory pseudotumor of the liver presents as a solitary or, less frequently, multiple space-occupying lesion, which the common imaging techniques do not clearly distinguish from primitive or metastatic hepatic malignancies. Biopsy of the lesion is therefore necessary for diagnosis. The case of inflammatory pseudotumor described here presented with radiologic features of multiple solid space-occupying lesions in the liver, associated with multiple osteolytic lesions in the ribs. Such an association, very suggestive of malignancy, has not yet been reported for inflammatory pseudotumors. Optimum management of this disease has not yet been standardized. The majority of patients are treated by hepatic resection, although spontaneous regression has also been described. In our case, rapid improvement of both hepatic and costal lesions was observed, although the patient did not receive any specific treatment.

Role of iron load on fibrogenesis in chronic hepatitis C.

BACKGROUND/AIMS: In chronic viral hepatitis, an enhanced iron load is related to lower response to interferon. Furthermore, iron, through the production of oxygen radicals, may stimulate hepatocyte necrosis and the activation of cells responsible for synthesis and deposition of extracellular matrix. We investigated the relationship between iron load, evaluated by serum assays, and liver fibrogenesis in chronic active viral hepatitis. METHODOLOGY: Serum iron, ferritin, transferrin saturation and serum markers of hepatic fibrogenesis (Laminin and the amino-terminal peptide of procollagen III-NPIIIP-) were assayed in 102 patients (47 females, 55 males, mean age 42.48 years) affected by chronic hepatitis C virus and in 81 healthy controls (47 males, 34 females). In hepatitis C virus patients (studied before alpha-interferon treatment) a semiquantitative score for portal inflammation, necrosis and fibrosis was applied to liver biopsy. RESULTS: Serum indices of iron load were higher in hepatitis C virus patients than in controls, and were higher in cirrhotic than in chronic hepatitis cases. Ferritin and serum iron were positively correlated with NPIIIP and laminin; moreover cases with ferritin levels over the normal limit for sex and age had higher levels of NPIIIP and laminin than cases with normal or poor iron status. CONCLUSIONS: Our data suggest that even a mild increase of iron load stimulates hepatic fibrogenesis, probably adding oxygen free radical injury to the damage of viral infection.

Sjögren's syndrome associated with autoimmune hepatitis. A case report.

Liver involvement in patients with primary Sjögren's syndrome is rare, usually without clinical significance and histologically characterized by a feature like stage 1 primary biliary cirrhosis. We describe herein a case of acute and severe autoimmune hepatitis in a patient suffering from primary Sjögren's syndrome. The diagnosis of Sjögren's syndrome was performed in 1989. In June 1995 the patient presented severe weakness, jaundice and elevation of transaminases; moreover IgG raised to 5560 mg/dl and ANA titre increased to 1:20480. The patient denied alcohol and drug use and a viral hepatitis was excluded. Antimitochondrial antibodies, anti-smooth muscle antibodies and antibodies against liver kidney microsomes were negative. An abdomen ultrasound examination revealed hepatomegaly, with irregular echogenic structure and lymphoadenomegaly near the celiac tripod. Liver biopsy demonstrated a picture of autoimmune hepatitis. The patient was treated with prednisone 50 mg/day and azathioprine 50 mg/day, with improvement in clinical and liver function indices. At present, the patient is given only 10 mg/day of prednisone. The association of Sjögren's syndrome with autoimmune hepatitis is very rare: in the literature only one other similar case has been reported.

[Intermittent chyluria in a young man]. / Chylurie intermittente chez un jeune homme.

Chyluria is the passage of chylus into urine resulting in fistulization through the lymphatic system and the urinary system. This rare condition is usually caused by filaria infestation or malformations, neoplasia or trauma. We report a case of a 18-year-old man. The patient presented milky urine which had appeared after angiography following minor leg trauma. Physical examination revealed asymmetry of the face and cutaneous dyschromia. Blood tests revealed hypogammaglobulinemia and altered CD4/CD8 ratio (0.6). Urine tests showed proteinuria (30 mg/dl), lipiduria (triglycerides 750 mg/dl) and density of 1025. Renal function was normal. Abdomen computed tomography and urography were normal. Cystoscopy revealed the presence of milky urine in the bladder and selective catheterization revealed that the origin was the right ureter alone. Ascendent pyelography did not reveal any malformation of the urinary tract; but after this the chyluria spontaneously disappeared. The patient was rehospitalized 3 months later for recurrence. Lymphography was then performed and revealed a dilated lymphatic network with minute lacunar images projecting into the right kidney. Chyluria again disappeared spontaneously and recurred sporadically over the next two years in a patient who remained in good physical condition. The etiology of chyluria in a patient without filaria infestation is problematic, particularly when the most common causes (tuberculosis, neoplasia, trauma) are excluded as in our case. The asymmetry of the face, together with cutaneous dyschromia and the presence of a subarachnoidea cyst in the right temporal region suggested our patient had multiple congenital malformations.

Decreased activity of scavenger enzymes in human hepatocellular carcinoma, but not in liver metastases.

