Fully covered self-expanding metal stents for benign colonic strictures.

BACKGROUND AND STUDY AIMS: Uncovered self-expanding metal stents offer effective relief for colonic obstruction. The aim of this study was to determine the effectiveness of fully covered self-expanding metal stents (FCSEMSs) in the treatment of benign colonic strictures. PATIENTS AND METHODS: All patients presenting with a symptomatic benign colonic stricture (occlusion or subocclusion) during a 6-year study period were treated with FCSEMSs. The stents were placed and removed 4 - 6 weeks later at one of 10 endoscopy centers. The efficacy of the stent (clinical and radiological signs of colonic decompression within 48 hours), technical success, stent retrieval, safety, and recurrence of symptoms were evaluated during follow-up. Univariate and multivariate analyses were performed to identify variables associated with clinical success, stent migration, and symptom recurrence. RESULTS: The study included 43 patients (24 men, 19 women; mean age 67.6 ± 10.4) with occlusive (n = 18) or subocclusive symptoms (n = 25) due to anastomotic (n = 40), post-ischemic (n = 2), or post-radiation (n = 1) strictures. Insertion was successful in all patients. Clinical success was obtained in 35 patients (81 %). Migration was observed in 27 patients (63 %). The median duration of stenting was 21 days (95 %CI 17.8 - 35.4 days). Multivariate analysis showed that stents more than 20 mm wide migrated significantly less often. Recurrence of obstructive symptoms was observed in 23 patients (53 %), irrespective of migration. No predictive factors for recurrence or clinical efficacy were found. CONCLUSIONS: FCSEMSs for treatment of symptomatic benign colonic strictures are safe and effective, despite a high rate of spontaneous migration.

Persistently normal alanine aminotransferase levels in HIV/HCV-coinfected patients: the role of steatosis.

OBJECTIVE: The frequency and significance of, and liver biopsy findings associated with, a persistently normal alanine aminotransferase (ALT) level in HIV/hepatitis C virus (HCV)-coinfected patients are poorly characterized. We analysed factors associated with persistently normal ALT levels, defined as at least three consecutive normal ALT values over a 6-month period, in a group of 381 HIV/HCV-coinfected patients. METHODS: Patients were categorized into two groups according to ALT values: group 1, patients with persistently normal ALT levels; and group 2, patients with elevated ALT values. Possible interactions with host factors, HIV and HCV viral factors, antiretroviral treatment and histological features were examined. RESULTS: Thirty-six patients (9.4%) had persistently normal ALT levels. None of the 36 patients had cirrhosis. Seven patients (19.4%) had a METAVIR fibrosis score of F3. In multivariate analysis, a lower mean METAVIR inflammation score [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.28-0.89; P=0.017], the absence of steatosis (OR 0.43, 95% CI 0.20-0.90; P=0.026) and HCV genotype 4 infection (OR 2.81, 95% CI 1.15-6.68; P=0.023) were associated with persistently normal ALT levels. CONCLUSION: The slower progression of chronic hepatitis in patients with persistently normal ALT levels could be related, in part, to a lower frequency of steatosis.

Low interleukin-10 production by monocytes of patients with a self-limiting hepatitis C virus infection.

Host factors seem to be crucial for the spontaneous clearance of hepatitis C virus (HCV). Monocytes play a pivotal role in innate immunity and help regulate adaptive responses. This study assesses the characteristics of monocytes from patients with self-limiting HCV infections. We studied 35 consecutive patients [11 with a self-limiting HCV infection, 16 chronically infected with HCV and sustained virological responders (SVR) following antiviral therapy, and eight chronically infected HCV but untreated] and eight healthy donors (HD). The production of interleukin (IL)-10, tumour necrosis factor-alpha (TNF-alpha) and IL-12p40 by monocytes stimulated with lipopolysaccharides(LPS) or HCV Core protein was measured by enzyme-linked immunoassay. Monocyte surface markers were analysed by flow cytometry. LPS and Core protein triggered IL-10 and TNF-alpha production, but monocytes from self-limiting infection patients produced significantly less IL-10 and TNF-alpha than those of SVR, chronically infected or HD (P < 0.05), while IL-12p40 production was unchanged. This cytokine production profile did not appear to be due to expansion of the CD14(+) CD16(+) monocyte subset or to a classical or alternative activation monocyte profile. Monocytes from self-limiting infection patients had more CCR7 than those from SVR or chronically infected patients (P < 0.05). Monocytes of self-limiting infection patients appear to produce little IL-10 and TNF-alpha in response to viral or unspecific stimulation and to have a higher CCR7 expression. This profile seems to be independent to a particular monocyte subset or activation state. Low IL-10 production may help establish an effective immune response and spontaneous HCV clearance.

