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BACKGROUND: Chronic infection with hepatitis C virus (HCV) is the most common infectious disease among heroin abusers, but it is recommended that specific treatment with interferon be delayed until at least 6 to 12 months after the end of drug addiction. OBJECTIVE: We investigated the response of heroin abusers to interferon treatment shortly after the end of detoxification treatment with methadone. METHODS: We studied 2 homogeneous groups of white Italian patients with chronic HCV infection: former male heroin abusers and males without a history of drug addiction. Tumor necrosis factor, interleukin-1beta, interleukin-2, activated monocytes, anti-HCV antibodies, HCV RNA, and alanine aminotransferase levels were assessed. Standard treatment was initiated with 5 MU interferon alpha-n2b administered subcutaneously once daily for 8 weeks. Patients with negative HCV-RNA findings at the end of 8 weeks received further treatment with 5 MU TIW subcutaneously for an additional 48 weeks. RESULTS: Thirty of 47 patients in group A (former heroin abusers) and 30 of 30 patients in group B (controls) completed the study. Heroin abusers presented a significantly enhanced response to treatment compared with the controls. After 8 weeks, HCV-RNA test results were negative in 27 of 30 patients in group A (90.0%) and in 25 of 30 in group B (83.3%) (P = NS). Onset of relapse occurred significantly later in heroin abusers (mean [SD], 53 [3] weeks) than in controls (26 [2] weeks) (P < 0.05). Cytokine levels and activated CD11 antigen-expressing monocytes were significantly (P < 0.001) higher in heroin abusers than controls. CONCLUSION: Heroin abusers with chronic HCV infection were successfully treated with interferon alpha-n2b soon after the end of detoxification treatment. [ABSTRACT FROM AUTHOR]

Background: The conventional antiviral treatment of chronic hepatitis related to hepatitis C virus (HCV) often leads to anemia. In this case, it is necessary to reduce ribavirin dose or stop treatment, thus reducing the rate of sustained virological response., Aim: We investigated whether epoetin alpha administration improves treatment adherence and leads to higher percentage of response at the end of therapy and sustained virological response., Methods: Two hundred and fourteen individuals with genotype 1b HCV-related chronic hepatitis underwent treatment with pegylated (peg)-interferon alpha-2A 180 μg once weekly and ribavirin 1,000-1,200 mg/day; 174 were responders. Forty individuals completed treatment with no hemoglobin reduction; 134 developed anemia during therapy. Anemic responders were distributed randomly into two groups: group 1 continued therapy with epoetin alpha addiction; group 2 continued antiviral therapy with ribavirin reduction only., Results: Patients in group 1 achieved better control of hemoglobin levels (13.8 ± 1.2 g/dl at the end of therapy) than those in group 2 (11.5 ± 0.8 g/dl). Sustained virological response was 59.7% in group 1 compared with 34.4% in group 2 (p<0.01)., Conclusions: In patients with 1b HCV-related chronic hepatitis who develop anemia during antiviral treatment, administration of epoetin alpha increases hemoglobin levels and the end-of-treatment rate and sustains virological response by improving treatment adherence.

Aim: Des-gamma-carboxy prothrombin (DCP) is an abnormal prothrombin, increased in serum of patients with hepatocellular carcinoma (HCC) as result of an acquired defect of post-translational carboxylation of prothrombin's precursor. It is unclear if the reduced activity of gamma-carboxylase is secondary to vitamin K deficiency or to an altered gene encoding this enzyme. The aim of this study was to evaluate the effect of vitamin K administration on DCP and alpha-fetoprotein (AFP) levels, to identify a relationship between vitamin K and DCP serum levels and to investigate mechanisms of serum elevation of DCP levels., Methods: The authors determined DCP and AFP serum levels and vitamin K concentration in 64 cirrhotics with HCC and in 60 cirrhotic subjects without HCC. In HCC subjects DCP and AFP levels were measured before and after vitamin K administration. A t-test for unpaired data was applied (P values <0.05 statistically significant)., Results: Only HCC patients had detectable levels of DCP and significant AFP levels. Administration of vitamin K reduced DCP but not AFP levels in HCC patients. No correlation was observed between vitamin K concentration and DCP levels: vitamin K concentration was similar both in HCC patients and in control group without HCC; HCC patients had the same vitamin K concentration regardless of elevated o reduced DCP levels after vitamin K administration., Conclusion: DCP detectable serum levels are the result not only of vitamin K deficiency or selective defects of carboxylase, because probably alterations of membrane receptors or cytoplasmatic transfers, that are necessary for the function of vitamin K, are involved.

