Methodological assessment of HCC literature.

Despite the fact that the hepatocellular carcinoma (HCC) represents a major health problem, very few interventions are available for this disease, and only sorafenib is approved for the treatment of advanced disease. Of note, only very few interventions have been thoroughly evaluated over time for HCC patients compared with several hundreds in other, equally highly lethal, tumours. Additionally, clinical trials in HCC have often been questioned for poor design and methodological issues. As a consequence, a gap between what is measured in clinical trials and what clinicians have to face in daily practice often occurs. As a result of this scenario, even the most recent guidelines for treatment of HCC patients use low strength evidence to make recommendations. In this review, we will discuss some of the potential methodological issues hindering a rational development of new treatments for HCC patients.

[Highlights in gastroenterology and hepatology 2010]. / Actualités en gastroentérologie et hépatologie.

This review highlights recent advances in gastroenterology and hepatology, including the treatment of Crohn's disease, of eosinophilic esophagitis, of chronic hepatitis C, and of hepatic encephalopathy as well as the role of high resolution manometry in the investigation of esophageal motility disorders. These new developments will be summarized and discussed critically, with a particular emphasis on their potential implications for current and future clinical practice.

[Management of chronic hepatitis B]. / Prise en charge de l'hépatite B chronique: un défi en évolution constante.

Chronic hepatitis B predisposes to the development of cirrhosis and hepatocellular carcinoma. Treatment of chronic hepatitis B is aimed at halting viral replication and, thereby, hepatic inflammation. Treatment indication should be established carefully and with full knowledge of the advantages and limitations of currently available antiviral drugs. Patients on long-term nudcleos(t)ide analogue treatment should be followed regularly in order to avoid the appearance of antiviral resistance. The purpose of this review is to provide a concise overview of the diagnosis and management of chronic hepatitis B.

[An update on the management of chronic hepatitis C]. / Le point sur le traitement de l'hépatite C chronique.

Treatment of chronic hepatitis C with pegylated interferon-a and ribavirin is now adapted individually based on the virological response on treatment. This approach should improve the tolerability while maintaining or even improving in some patients the efficacy of antiviral therapy. Several new antiviral drugs are currently being evaluated in advanced clinical trials, with very promising results. These new drugs should greatly broaden treatment options for chronic hepatitis C in the near future.

[Management of hepatocellular carcinoma]. / Prise en charge du carcinome hépatocettulaire en 2010.

Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors worldwide and its incidence has increased over the last years in most developed countries. The majority of HCCs occur in the context of liver cirrhosis. Therefore, patients with cirrhosis and those with hepatitis B virus infection should enter a surveillance program. Detection of a focal liver lesion by ultrasound should be followed by further investigations to confirm the diagnosis and to permit staging. A number of curative and palliative treatment options are available today. The choice of treatment will depend on the tumor stage, liver function and the presence of portal hypertension as well as the general condition of the patient. A multidisciplinary approach is mandatory to offer to each patient the best treatment.

[Highlights in hepatology]. / Actualités en hépatologie.

This review highlights recent advances in hepatology, including new insights into the clinical penetrance of hereditary hemochromatosis, the development of non-immunosuppressive cyclosporin A analogs for the treatment of chronic hepatitis C, thrombopoietin receptor agonists for thrombocytopenia in cirrhosis, the development of vasopressin V2 receptor antagonists (vaptans) for the management of ascites and hyponatremia in portal hypertension, the description of chronic hepatitis E in immunosuppressed patients, and the development of sorafenib as the first molecularly targeted therapy with a demonstrated benefit in the treatment of advanced hepatocellular carcinoma. These new developments will be summarized and discussed critically, with a particular emphasis on their potential implications for current and future clinical practice.

The PTPN22 1858T variant is not associated with primary biliary cirrhosis.

