Performance of rapid diagnostic tests for the detection of antibodies to hepatitis C virus in whole blood collected on dried blood spots.

Rapid diagnostic tests (RDTs) represent an attractive alternative to enzyme immunoassays. A total of 207 individuals, including 68 HCV-seronegative subjects, 10 patients with resolved infection and 129 patients with chronic HCV infection, were studied. The specificity of RDT detection of anti-HCV antibodies in whole blood was 100% with the four RDTs tested: OraQuick(®) HCV Rapid Antibody Test, First Response HCV Card Test, ASSURE HCV Rapid Test and MultiSure HCV Antibody Assay. Their diagnostic sensitivity varied between 98.6% and 100%. RDT detection of anti-HCV antibody in whole blood collected on dried blood spots appears to be a promising new tool for broadscale screening of HCV infection in high- to medium-risk populations.

Cost-effectiveness and budget impact of interferon-free direct-acting antiviral-based regimens for hepatitis C treatment: the French case.

We evaluated the cost-effectiveness and the budget impact of new DAA-based regimen use in France. A Markov model simulated chronic hepatitis C (CHC) treatment interventions with IFN-based and IFN-free regimens at stage of fibrosis ≥F3, ≥F2 or regardless of fibrosis stage, and treatment either with the least or the most expensive combination. It estimated quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). It also assessed the budget impact over 5 years of treating all CHC-screened patients, regardless of fibrosis, assuming ≤20 000 patients treated/year and priority to ≥F3. Sensitivity analyses were also conducted. For genotypes (G) 1-4, the initiation of IFN-free regardless of fibrosis was a cost-effective strategy compared to prior standard of care (SOC) initiated at stage F2: €40 400-88 300/QALY gained in G1; similar results were obtained for patients infected with G4. Considering G2-3, the most cost-effective strategy was IFN-based regimens regardless of fibrosis compared to prior SOC initiated at stage F2: €21 300 and €19 400/QALY gained, respectively; the strategy with IFN-free regimens being more effective but not cost-effective at current costs. The budget impact of treating all CHC-screened patients over 5 years would range between 3.5 and 7.2 billion €, depending on whether one considers the least or the most expensive combination of new DAAs and whether one treats G2-3 with IFN-based or IFN-free new DAAs. In France, treatment initiation with new DDAs regardless of fibrosis stage is cost-effective, but would add 3.5-7.2 billion € to an already overburdened medical care system.

Effects 4.5 years after an interactive GP educational seminar on antibiotic therapy for respiratory tract infections: a randomized controlled trial.

BACKGROUND: The few studies assessing long-term effects of educational interventions on antibiotic prescription have produced conflicting results. OBJECTIVES: Our aim was to assess the effects after 4.5 years of an interactive educational seminar designed for GPs and focused on antibiotic therapy in respiratory tract infections (RTIs). The seminar was expected to decrease antibiotic prescriptions for any diagnosis. METHODS: We conducted a randomized controlled parallel-group trial in a Paris suburb (France), with GPs as the randomization unit and prescriptions as the analysis unit. The intervention occurred in September 2004 and the final assessment in March 2009. Among 203 randomized GPs, 168 completed the study, 70 in the intervention group and 98 in the control group. Intervention GPs were randomized to attending only a 2-day interactive educational seminar on evidence-based guidelines about managing RTIs or also 1 day of problem-solving training. The primary outcome was the percentage of change in the proportion of prescriptions containing an antibiotic for any diagnosis in 2009 versus 2004. An intention-to-treat sensitivity analysis was performed using multiple imputation. RESULTS: After 4.5 years, absolute changes in the primary outcome measure were -1.1% (95% confidence interval: -2.2 to 0.0) in the intervention group and +1.4% (0.3-2.6) in the control group, yielding an adjusted between-group difference of -2.2% (-2.7 to -1.7; P < 0.001). Both intervention modalities had significant effects, and multiple imputation produced similar results. CONCLUSIONS: A single, standardized and interactive educational seminar targeting GPs significantly decreased antibiotic use for RTIs after 4.5 years.

Historical epidemiology of hepatitis C virus (HCV) in selected countries.

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6,358,000 cases in 2008 and Brazil with 2,106,000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

The state of hepatitis B and C in the Mediterranean and Balkan countries: report from a summit conference.

