Predictive Value of Circulating Tumor Cells Detected by ISET® in Patients with Non-Metastatic Prostate Cancer Undergoing Radical Prostatectomy.

There is an unmet need for reliable biomarkers to predict prostate cancer recurrence after prostatectomy in order to better guide the choice of surgical treatment. We have evaluated the predictive value of the preoperative detection of Circulating Tumor Cells (CTC) for prostate cancer recurrence after surgery. A cohort of 108 patients with non-metastatic prostate adenocarcinoma undergoing radical prostatectomy was tested for the presence of CTC before prostatectomy using ISET®. Disease recurrence was assessed by the increase in serum PSA level after prostatectomy. The following factors were assessed for statistical association with prostate cancer recurrence: the presence of CTC, serum PSA, Gleason score, and pT stage using univariate and multivariate analyses, with a mean follow-up of 34.9 months. Prostate cancer recurrence was significantly associated with the presence of at least 1 CTC at the preoperative time point (p < 0.001; Predictive value = 0.83). Conversely, the absence of prostate cancer recurrence was significantly associated with the lack of CTC detection at diagnosis (Predictive value = 1). Our multivariate analysis shows that only CTC presence is an independent risk factor associated with prostate cancer recurrence after prostatectomy (p < 0.001). Our results suggest that CTC detection by ISET® before surgery is an interesting candidate predictive marker for cancer recurrence in patients with non-metastatic PCa.

A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers.

BACKGROUND & AIMS: Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk. METHODS: Three cohorts (GenomALC-1: n = 1,690, GenomALC-2: n = 3,037, UK Biobank: relevant n = 6,898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10 years) were included. Cases were participants with alcohol-related cirrhosis. Controls had a history of similar alcohol consumption but no evidence of liver disease. Risk scores were computed from up to 8 genetic loci identified previously as associated with alcohol-related cirrhosis and 3 clinical risk factors. Score performance for the stratification of alcohol-related cirrhosis risk was assessed and compared across the alcohol-related liver disease spectrum, including hepatocellular carcinoma (HCC). RESULTS: A combination of 3 single nucleotide polymorphisms (SNPs) (PNPLA3:rs738409, SUGP1-TM6SF2:rs10401969, HSD17B13:rs6834314) and diabetes status best discriminated cirrhosis risk. The odds ratios (ORs) and (95% CIs) between the lowest (Q1) and highest (Q5) score quintiles of the 3-SNP score, based on independent allelic effect size estimates, were 5.99 (4.18-8.60) (GenomALC-1), 2.81 (2.03-3.89) (GenomALC-2), and 3.10 (2.32-4.14) (UK Biobank). Patients with diabetes and high risk scores had ORs of 14.7 (7.69-28.1) (GenomALC-1) and 17.1 (11.3-25.7) (UK Biobank) compared to those without diabetes and with low risk scores. Patients with cirrhosis and HCC had significantly higher mean risk scores than patients with cirrhosis alone (0.76 ± 0.06 vs. 0.61 ± 0.02, p = 0.007). Score performance was not significantly enhanced by information on additional genetic risk variants, body mass index or coffee consumption. CONCLUSIONS: A risk score based on 3 genetic risk variants and diabetes status enables the stratification of heavy drinkers based on their risk of cirrhosis, allowing for the provision of earlier preventative interventions. LAY SUMMARY: Excessive chronic drinking leads to cirrhosis in some people, but so far there is no way to identify those at high risk of developing this debilitating disease. We developed a genetic risk score that can identify patients at high risk. The risk of cirrhosis is increased >10-fold with just two risk factors - diabetes and a high genetic risk score. Risk assessment using this test could enable the early and personalised management of this disease in high-risk patients.

Sugar intake and craving during alcohol withdrawal in alcohol use disorder inpatients.