Acute renal failure following liver transplantation with induction therapy.

AIMS: To identify the predictive factors for acute renal failure (ARF) in a retrospective study of 100 orthotopic liver transplantations (OLT) performed in 94 patients between 2000 and 2003. METHODS: Acute renal failure (ARF) was defined using the RIFLE criteria, i.e. injury when creatinine doubles or GFR halves, and failure when creatinine trebles or GFR decreases by > 75%. Patients on dialysis pre OLT (n = 3) were excluded from the study. Immunosuppression included steroids, calcineurin inhibitors (CNIs), with (n = 32) or without mycophenolate mofetil. A total of 85% of patients also received induction therapy with antithymocyte globulins (29%) or anti-CD25 monoclonal antibodies (56%). RESULTS: 39 patients (41.5%) and 21 (22.3%) patients developed injury, and failure, respectively. Of these, 10 (10.6%) underwent dialysis. Univariate analysis revealed that acute renal dysfunction with a RIFLE score > or = 3 was significantly associated with a pre-operative serum creatinine level of > 100 micromol/l, pre-operative creatinine clearance of < 75 ml/mn, need for a transfusion (> 10 red packed units), post-operative diuresis of < 100 ml/h, use of vasopressive drugs, times to aspartate (AST) and alanine (ALT) aminotransferase peaks of > 20 and > 24 hours, respectively, relaparotomy, CNIs transient discontinuation, and the use of lower daily dosage of CNIs at post-OLT Days 3, 5, 7 and 15. In multivariate analysis, failure was significantly associated with time to AST peak (> 20 h) (OR 6.35 (1.2 - 33.6), p = 0.029), post-operative diuresis (< 100 ml/h) (OR 9.8 (2.03 47.3), p = 0.004), post-operative use of vasopressive drugs (OR 9.91 (2.02 - 48.7), p = 0.004), and transient CNIs withdrawal (OR 51.08 (7.58-344.1), p < 0.0001). Finally, the occurrence of ARF was significantly associated with an increased number of days on mechanical ventilation, on stay-in intensive care unit (ICU), and on overall hospitalization time. CONCLUSION: ARF is quite common after OLT and significantly increases the post-operative time at the hospital, thereby increasing the OLT cost. Its independent predictive factors are mainly related to perioperative events.

Evaluation of alpha-fetoprotein assay in ascitic fluid for the diagnosis of hepatocellular carcinoma.

Ascites and hepatocellular carcinoma are frequently associated. We evaluated the usefulness of alpha-fetoprotein assay in ascitic fluid versus the serum assay, for the diagnosis of hepatocellular carcinoma, in 125 patients with peritoneal effusions (31 patients with hepatocellular carcinoma, 14 with extra-hepatic malignancies and 80 with a benign effusion). Albumin and total protein were also assayed and cytological analysis of the ascitic fluid performed. Alpha-fetoprotein appeared to be lower in ascitic fluid than in serum. For a diagnostic specificity of 95%, the thresholds were 18.9 microg/l in serum and 4 microg/l in ascitic fluid and the diagnostic sensitivity of alpha-fetoprotein was identical in serum and ascitic fluid (67.7%). Various ratios between alpha-fetoprotein and albumin or total protein did not enhance the diagnostic performance. Thus alpha-fetoprotein concentration in ascitic fluid reflected the serum concentration and proved to be of similar value for the diagnosis of hepatocellular carcinoma, providing that the appropriate thresholds are considered.

