Prevalence and patient related factors associated with Extended-Spectrum Beta-Lactamase producing Escherichia coli and Klebsiella pneumoniae carriage and infection among pediatric patients in Tanzania.

Extended-Spectrum Beta-Lactamase (ESBL) producing Enterobacteriaceae (EPE) is increasing worldwide, though less documented in low-income settings. Here we determined the prevalence of EPE infection and carriage, and patient factors associated with EPE-carriage among pediatric patients in three health care levels in Tanzania. Between January and April 2016, 350 febrile children (median age 21 months) seeking care at a university or a regional referral hospital, or a health centre in Moshi municipality, Tanzania, were included. Socio-demographic characteristics were collected using a questionnaire. Rectal swabs and blood cultures were collected from all children (n = 350) and urinary samples from 259 children at admission. ESBL-phenotype and antimicrobial susceptibility were determined for Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli) isolates. Only one EPE case (E. coli) in blood and four in urine (one E. coli and three K. pneumoniae) were found, whereas (n = 90, 26%) of the children were colonized in feces (ESBL-E. coli; n = 76, ESBL-K. pneumoniae, n = 14). High resistance rates were seen in fecal ESBL-E. coli (n = 76) against trimethoprim-sulfamethoxazole (n = 69, 91%), gentamicin (n = 51, 67%), ciprofloxacin (n = 39, 51%) and chloramphenicol (n = 27, 35%) whereas most isolates were sensitive to amikacin (n = 71, 93%). Similar rates were seen for fecal ESBL-K. pneumoniae. Resistance to first line antibiotics were also very high in fecal E. coli not producing ESBL. No sociodemographic factor was associated with EPE-carriage. Children colonized with EPE were younger than 12 months (n = 43, 48%) and often treated with antibiotics (n = 40, 44%) in the previous two months. After adjustment for age children admitted to the intensive care unit had higher odds of EPE fecal carriage compared with those in the general wards (OR = 3.9, 95%CI = 1.4-10.4). Despite comparatively high rates of fecal EPE-carriage and previous antibiotic treatment, clinical EPE cases were rare in the febrile children. The very high resistant rates for the EPE and the non-ESBL producing E. coli to commonly used antibiotics are worrying and demand implementation of antibiotic stewardship programs in all levels of health care in Tanzania.

Development and external validation of a clinical prediction model for MRSA carriage at hospital admission in Southeast Lower Saxony, Germany.

In countries with low endemic Methicillin-resistant Staphylococcus aureus (MRSA) prevalence, identification of risk groups at hospital admission is considered more cost-effective than universal MRSA screening. Predictive statistical models support the selection of suitable stratification factors for effective screening programs. Currently, there are no universal guidelines in Germany for MRSA screening. Instead, a list of criteria is available from the Commission for Hospital Hygiene and Infection Prevention (KRINKO) based on which local strategies should be adopted. We developed and externally validated a model for individual prediction of MRSA carriage at hospital admission in the region of Southeast Lower Saxony based on two prospective studies with universal screening in Braunschweig (n = 2065) and Wolfsburg (n = 461). Logistic regression was used for model development. The final model (simplified to an unweighted score) included history of MRSA carriage, care dependency and cancer treatment. In the external validation dataset, the score showed a sensitivity of 78.4% (95% CI: 64.7-88.7%), and a specificity of 70.3% (95% CI: 65.0-75.2%). Of all admitted patients, 25.4% had to be screened if the score was applied. A model based on KRINKO criteria showed similar sensitivity but lower specificity, leading to a considerably higher proportion of patients to be screened (49.5%).

Prevalence, molecular epidemiology, and antimicrobial resistance of methicillin-resistant Staphylococcus aureus from swine in southern Italy.