To assess whether changes in sugar intake and craving occur during alcohol withdrawal in humans, we conducted a prospective, observational study in a university hospital addictions treatment center. Recruited patients had severe alcohol use disorder and were hospitalized for 7 days in the short-stay unit for alcohol withdrawal and then for 6 weeks in the rehabilitation unit. During the hospital stay, they had no access to alcohol but had full access to sweet products and beverages in a shop and vending machines located inside the hospital. Alcohol craving was assessed using a visual analogue scale on Days 1, 15, and 45. Sugar craving, sweet products stored by patients in their rooms, and weight were assessed on the same days. Thirty-five patients were included. Sugar craving increased in 14 patients during the hospital stay, whereas no change was observed in the remaining 21. Significant increases in both the amounts of sweet products stored in the patients' rooms (p < 0.02) and weight (p < 0.05) were observed only in the sugar craving group. During the same period, alcohol craving decreased significantly in all patients. Changes in tobacco smoking were not different according to the sugar craving status and therefore cannot explain the observed differences. In conclusion, increased intake and craving for sugar after alcohol withdrawal were observed in 40% of the patients included in our prospective study, and these results were similar to those of a study conducted in the alcohol post-dependent state model in rats.

Obesity, Diabetes, Coffee, Tea, and Cannabis Use Alter Risk for Alcohol-Related Cirrhosis in 2 Large Cohorts of High-Risk Drinkers.

INTRODUCTION: Sustained high alcohol intake is necessary but not sufficient to produce alcohol-related cirrhosis. Identification of risk factors, apart from lifetime alcohol exposure, would assist in discovery of mechanisms and prediction of risk. METHODS: We conducted a multicenter case-control study (GenomALC) comparing 1,293 cases (with alcohol-related cirrhosis, 75.6% male) and 754 controls (with equivalent alcohol exposure but no evidence of liver disease, 73.6% male). Information confirming or excluding cirrhosis, and on alcohol intake and other potential risk factors, was obtained from clinical records and by interview. Case-control differences in risk factors discovered in the GenomALC participants were validated using similar data from 407 cases and 6,573 controls from UK Biobank. RESULTS: The GenomALC case and control groups reported similar lifetime alcohol intake (1,374 vs 1,412 kg). Cases had a higher prevalence of diabetes (20.5% (262/1,288) vs 6.5% (48/734), P = 2.27 × 10-18) and higher premorbid body mass index (26.37 ± 0.16 kg/m2) than controls (24.44 ± 0.18 kg/m2, P = 5.77 × 10-15). Controls were significantly more likely to have been wine drinkers, coffee drinkers, smokers, and cannabis users than cases. Cases reported a higher proportion of parents who died of liver disease than controls (odds ratio 2.25 95% confidence interval 1.55-3.26). Data from UK Biobank confirmed these findings for diabetes, body mass index, proportion of alcohol as wine, and coffee consumption. DISCUSSION: If these relationships are causal, measures such as weight loss, intensive treatment of diabetes or prediabetic states, and coffee consumption should reduce the risk of alcohol-related cirrhosis.

Comparison of e-cigarette use characteristics between exclusive e-cigarette users and dual e-cigarette and conventional cigarette users: an on-line survey in France.

BACKGROUND AND AIMS: Completely substituting e-cigarettes (EC) for combustible tobacco cigarettes reduces exposure to toxicants and carcinogens. However, a large proportion of EC users (dual users) continue to smoke conventional cigarettes. This study aimed to compare estimated nicotine intake and e-cigarette use characteristics between exclusive EC users and dual users. DESIGN: Web-based anonymous cross-sectional survey. SETTING: France. PARTICIPANTS: A total of 3189 adults, current users of electronic cigarettes (EC). Data collection between 4 October 2014 and 11 November 2014. MEASUREMENTS: Primary outcome: estimated nicotine intake per day (mg) from participants' reports. SECONDARY OUTCOMES: duration, frequency of EC use and nicotine content of e-liquids used/day. Dual use was defined as using at least one cigarette per day while also using EC. FINDINGS: A total of 2836 respondents reported exclusive EC use and 353 reported being dual users. Backward stepwise logistic regression showed that dual users had higher estimated combined daily nicotine intake from e-liquids and cigarettes [estimate: 2.14, standard error (SE) = 0.26, adjusted odds ratio (aOR) = 8.48, 95% confidence interval (CI) = 5.11-14.09, P < 0.001], but lower daily nicotine intake from EC (estimate: -2.14, SE = 0.26, aOR = 0.12, CI = 0.07-0.196, P < 0.001) and reported fewer months of EC use (estimate: -0.31, SE = 0.14, aOR = 0.73, CI = 0.56-0.95, P = 0.022) compared with exclusive EC users. CONCLUSION: Dual e-cigarette users in France may have higher nicotine intake overall than exclusive e-cigarette users, but they may take in less nicotine from their e-cigarettes.