Aim: To estimate whether pretreatment serum iron levels, the HIC (hepatic iron concentration) and the distribution of hepatic iron identify the long-term "responders" and "non-responders" to therapy with peg-IFN and RBV, and whether the addition of phlebotomy could increase the likelihood of therapeutic response., Patients and Methods: 45 subjects with chronic hepatitis C were taking peg-IFN alpha-2a 180 microg once a week and RBV 1000 mg/die. The "responders" continued therapy with peg-IFN plus RBV, while, the "non-responders" were subjected to phlebotomy. After two weeks and subsequently every month the patients were subjected to blood test and clinical appraisal., Results: Hepatic iron storage meaningfully conditions the outcome of therapy with peg-IFN and RBV, its reduction by phlebotomy favourably correlates with response to treatment and, at last, the semiquantitative histological appraisal would have to be included in the pre-treatment work-up of patients with chronic hepatitis C., Conclusions: The study results, even though obtained on a small size of cases, allow to conclude that serum corporeal iron evaluation underestimates the real hepatic iron concentration; the hepatic iron concentration, in turn, negatively conditions the response to therapy with peg-IFN and RBV (by reducing the percentage of the fast virological response). Lastly, iron removal by phlebotomy favourably correlates with the response to treatment.

In medical practice we frequently encounter autoimmune syndromes, called "overlap-syndromes," which are of difficult nosographic classification because of the presence of sero-immunologic and clinical features common to various diseases having an autoimmune pathogenesis. Some of these syndromes have already been extensively described in scientific literature such as, for example, the presence of clinical and biohumoral alterations with hepatic and extrahepatic involvement, in the course of viral and autoimmune chronic hepatitis. The described clinical case can be classified as a new "overlap syndrome": Type 1 autoimmune hepatitis (AIH)/Primary pulmonary hypertension (PPH). Although the presence of pulmonary hypertension has been extensively described in the course of various connective tissue diseases (S.L.E., Mixed Connective Tissue Disease, Scleroderma, Hashimoto's Thyroiditis, Sjögren's Syndrome), in recent scientific literature, the association is quite rare. The interest in the described clinical case lies both in the possibility to classify it in the context of a more complex "overlap syndrome" AIH/PPH and in the correlated diagnostic and therapeutic implications. Therefore, in cases of primary pulmonary hypertension, a thorough immunological and hepatic functionality study is always recommended in order to ensure an early diagnosis and a prompt AIH treatment, thus warding off the risk of a rapid progression in cirrhosis.

PURPOSE: Only early detection of non-symptomatic patients is able to arrest the diffusion of the non-symptomatic HCV infection and lead to prompt treatment. Our aim was to attempt to correlate the presence of perihepatic lymph nodes and hepatitis C infection and to assess whether ultrasonography can have a role to promote specific investigations for pre-clinical diagnosis of virus C infection. METHOD: We performed a controlled study on a cohort of 7974 subjects from a town of 27000 inhabitants on the eastern coast of Sicily. Serologic hepatitis A, B and C markers, alanine aminotransferase levels and abdominal ultrasound examination according to size and number of peri-hepatic lymph nodes were performed on blind basis. RESULTS: One or more pathological lymph nodes were present in 684/7974 subjects. Haematochemical tests revealed the presence of anti-HCV positivity in 528/684 subjects with pathological lymph nodes and in 8/7290 subjects without pathological lymph nodes, there being a significant difference (P<0.0001) between the two groups. CONCLUSION: Our results confirm the association between perihepatic lymph nodes and virus C infection. Correct diagnostic assessment of this datum could lead not only to early diagnosis by specific blood test for HCV and consequent prompt aimed treatment, but could pave the way for efficacious territorial prevention and detection of an elevated percentage of likely non-symptomatic carriers.

Background: Endothelin-1 (ET-1) is able to determine functional and structural renal alterations and plasma levels of this vasoconstrictor peptide are increased in diabetic patients. In a selected group of type 2 normotensive diabetic patients with microalbuminuria, we investigated circulating ET-1 levels compared to a control group and verified whether there is a relationship between ET-1 levels and albumin excretion rate in diabetics., Subjects and Methods: Thirty-two microalbuminuric type 2 diabetic patients (12 males and 20 females; mean age 57 +/- 8 years) without hypertension, renal failure, hypercholesterolemia or atherosclerotic damage were selected. The control group was made up of 28 healthy subjects matched for sex and age. Blood pressure, creatinine clearance, serum cholesterol and plasma ET-1 values were determined in diabetic and control group. In diabetic patients, glycosilated hemoglobin and urinary albumin excretion rate were also assayed. Mean ET-1 values in diabetics and controls were compared using Student's t-test. Linear regression test was done to relate two variables. Statistical significance was set at p<0.05., Results: Mean ET-1 values were significantly higher in the diabetic group than in controls (11.77 +/- 1.16 pg/ml vs 8.9 +/- 2.1 pg/ml; p<0.05). No relationship (p>0.05) was found between circulating ET-1 and blood pressure, creatinine clearance, serum cholesterol and metabolic control in diabetics. There was a significant positive correlation (r=0.403; p=0.03) between plasma ET-1 levels and albumin excretion rate in diabetic patients., Conclusions: Our results showed that circulating ET-1 values were increased in microalbuminuric, normotensive, type 2 diabetic patients and correlated with albumin excretion rate. These findings confirm that endothelial dysfunction, as expressed by ET-1 levels, occurs early in these patients and support the hypothesis of a potential role for this peptide in development of microalbuminuria in diabetic nephropathy.