Better efficacy of a 12-month interferon alfa-2b retreatment in patients with chronic hepatitis C relapsing after a 6-month treatment: a multicenter, controlled, randomized trial. Le Groupe D'étude et De Traitement du Virus De L'hépatite C (Get.Vhc).

We studied the efficacy of three interferon alfa-2b (IFN-2b) regimens for the retreatment of patients with chronic hepatitis C (CHC) with prior complete response followed by relapse. Consecutive patients with CHC who had a complete biochemical response but relapse after a first course of 6 months of IFN with 3 million units (MU) given subcutaneously three times per week were enrolled in the study. Six to 24 months after the end of the first treatment, the patients were randomly assigned to receive IFN with either the same regimen (group 1), a regimen of 12 months with 3 MU (group 2), or a regimen of 6 months with 10 MU (group 3). Sustained biochemical response was defined as normal serum alanine transaminase (ALT) values during the follow-up and sustained virological response as a clearance of hepatitis C virus (HCV) RNA from the serum at the end of follow-up (6 months' posttreatment). Histological improvement was defined as a decrease of 1 point in Metavir score between the first liver biopsy and a biopsy performed at 6 months' postretreatment. Two hundred forty-seven patients were randomized: 75 to group 1, 91 to group 2, and 81 to group 3. In an intent-to-treat analysis, 12%, 36.3%, and 18.5% of patients had a sustained biochemical response after retreatment in groups 1, 2, and 3, respectively (P <.001); 13. 8%, 32.4%, and 17.2% of patients had a sustained virological response after retreatment in groups 1, 2, and 3, respectively (P <. 05). A low viral load and patients in group 2 were independently associated with a sustained biochemical response. A low Knodell score index before treatment, patients with a high level of ALT before retreatment, genotype 3, low viral load, and patients in group 2 were independently associated with sustained virological response. Younger age, a high level of ALT, a low level of gamma-glutamyl transferase before retreatment, low viral load, and patients in group 2 were independently associated with sustained biochemical and virological response. Among the 80 patients with repeated liver biopsies, 47.6% had improved histological activity scores; this improvement was associated with a sustained biochemical and virological response. In patients with CHC initially treated with 3 MU of IFN given subcutaneously three times per week over a 6-month period, and who subsequently developed a relapse after a biochemical response, retreatment with a regimen of 3 MU of IFN given three times per week for 12 months produced better biochemical and virological sustained response rates than regimens involving a higher dose or a shorter duration of retreatment. The biochemical and virological sustained response was associated with histological improvement.

Haemodynamic effects of molsidomine and propranolol in patients with cirrhosis.

Propranolol and molsidomine have both been shown to decrease the hepatic venous pressure gradient in patients with cirrhosis. The present study aimed at assessing the effects of the combination of these two drugs on splanchnic and systemic haemodynamics of cirrhotic patients. Fifteen patients with biopsy proven alcoholic cirrhosis had haemodynamic measurements under basal conditions, 60 min after oral administration of 4 mg molsidomine then 15 min after intravenous administration of 15 mg propranolol. As compared with baseline values, molsidomine was found to decrease mean arterial pressure (-7.9%, (P < 0.01), cardiac output (-7.3%, P < 0.01), pulmonary wedged pressure (-45.8%, (P < 0.05) and hepatic venous pressure gradient (-11.7%, P < 0.01). Propranolol decreased heart rate (-21%, P < 0.01), further decreased cardiac output (-20.6%, (P < 0.01) and hepatic venous pressure gradient (-10.5%, P < 0.01). As a whole, molsidomine plus propranolol decreased mean arterial pressure (-8%, P < 0.01), heart rate (-19%, P < 0.01), cardiac output (-26.5%, P < 0.01) and hepatic venous pressure gradient (-21%, P < 0.01). Pulmonary wedged pressure, liver blood flow and hepatic intrinsic clearance of indocyanine green were not significantly changed by the association of molsidomine and propranolol. We conclude that in patients with cirrhosis, molsidomine and propranolol potentiate their effects on hepatic venous pressure gradient. Such a combination could therefore prove useful in the treatment of portal hypertension.