BACKGROUND: Colonization by livestock-associated MRSA (LA-MRSA) has increasingly been reported in the swine population worldwide. The aim of this study was to assess the prevalence of MRSA nasal carriage in healthy pigs, including the black (Calabrese) breed, from farms in the Calabria Region (Southern Italy). Between January and March 2018, a total of 475 healthy pigs reared in 32 farms were sampled by nasal swabbing. MRSA isolates were characterized by spa, MLST and SCCmec typing, and susceptibility testing to 17 antimicrobials. RESULTS: 22 of 32 (66.8%) pig farms resulted positive for MRSA. The prevalence of MRSA was 46.1% (219 MRSA culture-positive out of 475 samples). MRSA colonization was significantly higher in intensive farms and in pigs with a recent or ongoing antimicrobial treatment. All 219 MRSA isolates were assigned to ST398. The most common spa types were t011 (37.0%), t034 (22.4%) and t899 (15.1%). A novel spa type (t18290) was detected in one isolate. An insertion of IS256 in the ST398-specific A07 fragment of the SAPIG2195 gene was detected in 10 out of 81 t011 isolates. Nearly all isolates carried the SCCmec type V element, except 11 isolates that carried the SCCmec type IVc. None of the isolates was positive for the Panton-Valentine leukocidin. All isolates were resistant to tetracycline. High resistance rates were also found for clindamycin (93.1%), trimethoprim/sulfamethoxazole (68.4%), fluoroquinolones (47.9-65.3%) and erythromycin (46.1%). None of the isolates was resistant to vancomycin and fusidic acid. Overall, a multidrug resistant phenotype was observed in 88.6% of isolates. CONCLUSIONS: We report a high prevalence of MRSA among healthy swine in Southern Italy farms, with higher isolation frequency associated with intensive farming. The epidemiological types identified in our study reflect those reported in other European countries. Our findings underscore the importance of monitoring the evolution of LA-MRSA in pig farms in order to implement control measures and reduce the risk of spread in the animal population.

Platelet m-calpain: a facile marker and STR polymorphism analysis for the identification of true carriers of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a neuromuscular-degenerative fatal disorder caused by mutations in the dystrophin gene. The incidence rate is one in 3300 live male births in every part of the world. A study into the detection of true carriers of DMD has been performed using gene deletion and non-deletion cases to devise a reliable and cost-effective diagnosis of DMD. The study uses a sample of 130 people (70 males and 60 females), consisting of 105 risk patients (60 male and 45 female) and 25 patients from normal carrying families, analyzed by CPK, M-PCR, Q-PCR and STR. This study aims to perform diagnosis of non-deletional and true carriers of DMD by enzyme-linked immunosorbent assay (ELISA), assessing the amount of m-calpain in the platelets of participants. In order to diagnose DMD patients, true carriers and controls, an ELISA has been standardized using polyclonal antibodies raised against m-calpain purified from human placenta. From the sample group, 45 at risk females were analyzed for m-calpain by quantitative ELISA. It was found that 90% of tests were informative, showing enhanced levels of m-calpain when compared to controls. The quantitative ELISA has proved to be an accurate, reliable, rapid and cost-effective test for DMD patients and true carriers, and also useful for the prenatal diagnosis.

Serum paraoxonase and arylesterase activities in various forms of hepatitis B virus infection.

The aim of this study was to determine and evaluate the activity of paraoxonase and arylesterase enzymes in various clinical forms of hepatitis B infection and to investigate the correlation between these parameters and chronic disease course/fibrosis. Overall, 40 patients diagnosed as hepatitis B carriers (CIHBV), 40 chronic active hepatitis B (CAHBV) patients, and 40 healthy adults (control group) between 18 and 65 years of age were enrolled the study. Serum paraoxonase and arylesterase activities were measured spectrophotometrically. Their activities were significantly lower in patients with CAHBV compared with CIHBV patients or with control group patients (P<0.001). There was a negative correlation between alanine aminotransferase levels and the activity of paraoxonase and arylesterase (r = -0.38, P = 0.001 and r = -0.28, P = 0.002, respectively). A statistically significant negative correlation was found between arylesterase activity in the sera of CAHBV patients and HBV DNA levels (ρ = -0.33, P = 0.03). On the contrary, no correlation was found between paraoxonase levels and HBV DNA levels (P>0.05). The histology activity index of CAHBV patients did not correlate with paraoxonase and arylesterase activities (P>0.05). In light of these findings, it may be assumed that during the progression of an inactive hepatitis B carrier to being actively infected, reduced paraoxonase and arylesterase activities may be observed.

