Lymphoblastoid interferon therapy in chronic hepatitis C: biochemical, virological and histological evaluation of two different doses.

Sixty patients of both sexes with biopsy-proven chronic hepatitis C were randomized to receive lymphoblastoid interferon 3 MU or 6 MU three times weekly for 6 months. A follow-up period of 3 months at the end of the therapy was scheduled. Thirty-two patients (53.3%) normalized alanine aminotransferase at the end of the therapy. Of these, 17 received 3 MU (56.7%) and 15 (50%) received 6 MU. Eighteen of the 32 patients (56.2%) relapsed in the follow-up period after treatment. No significant difference in relapse rate was observed between the two groups. The overall percentage of the non-responder patients was 36.6%. The treatment was discontinued because of non-compliance and/or side effects in six patients (10%): three in the 3-MU group and three in the 6-MU group. An improvement in liver histology was observed in about a quarter of chronic active hepatitis patients whose overall diagnosis changed to chronic persistent hepatitis. Knodell's score system showed a significant improvement (p < 0.05) with regard to peripheral necrosis, fibrosis and total score. HCV-RNA was positive at the beginning in all patients and it became undetectable in almost all responder patients. In some cases there was no correlation between viraemia and biochemical signs of liver disease. Our study shows that 6 MU does not increase the response rate compared to 3 MU. Moreover, the lower dose is able to improve the liver histology and to abolish the HCV viraemia in responder patients.

[Therapy of chronic non-A, non-B hepatitis with interferon alfa-2B. A controlled clinical study and long-term follow-up]. / Terapia dell'epatite cronica non-A non-B con alfa-2b interferone. Studio clinico controllato e follow-up a lungo termine.

In order to assess the efficacy of alpha-2b interferon (r-IFN) in the treatment of non-A non-B chronic hepatitis, 30 patients were randomised to receive r-IFN (3 MU subcutaneously three times a week for 24 weeks) or no therapy. A total of 21 males and 9 females, aged between 24-66 years old and who had had increased transaminase levels for at least one year, were included in the study. Three patients were ex-drug addicts and 6 had received blood transfusions whereas the cause of the infection in the remaining 21 patients was unknown. Hepatic biopsies performed prior to the study revealed persistent chronic hepatitis in 7 patients, active chronic hepatitis (ACH) in 19 patients and ACH with hepatic cirrhosis in 4 patients. Anti-HCV antibodies were present in 21 patients (70%). Transaminase values returned to normal in 11 (73%) of the 15 patients treated and remained unchanged in controls after 6 months of therapy. During the 18-month follow-up following the suspension of r-IFN treatment, transaminase values rose again to pre-treatment levels in 4 patients. Anti-HCV antibodies did not disappear in any of the patients who responded to therapy.

[The renin-angiotensin-aldosterone system in liver cirrhosis]. / Il sistema renina-angiotensina-aldosterone nella cirrosi epatica.

The role of the RAA system in the genesis of ascites in liver cirrhosis patients is not yet perfectly clear. The present study was conducted on 176 cirrhosis patients in order to investigate RAA system function, to assess the changes taking place in the various stages of the disease and to correlate such changes with the various kidney function parameters. The patients were divided into 3 groups as follows: Group I: patients without ascites on admission and with no history of the condition; Group 2: patients with ascites of recent onset and/or response to diuretic treatment; Group 3: patients with ascites not responsive to diuretic treatment. In Group 1, 19 patients (38%) reveal a significant reduction in renin activity together with portal hypertension and increased hydrosaline retention. In Group 2 renin activity was reduced in 4 patients (6%), aldosterone activity in 3 (4%). Progressive deterioration in liver function parameters and progressive activation of the RAA system combined with reduced sodiuria content were found in over 50% of these patients. The presence or absence of portal hypertension in this group was not related to significant changes in diuresis or sodiuria. In Group 3 renin was activated in 54 patients (89%), aldosterone in 58 (95%) and there was also a distinct reduction in sodiuria (96% of patients) and chloruria (100%). A substantial increase was also noted in the incidence of low blood sodium (53%) while portal hypertension was found in 97% of patients. On the basis of those data it may be hypothesised that high pressure inside the liver creates the stimulus for primary sodium retention. The decrease in effective blood volume after vasodilation, accentuated by low blood albumin and splanchnic venous stagnation may the stimulate the sympathetic nervous system and RAA system. Hyperaldosteronism only becomes the dominant factor in renal imbalance when the cirrhosis reaches the resistant ascites phase.

[Changes in antidiuretic hormone (ADH) in liver cirrhosis with resistant ascites]. / Modificazioni dell'ormone antidiuretico (ADH) nella cirrosi epatica con ascite resistente.

The pathogenetic role of ADH in determining hyponatremia in patients with liver cirrhosis is still much debated. Osmotic stimuli are not able to inhibit secretion of ADH in refractory ascites and under such conditions the reduction in effective plasma volume has been put forward as the main cause. Twenty patients with liver cirrhosis and refractory ascites were studied before and during extraction-concentration-reinfusion (ECR) of ascitic fluid by means of Rhodiascit. ADH, renin, aldosterone, blood and urine osmolarity, plasma and urinary concentration of sodium, potassium, chlorine, and the clearance of free water were evaluated. All patients presented high renin values (15.4 +/- 11.7 ng/ml), aldosterone (341 +/- 172 ng/ml), ADH (6.3 +/- 5.2 pg/ml). During ECR, a significant drop was observed in renin (p less than 0.001), aldosterone (p less than 0.001) urinary osmolarity (p less than 0.001) and an equality significant increase in diuresis (p less than 0.001), natriuria (p less than 0.005), kaliuria (p less than 0.001) while ADH presented an irregular course: in 11 cases it remained unchanged, in 3 it fell and in 6 it presented a constant increase. To conclude, data suggest that the diminished filtrate reaching the distal tubule constitutes the greatest cause of the inability to dilute urine in many patients with cirrhosis and that ADH is a permissive rather than a primary factor.

