Promotion of the mediterranean diet incancer long-survivors by means of the Med-Food Anticancer Program: a pilot study.

BACKGROUND: The intervention "Med-Anticancer Food Program" has proven to be effective in promoting the Mediterranean Diet, significantly increasing the Mediterranean Adequacy Index in healthy subjects. There are no studies that have investigated the effectiveness of this intervention in individuals who have had a diagnosis of cancer. OBJECTIVE: To perform a pilot study to assess the opportunity of employing the methodology of the Med-Anticancer Food Program in order to encourage "long-term cancer survivors" to adhere to the Mediterranean Diet, as well as healthy people, and this in order to apply the program to larger groups. METHODS: From the residents' register of Foggia, a city in southern Italy, forty adults of both sexes, over 25 years of age, were recruited at random and assigned (1:1) as follows: - Twenty healthy subjects to the intervention-1 group - Twenty long-term cancer survivors to the intervention-2 group. The Med-Anticancer Food Program was applied to both groups with an articulated intervention 11 weeks long, followed by a 52-week period of follow up. By means of a food diary of the last 3 days, the Mediterranean Adequacy Index values were calculated before intervention (T0), after a period of 11 weeks of interventions (T1) and at the end of the 52 weeks of follow-up period (T2). The H0 hypothesis of the study was that there are no differences between the two interventions in reaching by T1, and maintaining at T2, values of Mediterranean Adequacy Index around 7, considered the optimum for adherence to the Mediterranean diet. RESULTS: Out of the subjects assigned to the intervention-1 group (n = 20), 11 subjects have completed the 52-months follow-up (55.0% ); for intervention-2, 16 (80%) out of 20 have completed it. The average age of subjects was 52.1 years. The Mediterranean Adequacy Index, of intervention-1 group significantly increased from 2.8 (T0) to 9.2 (T1) and to 9.0 (T2) (p <0.0001); whereas, in the intervention-2 group, Mediterranean Adequacy Index moved from 2.4 (T0) to 10.2 (T1) and to 9.3 (T2) (p <0.0001). The difference of Mediterranean Adequacy Index between the two study groups at T1 and T2 was not significant. Such non-significance persists also after the stratification by sex and age obtained with Mantel-Haenszel procedure. The performance of the values of the laboratory parameters considered (folic acid, total cholesterol, alkyl resorcinol) was similar in the subjects of both intervention 1 and 2, without any difference, while considered at a basal level T0, at T1 and at the end of the follow-up period (T2). CONCLUSIONS: The results of our work suggest the feasibility of conducting the Med-Anticancer Food Program in long-term cancer survivors. The results of the pilot study show that such intervention, carried on a small number of long term cancer survivors, is adequate to assess its feasibility but, due to the limited size of our study, a confirmation is required through larger nutritional prevention intervention studies.

Safety of sofosbuvir-based regimens after liver transplantation: longitudinal assessment of renal function in the prospective ANRS CO23 CUPILT study.

BACKGROUND: In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir-based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable. AIM: To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time. METHODS: In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre-treatment, on-treatment and post-treatment periods were 9 months, 3-9 months and 4.5 months. Interactions between eGFR slopes and the pre-treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On-treatment eGFR slopes were separated in tertiles. Pre- and post-treatment eGFR slopes were compared globally and according to tertiles. RESULTS: The post-treatment eGFR slope was significantly better than pre-treatment eGFR slope (+0.18 (IQR -0.76 to +1.32) vs -0.11 (IQR -1.01 to +0.73) mL/min/1.73 m2 /month, P = 0.03) independently of the pre-treatment eGFR (P = 0.99), ribavirin administration (P = 0.26), mycophenolate mofetil administration (P = 0.51) and stage of fibrosis (F3 and F4 vs lower stages, P = 0.18; F4 vs lower stages, P = 0.08; F4 Child-Pugh B and C vs lower stages, P = 0.38). Tertiles of on-treatment eGFR slopes were -1.71 (IQR -2.54 to -1.48), -0.78 (IQR -1.03 to -0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73 m2 /month. Pre- and post-treatment eGFR slopes were not significantly different according to tertiles (respectively, P = 0.34, 0.08, 0.73). CONCLUSION: The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir-based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients.

