Progression of liver fibrosis can be controlled by adequate chelation in transfusion-dependent thalassemia (TDT).

A substantial proportion of patients with transfusion-dependent beta-thalassemia major suffer from chronic liver disease. Iron overload resulting from repeated transfusions and HCV infection has been implicated in the development of liver fibrosis. Hepatic siderosis and fibrosis were assessed in 99 transfusion-dependent thalassemia (TDT) patients using transient elastography (TE) and liver iron concentration (LIC) assessed by T2*MRI at baseline and after 4 years. Data were analyzed retrospectively. At baseline, the overall mean liver stiffness measurement (LSM) was 7.4 ± 3.2 kPa and the mean LIC was 4.81 ± 3.82 mg/g dw (n = 99). Data available at 4 ± 1.5 years showed a significant reduction in LSM (6.6 ± 3.2 kPa, p 0.017) and hepatic siderosis measured by LIC (3.65 ± 3.45 mg/g dw, p 0.001). This result was confirmed when considering patients with iron overload at the time of the first measurement (n = 41) and subjects treated with a stable dose of deferasirox over the entire period of observation (n = 39). A reduction of LSM, yet not statistically significant, was achieved in patients on combined deferoxamine + deferiprone, while the group on deferoxamine (n = 11) remained stable over time. HCV-RNA positivity was found in 33 patients at T0, 20 of which were treated during the observation period. Patients who underwent anti-HCV therapy showed a more evident reduction in LSM (9 ± 3 vs 7 ± 3.1 kPa, p 0.016). Adequate chelation therapy is mandatory in order to prevent liver disease progression in TDT. Patients could benefit from regular non-invasive assessment of liver fibrosis by TE to indirectly monitor treatment adequacy and therapeutic compliance.

Combination of deferasirox and deferoxamine in clinical practice: an alternative scheme of chelation in thalassemia major patients.

The availability of three iron chelators improved the scenario of chelation therapy for transfusion-dependent thalassemia (TDT) patients, allowing tailoring of drugs according to the goals expected for each patient. The use of Deferiprone/Deferoxamine (DFP/DFO) combined in different schemes has been reported since many years. Only recently data from combination of Deferasirox/Deferoxamine (DFX/DFO) have been reported showing that it can be safe and efficacious to remove iron overload, particularly in patients who do not respond adequately to a single chelating agent. We investigated the efficacy, tolerability and safety of combined DFX/DFO in thalassemia major patients. Ten TDT patients have started DFX/DFO for different reasons: 1) lack of efficacy in removing liver/cardiac iron with monotherapy; 2) agranulocytosis on DFP; and 3) adverse events with elevated doses of monotherapies. The study design included: cardiac and hepatic T2* magnetic resonance (CMR), transient elastography evaluation (Fibroscan), biochemical evaluation, and audiometric and ocular examinations. The drugs' starting doses were: DFO 32 ± 4 mg/kg/day for 3-4 days a week and DFX 20 ± 2 mg/kg/day. Seven patients completed the one-year follow-up period. At baseline the mean pre-transfusional Hb level was 9.4 ± 0.4 g/dl, the mean iron intake was 0.40 ± 0.10mg/kg/day, the median ferritin level was 2254 ng/ml (range 644-17,681 ng/ml). Data available at 1 year showed no alteration of renal/hepatic function and no adverse events. A marked reduction in LIC (6.54 vs 11.44 mg/g dw at baseline) and in median ferritin (1346 vs 2254 ng/ml at baseline) was achieved. A concomitant reduction of non-transferrin-bound iron (NTBI) at six months was observed (2.1 ± 1.0 vs 1.7 ± 1.2 µM). An improvement in cardiac T2* values was detected (26.34 ± 15.85 vs 19.85 ± 12.06 at baseline). At 1 year an increased dose of DFX was administered (27 ± 6 mg/kg/day vs 20 ± 2 mg/kg/day at baseline, p=0.01) with a stable dose of DFO (32 ± 4 mg/kg/day). Combined or alternated DFX/DFO can be considered when monotherapy is not able to remove the iron overload or in the presence of adverse events.

Feasibility and reproducibility of spleen transient elastography and its role in combination with liver transient elastography for predicting the severity of chronic viral hepatitis.