[Ferritin, CEA and TPA as tumor markers in breast neoplasms]. / Ferritina-CEA-TPA come markers neoplastici nelle neoplasie mammarie.

In order to assess the sensitivity and specificity of Ferritin, CEA and TPA as neoplastic markers in breast carcinomas, 91 patients all classified according to the TNM-UICC system were studied in a cancer clinic. The results of the analyses indicate that ferritin is apparently only influenced by the presence of metastatic neoplasias and that greater sensitivity is obtained if all three markers are employed simultaneously.

[Study of blood ferritin in cancer patients and its possible use as an indicator of an unfavorable prognosis]. / Studio della ferritinemia in pazienti neoplastici e sua possibile utilizzazione come indice prognostico sfavorevole.

Ferritinaemia levels were measured in 97 neoplastic patients and compared with the levels found in a healthy control group, in order to discover whether ferritinaemia had any significance as a neoplastic marker. Higher levels were encountered in all neoplastic patients (P less than 0.005) than in the control group. Levels were particularly high in the patients with metastasised tumours (especially breast cancer: P less than 0.001). The highest ferritinaemia levels were found in terminal patients (P less than 0.001).

[Function test of renal excretion of water and sodium after water loading in liver cirrhosis]. / Esplorazione funzionale della capacità escretoria renale di acqua e sodio dopo carico idrico nella cirrosi epatica.

Water loading was used as a diagnostic test in the study of renal excretion of water and sodium during the clinical stages of cirrhosis of the liver in 25 patients free from clinical and instrumental signs of ascites, 26 with treatable ascites, and 14 with intractable ascites. The water load consisted of 20 cc/kg water administered i.v. as a 5% glucose solution. Examination of diuresis in the ensuring 5 hr showed that: 1) clearance of free water is the most sensitive parameter for the detection of patients at short-term risk for the onset of ascites; 2) very low urinary sodium is an indicator of refractory ascites, whereas values are virtually the same and higher in subjects without ascites or with treatable forms; 3) chloruresis in only reduced significantly in cirrhosis with refractory ascites.

[Evaluation of blood ferritin in sideropenic anemia and its modifications in the course of divided-dose parenteral iron therapy]. / Valutazione della ferritinemia nell'anemia sideropenica e sue modificazioni in corso di terapia marziale parenterale refratta.

Changes in blood ferritin during divided dose parenteral iron therapy and the importance of ferritin evaluation in iron-deficiency anaemia were investigated in 20 women and 10 men with this diagnosis through withdrawals before and after treatment. In 6 subjects, blood ferritin values enabled the presence of iron deficiency to be ruled out, since they were high at the first control (in agreement with the histological examination of the marrow in the search for iron deposits). In sideropenic males, the difference between values at the time of diagnosis and those of normal controls was significant (p less than 0.001). The absence of this finding in the females may have been due to over-low values in the normal controls. Blood ferritin values during therapy gradually rose until its termination. The conclusion is drawn that at any rate in males the determination of blood ferritin can be a useful aid in the diagnosis of iron-deficiency anaemia, and in the demonstration of normal reserves after treatment.

[Paraneoplastic syndrome of disseminated intravascular coagulation in cardial carcinoma with multiple metastases]. / Sindrome paraneoplastica di coagulazione intravascolare disseminata in carcinoma cardiale con metastasi multiple.

A case of paraneoplastic DIC syndrome (asymptomatic carcinoma of the gastric fundus with multiple metastases) is described. Initially, differential diagnosis hesitated before thrombotic thrombocytopenic purpura (Moschowitz' syndrome), given the presence of grave microangiopathic haemolytic anaemia as a major symptom. The main characteristics of Moschowitz' syndrome and the most frequent causes of DIC are described in the discussion.

[The importance of thyroid hormone determination in the course of acute and chronic liver diseases]. / Importanza del dosaggio degli ormoni tiroidei in corso di epatopatie acute e croniche.

The RIA values of thyroid hormones in the course of acute and chronic liver disease were studied to see whether they were related to the severity of the picture in a series of 50 healthy subjects and 133 with various hepatopathies: 26 with acute viral hepatitis, 18 with alcoholic liver disease, 16 with alcoholic cirrhosis without ascites and 33 with ascites, 14 non-alcoholic cirrhosis without ascites and 24 with ascites. A reduction in T3 proportional to the seriousness of the clinical and laboratory findings was noted in chronic forms, whereas both T3 and T4 were high in acute viral hepatitis. There was no difference in T3 values in alcoholic and non-alcoholic cirrhosis of similar gravity, showing that the fall in serum T3 is not a specific alcohol-induced lesion. T3 less than 25 ng/100 ml proved the best index in the prediction of mortality (chi 2 = 20,5; p less than 0,0005).

[Changes in acid-base equilibrium and water-electrolyte balance in hepatic cirrhosis]. / Alterazioni dell'equilibrio acido-base ed idro-elettrolitico nella cirrosi epatica.

The acid-base and hydroelectrolyte balance were evaluated in 116 patients with cirrhosis of the liver divided (a posteriori) into subjects without ascites, those with tractable ascites, and those with intractable ascites. Alterations were much earlier and more frequent in the pre-ascitic stage. A fall in arterial blood O2 tension also proved a poor prognostic factor. The water load test and 24-hr determination of natriuria best reflected the clinical picture and should thus act as pointers to the correct planning of treatment.