Does surveillance for hepatocellular carcinoma in HCV cirrhotic patients improve treatment outcome mainly due to better clinical status at diagnosis?

BACKGROUND/AIMS: Cirrhotic patients with hepatitis C virus infection are a group at higher risk for hepatocellular carcinoma. Conventional screening programs detect only few early hepatocellular carcinomas that are eligible for radical treatment. Our aim was to compare characteristics of patients, modality of treatment, and outcome in anti-HCV positive cirrhotics with hepatocellular carcinoma diagnosed during follow-up, or incidentally. METHODOLOGY: Sixty-one hepatocellular carcinomas were consecutively diagnosed in cirrhotic anti-HCV patients from 1993-1998 among which 34 during biannual ultrasonographic-biochemical follow-up and the others incidentally. Child-Pugh's score, alpha-fetoprotein levels, uni- or multifocality of the tumor, and treatment and survival of the patients were then analyzed on the basis of modality of diagnosis. RESULTS: Surgical treatment was feasible only in a minority of patients. Radical and palliative treatment was more frequent among patients with HCC diagnosed during follow-up. Child-Pugh's score was lower in these patients, moreover their survival rate was better. Analysis of survival of patients treated with the same procedure and grouped by modality of diagnosis did not demonstrate any differences. Regression analysis showed that patients with a lower Child-Pugh's score, one nodule, with a tumor diagnosed during follow-up and who were treated had a better survival rate. CONCLUSIONS: In our population surveillance did not detect a higher percentage of curable HCC. Nevertheless the results of palliative treatment and of curative treatment overlapped. Overall better outcome was observed in patients with preserved liver function whatever the treatment. Surveillance allowed us to diagnose HCC in patients with these characteristics thus leading to an improved survival rate.

13CO2 excretion in breath of normal subjects and cirrhotic patients after 13C-aminopyrine oral load. Comparison with MEGX test in functional differentiation between chronic hepatitis and liver cirrhosis.

BACKGROUND/AIMS: Liver function can be evaluated using 13C breath tests that explore liver Cytochrome P450 activity. Aminopyrine is one of the first compounds used in liver function testing. Lidocaine metabolism to monoethylglycinexylidide is also a valid tool to assess liver function. Although liver Cytochrome P450 metabolizes both compounds, lidocaine metabolism is flow-dependent while aminopyrine metabolism does not depend on liver blood flow. METHODOLOGY: The 1st part of the study evaluated the appearance and disappearance rate of 13CO2 in the breath of both normal subjects and in cirrhotic patients, so as to establish optimal sampling times and to evaluate the amount of time needed before performing a subsequent breath test. The 2nd part of the study compared the aminopyrine breath test with the monoethylglycinexylidide test in patients with chronic hepatitis or cirrhosis. RESULTS: Complete 13CO2 disappearance was recorded 24 hours after the test in normal subjects, while it took 3 days to disappear from the breath of cirrhotic patients. Breath sampling at 60, 120 and 180 min were equally valid in differentiating chronic hepatitis from cirrhosis. The aminopyrine breath test and monoethylglycinexylidide test showed a good yet not close correlation. CONCLUSIONS: This study showed that in cirrhotic patients a 13C breath test can be performed 3 days after the previous one. In chronic hepatitis and cirrhotic patients, the aminopyrine breath test and the monoethylglycinexylidide test evaluated similar, but not identical, hepatic subfunctions, suggesting that multiple 13C breath test using different substrates could explore liver function better.

Isotope ratio mass spectrometry (IRMS) versus laser-assisted ratio analyzer (LARA): a comparative study using two doses of.