The minor allele of a single nucleotide polymorphism (SNP) in the PTPN22 gene (1858T) encoding the Lyp-tyrosine phosphatase has been recently associated with multiple autoimmune disorders, raising the possibility that this variant may also represent a risk allele for primary biliary cirrhosis (PBC). We therefore investigated the possible association of the PTPN22(1858T) variant with PBC in a Canadian population. We studied 160 Caucasian patients with biopsy and antimitochondrial antibodies (AMA)-proven PBC who were genotyped for the PTPN22(C1858T) SNP using a single-base primer extension assay and mass spectrometry. The frequency of the PTPN22(1858T) allele was then compared between the patients and 290 healthy controls. No association was detected between the PTPN22(1858T) allele and PBC, the frequency of this variant being similar in patients with PBC (7.5%) and controls (8.4%). Restricting the analysis to patients with PBC with any second autoimmune condition or specifically with sicca syndrome or autoimmune thyroid disease also revealed no association with this variant. Thus the PTPN22(1858T) variant is not associated with PBC or with the combination of PBC and a second autoimmune disease. These data suggest that this variant does not confer risk for PBC and does not account for the frequent presence of other autoimmune diseases in patients with PBC.

[Hepatology]. / Hépatologie.

Therapy by pegylated interferon-alpha (PEG-IFN-alpha), lamivudine and adefovir have significantly improved treatment perspectives for patients with chronic hepatitis B. New nucleos(t)ide analogues should permit the development of more effective combination therapies. In autoimmune hepatitis, if there is no response or an intolerance to therapy with prednisone and imurek, administration of mycophenolate mofetil should be envisaged. Ursodeoxycholic acid (UDCA) therapy, at a dosage of 13-15 mg/ kg/day, remains the treatment of choice for primary biliary cirrhosis and should be administered at an early stage to improve patients' survival. In the treatment of nonalcoholic fatty liver disease, thiazolidinediones show considerable promise, but further clinical studies are required in order to prove their efficacity and safety.

Severe haemorrhage following abdominal paracentesis for ascites in patients with liver disease.

BACKGROUND: Bleeding is a recognized complication of abdominal paracentesis. Special concern has been raised when it is performed in patients with liver failure because of coagulation disorders and collaterals in the abdominal wall. AIM: To assess the clinical characteristics of patients who developed haemorrhagic complications after paracentesis. METHODS: We reviewed all cases of severe haemorrhage occurring after paracentesis in patients admitted to the Liver Unit of our institution between 1994 and 2004. RESULTS: Nine cases were identified among 4729 procedures. The occurrence of severe haemorrhage represented 0.19% of all procedures with a death rate of 0.016%. Bleeding was not related to operator experience, elevated international normalized ratio or low platelets. It occurred in patients with high model for end-stage liver disease and Child-Pugh scores. Furthermore, some degree of renal failure was present in all but one patient. CONCLUSION: Severe haemorrhage after abdominal paracentesis in patients with liver disease occurs in 0.2% of cases. It occurs in patients with severe liver failure and is often associated with significant pre-existing renal dysfunction.

[When and how to treat hepatitis B and C?]. / Quand et comment traiter les hépatites B et C?

The introduction of pegylated interferon-alpha (PEG-IFN-alpha) as well as lamivudine and adefovir has greatly improved the perspectives for patients with chronic hepatitis B. In addition, new nucleos(t)ide analogues are currently being evaluated and may allow the development of effective combination therapy regimens in the future. In the absence of resistance development, lamivudine reduces the risk of decompensation and hepatocellular carcinoma in patients with cirrhosis. Current standard therapy of chronic hepatitis C, PEG-IFN-alpha combined with ribavirin, results in a sustained virologic response in 20-80% of patients, depending on the viral genotype and additional factors, such as ethnicity, fibrosis stage, body mass index, viral load, alcohol consumption, and coinfections. Novel antiviral strategies are currently being explored.

[Auto-immune liver diseases and their treatment]. / Les hépatopathies auto-immunes et leurs traitements.