To investigate the role of oxygen free radicals in hepatocellular carcinoma we assayed tissue scavenger enzymes (superoxide dismutase and selenium-dependent glutathione peroxidase) in liver homogenate, plasma concentrations of vitamins A and E and the serum selenium level from 19 control patients, 23 cases of hepatocellular carcinoma and 18 cases of metastases to liver from different carcinomas. In hepatocellular carcinoma tissue the enzyme activities were all significantly lower than in control liver and in metastases-bearing liver; the enzyme activities of the latter tissues were not different from control liver. In contrast, normal liver adjacent to the hepatocellular carcinoma had decreased activity of superoxide dismutase. Serum selenium concentrations were significantly decreased in patients with hepatocellular carcinoma and those with liver metastases, while vitamin A was significantly decreased only in the former. These findings suggest that hepatocellular carcinoma develops in liver with severe impairment of cellular antioxidant systems, since, in patients with liver metastases from different cancers, despite low selenium concentrations, cellular scavenger enzymes have normal activities.

[Free radicals in human pathology]. / I radicali liberi nella patologia umana.

The role of free radicals has been suggested in many different diseases; the molecular mechanisms of radical-induced damage have been widely investigated: the main effects on cellular components are lipid peroxidation, protein denaturation and DNA damage causing alteration in membrane functions, impaired enzyme activity and genetic alterations, including cancer. Since oxidative metabolism produces some radicals, aerobic organisms acquired a complex defensive system against radical attack, based on localization of oxidative reactions, enzymes that scavenge free radicals or their products and antioxidant vitamins. Diseases may arise from increased exposure to radicals or from impaired efficiency of protective systems. The role of oxygen radicals in cancerogenesis, alcoholic liver disease and the aging process is also briefly discussed.

Serum copper and ceruloplasmin in early and in advanced hepatocellular carcinoma: diagnostic and prognostic relevance.

To evaluate the prognostic value of serum copper (S-Cu) and ceruloplasmin and their pathophysiologic significance in human hepatocellular carcinoma (HCC), we studied 49 patients with HCC (20 of which were submitted to partial hepatectomy) compared with 110 patients with liver cirrhosis. In HCC both S-Cu and ceruloplasmin were higher than in cirrhosis; moreover, S-Cu was correlated with the extension of HCC, evaluated by instrumental data and by surgical inspection. In cirrhotic patients, mean S-Cu was 122.9 micrograms/dl (SD, 29.3), in early HCC, 153.0 micrograms/dl (SD, 34.5), and in advanced HCC, 193.1 micrograms/dl (SD, 37.7). Variance analysis gave F = 59.4. In HCC patients S-Cu was positively correlated with ceruloplasmin and with fibrinogen. Survival, evaluated by Mantel's test stratified for surgical therapy, was longer in patients with S-Cu levels lower than 175 micrograms/dl and in those at an earlier stage. We therefore conclude that S-Cu has a relevant diagnostic value in detecting HCC also in early stage and allows prognostic evaluation as regards survival.

Procollagen III peptide and fibronectin in alcohol-related chronic liver disease: correlations with morphological features and biochemical tests.

In order to clarify the significance of procollagen III peptide (PIIIP) and fibronectin (FN) blood concentration in alcohol related chronic liver disease (ALD), we have investigated their relationships with histological liver features and biochemical liver tests in 44 ALD patients. PIIIP was measured in serum by radioimmunoassay whereas FN was determined in plasma using an immunonephelometric method. In each liver biopsy, steatosis, portal infiltrate, lobular necro-inflammation, portal fibrosis and lobular fibrosis were semiquantitatively assessed by scoring from 0 to 3. A close correlation of PIIIP was found with morphological features of fibrosis (both of lobular and portal type), but not with necro-inflammation or steatosis. PIIIP was also positively correlated with ALP and GGT and exhibited a good diagnostic value in liver fibrosis. On the contrary, FN did not distinguish between normals and patients and was not correlated with any morphological liver feature or biochemical liver test. We also conclude that serum NP3P effectively reflects liver fibrosis, whereas plasma FN seems not related to any of the main histological aspects of liver damage in ALD.

Catalase activity in human hepatocellular carcinoma (HCC).

Liver catalase activity, one of the free-radical scavenger enzymes, has been measured in 22 normal subjects and compared with that of 13 patients suffering from hepatocellular carcinoma. The activity was estimated both in tumor tissue and in tumor-free tissue. A significant reduction of catalase activity was noted in tumor tissue (p less than 0.001) as well as in the adjacent tumor-free tissue (p less than 0.02). In patients with hepatoma, the serum iron level was lower than in normal (p less than 0.01) and was correlated with enzyme activity (r = 0.958). These findings suggest that in hepatocarcinoma the free radical scavenger system is impaired.

Reduction of liver glutathione peroxidase activity and deficiency of serum selenium in patients with hepatocellular carcinoma.

Twelve adults with hepatocellular carcinoma (HCC) and 8 individuals with histologically normal liver, were measured for serum selenium concentration and glutathione peroxidase (GSH-Px) of liver tissue. It was found a reduced serum selenium and liver GSH-Px in patients with HCC. Serum selenium concentration and the enzyme activity were positively correlated (p less than 0.01). The increased risk of carcinoma in selenium deficiency may be partially due to a reduced activity of GSH-Px, one of the most important scavenger enzymes of oxygen toxic radicals.