Acute colitis: differential diagnosis using multidetector CT.

AIM: To investigate the utility of multidetector CT (MDCT) in helping to establish the underlying cause of acute colitis. METHODS AND MATERIALS: All patients who had acute colitis with a well-identified cause and underwent abdomen 64-MDCT were included in the study. MDCT images were retrospectively analysed in a blinded fashion and the CT findings were correlated with the eventual aetiological diagnosis. RESULTS: The study population included 105 patients. Acute colitis was related to inflammatory bowel disease in 43 cases. MDCT was used to identify six relevant signs of inflammatory colitis: the "comb" sign (p < 0.001), enlarged lymph nodes (p < 0.001), abscess (p = 0.026), fibro-fatty infiltration (p = 0.007), small bowel involvement (p < 0.001), and the absence of an "empty colon" sign (p = 0.045). Multivariate logistic regression analysis identified three independent signs of inflammatory colitis: the "comb" sign, small bowel involvement, and enlarged lymph nodes. Acute colitis was related to bacterial infection in 35 cases. Five signs were significantly associated with infectious colitis: continuous distribution (p = 0.020), an "empty colon" sign (p = 0.002), absence of fat stranding (p = 0.013), and absence of a "comb" sign (p = 0.010) and absence of enlarged lymph nodes (p = 0.035). Multivariate analysis identified three independent signs: the "empty colon" sign and absence of fat stranding and of a "comb" sign. The remaining causes were ischaemic colitis (n = 21) and drug-related colitis (n = 6). MDCT examination provided five relevant signs of ischaemic colitis: fat stranding (p = 0.002), discontinuous distribution (p < 0.001), and absence of enlarged lymph node (p < 0.001), a "comb" sign (p = 0.006) and small bowel involvement (p = 0.037). CONCLUSIONS: MDCT provides certain suggestive signs that may be helpful in distinguishing the underlying aetiological cause of acute colitis.

Long-term outcome of chronic hepatitis C in a population-based cohort and impact of antiviral therapy: a propensity-adjusted analysis.

This population-based study aimed to assess the determinants of the outcome of chronic hepatitis C with analysis of the impact of antiviral therapy with or without sustained virological response (SVR) on cirrhosis decompensation, hepatocellular carcinoma, liver-related and non-liver-related mortality. A total of 1159 HCV-positive patients newly detected between 1994 and 2001 were included. For each outcome, the prognostic effect of patients' baseline characteristics was estimated by time-dependent Cox models using age as the time-scale and adjusting for treatment received during follow-up. The impact of antiviral therapy was assessed by using a propensity score in a sample including 184 patients treated in the first 24 months following diagnosis who were matched to 184 untreated patients. At the end of a 59-month median follow-up, 100 cases of compensated disease, 58 liver cancer and 163 deaths (55 liver related) were recorded. The 5-year rates of decompensated cirrhosis, hepatocellular carcinoma, liver-related and non-liver-related death were 4.4%, 2.7%, 5.0% and 8.9%, respectively. Multivariate analyses identified two variables with pejorative influence: alcohol consumption (RR = 4.29 for CD; RR = 5.76 for HCC; RR = 6.69 for liver-related death; P < 0.0001); HCV diagnosis unrelated to systematic screening (RR = 2.25 for CD; RR = 3.05 for HCC; RR = 4.31 for liver-related death, P < 0.03). In the matched subset, no significant benefit of antiviral therapy was observed. Nevertheless, among the 144 patients who achieved SVR, no death was observed. This population-based study showed substantial rates of decompensated cirrhosis, hepatocellular carcinoma and non-liver-related mortality. Alcohol consumption and absence of systematic screening were significant determinants of poor outcome, whereas treatment did not have significant influence.

Personalized management of patients with inoperable alveolar echinococcosis undergoing treatment with albendazole: usefulness of positron-emission-tomography combined with serological and computed tomography follow-up.

The present study aimed to identify a sub-group of inoperable alveolar echinococcosis (AE) patients undergoing long-term treatment with benzimidazole (BZM) who presented with an evolution suggestive of a parasitocidal effect. An evolution compatible with parasite death was observed in five patients.

[Hepatopulmonary syndrome]. / Le syndrome hépatopulmonaire.