Evaluation of serum matrix metalloproteinase (MMP)-9 to MMP-2 ratio as a biomarker in hepatocellular carcinoma.

BACKGROUND/AIMS: Serum matrix metalloproteinase (MMP)-9/ MMP-2 ratios are highly associated with alpha-fetoprotein levels in patients with chronic hepatitis B. In this study, we evaluate the clinical usefulness of this ratio as a biomarker in hepatitis B virus-related hepatocellular carcinoma (HCC). METHODOLOGY: Serum samples from 181 chronic hepatitis B patients (52 healthy carriers, 47 chronic hepatitis patients, 50 cirrhosis patients, and 32 HCC patients) were collected. MMP-9/ MMP-2 ratio was determined by zymography. The results were analyzed using the Receiver-Operating Characteristic (ROC) curve. RESULTS: Serum MMP-9/ MMP-2 ratios in HCC patients were significantly higher than those in healthy carriers, chronic hepatitis patients, and cirrhosis patients (p = 0.004, 0.034, and < 0.001, respectively). The sensitivity and specificity at the optimal cutoff (0.97) were 69.7% and 73.4%, respectively. Significantly higher MMP-9/ MMP-2 ratios were found in advanced, inoperable HCC patients, compared to those in early stage HCC patients (p = 0.005). No significant difference was found for alpha-fetoprotein levels between these two groups (p = 0.312). CONCLUSIONS: The serum MMP-9/ MMP-2 ratio can be used as an accessory diagnostic marker in hepatitis B virus-related HCC. This ratio is useful in distinguishing between patients with early stage HCC and those with advanced HCC.

HCV carriers with normal alanine aminotransferase levels: healthy persons or severely ill patients? Dealing with an everyday clinical problem.

Approximately 30% of patients with chronic HCV infection show persistently normal ALT levels. Although formerly referred to as 'healthy' or 'asymptomatic' HCV carriers, and thus historically excluded from antiviral treatment, it has now become clear that the majority of these patients have some degree of histological liver damage that may be significant in up to 20% of patients and might progress toward a more severe degree of liver fibrosis. A significant proportion of patients (> or =20%) experience periods of increased serum ALT (flare) associated with enhanced disease progression. However, controversies still exist in clinical practice regarding the definition of 'persistent' ALT normality, the virological and histological features of these subjects, the need for liver biopsy, the role of non invasive tools for the assessment of liver fibrosis (transient hepatic elastography, fibroscan), and the natural history and optimal management of chronic hepatitis C with normal ALT. The advent of new therapeutic options (pegylated interferons plus ribavirin) has shifted treatment targets toward eradication of underlying infection, with therapy decision based on age, severity of disease and likelihood of response rather than on aminotransferase levels. This review does approach the main unresolved issues on this topic in the form of a dialog between a hepatologist and a patient with HCV infection but normal alanine aminotransferase levels, trying to give evidence-based answers to the more frequently asked questions from patients and their physicians.

Antiviral treatment of HCV carriers with persistently normal ALT levels.

