To assess the relationship between the type of chronic liver diseases (CLDs), clinical severity and patients' HRQoL. A naturalistic, multicentre study has been conducting to identify and test quality of care indicators. Adult CLDs patients (age>18 years) have been enrolling at gastroenterology unit of 3 Italian hospitals. We are collecting socio-demographic, clinical and HRQoL data with the EQ-5D-3L. Patients are sub-grouped according to CLD type and to clinical severity using the modified Child-Turcotte-Pugh score: with this instrument, patients are classified as non-cirrhotic, early cirrhotic (class A), advanced cirrhotic (classes B and C). We conducted Kruskall-Wallis tests to assess relationship between EQ-5D-VAS score and disease type or severity score. Results are based on data from 2,221 patients (67% male, median age=62 years), classified into the following subgroups: HCV or HBV chronic hepatitis (36.0%), compensated cirrhosis (CC, 23.5%), hepatocellular carcinoma (HCC, 19.8%), decompensated cirrhosis (DC, 13.5%), patients in evaluation or listed for liver transplant (LT, 7.2%). Non-cirrhotic patients (HCV or HBV chronic hepatitis) had significantly (p<0.001) higher median VAS (80) than patients with any other CLD types (70). In contrast, patients listed for LT had the lowest (p<0.05) median VAS (65) and the highest proportion of patients (58.1%) in Child class B-C. DC patients had a median VAS not significantly different from that of HCC or CC patients (70 versus 70 and 73, respectively). On the other hand, DC patients in child class A showed a significantly (p<0.05) higher median VAS (72.5) than HCC and CC patients in class B-C, who had a median VAS of 70 and 60, respectively. HRQoL of CLDs patients is significantly related with the Child-Turcotte-Pugh severity score. These results could be useful to understand the impact of the disease severity on patients' HRQoL and guide some decisions in clinical care.

Liver Diseases (LDs) are prevalent and generate high human and economic costs to the society. Efficient strategies of diagnosis and treatment are necessary to improve patients' health and reduce costs. Our aim was to identify healthcare quality indicators (HCQIs) to measure quality of care provided to LD patients. This work was conducted using a modified Delphi methodology based on a two-stage rating process. We organized 7 expert panels, involving 8-10 hepatologists each. Each panel focused on one/few condition(s): hepatitis B, hepatitis C, cirrhosis, hepatocellular carcinoma, autoimmune hepatopathies and cholangiopathies, metabolic hepatopathies, liver transplant. For each condition a preliminary set of HCQIs was identified and discussed by the panel, according to evidence and experience. Then, each panel member performed a first independent rating of all HCQIs using the RAND 9-point agreement scale (RAS; 1=totally disagree to 9=totally agree). Median scores of each HCQI were calculated and then used to rate again the HCQIs in the light of these results. After this second rating, a disagreement index (DI) was calculated to identify and accept (if DI≤1) indicators with median RAS≥7. The final set of HCQIs was selected. The final list included 8 valid HCQIs for hepatitis B, 7 for hepatitis C, 4 for compensated cirrhosis, 8 for decompensated cirrhosis, 10 for hepatocellular carcinoma, 12 for autoimmune hepatopathies and cholangiopathies, 11 for metabolic hepatopathies and 15 for liver transplant. Health-Related Quality-of-Life was included as a further HCQI in all conditions. We identified and proposed a set of indicators as a tool to assess the quality of care provided to patients affected with LDs. After a validation process, which is being performed, their use could help clinicians and budget holders in understanding and improving the efficiency of the health care provided.

BACKGROUND:Ascites is one of the most frequent severe complications in patients with liver cirrhosis. The treatment of this chronic disease usually requires the prolonged use of albumin, frequently continued even after patients' discharge from the hospital. AIMS:Aim of the study was to define a consensus among Italian physicians with regard to the use of albumin in patients with decompensated cirrhosis and ascites. METHODS:The study adopted the Delphi technique to conduct the consensus activities. All controversial issues related to the use of albumin were identified by the experts' board and proposed to the 68 participating hepatology centres through two subsequent questionnaires. The questionnaires, returned by the specialists involved, were collected and the answers classified to verify the elements on which a consensus was reached. RESULTS:The home use of albumin can help to improve the patient's general conditions and well-being. About 77% of the experts involved considered likely that albumin administration could shorten hospital stays or could reduce the number of hospital admissions. The results of the study, along with a socioeconomic analysis, were presented to the Italian Drug Commission, which subsequently removed the specific hypoalbuminemia level as a prerequisite for having the drug reimbursed by the National Health Service. CONCLUSIONS:For an outpatient prescription, the hypoalbuminemia limit of 2.5 g/dl or less is not sufficient, while the decision whether to administer the drug requires the evaluation of patient's overall clinical conditions as an essential criterion for the prescription of a home treatment with albumin.