Liver transient elastography (L-TE) is a reliable, noninvasive predictor of disease severity in chronic liver disease of viral aetiology (CLD). Owing to the relationships among severity of CLD, portal hypertension and spleen involvement, the assessment of splenic stiffness (S-TE) may have an added value in staging CLD. Of 132 CLD patients of viral aetiology, 48 with myeloproliferative disorders (MD) and 64 healthy volunteers (HV), were concurrently investigated by both L-TE and S-TE. Liver disease severity was staged by liver biopsy (LB; Metavir) taken concurrently with TE examination and upper gastrointestinal tract endoscopy for gastro-oesophageal varices. The S-TE inter-observer agreement was analysed by an intra-class correlation coefficient (ICC); L-TE and S-TE accuracy was evaluated by receiver operating characteristic (ROC) curve analysis. Logistic regression analysis assessed the independent effect of L-TE and S-TE as predictors of hepatic fibrosis stage. S-TE failed in 22 CLD (16.6%), 12 (25%) MD and 12 (18%) HV. In the three groups, the ICC was 0.89 (0.84-0.92), 0.90 (0.85-0.94) and 0.86(0.80-0.91), respectively. In the CLD group, L-TE and S-TE independently predicted significant fibrosis (OR 5.2 and 4.6) and cirrhosis (OR 7.8 and 9.1), but at variance from L-TE, S-TE was independent from liver necroinflammation and steatosis. The NPV of S-TE for gastro-oesophageal varices was 100% using a 48 kPa cut-off. In CLD, spleen stiffness alone or in combination with hepatic stiffness can be reliably and reproducibly assessed by TE with the added value of improving the noninvasive diagnosis of severe liver disease and excluding the presence of oesophageal varices.

Transient elastography predicts fibrosis progression in patients with recurrent hepatitis C after liver transplantation.

OBJECTIVE: Transient elastography (TE) allows non-invasive evaluation of the severity of liver disease in patients with chronic hepatitis C. This procedure, however, warrants further validation in the setting of liver transplantation (LT), including patients under follow-up for recurrent hepatitis C. SETTING: Tertiary referral hospital. PATIENTS: 95 patients (75 males) transplanted for end-stage liver disease due to hepatitis C virus. INTERVENTIONS: Paired liver biopsy (LB) and TE were carried out 6-156 (median, 35) months after LT. 40 patients with recurrent hepatitis C sequentially evaluated 6-21 months apart. MAIN OUTCOME MEASURES: Clinical, laboratory and graft histological features influencing TE results. RESULTS: Median TE values were 7.6 kPa in the 90 patients with a successful TE examination, being 5.6 kPa in the 30 patients with Ishak fibrosis score (S) of 0-1, 7.6 kPa in the 38 with S2-3; 16.7 kPa in the 22 with S4-6, (p < 0.0001). Areas under the ROC curves were 0.85 (95% CI, 0.76 to 0.92) for S > or = 3, 0.90 (95% CI, 0.82 to 0.95) for S > or = 4 with 7.9 and 11.9 kPa optimal TE cut-off (81% and 82% sensitivity, 88% and 94% negative predictive value, respectively). Fibrosis, necroinflammatory activity and higher than 200 IU/l gamma-glutamyl transpeptidase levels independently influenced TE results. During post-LT follow-up, TE results changed in parallel with grading (r = 0.63) and staging (r = 0.71), showing 86% sensitivity and 92% specificity in predicting staging increases. CONCLUSIONS: TE accurately predicts fibrosis progression in LT patients with recurrent hepatitis C, suggesting that protocol LB might be avoided in patients with improved or stable TE values during follow-up.

Elective surgery for benign liver tumours.

BACKGROUND: Benign liver tumours (haemangioma, focal nodular hyperplasia, and hepatic adenoma) have different prevalence and prognosis. Spontaneous rupture and malignant transformation can complicate hepatic adenoma. Elective surgery is controversial, and indications are represented by uncertain diagnosis, presence of symptoms, and prevention of major complications. OBJECTIVES: To assess the beneficial and harmful effects of elective surgery of benign liver tumours. We identified 31 cases series. These were small (with less than 60 participants) and the types of tumours mixed. These studies reported no significant mortality, but in the six studies with mortality it ranged from 1% to 17%. SEARCH STRATEGY: The Cochrane Hepato-Biliary Group Controlled Trials Register and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (searches in Issue 1, 2006), MEDLINE, EMBASE, CancerLit, and Science Citation Index Expanded (SCI-EXPANDED) (searched December 2005). A further search included the proceedings of major hepatological and surgical congresses (Annual Meetings of the American Association for the Study of the Liver (AASLD) and European Association for the Study of the Liver (EASL)), and examination of the references of relevant papers and reference lists of the identified studies. SELECTION CRITERIA: Randomised clinical trials in adult patients with benign liver tumours without indications for emergency surgery in which elective surgery (resection) versus no intervention or sham operation are compared. DATA COLLECTION AND ANALYSIS: All trials identified through searches were evaluated for eligibility for inclusion. We intended to extract relevant data in order to analyse the outcomes as per our published protocol using intention-to-treat analysis. MAIN RESULTS: We could not identify any randomised clinical trials. AUTHORS' CONCLUSIONS: We were unable to find evidence supporting or refuting elective surgery for patients with benign liver tumours. We need large, long-term randomised clinical trials with adequate methodology to assess the benefits and harms of elective surgery.