The burden of disease due to chronic viral hepatitis constitutes a global threat. In many Balkan and Mediterranean countries, the disease burden due to viral hepatitis remains largely unrecognized, including in high-risk groups and migrants, because of a lack of reliable epidemiological data, suggesting the need for better and targeted surveillance for public health gains. In many countries, the burden of chronic liver disease due to hepatitis B and C is increasing due to ageing of unvaccinated populations and migration, and a probable increase in drug injecting. Targeted vaccination strategies for hepatitis B virus (HBV) among risk groups and harm reduction interventions at adequate scale and coverage for injecting drug users are needed. Transmission of HBV and hepatitis C virus (HCV) in healthcare settings and a higher prevalence of HBV and HCV among recipients of blood and blood products in the Balkan and North African countries highlight the need to implement and monitor universal precautions in these settings and use voluntary, nonremunerated, repeat donors. Progress in drug discovery has improved outcomes of treatment for both HBV and HCV, although access is limited by the high costs of these drugs and resources available for health care. Egypt, with the highest burden of hepatitis C in the world, provides treatment through its National Control Strategy. Addressing the burden of viral hepatitis in the Balkan and Mediterranean regions will require national commitments in the form of strategic plans, financial and human resources, normative guidance and technical support from regional agencies and research.

The state of hepatitis B and C in Europe: report from the hepatitis B and C summit conference*.

Worldwide, the hepatitis B virus (HBV) and the hepatitis C virus (HCV) cause, respectively, 600,000 and 350,000 deaths each year. Viral hepatitis is the leading cause of cirrhosis and liver cancer, which in turn ranks as the third cause of cancer death worldwide. Within the WHO European region, approximately 14 million people are chronically infected with HBV, and nine million people are chronically infected with HCV. Lack of reliable epidemiological data on HBV and HCV is one of the biggest hurdles to advancing policy. Risk groups such as migrants and injecting drug users (IDU) tend to be under-represented in existing prevalence studies; thus, targeted surveillance is urgently needed to correctly estimate the burden of HBV and HCV. The most effective means of prevention against HBV is vaccination, and most European Union (EU) countries have universal vaccination programmes. For both HBV and HCV, screening of individuals who present a high risk of contracting the virus is critical given the asymptomatic, and thereby silent, nature of disease. Screening of migrants and IDUs has been shown to be effective and potentially cost-effective. There have been significant advances in the treatment of HCV and HBV in recent years, but health care professionals remain poorly aware of treatment options. Greater professional training is needed on the management of hepatitis including the treatment of liver cancer to encourage adherence to guidelines and offer patients the best possible outcomes. Viral hepatitis knows no borders. EU Member States, guided by the EU, need to work in a concerted manner to implement lasting, effective policies and programmes and make tackling viral hepatitis a public health priority.

A 20-year experience of electron microscopy in the diagnosis of primary ciliary dyskinesia.

Transmission electron microscopy (TEM) analysis of ciliary ultrastructure is classically used for the diagnosis of primary ciliary dyskinesia (PCD). We report our extensive experience of TEM analysis in a large series of patients in order to evaluate its feasibility and results. TEM analysis performed in 1,149 patients with suspected PCD was retrospectively reviewed. Biopsies (1,450) were obtained from nasal (44%) or bronchial (56%) mucosa in children (66.5%) and adults (33.5%). TEM analysis was feasible in 71.4% of patients and showed a main defect suggestive of PCD in 29.9%. TEM was more feasible in adults than in children, regardless of the biopsy site. Main defects suggestive of PCD were found in 76.9% of patients with sinopulmonary symptoms and in only 0.4% of patients with isolated upper and 0.4% with isolated lower respiratory tract infections. The defect pattern was similar in children and adults, involving dynein arms (81.2%) or central complex (CC) (18.8%). Situs inversus was never observed in PCD patients with CC defect. Kartagener syndrome with normal ciliary ultrastructure was not an exceptional condition (10.2% of PCD). In conclusion, TEM analysis is feasible in most patients and is particularly useful for PCD diagnosis in cases of sinopulmonary syndrome of unknown origin.

The impact of the prevention programme of hepatitis C over more than a decade: the French experience.

