Noradrenalin vs terlipressin in patients with hepatorenal syndrome: a prospective, randomized, unblinded, pilot study.

BACKGROUND/AIMS: Treatment of hepatorenal syndrome (HRS) is based on vasoconstrictors. Terlipressin is the one with the soundest evidence. Noradrenalin has been suggested as an effective alternative. The current study was aimed at assessing the efficacy and safety of noradrenalin vs terlipressin in patients with HRS. METHODS: Twenty-two consecutive cirrhotic patients with HRS (9 with HRS type 1; 13 with HRS type 2) were included. Patients were randomly assigned to be treated with noradrenalin (0.1-0.7 microg/kg/min) and albumin (10 patients) or with terlipressin (1-2 mg/4h) and albumin (12 patients). Treatment was administered until HRS reversal or for a maximum of two weeks. Patients were followed-up until liver transplantation or death. RESULTS: Reversal of HRS was observed in 7 of the 10 patients (70%) treated with noradrenalin and in 10 of the 12 patients (83%) treated with terlipressin, p=ns. Treatment led in both groups to a significant improvement in renal and circulatory function. No patient developed signs of myocardial ischemia. CONCLUSIONS: Data from this unblinded, pilot study suggest that noradrenalin is as effective and safe as terlipressin in patients with HRS. These results would support the use of noradrenalin, a cheap and widely available drug, in the management of these patients.

Hepatic involvement in larva migrans of Toxocara canis: report of a case with pathological and radiological findings.

Patients with the clinical syndrome of visceral larva migrans as a result of Toxocara species, have typical lesions in the liver consisting of granulomas that contain numerous eosinophils and often Charcot-Leyden crystals. This syndrome is rarely taken into account in patients with cholestatic syndrome, especially when hypereosinophilic reaction is absent. We report the case of a 47-year-old immunocompetent woman who presented with abdominal pain, in whom multiple focal liver lesions were discovered. She had come in contact with dogs. Diagnosis of toxocariasi was done. A good clinical response has been obtained by treating with thiabendazole. We present the findings of various imaging studies of the patient. This report shows that visceral larva migrans may be the cause of a chronic liver disease and should be suspected also in patients without fever and hypereosinophilia with cryptogenic cholestatic and focal liver lesions.

Systemic nitric oxide production and renal function in nonazotemic human cirrhosis: a reappraisal.

OBJECTIVES: Several studies in human cirrhosis have demonstrated increased nitric oxide (NO) production. In experimental animals, intracerebroventricular administration of NO donors causes a marked depression of the endogenous dopaminergic activity, a function known to be physiologically recruited and exerting a natriuretic function in patients with compensated cirrhosis. The aim of this study is to evaluate the interaction between the systemic plasma levels of NO, the endogenous dopaminergic activity and the main parameters of renal function in patients with liver cirrhosis of differing degrees of severity. METHODS: A total of 21 patients (11 with preascitic and 10 with nonazotemic diuretic-free ascitic cirrhosis) and 10 healthy control subjects underwent the following tests: a) basal plasma renin activity (PRA) and aldosterone levels; b) renal clearances of sodium, potassium, inulin, para-minohippurate and lithium (the latter being a measure of the fluid delivery to the distal nephron); c) NO systemic plasma levels measured through paramagnetic resonance spectroscopy as nitrosylhemoglobin complexes; d) endogenous dopaminergic activity, evaluated by means of the incremental prolactin and aldosterone plasma levels after dopaminergic blockade with i.v. metoclopramide. RESULTS: NO plasma values and endogenous dopaminergic activity, although significantly increased with respect to healthy controls, were not different in the two groups of patients. The plasma NO/PRA ratio was significantly higher in the group of compensated patients with respect to ascitic cirrhotics (respectively, 18.3 +/- 11.8 vs 3.5 +/- 2.6 A.U./ng/ml/h, p < 0.001). Compared with compensated cirrhotics, patients with ascites showed significantly lower values of glomerular filtration rate (GFR) and renal plasma flow (RPF). Interestingly, GFR values were substantially the same in the ascitic patients and the control subjects. Compensated patients displayed a significant positive correlation between metoclopramide-induced incremental aldosterone plasma levels (i.e., endogenous dopaminergic tone) and fractional excretion of sodium (r = 0.58; p < 0.05). In the group of compensated patients, NO levels correlated inversely with creatinine plasma concentrations (r = -0.85; p < 0.001) and directly with inulin clearance (r = 0.65; p < 0.05). CONCLUSIONS: These data show that, at least in compensated cirrhotic patients, the stimulation of systemic NO production and the increased dopaminergic function may be mechanisms preventing renal perfusion, GFR, and fractional excretion of sodium from precocious reductions.

Multicentre randomized placebo-controlled trial of ursodeoxycholic acid with or without colchicine in symptomatic primary biliary cirrhosis.