There are three main types of auto-immune liver disease, auto-immune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis. In the case of auto-immune hepatitis, prednisone therapy, with or without azathioprine, can improve quality of life and halt progression to cirrhosis. If there is no response or if the therapy is poorly tolerated, mycophenolate mofetil or cyclosporin should be considered. Ursodeoxycholic acid (UDCA), at a dosage of 13 to 15 mg/kg/day slows the progression of fibrosis in patients with primary biliary cirrhosis. Pruritus may be treated with cholestyramine, rifampicin or opiate antagonists. Ursodeoxycholic acid at a dosage of 20 to 30 mg/kg/day will slow the evolution of fibrosis.

Intravenous ibandronate in men with osteoporosis: an open pilot study over 2 years.

In the treatment of osteoporosis, the tolerance of oral bisphosphonates is often low. The high potency of ibandronate allows iv bolus injections that can be repeated every 2 to 3 months. However, the best dose and time interval of the treatment with iv ibandronate is still debated. Efficacy of 2-mg ibandronate injected every 3 months was tested in men with osteoporosis over 2 yr, in a prospective, open study. Fourteen men with primary osteoporosis, mean age 57 +/- 12 yr (range: 40-73), received 2-mg ibandronate iv every 3 months over 2 yr. All got 1 g/day calcium and 880 UI/day vitamin D for 2 yr. Bone mineral density (BMD) increased after 2 yr by 6.7 +/- 1.5% (mean change +/- SEM) at lumbar spine (p<0.001), by 3.2 +/- 08% at trochanter (p<0.001) and by 1.4 +/- 1.1% at femoral neck (ns). Serum beta-crosslaps and osteocalcin decreased significantly by 30-45 and 30%, respectively, during the 2 yr of treatment. Serum calcium increased from the lower to the middle tertile of the normal range during the 2 yr of the study. The observed decrease of bone remodelling and the increase of BMD are of the same magnitude as those described with oral bisphosphonates. The increase of plasma calcium confirms the positive effect of the supplementation with calcium and vitamin D. These results suggest that 3 months are a good interval between two doses of iv ibandronate, when 2 mg are given.

Overuse and underuse of colonoscopy in a European primary care setting.

BACKGROUND: Efforts to decrease overuse of health care may result in underuse. Overuse and underuse of colonoscopy have never been simultaneously evaluated in the same patient population. METHODS: In this prospective observational study, the appropriateness and necessity of referral for colonoscopy were evaluated by using explicit criteria developed by a standardized expert panel method. Inappropriate referrals constituted overuse. Patients with necessary colonoscopy indications who were not referred constituted underuse. Consecutive ambulatory patients with lower gastrointestinal (GI) symptoms from 22 general practices in Switzerland, a country with ready access to colonoscopy, were enrolled during a 4-week period. Follow-up data were obtained at 3 months for patients who did not undergo a necessary colonoscopy. RESULTS: Eight thousand seven hundred sixty patient visits were screened for inclusion; 651 patients (7.4%) had lower GI symptoms (mean age 56.4 years, 68% women). Of these, 78 (12%) were referred for colonoscopy. Indications for colonoscopy in 11 patients (14% of colonoscopy referrals or 1.7% of all patients with lower GI symptoms) were judged inappropriate. Among 573 patients not referred for the procedure, underuse ranged between 11% and 28% of all patients with lower GI symptoms, depending on the criteria used. CONCLUSIONS: Applying criteria from an expert panel of nationally recognized experts indicates that underuse of referral for colonoscopy exceeds overuse in primary care in Switzerland. To improve quality of care, both overuse and underuse of important procedures must be addressed.

Is the diagnostic yield of upper GI endoscopy improved by the use of explicit panel-based appropriateness criteria?