This study was carried out to compare the measurements and the diagnostic accuracy of the traditional expensive IRMS and the new economical LARA system using two doses of [13C]urea + two different test meals in patients undergoing upper gastrointestinal endoscopy, both before and after anti-Helicobacter treatment. A total of 354 dyspeptic patients underwent endoscopy with gastric biopsies to diagnose H. pylori infection by CLO-test and histology. No patients had taken antibiotics, bismuth, or antisecretory drugs in the 4 weeks before testing. After overnight fasting, breath samples were collected simultaneously in both plastic and glass tubes at baseline and at 30 and 60 min after urea ingestion. In 237 patients 100 mg [13C]urea + Ensure and in 117 patients 75 mg [13C]urea + citric acid were given. The test was also performed with the two urea dosages and meals in 67 and 64 infected patients, respectively, four weeks after anti-Helicobacter therapy. H. pylori was considered eradicated when both biopsy-based tests were negative. A delta value >5 per thousand was considered positive. Breath samples with insufficient CO2 levels at both 30 and 60 min were excluded from final analysis (N = 37 in pre- and N = 8 in posttreatment). There was excellent agreement between overall delta values of the two machines with both [13C]urea 100 mg + Ensure and [13C]urea 75 mg + citric acid. The 95% CI of the difference against the mean was wider with the former (mean -1.3, +6.3, and -9.4) than with the latter urea dosage and test meal (mean -1.2, +5.2 and -8.1). LARA and IRMS were equally effective (P = NS) in distinguishing infected from uninfected patients before therapy using both doses of [13C]urea and test meals (sensitivity ranged from 95% to 99% and specificity from 95% to 97%). This good performance was maintained in the posttreatment phase (sensitivity ranged from 90% to 100% and specificity from 90% to 97%), without any statistical difference among the various combinations (P = NS). The LARA system is a valid alternative to IRMS in the diagnosis of H. pylori infection. Both machines provide highly reliable results after 30 min, so that the 60 min sample can be avoided. The dose of 75 mg + citric acid suffices to ensure an accurate UBT. The test performed with both devices and [13C]urea dosages is very effective also for posttherapy evaluation of H. pylori status.

Steatosis and bile duct damage in chronic hepatitis C: distribution and relationships in a group of Northern Italian patients.

BACKGROUND/AIMS: Hepatitis C virus (HCV) related disease follows a long, benign course and most affected patients have mild disease. Liver biopsy is mandatory to grade and stage the disease. Characteristic, though non-specific, HCV histological lesions such as bile duct damage and steatosis have been singled out but their association with non-histological parameters has not been completely defined. Our aim was to study the relationships among these histological lesions and clinical, biochemical, functional and virological characteristics in a group of Northern Italian patients with chronic hepatitis. METHODS: We studied 172 patients with HCV-related chronic hepatitis. Patients were divided into groups on the basis of histology including bile duct damage and steatosis. Clinical, biochemical, functional and virological profiles were related to histological findings. RESULTS: Histological grading and staging of disease increased as the age of patients increased. Steatosis was present in 70% of our patients and was related to a higher degree of fibrosis and to decreased functional activity. The prevalence of bile duct damage was 20%. This lesion was present in older patients with higher staging and impaired liver function. Biochemically it was associated with an increase in aspartate aminotransferase, gammaglutamyltranspeptidase, alkaline phosphatase, and total bilirubin. CONCLUSIONS: In the population we studied, HCV chronic hepatitis was predominantly a mild disease. Moreover both steatosis and bile duct damage were also mild. Steatosis was associated with fibrosis and this might influence liver metabolic function. Bile duct lesions were found in older patients with advanced disease showing biochemical evidence ofcholestasis. The molecular role HCV might play in the pathogenesis of these histological features should be addressed in further studies.

Probability of non-response during interferon therapy in patients with chronic hepatitis C.

BACKGROUND/AIMS: About 50% of patients with chronic hepatitis C do not respond to interferon therapy and this failure is expensive. The aim of this study was to identify possible predictive factors of biochemical non-response during interferon therapy among biochemical, virological (HCV genotype), histological (Knodell's score) and pharmacokinetic (monoethylglycinexylidide formation test) pre-treatment parameters. METHODOLOGY: Our study included 60 patients with chronic hepatitis C undergoing a course of Interferon therapy. Patients whose serum ALT levels were normal at the 3rd month of therapy and remained so until the end of treatment were regarded as responders. RESULTS: In univariate analysis, only the gamma-glutamyltransferase (gamma-GT) and the gamma-GT/alanine aminotranferase ratio were significantly higher in non-responder patients. Multivariate logistic analysis showed that high gamma-GT levels, high histological activity index, low monoethylglycinexylidide formation rate and viral genotype 1 were the best combination for the identification of non-responder patients (16.7% error rate). By adding alanine aminotranferase modification at the 1st month of therapy the probability error was reduced to 5%. CONCLUSIONS: These results show that the combination of biochemical, histological, virological and pharmacokinetic pre-treatment variables, associated with alanine aminotranferase modification at the 1st month of therapy, can predict non-response to interferon and allow therapeutic modifications.

