Distribution of TAS2R38 bitter taste receptor phenotype and haplotypes among COVID-19 patients.

Bitter taste receptor TAS2R38 is expressed in the respiratory tract and can respond to quorum-sensing molecules produced by pathogens, stimulating the release of nitric oxide, with biocidal activity. TAS2R38 presents two main high-frequency haplotypes: the "taster" PAV and the "non-taster" AVI. Individuals carrying the AVI allele could be at greater risk of infections, including SARS-CoV-2. The aim of this study was to assess the frequency of PAV and AVI alleles in COVID-19 patients with severe or non-severe symptoms compared to healthy subjects to further corroborate, or not, the hypothesis that the PAV allele may act as a protecting factor towards SARS-CoV-2 infection while the AVI one may represent a risk factor. After careful selection, 54 individuals were included in the study and underwent genetic analysis and PROP phenotype assessment. Our investigation could not point out at a significant relationship between single nucleotide polymorphisms responsible for PROP bitterness and presence/severity of SARS-CoV-2 infection, as previous studies suggested. Our results uncouple the direct genetic contribution of rs10246939, rs1726866 and rs713598 on COVID-19, calling for caution when proposing a treatment based on TAS2R38 phenotypes.

Effect of industrial processing and storage procedures on oxysterols in milk and milk products.

Oxysterols are products of enzymatic and/or chemical cholesterol oxidation. While some of the former possess broad antiviral activities, the latter mostly originate from the deterioration of the nutritional value of foodstuff after exposure to heat, light, radiation and oxygen, raising questions about their potential health risks. We evaluated the presence of selected oxysterols in bovine colostrum and monitored the evolution of their cholesterol ratio throughout an entire industrial-scale milk production chain and after industrially employed storage procedures of milk powders. We report here for the first time the presence of high levels of the enzymatic oxysterol 27-hydroxycholesterol (27OHC) in concentrations of antiviral interest in bovine colostrum (87.04 ng mL-1) that decreased during the first postpartum days (56.35 ng mL-1). Of note, this oxysterol is also observed in milk and milk products and is not negatively affected by industrial processing or storage. We further highlight an exponential increase of the non-enzymatic oxysterols 7ß-hydroxycholesterol (7ßOHC) and 7-ketocholesterol (7KC) in both whole (WMPs) and skimmed milk powders (SMPs) during prolonged storage, confirming their role as reliable biomarkers of cholesterol oxidation over time: after 12 months, 7ßOHC reached in both SMPs and WMPs amounts that have been found to be potentially toxic in vitro (265.46 ng g-1 and 569.83 ng g-1, respectively). Interestingly, industrial processes appeared to affect the generation of 7ßOHC and 7KC differently, depending on the presence of fat in the product: while their ratios increased significantly after skimming and processing of skimmed milk and milk products, this was not observed after processing whole milk and milk cream.

Relevance of CD38 expression on CD8 T cells to evaluate antiretroviral therapy response in HIV-1-infected youths.

Surrogate markers for monitoring immuno-virological discordant responders, in addition to plasma viral load and CD4 cells, are still lacking. We assessed the diagnostic utility of CD38 expression on CD8 T cell assay, alone or in association with lymphocyte proliferation to mycotic antigens, in evaluating antiretroviral response. 28 vertically HIV-infected youths, 21 HAART- and seven 2 nucleotide reverse transcriptase inhibitors-treated, were enrolled in a retrospective study. Responders (57.1%) and non-responders (42.9%) to stable antiretroviral therapy for a minimum of 6 months, on the basis of viral load and CD4 T cells, comprehensively evaluated by CD38 expression on CD8 T lymphocytes [measured as CD38 antibody bound per CD8 T cell (CD38 ABC) and %CD38+ of total CD8 T cells (%CD38/CD8)] and lymphocyte proliferation to P. jiroveci, C. albicans, C. neoformans, A. fumigatus at a single time point after treatment, were selected. CD38 expression > or =2401 CD38 ABC and > or =85% CD38/CD8 cut-off points, accurately discriminates responders versus non-responders, both measures resulting in 75.0% (CI 42.8-94.5) sensitivity (identification of non-responder) and 93.8% (CI 69.8-99.8) specificity (identification of responder), when considered as single assays. The association '> or =2401 CD38 ABC or > or =85% CD38/CD8' improved sensitivity to 83.3% (CI 51.6-97.9), while the association '<2401 CD38ABC (or <85% CD38/CD8) and lymphoproliferative response positive to > or =2 tested organisms' improved specificity to 100% (CI 79.4-100). In conclusions, CD38 expression and mycotic antigen-specific T-cell proliferation may be used as additional parameters to existing criteria to evaluate antiretroviral response in immuno-virological discordant patients.