BACKGROUND: Increasing the appropriateness of use of upper gastrointestinal (GI) endoscopy is important to improve quality of care while at the same time containing costs. This study explored whether detailed explicit appropriateness criteria significantly improve the diagnostic yield of upper GI endoscopy. METHODS: Consecutive patients referred for upper GI endoscopy at 6 centers (1 university hospital, 2 district hospitals, 3 gastroenterology practices) were prospectively included over a 6-month period. After controlling for disease presentation and patient characteristics, the relationship between the appropriateness of upper GI endoscopy, as assessed by explicit Swiss criteria developed by the RAND/UCLA panel method, and the presence of relevant endoscopic lesions was analyzed. RESULTS: A total of 2088 patients (60% outpatients, 57% men) were included. Analysis was restricted to the 1681 patients referred for diagnostic upper GI endoscopy. Forty-six percent of upper GI endoscopies were judged to be appropriate, 15% uncertain, and 39% inappropriate by the explicit criteria. No cancer was found in upper GI endoscopies judged to be inappropriate. Upper GI endoscopies judged appropriate or uncertain yielded significantly more relevant lesions (60%) than did those judged to be inappropriate (37%; odds ratio 2.6: 95% CI [2.2, 3.2]). In multivariate analyses, the diagnostic yield of upper GI endoscopy was significantly influenced by appropriateness, patient gender and age, treatment setting, and symptoms. CONCLUSIONS: Upper GI endoscopies performed for appropriate indications resulted in detecting significantly more clinically relevant lesions than did those performed for inappropriate indications. In addition, no upper GI endoscopy that resulted in a diagnosis of cancer was judged to be inappropriate. The use of such criteria improves patient selection for upper GI endoscopy and can thus contribute to efforts aimed at enhancing the quality and efficiency of care. (Gastrointest Endosc 2000;52:333-41).

Performance of panel-based criteria to evaluate the appropriateness of colonoscopy: a prospective study.

BACKGROUND: Prospective data describing the appropriateness of use of colonoscopy based on detailed panel-based clinical criteria are not available. METHODS: In a cohort of 553 consecutive patients referred for colonoscopy to two university-based Swiss outpatient clinics, the percentage of patients who underwent colonoscopy for appropriate, equivocal, and inappropriate indications and the relationship between appropriateness of use and the presence of relevant endoscopic lesions was prospectively assessed. This assessment was based on criteria of the American Society for Gastrointestinal Endoscopy and explicit American and Swiss criteria developed in 1994 by a formal panel process using the RAND/UCLA appropriateness method. RESULTS: The procedures were rated appropriate or equivocal in 72.2% by criteria of the American Society for Gastrointestinal Endoscopy, in 68.5% by explicit American criteria, and in 74.4% by explicit Swiss criteria (not statistically significant, NS). Inappropriate use (overuse) of colonoscopy was found in 27.8%, 31.5%, and 25.6%, respectively (NS). The proportion of appropriate procedures was higher with increasing age. Almost all reasons for using colonoscopy could be assessed by the two explicit criteria sets, whereas 28.4% of reasons for using colonoscopy could not be evaluated by the criteria of the American Society for Gastrointestinal Endoscopy (p < 0.0001). The probability of finding a relevant endoscopic lesion was distinctly higher in the procedures rated appropriate or equivocal than in procedures judged inappropriate. CONCLUSIONS: The rate of inappropriate use of colonoscopy is substantial in Switzerland. Explicit criteria allow assessment of almost all indications encountered in clinical practice. In this study, all sets of appropriateness criteria significantly enhanced the probability of finding a relevant endoscopic lesion during colonoscopy.

Reliability of panel-based guidelines for colonoscopy: an international comparison.