To assess the impact of the French national hepatitis C prevention programme initiated in 1999, we analysed trends in hepatitis C virus (HCV) prevalence, testing and characteristics of HCV-infected patient at first referral from 1994 to 2006. We used four data sources: Two national population-based sero-prevalence surveys carried out in 1994 and 2004; two surveillance networks, one based on public and private laboratories throughout France and the other on hepatology reference centres, which aim to monitor, respectively, trends of anti-HCV screening and of epidemiological-clinical characteristics of HCV patients at first referral. Between 1994 and 2004, the anti-HCV prevalence for adults aged 20-59 years decreased from 1.05 (95% confidence interval 0.75-1.34) to 0.71 (0.52-0.97). During the same period, those anti-HCV positive with detectable HCV RNA decreased from 81 to 57%, whereas, the proportion of anti-HCV positive persons aware of their status evolved from 24 to 56%. Anti-HCV screening activity increased by 45% from 2000 to 2005, but decreased in 2006 (-10%), while HCV positivity among those tested decreased from 4.3 to 2.9%. The proportion of cirrhosis at first referral remains around 10% between 2001 and 2006, with many patients with excessive alcohol consumption (34.7% among males) or viral co-infections (HIV seropositivity for 5.2% patients). Our analysis indicates that the national programme had a positive impact at the population level through improved prevention, screening and management. There is still a need to identify timely those at risk for earlier interventions, to assess co-morbidities better and for a multidisciplinary approach to HCV management.

Hepatitis G virus: a suitable marker of in vivo efficacy for pathogen inactivation.

Being an orphan virus despite a large number of investigations, hepatitis G virus is a blood-borne agent for which screening is not required in blood donations. The in vivo efficacy of pathogen inactivation methods could be assessed by the absence of hepatitis G virus markers after transfusion of pathogen-inactivated blood products, in recipients susceptible to infection before the transfusion.

Is hypogastric artery embolization during endovascular aortoiliac aneurysm repair (EVAR) innocuous and useful?

INTRODUCTION: We hypothesized that the coverage of the hypogastric artery with a stent-graft causes an occlusion of the artery in its proximal segment, allowing collateral network formation in distal segments of the artery. In contrast, hypogastric embolisation may cause the formation of microthrombi that tend to disseminate leading to embolic occlusion of secondary branches and collaterals. This phenomenon worsens pelvic ischemia. To answer this question we compared two groups of patients with aortoiliac aneurysms treated with or without coil embolization to assess 1) The occurrence and evolution of buttock ischemia and 2) the effect on endoleak. MATERIALS/METHODS: Between October 1995 and January 2007, 147 out of 598 EVAR patients (24.6%) required occlusion of one or both hypogastric arteries. 101 were available for over one year of follow-up. Group A included 76 patients (75%) who underwent coil embolization before EVAR and group B 25 patients (25%) who had their hypogastric artery covered by the sole limb of the stent. Patient demographics, aneurysm characteristics, operative details, immediate and long term clinical outcomes, and CT-scan evaluation were stored prospectively in a specific data base and analyzed retrospectively. RESULTS: They were 96 males (95%). Mean age was 72.1+/-9.5 years. One month postoperatively, 51 patients (50.0%) suffered from buttock claudication. After six months, 34 patients were still disabled (34%), 32 in Group A (42%) and 2 in Group B (8%) (p=0.001). Post-operative sexual dysfunction occurred in 19 (19.6%) without statistical difference between the two groups. Type 2 endoleaks occurred in 12 patients (16.0%) in group A and 4 patients (16.0%) in group B (p=1). Endoleak from the hypogastric artery occurred in one patient in each group. Univariate analysis showed that predictive factors of long term (over six months) buttock claudication were embolization (p<0.001), younger age (p<0.03), coronary disease (p=0.06) and left ventricular dysfunction (p<0.01). The logistic regression analysis showed that buttock claudication was independently associated with embolization OR=9.1[95%CI=1.9-44] and left ventricular dysfunction OR=4.1[95%CI=1.3-12.7]. CONCLUSIONS: Coil embolization of hypogastric artery during EVAR is not an innocuous procedure and may not reduce the rate of type II endoleak.

Abdominal aortic aneurysm sac behavior following Cook Zenith graft implantation: a five-year follow-up assessment of 212 cases.