[Substitutive therapies in sepsis and acute renale failure]. / Trattamenti emergenti e/o alternativi nell'nsufficienza renale acuta associata a sepsi.

Substitutive treatment of sepsis associated acute renal failure is an emergent challenge in the intensive care unit due to the number of cases and to the high mortality rate. Standard hemofiltration is unable to improve survival, since a high mortality rate is sustained by the septic process. New therapeutic approaches currently available are based on the increased clearance of molecules ranging 10-30 kDa considered important in the physiopathology of sepsis and multiorgan failure. Clinical experiences in progress are: (1) adsorption resins able to bind bacterial products, cytokines, anaphylotoxins and several inflammation mediators; (2) the bioartificial kidney, that is the addition to hemofilter of human tubular cell culture grown in devices in order to mimic metabolic tubular function to a traditional hemofilter; (3) increased exchange volumes (high volume hemofiltration), up to 0-100 L/24 hr and; (4) increased membrane permeability associated with either discarded ultrafiltrate (high cut-off membranes) or plasma substitution plasmapheresis with regeneration by sorbents technology (C FA). Generally, by applying these new technologies to septic shock patients, the observed survival was higher than that predicted by the gravity score. While these results are encouraging, they are not conclusive and need further study.

Trans-catheter arterial chemoembolisation for hepatocellular carcinoma in patients with viral cirrhosis: role of combined staging systems, Cancer Liver Italian Program (CLIP) and Model for End-stage Liver Disease (MELD), in predicting outcome after treatment.

BACKGROUND: Trans-catheter arterial chemoembolisation (TACE) is the most common palliative treatment for hepatocellular carcinoma (HCC). The therapeutic options depend both on the characteristics of the tumour and on functional staging of the cirrhosis. AIM: To evaluate the effects of TACE on the survival of cirrhotic patients with HCC according to different staging systems [Okuda score, Cancer Liver Italian Program (CLIP) score, Model for End-stage Liver Disease (MELD) score] and in relation to the side-effects of TACE. METHODS: Fifty cirrhotic patients, 36 CTP class A and 14 class B, underwent 106 TACE treatments with mitoxantrone. Survival at 12, 24, and 36 months was evaluated. RESULTS: MELD at 12 months and CLIP at 24 months were identified as significant variables associated with survival. Combined cut-offs of CLIP and of MELD identified four subgroups of patients with different survivals, at 12, 24 and 36 months, respectively: CLIP >or= 2 and MELD >or= 10 (63%, 20% and 0%), CLIP < 2 and MELD >or= 10 (73%, 40% and 22%), CLIP >or= 2 and MELD < 10 (73%, 40% and 22%) and CLIP < 2 and MELD < 10 (100%, 63% and 50%). Post-TACE side-effects proved to have no influence on survival. CONCLUSION: In patients with poor probability of survival (CLIP >or= 2 and MELD >or= 10), TACE must be planned with a great deal of caution, while in patients with possibly good outcomes (CLIP < 2 and MELD < 10), more 'aggressive' therapy should be taken into consideration.

Thermal convection in fluidized granular systems

Thermal convection is observed in molecular dynamic simulations of a fluidized granular system of nearly elastic hard disks moving under gravity, inside a square box. Boundaries introduce no shearing or time dependence, but the energy injection comes from a slip (shear-free) thermalizing base. The top wall is perfectly elastic and lateral boundaries are either elastic or periodic. The spontaneous temperature gradient appearing in the system due to the inelastic collisions, combined with gravity, produces a buoyancy force that, when dissipation is large enough, triggers convection.