Determination of MoCA Cutoff Score in Patients with Alcohol Use Disorders.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) score is a convenient and promising tool for estimating alcoholic patients' global cognitive functioning, a major challenge for all specialized alcohol treatment centers. However, whether or not the score should be corrected for education level and whether the proposed cutoff is relevant in patients with alcohol use disorders (AUD) should be determined. METHODS: We compared the MoCA scores in patients hospitalized for AUD with and without cognitive impairment assessed by a battery of neuropsychological (NP) tests. Sensitivity, specificity, and cutoff of the MoCA score were analyzed using receiver operating characteristic curve analysis. RESULTS: Thirty-one patients with and 25 without cognitive impairment were included in the study. There were 40 men and 16 women, with a mean age of 49.5 years. The mean uncorrected MoCA score was 23.1 ± 3.3 in those with and 27.0 ± 1.9 in those without cognitive impairment. NP tests were significantly correlated with the MoCA score. Uncorrected MoCA scores identified more than 80% of the patients with a cutoff score equal to 26, to obtain similar accuracy with the corrected score required using a cutoff score equal to 27. CONCLUSIONS: Our results confirm that the MoCA test is a convenient and reliable screening tool to measure cognition defects in alcoholic patients. As using the 1-point education adjustment increases the cutoff score by 1 point, it is suggested to use the noncorrected score and the usual cutoff, that is, 26. Being easy to administer and only moderately time-consuming, the MoCA score should be used extensively in addiction treatment centers.

BRIP1 coding variants are associated with a high risk of hepatocellular carcinoma occurrence in patients with HCV- or HBV-related liver disease.

The molecular mechanisms of hepatocellular carcinoma (HCC) carcinogenesis are still not fully understood. DNA repair defects may influence HCC risk. The aim of the study was to look for potential genetic variants of DNA repair genes associated with HCC risk among patients with alcohol- or viral-induced liver disease. We performed four case-control studies on 2,006 European- (Derivation#1 and #2 studies) and African-ancestry (Validation#1 and #2 studies) patients originating from several cohorts in order to assess the association between genetic variants on DNA repair genes and HCC risk using a custom array encompassing 94 genes. In the Derivation#1 study, the BRIP1 locus reached array-wide significance (Chi-squared SV-Perm, P=5.00×10-4) among the 253 haplotype blocks tested for their association with HCC risk, in patients with viral cirrhosis but not among those with alcoholic cirrhosis. The BRIP1 haplotype block included three exonic variants (rs4986763, rs4986764, rs4986765). The BRIP1 'AAA' haplotype was significantly associated with an increased HCC risk [odds ratio (OR), 2.01 (1.19-3.39); false discovery rate (FDR)-P=1.31×10-2]. In the Derivation#2 study, results were confirmed for the BRIP1 'GGG' haplotype [OR, 0.53 (0.36-0.79); FDR-P=3.90×10-3]. In both Validation#1 and #2 studies, BRIP1 'AAA' haplotype was significantly associated with an increased risk of HCC [OR, 1.71 (1.09-2.68); FDR-P=7.30×10-2; and OR, 6.45 (4.17-9.99); FDR-P=2.33×10-19, respectively]. Association between the BRIP1 locus and HCC risk suggests that impaired DNA mismatch repair might play a role in liver carcinogenesis, among patients with HCV- or HBV-related liver disease.