AIM: Aneurysm shrinkage is an expected outcome after stent-grafting for abdominal aortic aneurysm (AAA). A worrying problem following repair is progressive enlargement indicating persistent sac pressurization: in this setting not all grafts are equal. The Cook Zenith device (CZ) became available on the European market in 1999. While multicenter studies on the device have shown favorable clinical results at mid-term follow-up, few have focused on sac behavior. This study evaluated AAA sac behavior and predictive factors of its evolution by assessing the five-year results obtained with the CZ graft in a single-institution experience. METHODS: All consecutive elective surgery patients treated with a CZ graft for infrarenal aortic or aortoiliac aneurysm repair from January 2000 to November 2004 in our institution were included prospectively in the study and followed at 1, 6, 12, 18, 24 months and yearly thereafter. Pre-, intra- and postoperative data were recorded in a computerized database. Computed tomography (CT) scans were reviewed by a senior radiologist to identify any abnormalities including endoleak and graft malfunction. Pre- and postoperative maximum sac diameters were derived from measurements of CT findings and then compared. A change of at least 8 mm in sac size was considered significant. Overall results are expressed according to the Committee on Reporting Standards of AAA treatment. Factors that may have influenced sac behavior were analyzed by dividing the patients into 3 groups according to whether the sac diameter remained unchanged (group 1), had increased (group 2) or regressed (group 3). Statistical analysis of the demographic and CT-scan data was then performed. RESULTS: The study sample was 212 consecutive patients (mean age 72.8+/-9.0 years); the mean aneurysm diameter before treatment was 55.5+/-9.8 mm. All stent grafts were successfully implanted. The 30-day mortality rate was 0.94% (2/212); the morbidity rate was 11.7% (25/212). The primary technical success rate was 93.40%; the assisted primary technical success and secondary technical success rates were 96.63% and 99.52%, respectively. The mean follow-up period was 17.7+/-14.7 (1-60) months. The cumulative survival probability was 94%, 84.2%, and 72.9% at 12, 24, and 36 months, respectively. The endoleak-free survival probabilities at 12 and 24 months were 75.7% and 62.8%, respectively. The free of intervention survival rates were 82.1%, 68.9% and 60.6% at 12, 24 and 38 months, respectively. At five years follow-up, the overall clinical success rate was 49.5%. If changes in sac diameter occurred, they were noted at 13 months on average. Sac size remained unchanged in 115 (54.3%) patients (group 1), increased in 9 (4.2%) (group 2), and regressed in 88 (41.5%) (group 3). Neither preoperative patient demographics nor aneurysm characteristics were found to be predictive of sac behavior. Aortouniliac graft configuration was predictive of sac shrinkage (P=0.020). Endoleak was more frequent among patients in groups 1 (27/115; 23%) and 2 (5/9; 56%) than among those in group 3 (9/88;10%) (P=0.001). Reduction in aneurysm sac diameter was less marked in patients with any type of endoleak (P=0.0003). CONCLUSION: The CZ grafts offered satisfactory overall results up to five years of follow-up; nevertheless, sac diameter increased in 4.25% of patients. Endoleak was a predictive factor of a lack of sac shrinkage, while aortouniliac graft configuration was predictive of sac shrinkage.

Impact of written information describing postoperative pain management on patient agreement with proposed treatment.

BACKGROUND AND OBJECTIVES: Because patients who are to undergo surgery must give their consent to planned postoperative care, clear and complete information on postoperative pain management should be given. The aim of this quality-of-care study was to evaluate by inquiry the impact of written information describing postoperative pain management on the quality and type of information retained, and patient participation in discussing and agreeing to the postoperative pain management programme during the presurgical anaesthesiology consultation. METHODS: Prospective before and after interventional surveys, each lasting 3 weeks and conducted at a 6-month interval (time required to prepare the written information), used a standardized anonymous questionnaire given to patients after the anaesthesiology consultation. Questions requiring a 'yes' or 'no' response assessed the quality of information and what information was retained by the patient, the extent of the patient's interaction during the discussion with the anaesthesiologist and his/her agreement with the postoperative pain management programme. RESULTS: Among the 180 before-group patients included, 16.7% reported receiving verbal information during the anaesthesiology consultation, none retained all seven principal side-effects of morphine, 14.4% considered the information to be thorough, 20.6% understood it, 16.7% claimed that it had helped them participate in the discussion and 14.4% concurred with the postoperative pain management programme. Compared to the before inquiry, significantly higher percentages of the 107 after-group patients (given written information before the anaesthesiology consultation) responded as having received verbal information during the anaesthesiology consultation (57.0%), retained morphine's main side-effects (12.1%), deemed the information thorough (58.9%) and understandable (53.3%), had participated in the discussion (47.7%) and agreed with the postoperative pain management programme (51.4%). CONCLUSION: Written information on postoperative pain management distributed before the presurgical anaesthesiology consultation improved the quality of information retained, facilitated discussion with the anaesthesiologist and patient agreement with the postoperative pain management programme.