Effects of beta-adrenoreceptor antagonists on cerebral blood flow of cirrhotic patients with portal hypertension.

The current study evaluated the effect of two beta adrenergic-blocking agents, propranolol (PRP) and atenolol (ATN), versus placebo on cerebral blood flow (CBF) of three homogeneous groups of cirrhotic patients with portal hypertension. CBF was measured by the noninvasive 133-Xenon inhalation method at rest and 1 hour after a single oral dose of PRP (40 mg), or ATN (100 mg), or placebo. Blood pressure and heart rate (HR) were measured at the beginning of each examination, and end-tidal pCO2(PeCO2) was monitored. The HR decreased significantly in both the PRP and ATN groups (P less than .01), whereas no changes were recorded for both PeCO2 and mean arterial blood pressure (MABP). The comparisons of the CBF differences among groups (ANOVA with the significance levels adjusted by the Bonferroni's correction) showed a significant increase in CBF after ATN as compared with both placebo (P less than .02) and PRP (P less than .01), whereas no significant differences were seen after PRP as compared with placebo. Our results confirm that PRP does not significantly affect CBF, whereas ATN induces an increase in CBF, although the underlying mechanism is difficult to explain.

Utility of alpha-glutathione S-transferase assessment in chronic hepatitis C patients with near normal alanine aminotransferase levels.

OBJECTIVES: To study whether determining alpha-glutathione S-transferase (alpha-GST) might improve the assessment of chronic hepatitis C (CHC) patients with near normal alanine aminotransferase levels (NNA). DESIGN AND METHODS: We studied 119 viraemic CHC patients. They were subdivided into two groups according to the pattern of alanine aminotransferase (ALT) alteration, i.e. consistently above (HA) or below (NNA) twice the upper normal value. In these patients we assessed alpha-GST and correlated its levels to clinical, histological, and virological findings, further evaluating whether alpha-GST might improve the assessment of CHC patients with NNA. RESULTS: alpha-GST showed a significant correlation with aminotransferases, though not with histological necroinflammatory activity and fibrosis or with hepatitis C virus RNA levels. Twenty-seven patients had NNA (23%), and within this subgroup of patients alpha-GST identified a subset of patients with a higher viral load. CONCLUSIONS: alpha-GST in CHC patients is related to hepatocellular necrosis parameters, but unrelated both to histology and to viraemia. However, in patients with NNA, alpha-GST identified a subgroup of patients with a higher viral load. In this subgroup of patients alpha-GST alteration likely represents the expression of a more severe damage. Because this injury is not detectable by the usual biochemical or histological work-up, we suggest that alpha-GST could a useful tool for monitoring liver damage over time.

Maternal dietary PUFAs intake and human milk content relationships during the first month of lactation.

Maternal dietary fatty acids (FFAs) intake and corresponding human milk composition relationships have been assessed throughout the first month of lactation in 34 lactating women consecutively enrolled. All mothers were on their habitual diet. Food records (95 items) were administered to the mothers, six-times during the first month of lactation (1 day after delivery, 4, 7, 14, 21, and 28 days after colostrum appearance) and referred to maternal dietary intake of the day before. Milk collected on day 1 was considered as colostrum, day 4 and 7 samples as transitional milk, and day 14, 21 and 28 samples as mature milk. Five gas chromatographic analyses were performed on each sample. Statistics were made using Friedman's and Pearson's test. Maternal dietary saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) were significantly related to the corresponding milk pattern in the phase of transitional milk (P<0.01), while total polyunsaturated (PUFAs) content was significantly related only to the mature milk (P<0.01); in this phase about 42% of the variations occurring in PUFAs milk content can be related to variation of maternal PUFAs dietary intake. The results in the present study provide evidence of the relationships between maternal diet and milk composition. The degree of correlation between maternal diet and PUFAs milk content increases throughout milk maturational process and reaches significance only in mature milk. This would imply that advancing lactation, milk PUFAs provision sources gradually shift from adipose tissue catabolism to maternal diet.