The 13C urea breath test in the diagnosis of Helicobacter pylori infection.

The urea breath test (UBT) is one of the most important non-invasive methods for detecting Helicobacter pylori infection. The test exploits the hydrolysis of orally administered urea by the enzyme urease, which H pylori produces in large quantities. Urea is hydrolysed to ammonia and carbon dioxide, which diffuses into the blood and is excreted by the lungs. Isotopically labelled CO2 can be detected in breath using various methods. Labelling urea with 13C is becoming increasingly popular because this non-radioactive isotope is innocuous and can be safely used in children and women of childbearing age. Breath samples can also be sent by post or courier to remote analysis centres. The test is easy to perform and can be repeated as often as required in the same patient. A meal must be given to increase the contact time between the tracer and the H pylori urease inside the stomach. The test has been simplified to the point that two breath samples collected before and 30 minutes after the ingestion of urea in a liquid form suffice to provide reliable diagnostic information. The cost of producing 13C-urea is high, but it may be possible to reduce the dosage further by administering it in capsule form. An isotope ratio mass spectrometer (IRMS) is generally used to measure 13C enrichment in breath samples, but this machine is expensive. In order to reduce this cost, new and cheaper equipment based on non-dispersive, isotope selective, infrared spectroscopy (NDIRS) and laser assisted ratio analysis (LARA) have recently been developed. These are valid alternatives to IRMS although they cannot process the same large number of breath samples simultaneously. These promising advances will certainly promote the wider use of the 13C-UBT, which is especially useful for epidemiological studies in children and adults, for screening patients before endoscopy, and for assessing the efficacy of eradication regimens.

Progressive liver functional impairment is associated with an increase in AST/ALT ratio.

The ratio of serum aspartate aminotransferase to alanine aminotransferase (AST/ALT ratio) has been proposed as a noninvasive method of assessing liver fibrosis and cirrhosis. Our aims were to confirm the usefulness of the AST/ALT ratio in diagnosing cirrhosis noninvasively as well as to verify the existence of a relationship between the ratio and liver functional impairment. In all, 348 patients (177 with chronic hepatitis, 171 with cirrhosis) were retrospectively evaluated and the AST/ALT ratio was related to monoethyl glycine xylidide (MEGX) formation. Moreover, in a subgroup of 54 patients we analyzed the relationships among the AST/ALT ratio and indocyanine green clearance and half-life. The AST/ALT ratio was able to separate patients with mild fibrosis from those with severe fibrosis and cirrhosis. The AST/ALT ratio, MEGX, prothrombin activity, and platelet count were selected by multivariate analysis as variables associated with cirrhosis. The AST/ALT ratio showed significant correlations both with MEGX formation and with indocyanine green clearance and half-life. The alterations of indocyanine green kinetics, which depend upon liver blood flow and uptake, were likely due to progressive fibrosis. These findings might partially explain the increase in the AST/ALT ratio as disease progresses.

Interferon retreatment in chronic hepatitis C: which patients to choose, and what schedule to use.

UNLABELLED: OBJECTIVE; To evaluate the results of a large cohort of non-responder or relapsing responder patients with chronic hepatitis C retreated with various schedules of interferon (IFN). METHODS: Our study included 276 patients (158 non-responders and 118 relapsing responders) who underwent IFN retreatments. Among the non-responder group, 158 patients underwent further courses of IFN. In particular, 108 patients underwent one course of IFN retreatment, 40 patients underwent two courses, eight patients underwent three courses, and two patients underwent four courses. Regarding the relapsing responder group, the 118 patients were retreated with the same dosage for varying periods. In particular, 50 patients were treated for 6 months, 43 patients for 12 months, and 25 for 24 months. Patients in the subgroups of IFN retreatment were homogeneous as far as age and gender distribution, as well as virological and histological characteristics, are concerned. Qualitative and quantitative HCV-RNA was evaluated at baseline, at the end of treatment and at the last check-up of follow-up. HCV genotype was determined on baseline serum samples. Alanine transaminase (ALT) levels were tested monthly. RESULTS: Long-term biochemical (normal ALT levels) and virological (HCV-RNA negative) response was obtained in 2.6% of non-responder retreated patients, and in 33.9% of relapsing responder retreated patients. Evaluation of response on the basis of the duration of treatment showed that 48%, 19% and 16% of relapsing responder patients retreated for 24, 12 and 6 months, respectively, obtained long-term biochemical and virological response. CONCLUSION: Non-responder patient retreatment is inefficient especially in cirrhotic and/or genotype 1 b patients. IFN retreatment is warranted in relapsing responder patients. In particular, 24-month therapy induces significant long-term biochemical and virological response.