Liver stiffness measurement reliability and main determinants of point shear-wave elastography in patients with chronic liver disease.

BACKGROUND: Liver stiffness (LS) measured by transient elastography (TE) accurately predicts the severity of chronic liver diseases (CLD). Point quantification shear-wave elastography (pSWE) is a new technique incorporated into a conventional ultrasound system for measuring LS. We evaluated pSWE feasibility, reproducibility and diagnostic accuracy in consecutively recruited CLD patients who concomitantly underwent TE and liver biopsy. AIM: To evaluate pSWE feasibility, reproducibility and diagnostic accuracy in consecutively recruited CLD patients who concomitantly underwent TE and liver biopsy. METHODS: Over 2 years 186 CLD patients (116 males, 132 viral hepatitis) consecutively underwent pSWE (10 valid measurements by ElastPQ) blindly performed by two raters. A further operator performed TE. Inter-observer agreement for pSWE was analysed by intraclass correlation coefficient (ICC) and correlated with histological liver fibrosis (METAVIR). Main determinants of pSWE were investigated by linear regression model. RESULTS: Three hundred and seventy-two (100%) reliable measurements were obtained by pSWE and 184 by TE (99%). LS was 8.1 ± 4.5 kPa for pSWE with the first rater and 8.0 ± 4.2 kPa with the second one vs. 8.8 ± 3.6 kPa for TE. pSWE ICC was 0.89 (95% CI 0.85-0.91), not influenced by age, sex, BMI, liver enzymes, liver aetiology. ICC increased over time with year 1 at 0.86 and 95% CI 0.81-0.90 vs. year 2 at 0.92 and 95% CI 0.87-0.95. Liver fibrosis was the only independent determinant of LS on pSWE. The AUROCs for diagnosing F ≥ 2, F ≥ 3 and F = 4 were 0.77, 0.85 and 0.88 for pSWE vs. 0.81, 0.88 and 0.94 for TE. After 1-year training they were 0.86, 0.94 and 0.91. CONCLUSION: Point quantification shear-wave elastography reliably and reproducibly evaluates liver stiffness, matching transient elastography for accuracy after a 1-year learning curve or 130 examinations.

The mitochondrial superoxide dismutase A16V polymorphism in the cardiomyopathy associated with hereditary haemochromatosis.

The A16V mitochondrial targeting sequence polymorphism influences the antioxidant activity of MnSOD, an enzyme involved in neutralising iron induced oxidative stress. Patients with hereditary haemochromatosis develop parenchymal iron overload, which may lead to cirrhosis, diabetes, hypogonadism, and heart disease. The objective of this study was to determine in patients with haemochromatosis whether the presence of the Val MnSOD allele, associated with reduced enzymatic activity, affects tissue damage, and in particular heart disease, as MnSOD knockout mice develop lethal cardiomyopathy. We studied 217 consecutive unrelated probands with haemochromatosis, and 212 healthy controls. MnSOD polymorphism was evaluated by restriction analysis. The frequency distribution of the polymorphism did not differ between patients and controls. Patients carrying the Val allele had higher prevalence of cardiomyopathy (A/A 4%, A/V 11%, V/V 30%, p = 0.0006) but not of cirrhosis, diabetes, or hypogonadism, independently of age, sex, alcohol misuse, diabetes, and iron overload (odds ratio 10.1 for V/V, p = 0.006). The frequency of the Val allele was higher in patients with cardiomyopathy (0.67 v 0.45, p = 0.003). The association was significant in both C282Y+/+ (p = 0.02), and in non-C282Y+/+ patients (p = 0.003), and for both dilated (p = 0.01) and non-dilated stage (p = 0.04) cardiomyopathy, but not for ischaemic heart disease. In patients with hereditary haemochromatosis, the MnSOD genotype affects the risk of cardiomyopathy related to iron overload and possibly to other known and unknown risk factors and could represent an iron toxicity modifier gene.