Effects of reduced glutathione and n-acetylcysteine on lidocaine metabolism in cimetidine treated rats.

The aim of this work was to evaluate the effects of exogenous glutathione (GSH) and N-acetylcysteine (NAC) on the formation of monoethylglycinexylidide (MEGX) from lidocaine in rats with and without the administration of cimetidine. GSH and NAC were administered intraperitoneally (i.p.) (1 mmol/kg) 1 hour before treatment with cimetidine (0.5 mmol/kg) or saline, and 1 hr later all rats were injected i.p. with lidocaine (1 mg/kg). Blood samples were drawn 30 min after the lidocaine injection. MEGX and lidocaine serum concentrations were determined by means of fluorescence polarization immuno-assay using the TDX system. Cimetidine produced a decrease in MEGX levels (from 210 +/- 18 to 164 +/- 13 ng/mL) and a parallel increase in lidocaine levels (from 73 +/- 22 to 172 +/- 47 ng/mL), consistent with cytochrome P-450 3A inhibition. Both GSH and NAC produce a significant decrease in MEGX levels (151 +/- 16 and 139 +/- 14 ng/mL, respectively), but no significant increase in lidocaine levels were found. As compared to the cimetidine group, pre-treatment using either GSH or NAC with cimetidine produced a marked decrease in lidocaine levels (37 +/- 27 and 63 +/- 28 ng/mL, respectively) and no modification of MEGX levels (155 +/- 12 and 165 +/- 22 ng/mL, respectively). These results suggest that GSH and NAC might accelerate the lidocaine metabolism while counteracting the inhibitory effect of cimetidine.

Cholestasis is the main determinant of abnormal CA 19-9 levels in patients with liver cirrhosis.

BACKGROUND/AIMS: Altered CA19-9 levels are commonly found in patients with liver cirrhosis though a clear explanation for this finding has not yet been given. The aim of this study was to investigate whether CA19-9 levels might be related to alterations in biochemical parameters and/or to functional impairment in cirrhotic patients with and without hepatocellular carcinoma. METHODS: We studied 126 patients with liver cirrhosis, 60 of whom also had hepatocellular carcinoma. CA19-9 values were related to clinical, biochemical and functional parameters. In half of the patients CA19-9 levels were related to the monoethylglycinexylidide test, which is a dynamic liver function test. RESULTS: In more than half the cases CA19-9 values were above the upper limit. Liver function worsening as assessed by Child-Pugh's score and monoethylglycinexylidide test did not seem to influence the alteration of the marker. By contrast, in univariate analysis CA19-9 correlated with aminotransferases, gamma-glutamyltransferase and alkaline phosphatase. Multivariate analysis showed that besides alkaline phosphatase also the presence of hepatocellular carcinoma might influence the alteration of CA19-9, although the marker was of no use for the diagnosis of liver cancer in patients with altered though not diagnostic alpha-fetoprotein levels. CONCLUSIONS: In our study we confirmed the correlation of CA19-9 levels with cholestasis and cytolysis parameters. Moreover, we found no association between CA19-9 levels and impaired liver function as assessed by means of the Child-Pugh's score and the monoethylglycinexylidide test, which is cholestasis-independent and explores liver metabolic and clearance activities. The cholestatic picture that characterizes liver cirrhosis might enhance the expression and passage of the marker from the bile to the blood. The addition of CA19-9 assessment is not useful for the diagnosis of hepatocellular carcinoma in patients with non-diagnostic levels of alpha-fetoprotein. Caution should therefore be used when evaluating CA19-9 in cirrhotic patients with cholestasis, since false positive results may occur.

Serum pro-collagen III peptide levels are related to lobular necrosis in untreated patients with chronic hepatitis C.