Viral kinetics analysis and virological characterization of treatment failures in patients with chronic hepatitis C treated with sofosbuvir and an NS5A inhibitor.

BACKGROUND: The combination of sofosbuvir (SOF) plus an NS5A inhibitor for 12 weeks is highly efficacious in patients with chronic hepatitis C. As the costs of generic production of sofosbuvir and NS5A inhibitor are rapidly decreasing, the combination of these DAAs will be the standard treatment in most low- to middle-income countries in the future. AIM: To identify key predictors of response that can be used to tailor treatment decisions. METHODS: A cohort of 216 consecutive patients infected with HCV genotype 1 (1a: n = 57; 1b: n = 77), 2 (n = 4), 3 (n = 33) or 4 (n = 44) were treated with sofosbuvir (SOF) + daclatasvir (n = 176) or SOF + ledipasvir (n = 40) for 12 weeks. The viral kinetics was analysed using the biphasic model and the cure boundary was used to predict time to clear HCV. RESULTS: The overall SVR rate was high (94.4%; n = 204), regardless of the time to viral suppression or low-level viraemia at the end of treatment. The model-based predicted HCV RNA levels at the end of treatment could not differentiate patients who did from those who did not achieve SVR. The presence of NS5A resistance-associated substitutions [position 28 (OR = 70.3, P<.001) and/or 31 (OR = 61.6, P = .002)] at baseline was predictive of virological failure in cirrhotic patients but was not associated with on-treatment viral kinetics. CONCLUSION: This real-world study confirms the excellent results of clinical trials with therapies based on a combination of SOF plus an NS5A inhibitor. It suggests that a personalized approach including baseline NS5A inhibitor resistance testing may inform treatment decisions in cirrhotic patients.

Atrial natriuretic factor in chronic obstructive lung disease with pulmonary hypertension. Physiological correlates and response to peptide infusion.

To investigate the physiological role of atrial natriuretic factor (ANF) in patients with hypoxic pulmonary hypertension secondary to chronic obstructive lung disease (COLD), we infused synthetic alpha-human ANF in seven such patients, and investigated the physiological correlates to circulating peptide levels in 24 patients with COLD. ANF infusion, at incremental rates of 0.01, 0.03, and 0.1 micrograms/kg.min, increased basal plasma immunoreactive (ir) ANF (136 +/- 38 pg/ml) by 3-, 10-, and 26-fold, respectively, and reduced pulmonary artery pressure (from 33 +/- 3 to 25 +/- 2 mmHg, P less than 0.001) and systemic arterial pressure (from 88 +/- 4 to 79 +/- 4 mmHg, P less than 0.001) in a dose-related fashion. Cardiac index increased by 13.5% (P less than 0.01) while heart rate was unchanged. Cardiac filling pressures decreased at 0.1 micrograms/kg.min ANF. Pulmonary and systemic vascular resistance fell by 37% (P less than 0.001) and 19% (P less than 0.001), respectively. Arterial oxygenation was impaired during ANF infusion, suggesting partial reversal of hypoxic pulmonary vasoconstriction. Plasma renin activity remained unchanged but aldosterone fell by 44% (P less than 0.01). The levels of plasma irANF in 24 patients correlated directly with the degree of hemoconcentration (r = 0.67, P less than 0.001), respiratory acidosis (r = -0.65, P less than 0.001), and pulmonary hypertension (r = 0.52, P less than 0.01). The results suggest that ANF may serve as a potent pulmonary vasodilator involved in the circulatory homeostasis of patients with COLD.

Prospective assessment of rapid diagnostic tests for the detection of antibodies to hepatitis C virus, a tool for improving access to care.