Approximately 30% of patients with chronic HCV infection show persistently normal alanine aminotransferase levels (PNAL). The prevalence of HCV carriers with normal liver seems to be very low (less than 15-20%). Liver disease is usually minimal/mild and fibrosis is generally absent or minimal, although the association of normal alanine aminotransferase (ALT) with cirrhosis or with liver cancer has been reported. In all studies, liver histology was, on average, significantly less severe in subjects with PNAL than with abnormal ALT. Although the majority of data seem to show that HCV carriers with normal ALT have mild and stable disease, with a favourable prognosis, several studies reported a significant progression of fibrosis in approximately 20-30% of the patients with ALT normality, and the development of HCC in some cases has been described, despite persistent ALT normality. Sudden worsening of disease with ALT increase and histological deterioration has been described after up to 15 years of follow-up, in particular in patients harboring genotype 2. As to antiviral treatment, it has been clearly stated that it no longer seems reasonable to affirm that sustained response rates for patients with normal ALT levels are any different than those for patients with elevated ALT levels when the combination of pegylated interferon (IFN) and ribavirin is used. The issue at hand is whether or not patients with mild disease should be treated. There are numerous other factors which impact on this decision, including genotype, histology, patients motivation, symptoms, co-morbid illness, and the age of the patient.

Effect of chronic hepatitis C virus infection on inflammatory lipid mediators.

BACKGROUND: Platelet-activating factor (PAF), a powerful phospholipid mediator of inflammation, is degraded by plasma PAF-acetyl-hydxolase (pPAF-AH), an enzyme which circulates in serum mainly in a complex with lipoproteins that confer its biological activity. Hepatitis C virus (HCV) is linked to lipoproteins in serum too. Reduced pPAF-AH activity was observed in several diseases, including systemic vasculitis. AIM: To evaluate if chronic HCV infection could alter pPAF-AH physiological functions. SUBJECTS: 145 subjects were studied: 56 HCV- and 52 HBV-infected patients (pathologic controls); 37 healthy subjects (healthy controls). METHODS: pPAF-AH activity, PAF and Apo B100 titers were determined in plasma; enzyme expression levels were evaluated in monocyte-derived macrophages. HCV-RNA was detected in plasma, peripheral blood mononuclear cells and liver samples. RESULTS: HCV-infected patients showed an increase of PAF levels following a significant decrease of pPAF-AH activity. A recovery of pPAF-AH activity occurs only in patients who clear HCV after the antiviral treatment. Expression levels of pPAF-AH mRNA and Apo B100 titers were not modified in HCV patients in comparison to controls. CONCLUSION: In light of these results, it is tempting to hypothesize that during chronic HCV infection, the PAF/pPAF-AH system may be altered and this condition may contribute to HCV-related vascular damage.

[The follow-up of serum aminotransferase levels and investigation of hepatitis B virus load in inactive HBsAg carriers]. / Inaktif HBsAG tasiyicilarinda serum alanin aminotransferaz izlemi ve hepatit B virus yükünün arastirilmasi.

The aim of this study was to follow-up the serum alanine aminotransferase (ALT) levels in inactive HBsAg carriers during one year period and investigate the association between hepatitis B virus (HBV) DNA levels detected at the end of the year. At May 2005, 61 patients with HBeAg negative/anti-HBe positive chronic HBV infection, followed in our viral hepatitis clinic were included to the study. The patients' ultrasonographic examination of the liver were normal, they had no history of taking alcohol or routine medication, were anti-HCV seronegative and had normal ALT levels during the last 6 months and at the beginning of the study. Serum ALT levels of patients were followed in the 3rd, 6th and 12th months of the study, and blood HBV-DNA levels were analysed quantitatively in 12th month. During the one year period 89% (54/61) of the patients yielded continously normal ALT levels, while 11% (7/61) showed at least one ALT value above the normal levels (ALT > 1.2x). Total HBV-DNA positivity rate was found as 59% (36/61). In inactive HBsAg carrier group,--namely HBeAg negative and serum ALT levels constantly normal--57.4% (31/54) of patients were HBV-DNA positive and 23 (42.6%) were negative. Amongst the HBV-DNA positive patients the viral load were detected as 10(4)-10(5) copies/ml in six (19.4%), and <10(4) copies/ml in 25 (80.6%) patients. In patients who had at least one ALT value above normal limits, 71.4% (5/7) of them were found HBV-DNA positive; two with HBV-DNA values of >10(5) copies/ml and three with values between 10(4)-10(5) copies/ml. In conclusion, although ALT levels may be normal, it should always be taken into consideration that more than half of inactive HBsAg carriers exhibited low level viral replication, thus HBV-DNA and liver enzyme levels should be monitored routinely in order not to miss the acute manifestations.