OBJECTIVE: Liver biopsy is mandatory for correctly grading and staging chronic hepatitis activity. Nevertheless, serum markers of fibrogenesis may be useful to help us understand the mechanisms of the fibrogenic process, to follow-up patients, and to establish the efficacy of therapy. In this study, our aim was to identify the relationships between pro-collagen III peptide (PIIIP) serum levels and detailed liver histology in a group of untreated patients with chronic hepatitis C (CHC). METHODS: We studied 147 CHC patients. Correlation analysis of PIIIP serum levels was performed in 109 patients, after having excluded those with alcohol abuse or concomitant hepatitis B virus infection. PIIIP serum levels were assessed using an assay that measures both Col 1-3 peptide (reflecting collagen synthesis) and Col 1 peptide (reflecting collagen degradation). Relationships of serum PIIIP with histology was carried out by evaluating grading and staging separately. Moreover, each component of the necro-inflammatory score was also taken into consideration. RESULTS: PIIIP levels were abnormal in 101 patients (93%). Moreover, PIIIP levels were no different between patients with (12.1 +/- 6.3 ng/ml) or without (13 +/- 5.8 ng/ml) fibrosis. In univariate analysis, no relationship was observed with fibrosis (rs = 0.033, not significant), while PIIIP levels were significantly correlated with lobular necrosis only (rs = 0.295, P = 0.0020). Multivariate analysis confirmed this latter finding (P = 0.0150). Among biochemical parameters, PIIIP showed relationships with aminotransferase (AST, rS = 0.294, P = 0.0022; ALT, rs = 0.236, P = 0.0142) and alkaline phosphatase (rs = 0.146, P = 0.0223). CONCLUSIONS: In patients with CHC, serum PIIIP levels reflect histological parameters strictly related to fibrogenesis. Therefore, PIIIP is a useful tool to evaluate ongoing fibrogenic activity of CHC. A complete histological score is needed in order to understand the relationships between biochemical markers of fibrogenesis and histology.

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.

Liver iron accumulation in chronic hepatitis C patients without HFE mutations: relationships with histological damage, viral load and genotype and alpha-glutathione S-transferase levels.

BACKGROUND: Host and viral factors have been suggested as possible causative factors for the presence of liver iron accumulation in chronic hepatitis C. However, there is no agreement regarding the influence of liver iron accumulation on the biochemical and histological severity of chronic hepatitis C. Moreover, data concerning the relationships between both viral load and genotype and liver iron accumulation are scanty. AIMS: To evaluate the biochemical, histological and virological assessment of a group of chronic hepatitis C patients without risk factors for iron overload, on the basis of the presence, degree and distribution of liver iron accumulation. METHODS: Fifty-three chronic hepatitis C patients (34 men, 19 women; age 44 +/- 11 years) with no risk factors for liver iron accumulation and showing no HFE mutations were chosen from a broader cohort of chronic hepatitis C patients. The presence, degree and distribution of liver iron accumulation were assessed using Deugnier's score. Relationships between the presence of liver iron accumulation and grading and staging were carried out separately. Hepatitis C virus RNA serum levels and viral genotype were compared in patients with or without liver iron accumulation. Alpha glutathione S-transferase serum levels were assessed in all patients. RESULTS: Overall, liver iron accumulation was mild and was present in 19 patients (36%). It was associated with male gender (P = 0.0358), and was reflected by high serum iron levels (P = 0.001) and high ferritin levels (P < 0.0001). Hepatitis C virus RNA levels and genotype were not associated with the presence of liver iron accumulation. In multivariate analysis, ferritin was the only variable significantly associated with liver iron accumulation (P < 0.0001). Grading was higher in patients with liver iron accumulation regardless of the site of iron deposition. Fibrosis was present in all patients with iron overload; these patients were more frequently cirrhotic. Moreover, patients with mesenchymal or mixed deposition had higher staging than patients with hepatocytic or no iron deposition. This feature was reflected by higher alpha-glutathione S-transferase levels. CONCLUSIONS: Liver iron accumulation is mild in chronic hepatitis C patients without HFE mutations and is mainly reflected by serum ferritin levels. Viral characteristics do not seem to play a role in iron deposition. Liver iron accumulation is associated with higher grading, advanced fibrosis and cirrhosis. Moreover, higher staging is associated with mesenchymal or mixed iron deposition. In these patients, higher alpha-glutathione S-transferase levels seem to reflect more complex damage.