Laser therapy has gained wide acceptance and application in many medical disciplines. Side effects of laser therapy are rare and the most frequent mainly involve the skin. We describe a patient affected by familial adenomatous polyposis that had been repeatedly controlled and treated endoscopically using an Nd:Yag laser. He presented with a progressive hyperdynamic portal syndrome with ascites caused by some arterovenous fistulas. We hypothesize that a rare side effect of the laser treatment may have caused ischemic and coagulative tissue inflammation that triggered off the pathological communications between the arterial and portal circulation.

Background: Numerous experimental findings have underlined the relationships between liver damage and production of oxygen-derived free radicals during inflammation. In chronic hepatitis C liver disease this damage may be attributed to altered oxide-reductive balance and glutathione (GSH) depletion. Moreover, it may be linked to chronic inflammation provoked by the replicative activity of the hepatitis C virus and its relationships with immune system cells. Our aim was to assess the effects of combined IFN + NAC treatment to compare the effects of interferon alpha-n1 associated with N-acetyl cysteine treatment with the results observed using interferon therapy alone., Experimental Design: prospective randomised study., Setting: Ambulatory and hospitalised care., Patients: 77 selected patients affected by chronic C hepatitis., Interventions: our patients were investigated by laboratory tests (ALT values, RIBA test, HCV-RNA, oxide-reductive balance), liver biopsy and liver US. The recruited subjects were treated with interferon and N-acetyl cysteine or with interferon alone., Results: Our findings confirmed the presence of oxidative stress in patients with chronic hepatitis C and showed earlier relapse in patients treated with interferon alone. The difference between the results in patients treated with interferon and N-acetyl cysteine and those on interferon alone was significant., Conclusions: The good results and absence of side effects in patients treated with interferon + N-acetyl cysteine recommend wider use of this association.

Background and Aims: The authors searched for perihepatic lymph nodes during ultrasonography performed for other symptoms in 1222 Sicilian outpatients in order to assess the incidence and possible significance of the association of perihepatic lymph nodes and chronic hepatitis C., Method: One or two lymph nodes were observed in 184/1222 patients, and 142 of these 184 were anti-hepatitis C virus (HCV) positive., Results: Our results confirmed a very high incidence of perihepatic lymphadenopathy during chronic hepatitis. The concomitant presence of HCV virus and perihepatic lymph nodes may confirm the marked lymphotropism of this virus., Conclusion: As anti-HCV positivity is frequent in asymptomatic subjects with normal alanine aminotransferase concentrations, the authors believe that searching for sentinel perihepatic lymph nodes during abdominal ultrasonography could be recommended in routine diagnostic screening for HCV infection. Any perihepatic lymph nodes detected by this method could pinpoint subjects for whom more specific examinations are required, especially in areas where the virus is particularly endemic.

Background/aims: Numerous data have suggested that there may be a relationship between Helicobacter pylori (H. pylori) infection and extragastric diseases, including dermatological pathologies. We studied some cases of Hide's Prurigo Nodularis (NP), a very itchy skin disease of unknown origin, in order to asses whether there is a pathogenic correlation between PN and H. pylori infection., Methodology: Prurigo Nodularis had been diagnosed clinically and histologically in 42 outpatients (27 females and 15 males with mean age of 62 +/- 5 years). All patients were screened for H. pylori infection by esophagogastroduodenoscopy, histologic examination and specific immuno-enzymatic determination. Specific pharmacological treatment was administered to all patients with H. pylori infection., Results: H. pylori colonization was observed in 40/42 patients examined and 32/40 patients presented some immunologic alterations. After the pharmacological treatment, endoscopy and rapid urease test confirmed eradication of H. pylori in 39/40 cases; itching was greatly reduced in the latter and microscopic examination of repeated skin biopsies revealed an improved histologic picture in patients affected by PN associated with H. pylori infection., Conclusions: The concomitant presence of skin disease, H. pylori infection and immune disorders infers that there may be a pathogenic connection between bacterial infection and the inflammatory alteration of PN. We believe that the pharmacologic treatment induced remission of the skin lesions by direct control of H. pylori chronic infection; in fact, H. pylori may have triggered or enhanced the vasculitis which, in turn, may have enhanced the clinical signs and inflammatory histologic component of PN.