Prevalence of Psychoactive Substance Consumption in People With Obesity.

OBJECTIVE: The aim of this study was to evaluate the prevalence and the kind of psychoactive substances consumed by people with obesity. METHODS: Patients were included at their first visit for bariatric surgery. Socio-demographic characteristics, anxiety, depressive disorders and psychoactive substance consumption were assessed. The prevalence of psychoactive substance consumption was compared to that of the general population reported by the French National Institute of Prevention and Health Education. RESULTS: One hundred (100) patients were consecutively recruited: 60 women (mean age 41 ± 14 years) and 40 men (mean age 46 ± 13 years). Sixty-seven percent of subjects consumed alcohol. Consumption rates of cannabis (21% vs. 10%), cocaine (7.0% vs. 0.8%) and amphetamine (6.0% vs. 0.3%) were significantly (p < .0001) higher in people with obesity than in the general population. CONCLUSIONS: People with obesity have an excess risk of amphetamine, cocaine and cannabis consumption. This consumption may increase the risk of cardiovascular and psychiatric morbidity and should therefore be detected before surgery.

A Proof of Concept, Phase II Randomized European Trial, on the Efficacy of ALF-5755, a Novel Extracellular Matrix-Targeted Antioxidant in Patients with Acute Liver Diseases.

OBJECTIVE: No efficient medical treatment is available for severe acute hepatitis (SAH) except N-acetylcysteine for acetaminophen-induced acute liver failure. The human C-type lectin Reg3α, referred to as ALF-5755, improved survival in an animal model of acute liver failure and was well tolerated in a phase 1 trial in humans. We performed a phase 2a trial of ALF5755 in non-acetaminophen induced SAH. DESIGN: double-blind, randomized, placebo-controlled study. The primary end-point was the improvement in the coagulation protein synthesis assessed by the change of Prothrombin (PR) during the 72 hours following treatment initiation calculated as PRH0 minus PRH72 divided by 72 (PR slope H0H72). Intention to treat (ITT) and per-protocol (PP) analysis of the entire group and the Hepatitis B virus (HBV)/AIH (auto-immune hepatitis) sub-group were done separately. RESULTS: 57 patients were included. Twenty-eight received ALF-5755, 29 the placebo. Etiologies were: Hepatitis A (n = 10), HBV (n = 13), AIH (n = 9), drug-induced (n = 8), other (n = 17). On the whole group, nor the PR slope H0H72 (0.18±0.31 vs 0.25±0.32), nor the transplant-free survival rate at day 21 (75 vs 86%) differed between groups. Conversely, in the HBV-AIH subgroup, in which ALF was more severe, PR slope H0-H72 was higher in the ALF-5755 arm, the difference being significant in PP analysis (0.048±0.066 vs -0.040±0.099, p = 0.04); the median length of hospitalization was lower in the ALF-5755 group (8 vs 14 days, p = 0.02). CONCLUSION: ALF-5755 was not efficient in a ITT analysis performed on the whole sample; however it led to a significant, although moderate, clinical benefit in a PP analysis of the sub-group of patients with HBV or AIH related SAH. As HBV is the major cause of SAH in Asia and Africa and AIH a growing cause, this study emphasizes the need to pursuit the evaluation of this novel medical treatment of SAH. TRIAL REGISTRATION: ClinicalTrials.gov NCT01318525.

The prevalence of optic neuropathy in alcoholic patients--a pilot study.