Comparison of isotope ratio mass spectrometry and nondispersive isotope-selective infrared spectroscopy for 13C-urea breath test.

OBJECTIVES: The 13C-urea breath test (UBT) is a sensitive and noninvasive method to diagnose Helicobacter pylori infection, but mass spectrometry (IRMS) is very expensive. The aims of this study were to compare the new low-priced infrared spectroscopy with IRMS in detecting the infection and to assess the influence of feeding on test accuracy. METHODS: One hundred thirty-four patients with dyspeptic symptoms were recruited. Of these, 74 were infected and 60 uninfected on the basis of both CLO-test and histology. A subgroup of 37 patients (22 H. pylori-positive and 15 H. pylori-negative) was studied under fasting and nonfasting conditions on two different days. Duplicate breath samples were analyzed with two IRMS systems (Breath Mat and ABCA) and an infrared spectrometer (IRIS) before, 15 min, and 30 min after ingestion of 75 mg 13C-urea with citric acid. In 37 patients the test was repeated the day after the fasted one and was performed 60 min after a meal of 800 Kcal. RESULTS: There was a close correlation between IRIS and Breath Mat (r = 0.969 at 15 min and r = 0.977 at 30 min; p < 0.0001), IRIS and ABCA (r = 0.963 at 15 min and r = 0.985 at 30 min; p < 0.0001), and Breath Mat and ABCA (r = 0.987 at 15 min and r = 0.981 at 30 min; p = 0.0001). The sensitivity ranged from 97-100% at both times with all devices, although the specificity was slightly inferior with the infrared system than with the two IRMS machines (95% vs 98-100% at 30 min), but the difference was not significant (p = NS). Food intake produced three false negative results in all three machines and a systematic shift to lower 6 values in infected patients. CONCLUSIONS: Infrared spectroscopy can be considered a valid alternative to mass spectroscopy for the diagnosis of H. pylori infection. Fasting is required to guarantee an accurate test.

Head-to-head comparison of 1-week triple regimens combining ranitidine or omeprazole with two antibiotics to eradicate Helicobacter pylori.

BACKGROUND: Triple therapies containing omeprazole and ranitidine have been shown to be equivalent in eradicating H. pylori infection, but have been assessed either separately or head-to-head, only in small trials. AIM: To carry out a large randomized controlled study comparing omeprazole and ranitidine combined with two antibiotic combinations for 1 week. METHODS: Three hundred and twenty H. pylori-positive patients were randomly subdivided into four equal-sized groups and received one of the following treatments: OAM = omeprazole 20 mg b.d. + amoxycillin 1 g b.d. + metronidazole 500 mg b.d.; RAM = ranitidine 300 mg b.d. + amoxycillin 1 g b.d. + metronidazole 500 mg b.d.; OAC = omeprazole 20 mg b.d. + amoxycillin 1 g b.d. + clarithromycin 250 mg t.d.s.; RAC = ranitidine 300 mg b.d. + amoxycillin 1 g b.d. + clarithromycin 250 mg t.d.s. The assessment of H. pylori status was performed before and 4 weeks after the end of therapy by means of CLO-test and histology. H. pylori infection was considered to be eradicated when both tests were negative. RESULTS: OAM and RAM eradicated H. pylori in 89% and 85% of cases on per protocol (P = 0.48) and in 77% and 75% of cases on intention-to-treat analyses (P = 0.71). OAC and RAC eradicated H. pylori in 67% and 70% of cases on per protocol (P = 0.68) and in 57% and 64% of cases on intention-to-treat analyses (P = 0.41). In contrast, there was significant difference between OAM and OAC (P<0.01) and between RAM and RAC (P<0.05). Side-effects occurred in 15%, 10%, 17% and 16% of patients with respect to the above four subgroups. CONCLUSIONS: Omeprazole and ranitidine combined with two antibiotics for 1 week are equally effective in the eradication of H. pylori infection, and these results question the role of profound acid suppression in the eradication of the bacterium.