Lower plasma adiponectin is correlated to higher alanine aminotransferase independent of metabolic factors and hepatitis B virus carrier status.

BACKGROUND: Adiponectin has been linked to the metabolic syndrome and coronary artery disease in recent years. The animal and human data also suggest that adiponectin may be beneficial for liver functions. The aim of this study was to investigate the correlation between plasma adiponectin level and liver function tests in adults with or without chronic hepatitis B virus (HBV) infection. METHODS: We analysed the blood levels of liver enzymes and adiponectin in 140 apparently healthy adults, including 21 HBV carriers. RESULTS: We found that the plasma adiponectin levels were inversely correlated to aspartate aminotransferase (r = -0.314, P = 0.000) and alanine aminotransferase (ALT) (r = -0.430, P = 0.000). Among the HBV carriers, the ALT correlated with the plasma adiponectin levels (r = -0.521, P = 0.015). In linear regression models adjusting for age, sex and the other metabolic variables, the ALT was independently related to the plasma adiponectin levels (beta = -0.371 +/- 0.134, P = 0.007), even in HBV carriers (beta = -1.143 +/- 0.482, P = 0.034). The ALT was also independently correlated to the plasma adiponectin levels (beta = 0.552 +/- 0.132, P < 0.001) with adjustment for age, sex and insulin-resistance index by homeostasis model assessment, even in HBV carriers (beta = -1.202 +/- 0.562, P = 0.048). The subjects with normal ALT had a significantly higher least square mean of plasma adiponectin than those with abnormal ALT (4.01 +/- 0.19 vs 3.30 +/- 0.30, P = 0.014) with adjustment for age, sex, homeostasis model assessment insulin resistance and HBV status. CONCLUSION: ALT was inversely related to adiponectin levels, independent of the metabolic factors and HBV status. Whether there is any potential prognostic and therapeutic value of adiponectin in human liver diseases remains to be investigated.

Truncated gamma-glutamyl carboxylase in rambouillet sheep.

A flock of Rambouillet sheep was examined because of increased lamb mortality due to ineffective hemostasis at parturition. Decreased activities of coagulation factors II, VII, IX, and X, and severely reduced hepatic gamma-glutamyl carboxylase activity with adequate vitamin K 2,3 epoxide reductase activity was determined.(1,)(21) Parenteral vitamin K(1) supplementation did not improve vitamin K-dependent coagulation factor activities in 3 affected lambs. Affected lamb gamma-glutamyl carboxylase deoxyribonucleic acid was sequenced, and 4 single nucleotide polymorphisms (SNPs 2-5) of the gamma-glutamyl carboxylase gene were identified. Single nucleotide polymorphism-4 results in an arginine to stop codon (UGA) substitution, which prematurely terminates the peptide at residue 686 (R686Stop). This genotype (GATT/GATT) has a strong association with the coagulopathy observed in clinically affected lambs, P < 0.001. The frequency of SNP-3 in exon 11 (R486H) within the MARC 1.1 database is high in the US sheep population overall. Gamma-glutamyl carboxylase activity in hepatic microsomes from a SNP-3 homozygous lamb lacking the SNP-4 mutation (GACC/GACC) was similar to control sheep homozygous for arginine at 486 and also lacking SNP-4 (TGCC/TGCC), indicating that the R486H does not measurably impact gamma-glutamyl carboxylase activity. The remaining two SNPs (2 and 5) are located within non-coding intron sequences. These 4 SNPs allowed for determining the genotype associated with the observed fatal coagulopathy. Screening for the premature truncation (SNP-4) based on the presence of a Bbv I restriction site in clinically normal lambs but not in the homozygous affected lambs allows for detection of the heterozygous state (GATT/GACC), because carrier animals are clinically normal.