AIM: To establish the efficacy of combination therapy with ursodeoxycholic acid (UDCA) and colchicine in patients with symptomatic primary biliary cirrhosis (PBC), defined by the presence of liver cirrhosis, pruritus or bilirubin exceeding 2 mg/mL. METHODS: A total of 90 patients were randomly assigned to ursodeoxycholic acid 500 mg/daily plus placebo (UDCA group, n=44), or ursodeoxycholic acid at the same dosage plus colchicine, 1 mg/daily (UDCA/C group, n=46). The two groups were comparable for age, sex, stage of disease, severity of pruritus, bilirubin, and Mayo score. All patients underwent clinical, ultrasonographic, and biochemical examinations at entry and then every 6 months up to 3 years of follow-up. Patients with cirrhosis underwent endoscopy every 12 months. In a sub-group of patients without cirrhosis, who consented, liver biopsy was repeated at the end of the study. RESULTS: The number of treatment failures (i.e. dead, orthotopic liver transplantation (OLT), complications of cirrhosis, doubling of bilirubin, untreatable pruritus) was 11 (25%) in the UDCA group and four (9%) in the UDCA/C group (P < 0.05). No significant differences were observed in terms of improvement of liver enzymes related to cholestasis and cytolysis and of amelioration of pruritus. The Mayo score values increased less above the baseline values at 24 and 36 month-intervals in the UDCA/C group than in the UDCA group. Histological evaluation at baseline and at the end of the study was available for 15 patients with pre-cirrhotic stage. A significant reduction in histological grading score was observed in patients from the UDCA/C group, whereas no changes in these histological scores were observed in the UDCA group. CONCLUSIONS: The addition of colchicine to ursodeoxycholic acid in patients with symptomatic primary biliary cirrhosis results in a small but significant reduction of disease progress.

Lymphocytic gastritis and protein-losing gastropathy.

Lymphocytic gastritis is a histopathological entity of unknown aetiology which is characterized by dense surface and foveolar epithelial T-cell infiltration. We report here an uncommon clinical presentation in a young female presenting with unexplained recurrent weight loss and peripheral oedema. Endoscopic and histological features before and after successful therapy with omeprazole are described.

Percutaneous endoscopic gastrostomy: a long-term follow-up.

Percutaneous endoscopic gastrostomy (PEG) is the preferred method of long-term tube feeding, but only a few studies describe a long-term follow-up. The purpose of this study is to analyze the follow-up of PEG enteral feeding patients in the long term, and to report on the complication and survival rates. Between January 1991 and June 1995, we studied 136 patients (49% cancer and 51% non-cancer patients; male = 68%, female = 32%) after PEG insertion. One hundred twenty-eight patients had a long-term follow-up of over 31 d. The mean duration of PEG feeding was 277 +/- 358 d (range 31-1590): 17% of patients returned to oral feeding, 34% continued enteral nutrition, and 49% died. Major complications occurred in 3% of the patients: 1 aspiration pneumonia, 1 subcutaneous abscess. 2 buried bumper syndrome. Minor complications arose in 14% of our cases: 8 tube blockages, 4 tube dislodgements, 6 site infections. For the whole group of 136 patients, survival probabilities after PEG insertion at 1, 6, 12, and 24 mo were 90.5%, 52%, 42%, and 35%, respectively. After 180 d, the difference in survival probabilities between cancer and non-cancer patients became significant (P < 0.02). Median survival probability was 64% for non-cancer and 39% for cancer patients, and this trend did not change over 2 y.

Efficacy and safety of interferon alfa therapy in chronic hepatitis C with autoantibodies to liver-kidney microsomes.

Interferon alfa (IFN) therapy is efficacious in chronic viral hepatitides. It may, however, cause adverse immunologic reactions in patients with concomitant autoimmune phenomena. A minority of patients with chronic type C hepatitis have antibodies against liver and kidney microsomes (anti-LKM) in serum. We therefore carried out this study to find out whether IFN is safe and efficacious also in this subgroup. We treated 92 consecutive cases of chronic hepatitis C with IFN. Twelve patients had anti-LKM< and the remaining 80 tested negative to the anti-LKM. The hepatitis C virus (HCV) infection was diagnosed on the basis of positive anti-HCV and HCV-RNA tests. We compared the clinical and virological virological results of the therapy and the side effects found in the two groups. We found that the response to therapy and the outcome after 1 year of follow-up were similar. Treatment was discontinued in one anti-LKM-positive patient because of a drastic increase in ALT levels at the fourth month of therapy. No untoward effect was observed in the other cases. Hepatitis C patients with anti-LKM may be exposed to an increased risk of an adverse hepatitic reaction while being treated with IFN. However, we found that the extent of the risk was minimal compared with the expected benefits of the therapy. IFN is therefore recommended as the first therapy to choose in these patients. They must, however, be monitored more closely for possible liver dysfunction than the ordinary hepatitis C patient.

Primary biliary cirrhosis: lung involvement.