Hepatitis G virus infection in haemodialysis and in peritoneal dialysis patients.

The aim of this study was to detect hepatitis G virus RNA (HGV RNA) and antibodies against the virus envelope protein E2 (anti-E2) in 107 patients either on maintenance haemodialysis (n = 78) or peritoneal dialysis (n = 29) to evaluate the prevalence of HGV infection and to establish its role in liver disease. The total prevalence of HGV infection was of 15.4% among haemodialysis patients, whereas it was 10.3% among peritoneal dialysis patients. HGV RNA was detected in 2 haemodialysis patients (2.6%) and in 3 peritoneal dialysis patients (10.3%). Anti-E2 was found in 10 haemodialysis patients (7.8%), whilst all peritoneal dialysis patients resulted negative. In only 1 patient the alanine aminotransferase level was elevated. This patient underwent liver biopsy that did not reveal evidence of chronic hepatitis. The lower HGV prevalence in haemodialysis patients, when compared with data reported by other European authors, should be related to the lower rate of polytransfused patients in our series (29.5%). Multiple blood transfusions should be considered as the main factor to explain the different prevalence of HGV infection among various European dialysis centres. Detection of both antibody and viraemia is important to establish the real rate of the infection.

Histological and functional recovery in patients with multifocal atrophic gastritis after eradication of Helicobacter pylori infection.

BACKGROUND/AIMS: To assess the effect of Helicobacter pylori eradication on gastric histology and physiology in patients with multifocal atrophic gastritis over 1-year period. PATIENTS: Fourteen consecutive patients with histological evidence of chronic gastritis and Helicobacter pylori infection diagnosed by histology and serology entered this study. Patients with pernicious anaemia, gastric ulcer or carcinoma, duodenal ulcer, reflux oesophagitis and regular intake of nonsteroidal anti-inflammatory drugs were excluded. METHODS: Patients underwent triple anti-Helicobacter treatment for one week, which resulted successful in all subjects on the basis of negative CLO test and histology as well as 50% decrease in IgG antibodies after 4 weeks and 6 months of treatment, respectively. Histological and functional investigations were performed at baseline, 6 and 12 months after Helicobacter pylori eradication. Histological assessment of inflammatory cell infiltrates was performed on multiple biopsy specimens of the corpus and fundus. Functional tests were 24-hour continuous gastric pH-metry, fasting serum gastrin assay and pepsinogen I levels. RESULTS: There was a progressive significant improvement (p < 0.01-0.001) in acute and chronic inflammatory cell infiltrates in the gastric mucosa throughout the 12-month period. Functional recovery with increase in gastric acidity (p < 0.01) and decrease in gastrin and pepsinogen I levels (p < 0.001) was more evident at the 6-month than at the 12-month checkpoint after Helicobacter pylori eradication (p = NS for gastric pH and p < 0.02 for the other two variables) between 6 and 12 months. CONCLUSIONS: Eradication of Helicobacter pylori infection significantly improves the inflammatory status of oxyntic mucosa and this promotes an almost complete functional recovery. However, the non-parallel behaviour of gastric acidity, which was maximal at 6-month checkpoint, and histological parameters which continued to improve throughout the entire 12-month observation period, seems to indicate that removal of acid-inhibitory substances induced by Helicobacter pylori infection was also responsible for the more rapid recovery of gastric secretory function.

Optimal duration of therapy combining ranitidine bismuth citrate with clarithromycin and metronidazole in the eradication of Helicobacter pylori infection.