Hepatitis C virus carriers with persistently normal ALT levels: biological peculiarities and update of the natural history of liver disease at 10 years.

Some chronic hepatitis C (CHC) patients exhibit persistently normal alanine aminotransferase (ALT) levels (PNAL). Patients with PNAL experience significantly milder disease. In order to understand the differences between CHC patients with elevated ALT levels compared with those with PNAL better, we compared epidemiological, immunological and histological findings, in particular, the value of proliferating hepatocyte activity (PCNA) between the two groups of patients. We studied 40 chronic hepatitis C virus (HCV) carriers with increased ALT who underwent liver biopsy for histological diagnosis and determination of clinical prognosis, and 24 PNAL patients under follow-up for 10 years. Immunological response to different HCV genomic epitopes was tested in both the control group and in PNAL subjects. PCNA values from liver specimens of all patients as well as liver biopsies of PNAL patients at time points 0 and 5 years were calculated according to Hall et al.Age, sex and body mass index (BMI) were not significantly different between the two groups. The median liver histology stage was significantly higher in HCV carriers vs the PNAL group (2.5, range = 2-6 vs 1.5, range = 1-2; P < 0.01). Among PNAL patients, histological stage was not statistically different at the three time points considered. Interferon (IFN)-gamma production was comparable in the two groups. PCNA was significantly higher in the group with elevated ALT levels vs the PNAL group (8%, range = 4-15%vs 5% range = 3-8%; P < 0.05) and no statistically significant differences were found in PNAL patients at time points 0, 5 and 10 years. This study confirms that progression to cirrhosis is slow or absent in PNAL patients after 10 years of follow-up. Accordingly, the hepatic proliferative activity index is low and seems to be stable over time.

Evidence for prostaglandin-producing supressor cells in HCV patients with normal ALT.

Our objective was to verify the presence of prostaglandin-producing suppressor cells in response to hepatitis C virus antigens in peripheral blood mononuclear cells proliferation. Standard proliferation tests were performed in 31 patients: 20 with chronic hepatitis C after antiviral treatment [7 long-term responders (LTR), 7 relapsers (RR), 6 nonresponders (NR)], 7 with HCV infection with persistently normal aminotransferase levels (PNAL), and 4 with hepatocellular carcinoma. Six antigens were used from the core and NS3 regions. A modified proliferation assay consisting of the addition of indomethacin was also done. Lymphoproliferative responses to the HCV antigens were detectable in 27% (11/41) of test points of LTR, 10% (3/31) of RR, 26% (9/35) of NR, and 18% (7/39) of patients with PNAL. Indomethacin only had effect in PNAL patients, by increasing the frequency of reactivity from 18% (7/39) to 36% (14/39) tests points (P = 0.037); also, in three of these patients (43%) indomethacin strongly modified proliferation to core 31-50 and NS3 1248-1261 antigens, increasing both the frequency and stimulation index from 33% (6/18) to 72% (13/18) (chi2 = 5.43, P = 0.019) and 1.89 +/- 0.43 to 6.18 +/- 4.74 (P = 0.028), respectively. These results suggest that prostaglandin-producing suppressor may play a role in chronic HCV infection by inhibiting cellular immune responses in patients with persistently normal ALT.

Clinical significance of elevated serum interferon- inducible protein-10 levels in hepatitis C virus carriers with persistently normal serum transaminase levels.