Large-scale hepatitis C screening is required to prevent further spread of the infection, improve access to care in the context of new hepatitis C virus (HCV) drug regimens without interferon-alpha and subsequently reduce the risk of long-term complications of chronic liver disease. Rapid diagnostic tests (RDTs) represent an attractive alternative to enzyme immunoassay using blood from venepuncture. The aim of the present study was to prospectively assess the clinical performance of CE-marked RDTs detecting anti-HCV antibodies in fingerstick capillary whole blood and/or oral fluid. A total of 513 individuals, including 318 patients with chronic HCV infection, 25 patients with resolved HCV infection and 170 HCV-seronegative individuals, were prospectively enrolled. The specificity of RDTs with fingerstick whole blood varied from 98.8% to 100%. The clinical sensitivity was high for the OraQuick(®) and Toyo(®) tests (99.4% and 95.8%, respectively), but low for the Labmen(®) test (63.1%). The specificity and clinical sensitivity in crevicular fluid were both satisfactory for the OraQuick(®) test (100% and 97.6%, respectively). HCV antibody RDTs were easy and rapid to perform in the context of patient care. They were highly specific. Both the OraQuick(®) and Toyo(®) tests reached the expected level of performance for wide-scale use, with a performance advantage for the OraQuick(®) HCV test. RDTs appear to be a promising new tool for wide-scale screening of HCV infection in high-risk to medium-risk populations. Hence, careful assessment of the performance of HCV RDTs must be recommended before they can be implemented in clinical practice.

Activity of the interferon-induced 2',5'-oligoadenylate synthetase in patients with chronic hepatitis C.

The interferon-induced 2',5'-oligoadenylate synthetase (2-5OAS) is responsible, at least in part, for the antiviral state established in cells in response to viral infections. The purpose of this work was to study the relationship between hepatitis C virus (HCV) infection and 2-5OAS in patients with chronic hepatitis C. Peripheral blood mononuclear cells (PBMC) of 27 patients with chronic hepatitis C were investigated, as well as PBMC of 10 control subjects. Then, the patients were treated with 3 mu interferon-alpha 2a three times per week. At month 3 of therapy, PBMC were sampled. Of the total PBMC samples obtained, half were used for determination of in vivo 2-5OAS activity. The remaining cells were cultured for 24 h in either the absence or presence of 500 U/ml of interferon-alpha 2a for the determination of in vitro 2-5OAS activity. The mean basal in vivo 2-5OAS activities were 3.6 +/- 2.8 nmol/10(6) cells in patients versus 1.6 +/- 1.1 nmol/10(6) cells in controls (p < 0.01). Basal in vivo 2-5OAS activity did not correlate with mean HCV viremia, quantified by a "branched DNA"-based assay. Before treatment, interferon-alpha was detected in the serum of 2 patients in 27. After a 24 h culture of PBMC in the presence of interferon, in vitro 2-5OAS activity was significantly induced in the PBMC of both the patients and the controls. However, in vitro induction of 2-5OAS activity was significantly lower in the PBMC of the patients than in the PBMC of the controls (p < 0.01). At month 3 therapy, in vivo 2-5OAS activity was significantly induced (20.5 +/- 17.9; p < 0.0001). In vitro IFN inductions of 2-5OAS activity in PBMC before treatment and at month 3 of therapy were not significantly different. In conclusion, in vivo 2-5OAS activity is significantly induced in patients with chronic hepatitis C, but endogenously produced interferon-alpha does not seem to be involved. Chronic induction of 2-5OAS activity results in a decreased sensitivity of PBMC to exogenous interferon induction. Whether this phenomenon plays a role in the resistance of chronic hepatitis C to interferon therapy remains uncertain.

Increased incidence of oropharyngeal squamous cell carcinomas after liver transplantation for alcoholic cirrhosis.

BACKGROUND: THE aim of this study was to describe the features of posttransplantation tumors observed in a series of liver transplant recipients with special reference to patients receiving a transplant for alcoholic cirrhosis. METHODS: Among 171 consecutive liver transplant recipients, 90 patients who had received a first liver allograft for cirrhosis were studied. After liver transplantation, detection of de novo malignancies was prospectively undertaken and the characteristics of the patients in whom tumors occurred were compared with those in whom tumors did not develop. RESULTS: With a follow-up of 45.2+/-21.2 months, 11 tumors were observed in 90 patients (overall incidence of 12.2%). The incidence of tumors was higher in patients receiving a transplant for alcoholic cirrhosis than in patients receiving a transplant for nonalcoholic cirrhosis (26.7% vs. 5.0%, P<0.01). Squamous cell carcinoma (SCC) of the oropharynx or esophagus and posttransplant lymphoproliferative disorders were mainly observed. SCC (uvula in two cases, tongue in one case, esophagus in one case, pharynx in one case) occurred exclusively in patients transplanted for alcoholic cirrhosis (16.7% vs. 0%, P=0.001). The incidence of posttransplant lymphoproliferative disorders was similar in alcoholics and nonalcoholics (6.7% vs. 5%, NS). Survival was not influenced by the occurrence of SCC. CONCLUSION: The incidence of oropharyngeal SCC could be high in patients receiving a transplant for alcoholic cirrhosis. This could be due to an additional effect of posttransplantation immunosuppression in patients exposed to alcohol and tobacco before transplant. Careful posttransplantation screening of oropharyngeal SCC is warranted after liver transplantation for alcoholic cirrhosis.