BACKGROUND: Ranitidine bismuth citrate (RBC) co-prescribed with clarithromycin and metronidazole for 1 week has been shown to be an effective eradicating regimen for Helicobacter pylori. AIM: To determine the optimal duration of this regimen. METHODS: A series of 165 dyspeptic patients were recruited for this randomized, open, parallel-group study. They were subdivided into three groups receiving RBC 400 mg b.d. plus clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. for three different periods (4, 7 and 10 days). H. pylori infection was assessed by the concomitant positivity of CLO-test and histology performed at the pre-entry endoscopy. The bacterium was considered eradicated on the basis of a negative 13C-urea breath test performed at least 28 days after the completion of treatment. RESULTS: The three subgroups were well matched and 16 patients dropped out of the study for many reasons (six in the 4-day, five in the 7-day and five in the 10-day treatment regimens). Intention-to-treat cure rates were 60%, 84% and 85%, and the per-protocol rates 67%, 92% and 94% in the 4-day, 7-day and 10-day treatment regimens, respectively. There was a significant difference, P = 0.003-0.006 on intention-to-treat and P = 0.001-0. 002 on per protocol analysis between the 4-day and the 7-day and the 4-day and the 10-day periods, respectively. The 7-day and 10-day periods did not differ from each other. Side-effects were reported in 9%, 14% and 20% of the 4-, 7- and 10-day regimens. They led to stopping treatment in four cases (one in the 7-day and three in the 10-day period). There was no statistical difference among them. CONCLUSIONS: Reducing the duration of RBC-based triple therapy to 4 days provides a low and unacceptable rate of H. pylori eradication. As there is no difference between 7 and 10 days of treatment, 1 week represents the optimal time period for this kind of treatment, based on RBC plus two antibiotics.

Chronic hepatitis C. New therapeutic strategies.

BACKGROUND: Aim of this work was to evaluate the early viral decay induced by a daily therapy with alfa-interferon (IFN) and the presence of any synergistic effects of amantadine and ribavirin. METHODS: Twenty patients with a diagnosis of chronic hepatitis C were randomly assigned to receive a course of treatment with: IFN 3MU daily (6 pts); or IFN 3MU daily plus amantadine 200 mg (7 pts): or IFN 3MU daily plus ribavirin 1-1.2 g (7 pts) for 6 months. Blood samples were drown at baseline, at 6, 12, 24, 30 and 48 hrs after the first dose of IFN; at 3, 7, 15 days and at every month. Serum was separated within two hours from the collection and stored at -80 degrees C until use. Viraemia was evaluated qualitatively by the Cobas Amplicor (cut-off 1.00E+02 copies/ml) (Roche Diagnostics, Monza, Milan, Italy) and quantitatively by the Cobas Amplicor Monitor (cut-off 1.00E+03 copies/ml). The HCV genotype was determined for each patient by Inno-LiPA HCV II (Innogenetics, Ghent, Belgium). Liver function tests were evaluated at baseline, at 7 and 15 days and at every month. RESULTS: The analysis of the decay curves showed the presence of a three phase decline in the viraemia. At the end of therapy 7 out of the 20 patients (35%) had normal ALT and undetectable HCV-RNA (2 out of 6 in the IFN group: 33.3%, 3 out of 7: 42.8%; 2 out of 7: 28.6%, in the IFN plus amantadine and IFN plus ribavirin groups respectively). CONCLUSIONS: IFN is the major antiviral effector in the early stage of therapy. The observation of the kinetic curves shows a tendency for the ribavirin to induce a slightly steeper slope of decay in the first 48 hrs, while amantadine seems to induce a slightly deeper abatement of circulating viraemia after 48 hrs.

Can the MEGX test and serum bile acids improve the prognostic ability of Child-Pugh's score in liver cirrhosis?

BACKGROUND: Liver transplantation is nowadays the therapeutic option for end-stage liver disease. Correct disease staging is the main step towards improving the timing of listing for liver transplantation so as to avoid premature or late entry. The need for correct prognostic evaluation is due to the limited number of donors and to the increasing number of patients awaiting transplantation. Our aim was to verify whether Child-Pugh's score might be improved by adding the monoethylglycinexylidide (MEGX) formation test and/or serum bile acid determination. METHODS: We evaluated 182 cirrhotic patients (44 Child-Pugh class A, 97 class B, and 41 class C) of mixed aetiology referring to a tertiary care centre for functional staging of liver disease. These patients were prospectively followed-up for 12-72 months. During this period, 45 patients died, 46 received a transplant, and 91 survived without transplantation. The end-point of analysis was either survival or liver disease-related death at the 6th, 12th, 18th and 24th months of follow-up. The 46 transplanted patients were excluded from the study upon transplantation. RESULTS: In our study, a cut-off for Child-Pugh's score < 8 confirmed its usefulness, especially in short-term prognostic prediction, while mid- and long-term prediction improved by almost 10% by using the combination of a Child- Pugh's score > 8 and an MEGX value < 15 mg/l. Cox's multi-variate regression analysis indicated that MEGX values either with Child-Pugh's score or with prothrombin activity and ascites were independent prognostic variables. CONCLUSIONS: Besides confirming that Child-Pugh's score as the basis of prognostic evaluation of cirrhotic patients, these results suggest that the MEGX test might be a complement to the original score when a patient is being evaluated for a liver transplantation programme.