Hepatopulmonary syndrome is characterized by the presence of portal hypertension with or without cirrhosis, an increased alveolar-arterial oxygen partial pressure difference greater than or equal to 15 mm Hg, and dilated pulmonary capillaries. Hepatopulmonary syndrome is found in up to 20% of patients with cirrhosis and should be considered in any patient who develops dyspnea or hypoxemia. Contrast echocardiography is enough to make the diagnosis of hepatopulmonary syndrome. The exact pathophysiology of hepatopulmonary syndrome remains unknown but nitric oxide is an important factor underlying hepatopulmonary syndrome. Hypoxemia progressively deteriorates and worsens the prognosis of cirrhotic patients. Hypoxemic patients must be controlled regularly to optimise the timing of liver transplantation. Indeed, a preoperative PaO(2) of less than or equal to 50 mm Hg alone or in combination with an isotopic shunt fraction greater than or equal to 20% are the strongest predictors of postoperative mortality. There are currently no effective medical therapies for hepatopulmonary syndrome but garlic powder and iloprost inhalation demonstrate clinical improvements in the pre- and in the post-transplant period.

Specific phenotype associated with diabetes mellitus secondary to chronic hepatitis C infection.

AIM: A link between chronic hepatitis C virus (HCV) infection, Type 2 diabetes mellitus and insulin resistance has been suggested by several studies. However, HCV infection appears to be associated with insulin resistance but not with the metabolic syndrome. The aim of this study was to determine whether chronic HCV infection had an impact on the clinical characteristics of Type 2 diabetes. METHODS: We studied retrospectively a group of patients with diabetes mellitus associated with HCV infection (HCV-DM) and compared them with patients with conventional Type 2 diabetes (DM). RESULTS: The HCV-DM patients had a lower body mass index (P = 0.001) and systolic blood pressure (P = 0.04) compared with patients with DM diabetes. Ten patients (27.0%) in the HCV-DM group and 35 (47.3%) in the DM group had microalbuminuria (P = 0.04). DM patients had significantly higher serum creatinine levels than HCV-DM patients [87 (72-108) vs. 77 (64-86) micromol/l, P = 0.02; median (interquartile range)] but creatinine clearance (Cockroft Gault calculation) was similar. One HCV-DM patient (2.7%) and 44 DM patients (59.4%) were treated with hypolipidaemic therapy (P = 0.0001). Even although nearly two-thirds of the overall DM group were prescribed cholesterol-lowering drugs, DM patients had significantly higher total cholesterol, high-density lipoprotein cholesterol and triglyceride levels than HCV-DM patients. CONCLUSION: Our study provides further evidence that HCV-DM patients have specific clinical characteristics in comparison with classical DM patients. These data suggest an association between HCV virus infection and the development of insulin resistance or diabetes mellitus without the typical features of the metabolic syndrome.

[Hepar lobatum carcinomatusum: a rare cause of portal hypertension complicating hepatic metastases in breast cancer]. / L'hepar lobatum carcinomatosum: une cause rare d'hypertension portale compliquant les métastases hépatiques d'un carcinome mammaire.

SUMMARY: Hepar lobatum carcinomatosum is an acquired liver dysmorphy associated with liver metastases of carcinoma, usually breast carcinoma. It may cause portal hypertension. The pathogenesis of this condition appears to be related to multifocal occlusion of intrahepatic branches of the portal vein by neoplasic thrombi and desmoplastic changes. The prognosis is poor despite apparent tumor regression on imaging. We report a case of variceal bleeding revealing a hepar lobatum carcinomatosum. Magnetic resonance imaging supported this diagnosis which was suspected in the clinical context.

Coeliac disease in chronic hepatitis C: a French multicentre prospective study.