BACKGROUND: This study examined the reliability of explicit guidelines developed using the RAND-UCLA appropriateness method. METHODS: The appropriateness of over 400 indications for colonoscopy was rated by two multispecialty expert panels (United States and Switzerland). A nine-point scale was used, which was consolidated into three categories of appropriateness: appropriate, uncertain, inappropriate. The distribution of appropriateness ratings between the two panels and the intrapanel and interpanel agreement for categories of appropriateness were calculated for all possible indications. Similar statistics were calculated for a series of 577 primary care patients referred for colonoscopy in Switzerland. RESULTS: Over 80% of all indications (348) could be directly compared. The proportions of indications classified as appropriate, uncertain, or inappropriate were 28.4%, 24.7%, 46.6% and 33.0%, 23.0%, 44.0% for the U.S. and the Swiss panels, respectively. Interpanel agreement was excellent for all the possible indications (kappa value: 0.75) and lower for actual cases (kappa value: 0.51) because of lower agreement for the most frequently encountered indications. CONCLUSIONS: Good agreement between the two sets of criteria was found, pointing to the reliability of the method. Partial disagreement occurred essentially for a few, albeit frequently encountered, indications for use of colonoscopy in cases of uncomplicated lower abdominal pain or constipation.

Appropriateness of upper gastrointestinal endoscopy: comparison of American and Swiss criteria.

OBJECTIVE: Examine the reproducibility of the RAND method for developing criteria for the appropriateness of medical procedures. DESIGN: Comparison of two sets of explicit criteria for appropriateness of upper gastrointestinal (UGI) endoscopy, developed by separate expert panels from two countries. SETTING: United States, Switzerland. STUDY PARTICIPANTS: National experts from different medical specialties involved in the referral or application of UGI endoscopy. INTERVENTIONS: Each panel was presented with about 500 clinical scenarios (indications) that were rated on a nine-point scale as to the appropriateness of performing UGI endoscopy for a patient with that clinical presentation. MAIN OUTCOME MEASURES: (1) distribution of appropriateness ratings and intrapanel agreement categories between the two panels, (2) between-panel agreement of assigning appropriateness for comparable indications and, (3) percentage of indications with major between-panel differences. RESULTS: Ratings for 2/3 of indications could be compared. The Swiss panel showed higher intrapanel agreement (54.6% versus 46.2%, P = 0.002). Seventy-eight per cent of comparable indications were assigned to identical categories of appropriateness by both panels (kappa = 0.76, P < 0.001). For 93% of the 376 comparable indications, there were no major interpanel differences. CONCLUSION: Separate expert panels in different countries, using a standardized methodology, produce criteria for appropriateness of medical procedures that are similar. Given the resources being invested throughout the world in developing criteria and guidelines, international collaboration in seeking optimal use of limited health care resources should be intensified.

Underutilization of upper gastrointestinal endoscopy.

BACKGROUND & AIMS: Efforts to reduce costs in health care may raise concerns about underuse of medical procedures. This study prospectively assessed underuse of upper gastrointestinal endoscopy in a cohort of patients in whom we have recently published data on overuse of endoscopy. METHODS: Underuse was identified by formal necessity criteria for endoscopy, obtained by an explicit panel process. Outpatients were consecutively included in two clinical settings. Setting A consisted of 20 primary care physicians and 7215 patient visits that occurred within 1 month. Setting B consisted of 920 visits that occurred during 3 weeks at an outpatient clinic. RESULTS: During these 8135 visits, 611 patients complained of upper digestive symptoms; 63 of them underwent endoscopy. Underuse was identified in 72 patients (11.8%). The two clinical situations mainly responsible for underuse of endoscopy were uninvestigated peptic symptoms resistant to treatment and dysphagia. At first follow-up, 29 of the patients with initial underuse still fulfilled criteria of necessity (underuse rate, 4.7%). One-year follow-up showed underuse of endoscopy in 5 patients. CONCLUSIONS: This prospective evidence shows that underuse of a medical procedure exists. The estimated overuse and underuse of endoscopy in this cohort were approximately equal (5%). Improving quality of care will require reductions of both overuse and underuse of medical procedures.