The aim of this study was to assess the immunological profile in hepatitis C virus carriers with persistently normal serum transaminase levels. Forty-two serum HCV RNA positive patients with persistently normal serum transaminase levels (22 natural 'asymptomatic HCV carriers' and 20 biochemical responders to IFN therapy) and 23 complete responders to IFN therapy were enrolled. The HCV genotypes and serum HCV RNA levels were determined before IFN therapy in treatment responders, and at entry in the others. The serum levels of IFN-inducible protein-10 (IP-10) (a protein mainly induced by IFN-gamma), interleukin (IL)-10, and IL-4 were measured in all patients while the serum transaminase levels were normal. The serum transaminase levels and platelet counts were then monitored for the next 4 years and the changes in liver fibrosis were assessed. The serum levels of IP-10 in infected and biochemically normal patients were significantly higher than the levels in complete responders to therapy, whereas the serum levels of IL-10 and IL-4 did not vary significantly among the different groups. During the 4-year follow-up period, 10/20 (50%) biochemical responders and 12/22 (55%) asymptomatic carriers had an elevation of the serum transaminase levels. A significant (P=0.0370) increase in platelet count after 4 years and improvement in liver fibrosis were noted in treatment responders but not in infected patients. The weak but significant residual immune response as reflected by the increased serum IP-10 level may underlie the outcome of HCV carriers with persistently normal serum transaminase levels.

Risk of alanine aminotransferase flare-up among asymptomatic hepatitis C virus RNA carriers: a 10-year follow-up study.

AIMS: The aim of this study was to determine the cumulative rate of flare-up of serum alanine aminotransferase (ALT) level during a 10-year follow-up period, and characterize the clinical, virologic features in 120 hepatitis C virus (HCV) RNA-positive asymptomatic carriers with persistently normal ALT levels for 6 months. RESULTS: All flare-up cases occurred during the first 5 years of the present study, 27.4% of carriers showed ALT flare-up during this period, but none in the second half of the study. Multivariate analysis showed that C100-3 antibody (Ab) and anti-human T cell leukemia virus (HTLV)-I Ab were two independent and significant predictors of ALT flare-up in hepatitis C virus (HCV) RNA asymptomatic carriers (P = 0.04, P = 0.03, respectively). Liver biopsy was performed in 44 patients (11 with flare-up of ALT level, whereas 33 had normal ALT levels). Histological features of chronic hepatitis with lymphoid infiltration in the portal tracts were commonly observed in all specimens, and no differences were noted between the flare-up ALT group and the persistently normal ALT group. CONCLUSIONS: Our results indicated that flare-up of ALT levels in asymptomatic HCV-RNA carriers with normal ALT levels occurs during the first 5 years of diagnosis, and that the presence of C100-3 and anti-HTLV-I antibodies are good predictors of a transient rise in ALT.

Data differentiation and parameter analysis of a chronic hepatitis B database with an artificial neuromolecular system.

This paper describes the application of a biologically motivated system to the diagnosis of chronic hepatitis B. The system integrates intra- and inter-neuronal information processing so as to capture the biology-like gradual transformability of structure/function relationships. The system was applied to a clinical hepatitis B database, divided into two sets. The first set comprised 676 records, of which one half were chronic hepatitis B patients, and the other half healthy individuals. The second set included 375 records, of which one third were chronic hepatitis B patients; another third were hepatitis B carriers, and the remaining third healthy non-carriers. Each record consisted of ten examination items. Experimental results showed that the system was able to correctly differentiate 99.3 and 91.2% of the records in the first and the second sets, respectively. Differentiation means making a distinction between different categories of data in each set. After substantial learning with the first set, the system was then tested with the second set, and it was able to correctly differentiate 95. 7% of the records, suggesting a high differentiating capability in this system. This system demonstrated an effective self-organizing capability in determining significant and insignificant examination items from patterns of the clinical data. It also showed that some combinations of these items were more effective for determining whether one is infected with chronic hepatitis B than others.