Statistical evaluation of inter- and intra-laboratory variations of the Ames test, as related to the genetic stability of Salmonella tester strains.

A statistical analysis was performed on the data resulting from an international collaborative study of the Ames test according to a standardized experimental protocol, which involved the comparative testing of 4NQO (4 doses), in 3 separate experiments for each of the 38 participating laboratories, by using a common reference (R) culture and in-house laboratory (L) cultures of 5 strains of S. typhimurium. Despite some toxicity phenomena recorded at the highest dose of 4NQO, the majority of the dose-response curves in individual laboratories were linear on a bi-log scale and their mean values fitted a linear regression framework. Scattering of data around mean values of laboratories was Gaussian-like even at the highest dose of 4NQO, toxic effects being expressed as a dose-related increase of variance. A weighted least-square analysis could therefore take into account toxic effects without resorting to a sophisticated non-linear model incompatible with log transformation. Various analytical approaches--e.g. the weighted estimates of linear regression parameters, a multifactor (laboratory, experiment, dose, culture of each strain) analysis of variance with all the possible interactions, the assessment of correlations in individual laboratories and of coefficients of variation for induced and spontaneous mutability--could detect some statistically significant differences between L and R cultures. However, at a critical evaluation on an individual basis, only few of these differences, without any peculiar involvement of given strains, were convincing in view of the existence of real phenomena of genetic drift. Therefore, on the whole, the genetic drift of Salmonella tester strains appears to lend a negligible contribution to the considerable inter- and intra-laboratory variability detected in this study. With a background variability between replications averaging 26%, a dose-related variability was evident both between experiments (28-54%) and between laboratories (44-127%).

Fig leaf tanning lotion and sun-related burns: case reports.

A sun tan is considered a symbol of well-being in our society, but incorrect methods of sun exposure can create serious problems. We present two cases of severe sun-related burns caused by fig leaf decoction used as home-made tanning lotion. Twenty four-thirty six hours after application and sun exposure, patients developed a phytophotodermatitis characterised by erythema, and blister formation involving all the photoexposed areas (45-70% BSA). Their general conditions became rapidly critical and they were admitted to our Burn Centre. The patients were discharged after 11 and 26 days, respectively. Haemolytic anaemia and retinal haemorrhages presented as systemic complications due to the furocoumarins present in the fig leaf decoction.

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.

Lidocaine elimination and monoethylglycinexylidide formation in patients with chronic hepatitis or cirrhosis.

BACKGROUND/AIMS: The aim of this study was to evaluate the relationship between plasma elimination of lidocaine and monoethylglycinexylidide (MEGX) formation, which is considered to be a quantitative liver function test. METHODOLOGY: The study included ten healthy subjects and 54 patients: 27 with chronic hepatitis and 27 with cirrhosis. Lidocaine and MEGX were measured at 0, 2, 5, 10, 15, 30 min and then every 30 min for 180 min using the TDX system. RESULTS: In cirrhotic patients, the lidocaine half-life of the slow decline phase of the plasma disappearance curve (beta-HL) and the lidocaine half-life of hepatic elimination from the second compartment (K20-HL) proved to be significantly abnormal, as did all parameters of MEGX formation. In chronic hepatitis, both the lidocaine kinetics and the MEGX formation parameters were within the normal range. In chronic hepatitis patients, MEGX formation (AUC 0-180) was significantly correlated to K20-HL (rs = -0.633, p < 0.001) and to the rapid decline phase of the plasma disappearance curve (alpha-HL, rs = -0.483, p < 0.05). In cirrhotic patients, MEGX was significantly correlated to K20-HL (rs = -0.423, p < 0.05) and to beta-HL (rs = -0.500, p < 0.01). CONCLUSIONS: These results show that in chronic active hepatitis, MEGX formation from lidocaine is maintained as a metabolic process, whereas it is altered in cirrhotic patients. The interrelationship between lidocaine elimination and MEGX formation were somewhat different in the two liver diseases.