BACKGROUND: Alcohol has particularly toxic effects on the central and peripheral nervous systems. Optic neuropathy (ON) is one of these neurological complications. Its diagnosis has not been codified, and its prevalence is poorly known. The aim of this pilot study was to assess the prevalence of ON and identify risk factors in a cohort of patients hospitalized for alcohol withdrawal. METHODS: This was a single-center prospective study. A complete standardized eye examination was performed during the patient's alcohol withdrawal; The data collected included: sociodemographic status; the number of withdrawals; the type and amount of alcohol drunk, tobacco, and illicit drug consumption; and ophthalmological results. RESULTS: One hundred patients were included prospectively from January 2010 to June 2011 (67 men and 33 women) with a mean age of 47 ± 12 and 46 ± 10 years, respectively. The average alcohol consumption was higher for men than women: 207 ± 122 vs. 146 ± 92 g/d, p = 0.013. The most frequent definition of ON in the literature is a decrease in visual acuity associated with impaired color vision. Thirteen percent of men and 3% of women met these criteria. But monocular ON was observed in 22% of men and 18% women, and partial damage was demonstrated in 27% of men and 7% of women. CONCLUSIONS: ON is a relatively rare complication of chronic alcohol consumption, but the high prevalence of incomplete forms should prompt screening and early treatment.

Feasibility and Efficacy of an Addiction Treatment Program in Patients With Upper Aerodigestive Tract Cancer.

BACKGROUND: Continuing to smoke or to drink after the treatment of an upper aerodigestive tract (UADT) cancer is known to worsen the prognosis. We assessed the feasibility and efficacy of an addiction treatment program integrated into the cancer treatment. METHOD: In four units devoted to UADT tumors, we proposed an addiction treatment to all patients still drinking or smoking at the end of the cancer treatment; the abstinence rate was assessed 6 and 12 months later. RESULTS: One hundred and sixteen patients were included. Among the 73 patients still drinking and/or smoking at the end of the cancer treatment, 46.6% accepted an addiction treatment. In the latter, abstinence rate was increased, 52.2% versus 31.03% ( p = .07) at M12. In patients both drinking and smoking, addiction treatment doubled the rate of abstinence of both products (31% vs. 14%). CONCLUSION: Offering addiction treatment to patients with UADT cancer improves abstinence rate and helps maintain long-term withdrawal.

[Prognosis assessment of alcoholic liver disease: how and why?]. / Évaluation pronostique de la maladie alcoolique du foie : comment et pourquoi ?

Alcoholic liver disease (ALD) causes more than 5000 deaths per year in France. Most of those deaths could be prevented by an early diagnosis, which would give the patients the opportunity to modify their alcohol consumption while liver lesions are still reversible. Hepatic histology is the main parameter that predicts morbidity and mortality in patients with ALD. Non-invasive methods such as biomarker tests (e.g. FibroTest(®) or FibroMetre A(®)) or hepatic elastography (FibroScan(®)) may allow diagnosing alcohol-induced liver lesion without systematic biopsy. Despite promising preliminary results, those methods are not validated yet in ALD. A validation of non-invasive methods for ALD could allow a large screening of the severe forms of this pathology.

Impact of tobacco and alcohol consumption in patients registered on waiting list on early morbidity following liver transplantation.

BACKGROUND: Liver transplantation (LT) is a high-risk surgery associated with postoperative complications. Smoking and drinking are known risk factors of long-term post-LT complications, but their role in early complications is still questioned. PATIENTS AND METHODS: We retrieved from our medical files the data of all patients registered for LT and who had had a consultation with a physician specialized in substance abuse. Consumption of alcohol, tobacco, and drugs before and after registration for LT was assessed. RESULTS: One hundred and five patients were included. Pre-registration smoking and drinking rates were 75.3 and 69.5%, respectively. Forty-three patients continued smoking and nine continued drinking until LT. Mortality and early morbidity rates were not impacted by smoking or drinking. Active smokers had significantly increased prevalence of bacterial cholangitis in comparison to patients who stopped smoking when registered for LT. CONCLUSION: Persistent drinking in patients registered for LT is rare as compared to smoking; however, in our series, smoking until LT was not associated with major risk of early complication, except for cholangitis. This suggests that clinicians should take time to encourage patients to quit smoking and the intervention of a team specialized in substance abuse could be highly beneficial.