Close relation between cirrhosis and gallstones: cross-sectional and longitudinal survey.

BACKGROUND: Increased gallstone prevalence and incidence in cirrhosis have already been reported in different series, including a limited number of patients with cirrhosis. OBJECTIVE: To evaluate the frequency of gallstones and related risk factors in a large series of patients with cirrhosis. PATIENTS AND METHODS: The cross-sectional study involved 1010 patients with cirrhosis related to alcohol abuse, chronic viral infection, or miscellaneous causes (42%, 48%, and 10%, respectively) in Child class A, B, or C (48%, 36%, and 16%, respectively). In the longitudinal study gallstone development was monitored ultrasonographically in 618 patients free of gallstones at enrollment. RESULTS: The overall prevalence of gallstone(s) was 29.5% and increased significantly with age without differences according to sex or cause of cirrhosis. Multiple logistic regression analysis showed that only Child classes B and C were significantly related to a higher risk of gallstone (odds ratio, 1.63 for class C vs class A and 1.91 for class B vs class A; P = .001). During a mean+/-SD follow-up of 50 months+/-9 months, 141 (22.8%) of 618 patients developed gallstone(s), with an estimated cumulative probability of 6.5%, 18.6%, 28.2%, and 40.9% at 2, 4, 6, and 8 years, respectively. Multivariate analysis showed that Child class (hazard ratio, 2.8 for class C vs class A and 1.8 for class B vs class A; P = .002 and P = .001, respectively) and high-body mass index (hazard ratio, 1.31; P = .04) carried a significantly greater risk of gallstone formation. CONCLUSION: Cirrhosis per se represents a major risk factor for gallstones whose prevalence and incidence were far higher than those reported in a general population from the same area.

Gallstone disease and related risk factors in patients with Crohn disease: analysis of 330 consecutive cases.

BACKGROUND: The reported prevalence of gallstone disease (GD), defined as current gallstones or previous cholecystectomy for gallstones, in patients with Crohn disease ranges from 13% to 34%. The aim of this study was to characterize the still undefined risk factors of this complication. METHODS: A total of 330 consecutive patients with Crohn disease (189 males and 141 females aged 17-82 years, mean +/- SD age, 41 +/- 14 years) underwent liver ultrasonography. RESULTS: A diagnosis of GD was made in 78 patients (24%), 54 with current gallstones and 24 who had undergone previous cholecystectomy. Its frequency was comparable in males and females (23% vs 25%), but was significantly associated with age (P =.001), being 13%, 36%, and 51% in patients aged 44 years and younger, 45 to 59 years, and 60 years and older, respectively (P =.001). Its prevalence significantly differed according to the site of the disease at diagnosis (P =.02) and was unrelated to disease duration. Gallstone disease was more frequent in patients who had undergone surgery (34% vs 14%; P =.001) and was significantly associated with the number (P =.001) and site of bowel resections (P =.001), increasing from 28% in the patients who had undergone 1 resection to 53% in those having had 2 or more resections (P =.005) and being significantly higher in patients with a resection involving the ileocecal region. Multivariate analysis showed that age; site of disease at diagnosis; and the presence, number, and site of bowel resections were significantly related to GD. CONCLUSIONS: In patients with Crohn disease, the frequency of GD is significantly higher than that reported in the general population with comparable characteristics (z = 5.04, P<.001). Age; site of disease at diagnosis; and the history, number, and site of bowel resections are independently associated with GD.

Effectiveness of IFN-gamma for liver abscesses in chronic granulomatous disease.

In chronic granulomatous disease, interferon-gamma (IFN-gamma) significantly reduces the incidence and severity of recurrent infections, but its effectiveness administered ex novo during acute infection has been reported in only one case. In this report, we describe two adult brothers with chronic granulomatous disease treated successfully with IFN-gamma for acute liver abscesses. Two brothers with severe recurrent infections of unknown origin were hospitalized for septic fever, malnutrition, and ultrasonographic evidence of liver abscess. Autosomal recessive chronic granulomatous disease was diagnosed based on lack of superoxide anion production by phagocytes and absence of p47-phox protein. An antibiotic regimen specifically directed against Staphylococcus aureus was ineffective, whereas treatment with 50 microg/m2 IFN-gamma s.c. thrice weekly induced complete healing with scarring within 3 months. No septic recurrence was observed during a 4-year follow-up period. In chronic granulomatous disease, IFN-gamma is effective not only in preventing but also in healing life-threatening acute infections.