BACKGROUND: A prevalence of 1.2% of coeliac disease (CD) in patients with chronic hepatitis C was recently reported, suggesting a possible epidemiological link between these two diseases. However, other studies have not found this relationship. AIM: To conduct a French multicentre prospective study to assess the prevalence of CD in hepatitis C virus (HCV)-infected patients. METHODS: Between June 2003 and November 2005, 624 consecutive HCV-positive out-patients were tested for antiendomysial IgA antibodies (AEA), antigliadin IgA and IgG antibodies (AGA). Patients with positive AEA or IgA AGA and positive IgG AGA in a context of a high suspicion of CD were asked to undergo gastroscopy with duodenal biopsies. RESULTS: Isolated IgA AEA, IgA AGA and IgG AGA were 0.16%, 5.7% and 4.4%, respectively. Gastroscopy was required for 39 patients, 31 were performed (eight refusals), but only 25 duodenal biopsies were performed as six patients had cirrhosis. CD was never detected. CONCLUSIONS: The prevalence of CD in HCV-positive patients was 0% (95% confidence interval: 0-0.59%), but there is a low prevalence of CD in the whole French population.

Continuous infusion of high-dose omeprazole is more effective than standard-dose omeprazole in patients with high-risk peptic ulcer bleeding: a retrospective study.

UNLABELLED: High-dose omeprazole reduces the rate of recurrent bleeding after endoscopic treatment of peptic ulcer bleeding. However, the effectiveness of high-dose vs. standard-dose omeprazole in peptic ulcer bleeding has never been shown. AIM: To compare the benefits of high-dose vs. standard-dose omeprazole in peptic ulcer bleeding. METHODS: We reviewed the medical files of patients admitted between 1997 and 2004 for high-risk peptic ulcer bleeding who had undergone successful endoscopic treatment. We distinguished 2 periods: before 2001, standard-dose omeprazole (40 mg/day intravenously until alimentation was possible, then 40 mg/day orally for 1 week); after 2001, high-dose omeprazole (80 mg bolus injection, then 8 mg/h continuous infusion for 72 h, then 40 mg/day orally for 1 week). During both periods, patients subsequently received omeprazole, 20 mg/day, orally for 3 weeks. RESULTS: We enrolled 114 patients (period 1, n = 45, period 2, n = 69). Therapy with high-dose omeprazole significantly decreased the occurrence of poor outcome (27 vs. 12%, P = 0.04), rebleeding (24 vs. 7%, P = 0.01), mortality due to haemorrhagic shock (11 vs. 0%, P < 0.001) and need for surgery (9 vs. 1%, P = 0.05). CONCLUSIONS: In this retrospective study, high-dose omeprazole reduced the occurrence of rebleeding, need for surgery and mortality due to hemorrhagic shock in patients with high-risk peptic ulcer bleeding, as compared with standard-dose omeprazole.

Flumazenil vs. placebo in hepatic encephalopathy in patients with cirrhosis: a meta-analysis.

BACKGROUND: Randomized controlled trials testing flumazenil in hepatic encephalopathy have shown conflicting results. AIM: To compare flumazenil and placebo in hepatic encephalopathy in patients with cirrhosis. METHODS: An overview of randomized controlled trials comparing flumazenil and placebo in hepatic encephalopathy in patients with cirrhosis was performed. For each end-point, heterogeneity and treatment efficacy were assessed by Peto and Der Simonian methods. As most trials were crossover in nature, a sensitivity analysis was performed including the two treatment periods. RESULTS: Six double-blind randomized controlled trials, including 641 patients (326 treated with flumazenil and 315 with placebo), were identified. The treatment duration ranged from 5 min to 3 days. Heterogeneity tests between control groups were not significant. The mean percentages of patients with clinical improvement (five trials) were 27% in treated groups and 3% in placebo groups. This difference was significant by both methods (Peto: odds ratio=6.15; 95% confidence interval, 4.0-9.5; P < 0.001; Der Simonian: mean rate difference, 29%; 95% confidence interval, 17-41; P < 0.001). The mean percentages of patients with electroencephalographic improvement were 19% in treated groups and 2% in placebo groups. This difference was significant only with the Peto method (odds ratio=5.8; 95% confidence interval, 3.4-9.7; P < 0.001). The sensitivity analysis showed similar results. CONCLUSIONS: This meta-analysis shows that flumazenil induces clinical and electroencephalographic improvement of hepatic encephalopathy in patients with cirrhosis.

The influence of human immunodeficiency virus coinfection on chronic hepatitis C in injection drug users: a long-term retrospective cohort study.