Genome-wide association study identifies variants associated with progression of liver fibrosis from HCV infection.

BACKGROUND & AIMS: Polymorphisms in IL28B were shown to affect clearance of hepatitis C virus (HCV) infection in genome-wide association (GWA) studies. Only a fraction of patients with chronic HCV infection develop liver fibrosis, a process that might also be affected by genetic factors. We performed a 2-stage GWA study of liver fibrosis progression related to HCV infection. METHODS: We studied well-characterized HCV-infected patients of European descent who underwent liver biopsies before treatment. We defined various liver fibrosis phenotypes on the basis of METAVIR scores, with and without taking the duration of HCV infection into account. Our GWA analyses were conducted on a filtered primary cohort of 1161 patients using 780,650 single nucleotide polymorphisms (SNPs). We genotyped 96 SNPs with P values <5 × 10(-5) from an independent replication cohort of 962 patients. We then assessed the most interesting replicated SNPs using DNA samples collected from 219 patients who participated in separate GWA studies of HCV clearance. RESULTS: In the combined cohort of 2342 HCV-infected patients, the SNPs rs16851720 (in the total sample) and rs4374383 (in patients who received blood transfusions) were associated with fibrosis progression (P(combined) = 8.9 × 10(-9) and 1.1 × 10(-9), respectively). The SNP rs16851720 is located within RNF7, which encodes an antioxidant that protects against apoptosis. The SNP rs4374383, together with another replicated SNP, rs9380516 (P(combined) = 5.4 × 10(-7)), were linked to the functionally related genes MERTK and TULP1, which encode factors involved in phagocytosis of apoptotic cells by macrophages. CONCLUSIONS: Our GWA study identified several susceptibility loci for HCV-induced liver fibrosis; these were linked to genes that regulate apoptosis. Apoptotic control might therefore be involved in liver fibrosis.

IL28B alleles associated with poor hepatitis C virus (HCV) clearance protect against inflammation and fibrosis in patients infected with non-1 HCV genotypes.

UNLABELLED: Genetic polymorphisms near IL28B are associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV), two processes that require the appropriate activation of the host immune responses. Intrahepatic inflammation is believed to mirror such activation, but its relationship with IL28B polymorphisms has yet to be fully appreciated. We analyzed the association of IL28B polymorphisms with histological and follow-up features in 2335 chronically HCV-infected Caucasian patients. Assessable phenotypes before any antiviral treatment included necroinflammatory activity (n = 1,098), fibrosis (n = 1,527), fibrosis progression rate (n = 1,312), and hepatocellular carcinoma development (n = 1,915). Associations of alleles with the phenotypes were evaluated by univariate analysis and multivariate logistic regression, accounting for all relevant covariates. The rare G allele at IL28B marker rs8099917-previously shown to be at risk of treatment failure-was associated with lower activity (P = 0.04), lower fibrosis (P = 0.02) with a trend toward lower fibrosis progression rate (P = 0.06). When stratified according to HCV genotype, most significant associations were observed in patients infected with non-1 genotypes (P = 0.003 for activity, P = 0.001 for fibrosis, and P = 0.02 for fibrosis progression rate), where the odds ratio of having necroinflammation or rapid fibrosis progression for patients with IL28B genotypes TG or GG versus TT were 0.48 (95% confidence intervals 0.30-0.78) and 0.56 (0.35-0.92), respectively. IL28B polymorphisms were not predictive of the development of hepatocellular carcinoma. CONCLUSION: In chronic hepatitis C, IL28B variants associated with poor response to interferon therapy may predict slower fibrosis progression, especially in patients infected with non-1 HCV genotypes.

Pathological evolution of hepatitis C virus-"Healthy carriers".