Severe impairment of antioxidant system in human hepatoma.

Catalase (CAT), glutathione-peroxidase (GSH-Px) activity and reduced glutathione content (GSH) were measured in patients who had hepatocellular carcinoma, and values compared with those of normal liver and liver adjacent to neoplastic tissue. The results showed a remarkable reduction of CAT in tumor and corresponding tumor-free tissue (P less than 0.001 and P less than 0.02, respectively). All neoplastic samples had a significant lower activity of CAT than the corresponding adjacent tumor-free tissue (P less than 0.05). The GSH-Px activity of tumor tissue also was lower than normal (P less than 0.001) but similar to that of adjacent tissue. No correlation was noted between the two enzyme activities. Glutathione content was extremely low in tumor (P less than 0.001) and even in tumor-free tissue (P less than 0.05) when compared with normal liver. In all cases the content of GSH in neoplastic tissue was lower than that of the corresponding tumor-free tissue (P less than 0.05). Whereas in normal liver the activity of GSH-Px was positively correlated with the content of GSH, in the neoplastic tissue such a relationship disappeared. All these findings suggest that the antioxidant system of hepatocellular carcinoma cell is severely impaired.

Decreased activity of liver glutathione peroxidase in human hepatocellular carcinoma.

Glutathione peroxidase (GSH-Px) activity, one of the scavenger enzymes of oxygen active radicals, has been measured in hepatocellular carcinoma (HCC) of 17 patients and the values compared with the activity of adjacent tumor-free tissue and with those of 30 histologically normal livers. The results demonstrate a reduced GSH-Px activity in neoplastic tissue (21.19 vs 33.74 U/g prot.; P less than 0.001). However, the adjacent tumor-free liver also had a reduced activity when compared with normal tissue (23.15 vs 33.74 U/g prot.; P less than 0.01), but this value did not differ from that of HCC tissue. These data suggest that HCC might develop in a GSH-Px-deficient condition.

Diagnostic and prognostic value of serum copper and plasma fibrinogen in hepatic carcinoma.

To investigate the diagnostic and prognostic value of several biochemical tests in primary liver tumors, the authors studied 36 cases (4 cholangiocarcinomas and 32 hepatocellular carcinomas, 10 of which were associated with cirrhosis) and 47 cases of liver cirrhosis, all with morphologically proven diagnosis. Serum copper (SCu) and plasma fibrinogen (PF) appeared the most useful tests in differential diagnosis between tumors and cirrhosis. In liver tumors, mean SCu level was 200.50, standard deviation (SD) 47.17 micrograms/dl (121.40, SD 25.90 micrograms/dl in cirrhosis; P less than 0.001). PF level was 461.78, SD 151.25 mg/dl in tumors (275.30 SD, 124.40 mg/dl in cirrhosis; P less than 0.001). SCu had a good sensitivity (0.80) and a high specificity (0.92) at a cutoff value of 160 micrograms/dl; when the cutoff level was raised to 170 micrograms/dl, the specificity increased to 1, with a sensitivity of 0.77. The combination of SCu and PF improved the diagnostic value slightly. Moreover, with an estimated frequency of tumor in cirrhosis of 10%, SCu had a positive predictive value of 1 (cutoff, 170 micrograms/dl) and a negative predictive value of 0.97. In nine patients SCu levels decreased after surgical removal of tumor; five other patients, sequentially studied, showed an increase of SCu level that correlated with the progression of the disease. Finally, patients with longer survival had a lower SCu level. These findings suggest that SCu level may be used as a screening test for early detection of neoplastic degeneration, and it is correlated with the extension of tumor mass.

Glutathione-peroxidase and glutathione-reductase activities of normal and pathologic human liver: relationship with age.

Liver glutathione-peroxidase (L-GSH-Px) and glutathione-reductase (GSSG-Red) activities were measured in supernatants of liver tissues obtained from a total of 36 subjects. Sixteen of these patients had a functionally normal liver (control group), whereas of the remaining 20 patients, 10 were cirrhotic and 10 had a liver disease other than cirrhosis. The mean value of L-GSH-Px of the control group was 33.12 +/- 12.66 U/g protein, a value similar to that found in patients with liver disease. The L-GSH-Px of the control group was positively correlated with the age of the subjects (r = 0.620; p less than 0.02). In contrast, in patients with liver disease an opposite behaviour of the two parameters was noted (r = -0.497; p less than 0.05). L-GSH-Px activity tended to be higher in males than in females, whereas the erythrocyte glutathione-peroxidase (E-GSH-Px) of the same patients was higher in females, albeit not significantly. L-GSH-Px and E-GSH-Px were not correlated either in normal or in liver disease. The mean GSSG-Red of the control group was 40.63 +/- 11.10 U/g protein, which is not different from that of the group of liver patients. GSSG-Red was not correlated with L-GSH-Px or with the age of patients. In two patients with hepatoma, the GSH-Px activity of the cancer tissue was low and the GSSG-Red activity high.