Background/Aims: Assessment of chronic hepatitis C outcome in sustained responders to interferon requires prolonged observation and close monitoring, We prospectively studied the impact of sustained response on histology and clinically relevant outcomes.Methods: The 47 sustained responders (ten with cirrhosis) from two interferon trials involving 235 chronic hepatitis C patients (81 with cirrhosis) were included. Hepatitis C virus (HCV) RNA was assessed every 6 months, liver histological changes from baseline, 6-12 and 48-72 months after treatment discontinuation.Results: The mean follow-up was 102 +/- 19 months. HCV RNA became undetectable in 36/47 responders, Four responders, who had remained viremic, later relapsed. The histology progressively improved in non-viremic and viremic patients, with a more marked improvement in the former (P=0.0089), normalizing in 53 vs. 0% (P = 0.0220). No patient progressed to cirrhosis. One non-viremic cirrhotic patient developed a hepatocellular carcinoma, Non-responders from the two original trials had worse histological outcomes and those with cirrhosis had a higher rate of clinically relevant events compared with cirrhotics showing a sustained biochemical response (4.5 vs. 1.2 cases/100 person-years; CI for the difference, 0.3-6.3).Conclusions: Most sustained, virological responders without cirrhosis normalize liver histology in the long-term and are cured of the disease. Sustained responders remaining viremic still show histological improvement, albeit to a lesser extent. (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.

The aim of this study was to test K-17.22, an herbal formula which has been preliminarly shown to yield a significant transaminases decrease in HCV patients, in CCl 4 -induced liver toxicity. Wistar rats were allocated into 3 groups: A) given a s.c. injection of 0.1 mL/100 g body wt mixture of CCl 4 in olive oil (1 : 1 v/v) twice a day for 4 weeks; B) as A, plus oral administration of 50 mg/kg of K-17.22 dissolved in 5% glucose; C) as B but with K-17.22 given 1 week after the first injection of CCl 4 . Rats were sacrificed at the end of the study and blood and liver samples were obtained. As compared to control, group A showed a significant decrease of GSH (>45%, P 15-fold, P< 0.001) whereas both groups B and C showed only a mild transaminases increase (<3-fold, P<0.05). Group A showed a significant decrease of Y-protein fraction and of GST activity, as tested by both substrates (P<0.01 vs control). However, both these parameters were reverted to normal by K-17.22 (P<0.05 vs. A). A parallel in vitro study with hepatocyte culture showed that concentrations as low as 10 μg/mL of K-17.22 were able to significantly mitigate CCl 4 hepatocyte damage (P<0.05) comparably to 100 μg/mL silymarin, while 100 μg/mL proved to be more protective than either silymarin 100 μg/mL and of glycyrrhizin 10 μg/mL (P<0.05). These preliminary data suggest that K-17.22 exerts an highly protective and prolonged effect (either preventive and therapeutic) on GSH depletion in CCl 4 -induced liver injury, thing which might substantiate its potential use in clinical practice.