Chronic liver disease related to hepatitis C virus: age of patients seems to be a determinant of severity independently of viral genotype.

BACKGROUND: Hepatitis C virus infection accounts for varying severity of chronic liver disease. Clinical manifestations of infection have been related to different virus genotypes, with conflicting results. DESIGN: We performed a cross-sectional study on a Northern-Italian group of patients with chronic hepatitis, cirrhosis and hepatocellular carcinoma related to hepatitis C virus infection in order to verify the association of different viral strains and the outcomes of viral disease. METHODS: Two hundred and seventy-one patients referred to our unit for liver disease were studied and clinical, biochemical, histological, and functional parameters were investigated. RESULTS: Different viral genotypes were not associated with peculiar findings in any of the degrees of liver disease. However, a progressive age increase was associated with disease severity, although clinical and functional staging of cirrhotic patients with hepatocellular carcinoma was better compared to tumour-free cirrhotic patients. There was an increased prevalence of genotype 1b related to the age of the patients. In multivariate regression analysis the patients' age and apparent duration of infection were independently associated with the presence of cirrhosis and only the age of patients was associated to hepatocellular carcinoma. CONCLUSIONS: In the population we studied age of the patients seemed to be a determinant conditioning disease severity, likely reflecting older infections and long-standing liver disease. The prevalence of certain genotypes in varying degrees of liver disease could be an epiphenomenon which might also be explained by the changing prevalence of infecting strains over the past decades.

Chronic hepatitis induced by Jin Bu Huan.

BACKGROUND/AIMS: Jin Bu Huan and other Chinese herbal products are widely taken remedies. They have been developed as a natural alternative to traditional drugs in the treatment of various ailments. Their ability to induce several side effects such as acute hepatitis has already been described. We report a case of chronic hepatic damage following administration of Jin Bu Huan Anodyne tablets. METHODS: The patient, a 49-year-old man, developed biochemical signs of liver damage 2 months after beginning Jin Bu Huan intake (3 tablets/daily) including biopsy-proven chronic hepatitis with moderate fibrosis. Virological, autoimmune, metabolic or other hepatotoxic causes were excluded. Liver function impairment was resolved by discontinuing Jin Bu Huan intake. CONCLUSIONS: This case reinforces the already known hepatotoxicity of this product and should make us think more about the uncontrolled use of alternative products.

Effect of one-month treatment with nonsteroidal antiinflammatory drugs (NSAIDs) on gastric pH of rheumatoid arthritis patients.

The use of NSAIDs is strongly associated with peptic ulceration. The inhibition of prostaglandin synthesis with the consequent increase of gastric acidity is considered a possible mechanism. Therefore we decided to assess the effect of one-month treatment with NSAIDs on the circadian gastric pH of rheumatoid arthritis (RA) patients. We studied 11 consecutive patients (one man and 10 women, median age 55, range 26-72 years) with confirmed RA. None was H. pylori positive. A 24-hr gastric pH recording was performed both in basal conditions and after one-month treatment with either indomethacin 150 mg/day (eight cases) or ketoprofen 300 mg/day (three cases). Only the 10 female patients were eligible for final analysis, and six matched healthy subjects not taking NSAIDs were used as control group. The number of 24-hr pH readings for various pH thresholds was calculated for both populations. The highest acid levels (pH < 3.0) did not differ between the two pH profiles of the control group (7440 vs 7391, P = NS), while they predominated after the one-month NSAID treatment (10,339 vs 11,440, P < 0.001) in RA patients. These findings show that there is an increased gastric acidity after one-month of treatment with NSAIDs in female patients with RA of recent onset. This may sustain the rationale of using antisecretory agents to prevent gastroduodenal ulcerations in these patients.