Gallbladder motility in obesity, diabetes mellitus and coeliac disease.

We reviewed data on gallbladder motility in obesity, diabetes and coeliac disease. In obesity, a condition characterised by increased risk of gallstone(s), decreased gallbladder motility has heterogeneously been reported as a consequence of the different type of meals used to induce gallbladder contraction, characteristics of the population studied, technique used, and proportion of patients with hyperinsulinaemia. Moreover, recent studies have evaluated the effect of dietary restriction on gallbladder motility in obese patients. A two- to three-fold increase in the risk of cholesterol gallstone(s) has been reported in diabetic patients, mainly in relation to obesity and hypertriglyceridaemia. Furthermore, decreased gallbladder motility has been described and attributed to other factors, including underlying autonomic neuropathy, reduced gallbladder sensitivity to cholecystokinin and/or reduced number of cholecystokinin receptors on the gallbladder wall. Impaired gallbladder motility has been reported also in patients with coeliac disease in relation to reduced secretion of enteric hormones and/or decreased gallbladder sensitivity to them. In particular, untreated coeliacs, when compared to controls, showed low postprandial cholecystokinin and increased fasting somatostatin levels. Interestingly, the correlation between fasting somatostatin levels and gallbladder size has clearly been confirmed in patients affected by somatostatinoma or treated with somatostatin or its analogues. Gallbladder motility can be affected by various clinical conditions, such as obesity, diabetes mellitus and coeliac disease.

Clinical course of pregnant women with chronic hepatitis C virus infection and risk of mother-to-child hepatitis C virus transmission.

As far as concerns chronic hepatitis C virus infection in pregnant women, different points remain to be elucidated, such as the clinical course, the rate of mother-to-child hepatitis C virus transmission and, in particular, its route and the possible risk factors. This review aimed to analyse current data on the prevalence of chronic hepatitis C virus infection in pregnant women and its relationship with risk factors, the rate of mother-to-child hepatitis C virus transmission and the factors possibly involved, particularly the maternal hepatitis C virus viral load and the human immunodeficiency virus coinfection, and the type of delivery and feeding. Finally, the appropriate timing for HCV-RNA testing in newborns has been reviewed.

Gallstone disease and related risk factors in a large cohort of diabetic patients.

BACKGROUND AND AIM: The aim of this study of a large cohort of consecutive patients with diabetes mellitus was to investigate the still controversial questions concerning the prevalence and possible risk factors of gallstone disease in diabetics. PATIENTS AND METHODS: We enrolled 1337 consecutive patients (710 males aged 63 +/- 11 years and 627 females aged 65 +/- 11 years), of whom 1235 (92%) had type 2 and 102 (8%) had type 1 diabetes mellitus. The data were statistically analysed using multiple logistic regression analysis. RESULTS: The prevalence of gallstone disease was significantly higher in diabetics than in the general population with comparable characteristics (MICOL study) (332/1337 (24.8%) versus 4083/29684 (13.8%); z = 11.208, P = 0.0001) and this difference maintained its statistical significance even when only the North Italian centers involved in this nation-wide survey were considered (332/1337 (24.8%) versus 2469/18091 (13.6%); z = 11.225, P = 0.0001). A total of 332 diabetics (25%) had gallstone disease: 261 had stone(s) and 71 had previously undergone cholecystectomy for gallstone disease after a diagnosis of diabetes mellitus. The prevalence of gallstone disease was higher in the females (29% versus 22%, P = 0.003), and increased with age (13, 20 and 30% in patients aged < or = 40, 41-65 and > 65 years, respectively; P = 0.001), body mass index (24% in patients with a body mass index of < or = 30 and 30% in those with a body mass index of > 30 kg/m2; P = 0.001) and a positive family history of gallstone disease (31% versus 23%; P = 0.001). Gallstone disease was not significantly related to the type of diabetes, plasma total and HDL cholesterol and triglyceride levels, alcohol intake, smoking habits, physical activity, weight reduction in the last year, the use of oral contraceptives, parity or menopause. At multivariate analysis, increasing age, a higher body mass index and a positive family history maintained their statistical significance. CONCLUSIONS: In patients with type 1 or type 2 diabetes mellitus, the prevalence of gallstone disease was significantly related to age, body mass index and a family history of gallstone disease.