AIM: To determine factors associated with fibrosis progression in hepatitis C virus (HCV)-infected patients without significant initial pathological lesions. METHODS: Seventy six untreated HCV-infected patients with initially normal liver as defined by a Knodell score < or = 3, with 2 liver biopsies and detectable HCV-RNA were included. Markers of fibrosis progression were assessed. RESULTS: Median duration of infection and time between paired biopsies was 13 (95% CI: 1-28) and 4 (95% CI: 2-16) years respectively. Alanine-transaminase (ALT) activity was normal in 43.4% of cases. 50% demonstrated progression of the necro-inflammation and 34% of fibrosis after a median time evolution of 4 years (95% CI: 2-16). The median difference in the necro-inflammation and fibrosis score between biopsies was low, 1.5 and 0.0 respectively. Univariate analysis showed there was no difference between fibrosis activity or evolution according to genotype or viral load. A higher fibrosis progression (P = 0.03) was observed in patients with body mass index (BMI) > 25. Fibrosis progression correlated with the time interval between biopsies (P = 0.01). A significant progression of activity (1.7 vs 0.4, P < 0.05) or fibrosis (0.9 vs 0.0, P < 0.01) was observed in patients with elevated ALT. There was a significant correlation between activity progression and fibrosis progression (P = 0.003). Multivariate analysis demonstrated that fibrosis progression was associated with elevated ALT, BMI > 25 and the time interval between 2 biopsies. CONCLUSION: There is no fibrosis progression in 66% of patients without significant initial histopathological lesion. Fibrosis progression is associated with elevated ALT and BMI > 25.

Influence of liver biopsy on abstinence in alcohol-dependent patients.

BACKGROUND: Liver biopsy indication for the evaluation of alcoholic liver disease is controversial. Our aim was to investigate the influence of the biopsy on the patients' motivation for abstinence. METHODS: We retrospectively analysed, in a population of 324 patients hospitalized for alcohol withdrawal, the impact of liver biopsy on the following clinical outcomes: rapid loss to follow-up (immediately after hospital discharge), early relapse (< 3 months) and long-lasting abstinence (> 12 months). The biopsy was performed in 136 patients who had liver enzymes perturbations. Hepatic lesions were graded as mild (isolated steatosis and/or non-bridging fibrosis), moderate (bridging fibrosis and/or moderate alcoholic hepatitis) or severe (cirrhosis and/or marked alcoholic hepatitis) in 66 (48%), 41 (30%) and 29 (21%) cases, respectively. RESULTS: In univariate analysis, patients who had a liver biopsy were less likely to be rapidly lost to follow-up (12% versus 27%, P = 0.003) but had a lower rate of long-term abstinence (20% versus 34%, P = 0.025). In multivariate analysis, age was the only factor significantly associated with clinical outcome: older patients had higher rate of long-term abstinence (OR = 1.041; P = 0.010). Among patients who had a biopsy, those with severe hepatic lesions had a lower rate of rapid relapse than those with moderate or mild lesions (32% versus 68% and 56%, P = 0.018) but the rate of long-term abstinence was similar in the three groups. CONCLUSION: This observational study does not support the notion that liver biopsy has a significant influence on the maintenance of alcohol abstinence in patients with alcoholic liver disease.

FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest.

UNLABELLED: To optimize the management of patients with chronic hepatitis C virus (HCV) infection, noninvasive tests to determine the degree of hepatic fibrosis have been developed. The aims of this study were (1) to validate a simple, inexpensive, noninvasive test called FIB-4, which combines standard biochemical values (platelets, ALT, AST) and age, in a series of 847 liver biopsies performed in HCV-monoinfected patients; and (2) to compare the results of 780 FIB-4 and FibroTests performed the same day in a series of 592 HCV-infected patients. The FIB-4 index enabled the correct identification of patients with severe fibrosis (F3-F4) and cirrhosis with an area under the receiver operating characteristic curve of 0.85 (95% CI 0.82-0.89) and 0.91 (95% CI 0.86-0.93), respectively. An FIB-4 index <1.45 had a negative predictive value of 94.7% to exclude severe fibrosis with a sensitivity of 74.3%. An FIB-4 index higher than 3.25 had a positive predictive value to confirm the existence of a significant fibrosis (F3-F4) of 82.1% with a specificity of 98.2%. Using these ranges, 72.8% of the 847 liver biopsies were correctly classified. The FIB-4 index was strongly correlated to the FibroTest results for a score <1.45 or >3.25 (kappa = 0.561, P < 0.01). A FIB-4 value <1.45 or >3.25 (64.6% of the cases) was concordant with FibroTest results in 92.1% and 76%, respectively. CONCLUSION: For values outside 1.45-3.25, the FIB-4 index is a simple, accurate, and inexpensive method for assessing liver fibrosis and proved to be concordant with FibroTest results.