In this study we analyzed the influence of human immunodeficiency virus (HIV) infection on the course of chronic hepatitis C through multivariate analysis including age, alcohol consumption, immune status, and hepatitis C virus (HCV)-related virologic factors. Eighty HIV-positive and 80 HIV-negative injection drug users included between 1980 and 1995 were matched according to age, gender, and duration of HCV infection and followed-up during 52 months. The progression to cirrhosis was the primary outcome measure. The impact of HIV on HCV-RNA load, histologic activity index, response to interferon therapy, and liver-related death was also considered. In HIV-positive patients, chronic hepatitis C was characterized by higher serum HCV-RNA levels (P =.012), higher total Knodell score (P =.011), and poorer sustained response to interferon therapy (P =.009). High serum HCV-RNA level was associated with low CD4-lymphocyte count (P =.001). Necroinflamatory score was higher in HIV-positive patients (P =.023) independently of the CD4-lymphocyte count, whereas increased fibrosis was related to decreased CD4-lymphocyte count (P =.011). The progression to cirrhosis was accelerated in HIV-positive patients with low CD4 cell count (RR = 4.06, P =.024) and in interferon-untreated patients (RR = 4.76, P =.001), independently of age at HCV infection (P =.001). Cirrhosis caused death in 5 HIV-positive patients. The risk of death related to cirrhosis was increased in heavy drinkers (RR = 10.8, P =.001) and in HIV-positive patients with CD4 cell count less than 200/mm(3) (RR = 11.9, P =.007). In this retrospective cohort study, HIV coinfection worsened the outcome of chronic hepatitis C, increasing both serum HCV-RNA level and liver damage and decreasing sustained response to interferon therapy. Age and alcohol were cofactors associated with cirrhosis and mortality. Interferon therapy had a protective effect against HCV-related cirrhosis no matter what the patient's HIV status was.

Factors affecting liver fibrosis in human immunodeficiency virus-and hepatitis C virus-coinfected patients: impact of protease inhibitor therapy.

Hepatitis C virus (HCV)-related liver fibrosis progression is accelerated in human immunodeficiency virus (HIV)-infected patients. The effect of protease inhibitor (PI) therapy on liver fibrosis is unknown. The aim of this work was to analyze the impact of PI therapy on HCV-related liver fibrosis in HIV/HCV coinfected patients. We evaluated in a long-term follow-up retrospective cohort study the influence of antiretroviral therapy containing PI on liver fibrosis in 182 consecutive HIV/HCV coinfected patients. At liver biopsy, 63 patients had received PI and 119 patients had never been treated with PI. Relationships between liver histologic features, age, alcohol consumption, CD4 cell count, HIV-RNA load, and antiretroviral regimens were analyzed. Liver fibrosis stage was lower in patients receiving PIs by comparison with patients who had never received PIs (P =.03). The 5-, 15-, and 25-year cirrhosis rates were 2% versus 5%, 5% versus 18%, and 9% versus 27%, respectively, in patients who had received PIs compared with PI-untreated patients (P =.0006). Multivariate analysis identified 4 independent predictors of progression to cirrhosis: absence of protease inhibitor therapy (relative risk [RR] = 4.74, 95% confidence interval [CI], 1.34-16.67), heavy alcohol consumption (> or = 50 g daily) (RR = 4.71, 95% CI, 1.92-11.57), low CD4 cell count (<200/microL) (RR = 2.74, 95% CI, 1.17-6.41), and age at HCV contamination (> or = 20 years) (RR = 2.37, 95% CI, 1.04-5.38). In conclusion, protease inhibitor therapy might not accelerate progression to HCV-related cirrhosis. Furthermore, chronic use of antiretroviral therapy containing PI together with reduction of alcohol consumption and maintenance of high CD4 count could have a beneficial impact on liver fibrosis progression in HIV/HCV coinfected patients.

Treatment of chronic hepatitis C with amantadine hydrochloride in patients who had not responded to previous treatment with interferon-alpha and/or ribavirin.

Seven women and 3 men infected with hepatitis C virus, all of whom had failed to respond to therapy with either IFN-alpha or IFN and ribavirin, were treated with 200 mg/day of amantadine hydrochloride for 12 months. We found a significant decrease of serum ALT activity without any decrease in virus load. These results suggest that amantadine hydrochloride should not be used as monotherapy for patients who do not respond to treatment with IFN-alpha and/or ribavirin.