Quality-related variables at hepatological websites.

BACKGROUND: The amount of hepatology-related information available on the Internet has substantially increased, but little is known about the characteristics and quality of the websites. AIM: The aim of this study was to describe analytically and evaluate critically the information concerning three diseases of hepatological interest: chronic hepatitis, hemochromatosis and Caroli's disease. METHODS: In accordance with a validated method, the three search terms were entered into four English language search engines and the first five links of each were considered (a total of 60 sites). The characteristics of the websites were described and their quality was evaluated by three independent reviewers who assigned scores of 1-5 for accuracy, reliability and depth. The relationships between the site characteristics and quality scores were analysed by means of multiple logistic regression. RESULTS: The overall rating score was sufficient (>3) in 51% (95% confidence interval: 38-65%) of cases. The majority of the sites (73%) were aimed at patients rather than at physicians. Commercial sponsorship was significantly more frequent among the chronic hepatitis sites (45%) than among the hemochromatosis (15%) or Caroli's disease sites (0%) (P = 0.002); 61% of the commercial sites did not include a financial disclosure. The only variable that independently related to poor quality was the presence of commercial sponsorship (odds ratio 18.1; 95% confidence interval: 1.7-192.5). CONCLUSIONS: Hepatological websites are characterised by poor quality and are mainly aimed at patients. Quality is negatively affected by commercial interests, which are often undeclared. Guidelines for the certification and surveillance of websites relating to liver diseases are highly advisable.

[Survival and development of neoplasms in 56 patients with idiopathic hemochromatosis]. / Sopravvienza e sviluppo di neoplasie in 56 pazienti con emocromatosi idiopatica.

Fifty-six patients with idiopathic hemochromatosis (50 men and 6 women, mean age 49.7 +/- SD 11.1 and 60.8 +/- SD 10.3 years respectively) were studied and followed up for a median period of 44 months (range 3-168). At basal liver biopsy 44 patients had cirrhosis and 12 fibrosis. Iron depletion was achieved in 39 of the 46 cases who underwent iron removal by erythrocytapheresis. Eighteen patients died, 11 from malignancy and 7 from other causes. A total of 14 malignant neoplasms were observed (6 hepatocellular and 8 extrahepatic), of which 6 (5 hepatocellular and 1 pancreatic) were already evident at enrollment. Cumulative survival rates at 3, 5 and 8 years were 75.4%, 64.2% and 54.4% respectively, significantly lower than those in the general population. Probabilities of developing cancer in the 50 patients without cancer at diagnosis were 5.5%, 14.9% and 44.4% at 3, 5 and 8 years respectively.

[Cholecystectomy with laparoscopy and laparotomy. Analysis of the complications]. / Colecistectomia laparoscopica e laparotomica. Analisi delle complicanze.

Laparoscopic cholecystectomy (LC) has been adopted by many as the treatment of choice for uncomplicated biliary lithiasis; since an increasing number of surgeons use LC even in complicated cases, we examined our series in order to see if this is the correct procedure. We report on the results of our first 252 LC and compare them with our latest 66 open cholecystectomies, in order to evaluate number and importance of postoperative complications. Besides we compare complications in patients below and over 60 years of age to verify if age bears any significance. We found no difference in frequency of complications among patients younger or older than 60; highly significant is, on the contrary, the difference in complications between the two procedures, the incidence being much lower in the laparoscopic one. We state that LC is a safe and effective procedure and suggest it as the method of choice for the treatment of any symptomatic gallbladder stone disease.

Meta-analysis: nonsteroidal anti-inflammatory drugs in biliary colic.