Direct and indirect evidence for the reversibility of cirrhosis.

The aim of this study was to assess the reversibility of cirrhosis after therapy in a large series of patients with cirrhosis from various etiologies. We performed a retrospective study of 113 patients with biopsy-proven cirrhosis who underwent specific therapy and follow-up biopsies. Two pathologists performed blinded analyses of indirect biochemical and morphological signs of cirrhosis. Fourteen (12.4%) of the 113 cirrhotic patients had biopsy-proven disappearance of cirrhosis, defined as a decrease of 2 or greater in their METAVIR fibrosis score: 8 were related to hepatitis C virus, 3 to hepatitis B virus, and 3 to autoimmune cirrhosis. Necro-inflammatory activity decreased from 2.4 +/- 0.65 to 0.85 +/- 0.9 (P = .004), and fibrosis from 4 to 1.7 +/- 0.61 (P = .001). Prothrombin time (n = 1), platelet count (n = 2), serum albumin level (n = 2), and ultrasound abnormalities (n = 6) normalized in patients who had initial abnormalities. Hyaluronic acid and procollagen type III serum level decreased in all. In the 11 patients with regression of viral cirrhosis, 2 were nonresponders and 9 were responders, including 2 relapsers. The 3 patients with regressive autoimmune cirrhosis were complete responders to immunosupressive therapy. Using repeated liver biopsies, clinicobiochemical, radiologic, and endoscopic tests, we provide evidence for potential reversibility of cirrhosis after long-lasting suppression of the necro-inflammatory activity of liver disease.

Diagnostic accuracy of the fibrotest in hemodialysis and renal transplant patients with chronic hepatitis C virus.

BACKGROUND: An accurate diagnosis of hepatitis C virus (HCV)-related liver lesions is mandatory in dialysis patients and kidney recipients to better define the treatment of and contraindications to kidney transplantation. The aim of this study was to assess the diagnostic accuracy of the fibrotest (a noninvasive method to assess liver fibrosis in HCV on a scale from 0 to 1) in hemodialysis and renal transplant patients infected by chronic HCV. METHODS: In all, 110 patients with biopsy-proven HCV (60 renal transplant recipients and 50 hemodialysis patients), determined using the METAVIR scoring system, were studied. RESULTS: Forty-six percent of patients had fibrosis > or =F2. A positive predictive value of a score >0.6 for the presence of significant fibrosis by comparison with liver biopsy was 71%, and an negative predictive value of < 0.2 for excluding significant fibrosis was 77%, respectively. The areas under the ROC curves for the diagnosis of significant fibrosis were 0.66, 0.47, and 0.71 in the global population, hemodialysis patients, and renal transplant patients, respectively. In all, 75% of patients were correctly classified using the fibrotest. If biopsy was restricted to scores in the intermediate range (< 0.6 and >0.2), the index could reduce the indication for biopsy by 47%. The results did not differ significantly in hemodialysis and renal transplant patients. CONCLUSION: The fibrotest has a diagnostic value in hemodialysis and renal transplant patients which is similar to that reported in the general population (75%) and its use could avoid 32% of liver biopsies if it were interpreted in detail in nephrology patients.