Sub-clinical lung impairment, mostly represented by a reduced diffusion of alveolar gases, is a recognised complication of advanced primary biliary cirrhosis. The aim of the study was to evaluate the prevalence and type of pulmonary involvement in primary biliary cirrhosis and the relationship between lung function abnormalities and selected epidemiological and clinical variables. Sixty-one patients with different stages of primary biliary cirrhosis consecutively seen in our outpatient clinic were evaluated. The advancement of primary biliary cirrhosis was characterised by the histological stage, the presence of signs of portal hypertension and the Mayo Risk Score: a Cox regression model using serum bilirubin and albumin levels, prothrombin time, age and degree of oedema as selected variables. We measured static and dynamic lung volumes, by means of a spirometer, and diffusing capacity for carbon monoxide. Rheumatological disorders were evaluated by an independent rheumatologist. No patient complained of respiratory symptoms. Airway obstruction was present in one patient. In 24 patients (39%) the alveolar diffusion capacity was reduced. We did not find any significant relationship between diffusing capacity and smoking habits, advancement of liver disease and concomitant Sjogren syndrome. Reduced diffusion capacity showed a significant correlation with the presence of complete or incomplete CREST syndrome (p < 0.01) and with the presence of circulating anti-centromere antibodies (p < 0.05). Alveolar diffusion capacity is frequently impaired in patients with primary biliary cirrhosis, usually in the absence of clinical manifestations. These alterations mostly affect patients with concomitant CREST syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

[Percutaneous endoscopic gastrostomy]. / Gastrostomia endoscopica percutanea.

Surgical gastrostomies were first performed in the middle of the 19th century and modified during the following years, but the most important technical improvement was percutaneous endoscopic placement (PEG), in 1980 by Ponsky and Gauderer. This technique doesn't require anesthesia and it in possible also in patients with contraindications to surgical gastrostomy. The simple procedure involves a shorter hospitalization, lower risks and reduced costs. Many authors already reported the good results of this new technique, that can be performed on a day-hospital regimen as well. The main indications are head and neck cancers, neurologic diseases involving food intake capacity, cancer cachexia, obstruction of the GI tract when there is enough space for an endoscopic procedure. Every disease that can compromise food intake for a period longer than 60 days can find an indication in placing a percutaneous gastrostomy. The advantage for the patient is a much better psychological tolerance compared with a naso-gastric tube. Also the incidence of mechanical complications of a PEG is much lower. In our experience from October '90 to July '92 we followed 34 patients with PEG, 22 males and 12 females, with mean age of 69 years (range 41-88). We used 9-French tube placed using the pull-method technique. All patients received antibiotic therapy for 5 days. About 12 hours after PEG placement all patients began using the gastrostomy, initially with the administration of electrolyte solutions and later with enteral polymeric formulas. The constant increase led all patients to a 1500 non protein calories daily intake in 3-4 days.(ABSTRACT TRUNCATED AT 250 WORDS)

[Major clinical complications of hepatic cysts and angiomas. Report of 8 cases]. / Complicazioni cliniche maggiori di cisti ed angiomi epatici. Rapporto di otto casi.

The detection of hepatic cysts and hemangiomas has become relatively frequent after the diffusion of US imaging, but rarely they cause major clinical problems. We report our experience with 8 cases (4 cysts and 4 hemangiomas) which caused either signs and symptoms simulating a hepatic disease or compression on vascular structures with systemic consequences.

Hepatitis C virus-related chronic liver disease with autoantibodies to liver-kidney microsomes (LKM). Clinical characterization from idiopathic LKM-positive disorders.

This study was carried out on 33 patients who were sero-positive for liver-kidney microsomal antibodies (LKM) in order to examine clinical features and the presence of underlying hepatitis C virus infection. Twenty-four sera were positive for antibodies against HCV (anti-HCV) as detected by enzyme immunoassay and confirmed by recombinant immunoblot assay. These patients had chronic liver disease and the majority of those treated with interferon responded favourably. Three of the nine anti-HCV-negative patients had idiopathic chronic hepatitis and two responded favourably to steroids. Two patients were diagnosed as having toxic hepatitis and the other four had various extrahepatic disorders without evidence of liver involvement. The immunoblotting analysis showed reactivity with a 50 kDa microsomal protein which presumably corresponded to cytochrome P-450 db1 both in anti-HCV-positive and -negative sera. In addition a few anti-HCV-positive sera also reacted with a 35 kDa microsomal antigen. Autoimmune markers different from LKM were absent in both groups. The high prevalence of antibodies to the hepatitis C virus among LKM-positive sera confirms that this infection plays a role in forms of chronic hepatitis that had previously been labelled autoimmune. In patients with LKM the presence of anti-HCV may help to forecast a therapeutic response to interferon, while its absence may forecast response to steroid therapy.

Atypical chest pain: coronary or esophageal disease?

Retrosternal pain can be caused both by cardiac and esophageal disease. This work presents the results of cardiac and esophageal investigations in 55 patients, who had atypical chest pain. Isolated esophageal disease was found in 45% of the subjects while 14.5% had significant coronary arterial disease. Both diseases were found in 10.9% of the patients and neither disease in 29%. We conclude that esophageal disease is very frequent in patients with atypical chest pain but it does not always completely account for the symptoms. Such patients should, in our opinion, be submitted to an electrocardiographic stress test. If the result is positive or non-diagnostic, coronary cineangiography should be performed, irrespective of the results of esophageal investigations. If the electrocardiographic stress test is negative, coronary investigations can be deferred. Esophageal investigations can account for the symptoms in about half of such cases.