BACKGROUND/AIMS:It has been shown that alcohol impairs erythrocyte (red blood cell) membrane fluidity and lipid composition. The aim of this study was to test the effect of a novel acid-resistant antioxidant on the hemorrheology in alcoholics.METHODOLOGY:Thirty alcoholics (25 males, 5 females; mean age: 42 years; range: 31-54; 150 g ethanol/day for 3-5 years) were enrolled into the study. Patients were randomly and double-blindly allocated into 2 groups which were given, for a 2 week period, 18 g/day of Bionormalizer (obtained from biofermentation of carica papaya, pennisetum purpureum, sechium edule, Osato Res. Foundation, Gifu, Japan) dissolved in 5 mL of water at bedtime and 3 hours prior to examination. Placebo consisted of flavored sugar. Healthy teetotalers served as control. On the examination day, blood samples were taken for testing: routine tests, plasma glutathione, ascorbic acid, selenium, plasma lipid hydroperoxides and alpha-tocopherol. Erythrocytes were separated and tested for red blood cell malonyldialdehyde and glutathione content. The hemorheological studies were as follows: blood and plasma viscosity, whole blood filterability, red blood cell membrane fluidity by electron spin resonance, red blood cell aggregation index by photometric rheoscopy and red blood cell deformability by ektacytometry.RESULTS:As compared to healthy controls, alcoholics on placebo treatment showed no change of plasma viscosity but a significantly higher red blood cell malonyldialdehyde, blood viscosity (P < 0.05) and lower plasma glutathione, whole blood filterability and red blood cell fluidity (P < 0.01). No relationship appeared between biochemical tests and red blood cell membrane fluidity. Bionormalizer group showed a significant recovery to control values of either blood viscosity and whole blood filterability (P < 0.01) and a partial, although significant, improvement of red blood cell membrane fluidity, red blood cell malonyldialdehyde and plasma glutathione (P < 0.05). As compared to healthy control, red blood cell aggregation decreased in alcoholics (P < 0.05) and was not affected by Bionormalizer. However, Bionormalizer significantly improved the reduced red blood cell deformability (P < 0.05 vs. alcoholics) and this parameter correlated with red blood cell malonyldialdehyde (r: 0.62. P < 0.05).CONCLUSIONS:These preliminary data suggest that an effective antioxidant supplementation is able to improve the hemorrheology in alcoholics either by directly affecting the ethanol-related lipoperoxidation and xanthine oxidase system activation and/or by modifying red blood cell membrane characteristics.

In immunocompetent patients, specific human leukocyte antigen (HLA) class II alleles have been associated with the severity of hepatitis C virus (HCV)-related disease, in particular, HLA-DRB1*11 has been found to exert a protective effect. The authors have analyzed the role of HLA class I and II alleles in determining the frequency, timing, and progression of histologically proven recurrent hepatitis C in 89 patients who underwent a liver transplant for HCV-related cirrhosis. In addition, the influence of HLA mismatch between donor and recipient, HCV genotype, and use of steroid pulses was also evaluated. Median patient follow up was 35 months (range 4-119). HLA-DRB1 typing was performed by genomic analysis in all cases. Liver biopsies were obtained routinely and at least at yearly intervals. Histologically proven recurrent hepatitis was observed in 46 patients (52%), 10 patients progressing to stage 5-6 fibrosis in most cases within 2 years after transplant. By univariate analysis, 3 variables, HLA-B14, HLA-DRB1*04, and HLA-DRB1 donor/recipient mismatch, showed a significant effect on time to recurrent hepatitis C disease. These parameters were included in a multivariate regression model along with HCV genotype, treatment with steroid pulses and DRB1*11. HLA-B14, HLA-DRB1*04, and HLA-DRB1 donor/recipient mismatch were confirmed to provide a significant and independent contribution to the risk of hepatitic disease recurrence. As for the severity of the disease, none of the 10 patients with stage 5-6 hepatitis carried the HLA-DRB1*11 allele, in line with what was observed in nontransplant subjects. Our results suggest that in posttransplant recurrent hepatitis C, immunogenetic factors are relevant in determining HCV infection outcome.

BACKGROUND/AIMS:Thirty alcoholic patients and 24 teetotaler dyspeptic patients were considered and underwent baseline blood chemical evaluation and the Schilling test.METHODOLOGY:During gastroscopy, biopsy samples were taken to assay: routine histology, malonyldialdehyde, vitamin E and glutathione concentration and for testing vitamin B12-Intrinsic Factor binding. Examinations were repeated after 1-week supplementation with Bionormalizer.RESULTS:Plasma malonyldialdehyde level and lipid hydroperoxides concentration as well as either malonyldialdehyde and xanthine oxidase concentration in the gastric mucosa in alcoholics were significantly higher than in controls and despite unchanged alcohol consumption, significantly decreased after Bionormalizer supplementation. Gastric mucosal glutathione was markedly depressed in alcoholics and partly recovered after Bionormalizer supplementation. Although the alcoholics showed a normal intrinsic factor secretion in the gastric juice, they exhibited a markedly depressed intrinsic factor-cobalamin binding on the "ex vivo" study. Moreover, nearly 23% of them had an abnormal Schilling test. Both these impairments reverted to normal after Bio-normalizer supplementation.CONCLUSIONS:It can be postulated that the antioxidative action played by Bionormalizer, possibly due to its availability substrates for glutathione synthesis as well as to its effects on local oxidative burst from neutrophil, is able to recover a normal cobalamin absorption.