Maintenance of gastric pH above 6 with intravenous famotidine in patients with a bleeding duodenal ulcer.

BACKGROUND: The secondary prevention of bleeding from ulcers may be improved if antisecretory drugs are able to maintain a 24-h gastric pH close to neutral. AIM: To evaluate the effect of intravenous famotidine at a conventional dose of 40 mg/day on 24-h intragastric pH in patients with a bleeding duodenal ulcer, and to determine the dose required to maintain gastric pH > 6 by use of a Gastrojet (MIC, Switzerland) device (a pH meter-controlled programmable pump). METHODS: Twelve patients (nine men, three women), aged 24-78 years, admitted for a bleeding duodenal ulcer, were studied after active bleeding had stopped for at least 6 h. Gastric pH was recorded for two consecutive 24-h periods, each starting at 16.00 hours. The patients were fasted during these periods and received an infusion of 2.5 L of isotonic glucose. They were given famotidine, as a continuous i.v. infusion of 40 mg during one period, and at a rate determined by the Gastrojet during the other period (in a random sequence), with the aim of maintaining the gastric pH above 6. RESULTS: The 24-h median (interquartile range) pH and the mean (+/- S.E.M.) percentage of the 24-h period with a gastric pH > 6 were both significantly higher during the Gastrojet period than during the continuous infusion: 6.4 (6.3-6.5) vs. 5.7 (2.7-6.4) (P < 0.01) and 74 +/- 5% vs. 44 +/- 7% (P < 0.002), respectively. The mean dose of famotidine delivered by the Gastrojet was 172 mg (range: 101-200 mg). The entire available amount of famotidine (200 mg) was delivered in four of the 12 patients. The percentage of time at pH > 6 (mean +/- S.E.M.) was significantly higher at night (22.00 to 07.00 hours) than during the rest of the day (88 +/- 2 vs. 70 +/- 6%; P < 0.005) and the mean quantity of famotidine delivered per hour was significantly lower during the night (6.3 +/- 0.8 mg/h vs. 8.4 +/- 0.5 mg/h; P < 0.02). CONCLUSION: We conclude that 40 mg of famotidine delivered as a continuous i.v. infusion is not sufficient to maintain gastric pH > 6 for 24 h in duodenal ulcer patients. Our study with the Gastrojet device shows that it may be possible to achieve this goal by using a much larger dose, preferably delivered during the day.

Impact of moderate alcohol consumption on histological activity and fibrosis in patients with chronic hepatitis C, and specific influence of steatosis: a prospective study.

AIM: To evaluate the effects of minimal to moderate alcohol consumption on the severity of histological lesions in patients with chronic hepatitis C. METHODS: Daily alcohol intake (none, 1-20, 21-30, 31-50 g/day) and histological activity and fibrosis were recorded in 260 patients with chronic hepatitis C. RESULTS: The proportion of patients with moderate (A2) or marked (A3) activity increased gradually from 53.8% in abstinent patients to 86.5% for an intake between 31 and 50 g/day (P = 0.003). In multivariate analysis, age > 40 years, alcohol intake between 31 and 50 g/day and moderate or severe steatosis were independently related to histological activity. The proportion of patients with moderate (F2) or marked (F3) fibrosis or cirrhosis (F4) gradually increased from 29.0% in abstinent patients to 67.6% for an intake between 31 and 50 g/day (P < 0.001). Multivariate analysis also showed that alcohol intake between 31 and 50 g/day, moderate or severe steatosis and histological activity were independently related to fibrosis. The deleterious effect of alcohol intake on histological lesions differed according to gender. CONCLUSIONS: This study demonstrates that both activity and fibrosis gradually increase according to the amount of alcohol ingested, and that even moderate alcohol consumption, as low as 31-50 g/day in men and 21-50 g/day in women, may aggravate histological lesions in patients with chronic hepatitis C.