BACKGROUND: Biliary colic is a common manifestation of cholelithiasis, developing in about one-third of patients. Even if nonsteroid anti-inflammatory drugs (NSAIDs) have widely been used to relieve biliary pain, there is a lack of systematic review of treatments on this issue. AIM: To assess the potential benefits in terms of both pain control and reduction of complications, and the potential harms of NSAIDs in patients with biliary colic. METHODS: Data from randomised clinical trials (RCTs) comparing NSAIDs with no treatment, placebo or other drugs in patients with biliary colic, were collected from Medline and Embase. The outcome measures were expressed as odds ratio and relative risk and then pooled using fixed or random-effect models. RESULTS: Eleven RCTs involving 1076 subjects (268 men, 808 women; 18-86 years), including 442 controls were analysed. In comparison with placebo, NSAIDs led to a significantly higher proportion of patients with complete pain relief (RR 3.77, 95%CI 1.65-8.61; I(2) : 73%) and a significantly lower rate of complications (RR 0.53, 95% CI 0.31-0.89; I(2) : 35%). In comparison with other drugs, NSAIDs were more efficacious in controlling pain than spasmolytics (RR 1.47, 95% CI 1.03-2.10; I(2) : 55%); there was no difference between NSAIDs and opioids (RR 1.05, 95% CI 0.82-1.33; I(2) : 74%). CONCLUSIONS: In patients with biliary colic NSAIDs are the first-choice treatments as they control pain with the same efficacy of opioids and significantly reduce the proportion of patients with severe complications. However, the lack of high-quality RCTs and the presence of consistent heterogeneity among studies may partially flaw these results.

Dual cut-off transient elastography to assess liver fibrosis in chronic hepatitis B: a cohort study with internal validation.

BACKGROUND: Transient elastography has gained popularity to stage liver fibrosis in chronic viral hepatitis, however, diagnostic cut-offs for severe fibrosis in chronic hepatitis B are poorly defined. AIM: To evaluate an algorithm with two distinct cut-offs for positive and negative prediction of significant fibrosis and cirrhosis in chronic hepatitis B patients. METHODS: Two cohorts of treatment-naïve patients with chronic hepatitis B (125 training and 92 validations) were consecutively and concurrently examined by percutaneous liver biopsy and transient elastography. Fibrosis was staged by Metavir (significant fibrosis = F ≥ 2; cirrhosis = F4) in ≥ 2 cm long liver tissue cores. RESULTS: A >13.1 kPa positive and a ≤ 9.4 kPa negative cut-off for cirrhosis had a >90% sensitivity and specificity, with an accuracy of 94%. The corresponding cut-offs for F ≥ 2 were >9.4 and ≤ 6.2 kPa, thus classifying 56% of patients with an overall accuracy of 90%. In the validation cohort, F4 and F ≥ 2 were predicted by the above transient elastography cut-offs with an overall accuracy >90%. In 165 patients with higher than upper limit of normal transaminase activity the dual cut-off algorithm of transient elastography was as accurate as in the 52 patients with normal alanine aminotransferase values in the prediction and exclusion of cirrhosis, only. CONCLUSIONS: A dual cut-off algorithm allowed for correctly classifying both significant fibrosis and cirrhosis in the majority of the patients with chronic hepatitis B, independent of alanine aminotransferase values, thus reducing the need for liver biopsy investigations.

Chromogranin A levels in chronic liver disease and hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the relevant cause of death in patients with compensated cirrhosis. Alpha-fetoprotein (AFP) is used for screening HCC, with limited success. AIM: We evaluated plasma chromogranin A (CgA) as a marker of HCC. PATIENTS: CgA plasma levels and AFP serum levels were prospectively measured in 30 patients with HCC, 14 with cirrhosis, 79 with chronic hepatitis and 65 controls. METHODS: CgA was measured with an enzyme-linked immunosorbent assay (DAKO A/S Glostrup, Denmark). AFP was measured by electrochemiluminoimmunoassay (Elecsys, Roche S.p.A., Italy). RESULTS: CgA levels were significantly higher in the three groups of patients than in controls and in patients with HCC they were significantly higher than in chronic hepatitis patients [median 44.5 (interquartile range 21-145.9)U/L vs. 15.3 (10.9-29.25)U/L, p<0.001]. AFP values were above the upper reference limit in 75% of patients with HCC, 50% of cirrhotic patients and 11% of chronic hepatitis patients (p<0.005). CgA values significantly correlated with AFP levels (r(s)=0.42, p<0.0001). The overall diagnostic accuracy of CgA was 75% (CI 66-82), with a sensitivity of 70% (CI 50.6-85.2) and a specificity of 67% (CI 55.9-76.3). CONCLUSIONS: Despite the evidence of higher CgA levels in patients with HCC, this test has low-diagnostic accuracy. Its pathophysiological meaning remains unknown, even if it could suggest an endocrine phenotype of HCC.