A case of familial Bardet-Biedl syndrome (BBS) in a 64-year-old woman is presented; it is characterized by abdominal obesity (BMI: 38.28; WHR: 0.98), slight mental retardation, polydactyly, pigmentary retinopathy and moderate renal failure, with insulin-resistant diabetes mellitus and severe inflammation of the left limb with necrosis of the last toe (the sixth) of the left foot. Four brothers and sisters of the patient presented the same syndrome. The patient had had healthy offsprings. The review of current literature indicates that BBS is a genetic autosomal recessive disease, formerly grouped with Laurence-Moon-Biedl syndrome but today considered as a separate entity. It is characterized by obesity, mental retardation, dysphormic extremities (syndactyly, brachydactyly or polydactyly), retinal dystrophy or pigmentary retinopathy, hypogonadism in males, and renal structural abnormalities or functional impairment. Extra- and intrafamilial variability of expressivity and severity of the various clinical manifestations was reported, among affected families and also in the same family. BBS is a rare but important syndrome, that should be known by the endocrinologist and the specialist in internal medicine, because it has an adverse prognosis, with early onset of blindness, insulin-resistant diabetes mellitus and severe renal impairment. Renal failure is a frequent cause of death early in life, even in the infant-juvenile years.

Methods: We investigated plasma and urinary endothelin-1 levels in eleven cirrhotic patients and ten healthy control subjects, to evaluate whether endothelin is involved in renal functional alterations of liver cirrhosis., Results: No significant difference in plasma ET-1 levels was observed between the two groups (p > 0.05) but urinary ET-1 excretion was significantly higher in cirrhotics than in controls (p < 0.001). Creatinine clearance (mean 56 +/- 7.6 ml/min) showed an inverse correlation with plasma ET-1 levels (p < 0.05) in cirrhotics., Conclusions: We believe this may be caused by enhanced local ET-1 activity linked to an up-regulation of its specific receptors and/or increased renal synthesis, resulting in augmented urinary excretion.

Background: We assessed plasma endothelin-1 (ET-1) concentrations in a group of hypertensive subjects in order to determine the possible presence of a disorder of ET-1 production and release., Methods: A selected cohort of hypertensive subjects was compared with a control group. Plasma levels of ET-1 in baseline conditions and after cold the pressor test (CPT) were measured. All subjects were studied as outpatients. Twenty-one male hypertensive patients were compared with 15 male controls. The hypertensive patients had undergone clinical examinations to rule out the presence of vascular damage. Clinical examination of the controls was performed to rule out hypertension. Patients with essential hypertension were 21 males, age: 57+/-7 years, body mass index 22.3+/-11.2 kg/m2. We assessed plasma ET-1 in baseline conditions and after a cold pressor test., Results: Means +/-SD baseline concentrations of ET-1 were 12.47+/-2.41 pg/ml in hypertensives and 8.2+/-3.8 pg/ml in controls (p<0.01). Mean +/-SD post CPT plasma ET-1 was 12.55+/-2.83 pg/ml in hypertensive subjects and 8.6+/-1.9 pg/ml in controls (p<0.01). CPT did not modify plasma ET-1 concentrations in either group. CPT significantly raised arterial pressure only in hypertensive subjects., Conclusions: These results lead us to postulate the presence of a disorder of ET-1 production and release in hypertensive subjects.

The case of a woman admitted to hospital various times because of the onset of a mantle-like oedematous syndrome is reported. Observations revealed a narrowing at the level of the internal jugular and right subclavian veins with total obliteration of the right anonymous vein caused by previous thrombosis induced by intravenous implantation of a pace-maker.

Thrombophilia is characterised by elevated thrombotic and embolic risk and may be caused by congenital or acquired coagulating inhibitor deficit. A young man was repeatedly admitted to Emergency Medicine Units because of pain, oedema and slight functional impairment of the left leg, and recurrent thrombophlebitis was diagnosed. During the most recent hospitalization, vena cava thrombosis was diagnosed and therapeutic management consisted of application of a caval filter and administration of dicoumarin anticoagulants. This case can be classified as a hereditary protein S deficiency with APC-resistance. However, non-strenuous, protracted and repeated physical trauma may have acted synergically with the congenital coagulation inhibitor deficiency, determining the thrombotic episodes, which are probably provoked by transient and functional alterations of the non-thrombogenic properties of the endothelium.