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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., (© 2021. The Author(s).)

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%).

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.

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., (This journal is © The Royal Society of Chemistry 2012)

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., (© 2011 Wiley-Liss, Inc.)

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., (Copyright 2009 Elsevier B.V. All rights reserved.)

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

Since the discovery of hepatitis C virus, the availability of serological hepatitis C virus screening has led to the identification of many subjects with normal aminotransferase levels who are chronically infected by the hepatitis C virus. To date, the epidemiology and natural history of subjects with normal aminotransferase levels are far from being clarified. Further, whether subjects with persistently normal aminotransferase levels should routinely undergo liver biopsy is still extremely controversial, and benefit from interferon treatment in this group of patients is yet to be proven. On account of the consistent normality of aminotransferases, it is not easy to calculate the rate of persons with normal aminotransferase levels among chronic hepatitis C virus carriers, nor their prevalence in the general population. It has been estimated that up to 25% of patients with chronic hepatitis C virus infection have persistently normal aminotransferase levels (10% to 40%, according to different studies). Most studies showed a clear prevalence of females, ranging from 58% to 90%. Liver biopsy shows some degree of chronic liver disease in up to 80% of these subjects, although in the majority, histological damage is mild and probably does not progress to more severe liver disease, moreover, the progression to fibrosis is slower than in patients with elevated aminotransferase levels. Virological features of these subjects (hepatitis C virus genotype distribution, viral load, quasispecies diversity) do not differ with respect to patients with elevated aminotransferase levels although a higher frequency of non 1 hepatitis C virus types has been reported. To date, no biochemical or virological tools to assess the presence and severity of liver damage exist. Antiviral treatment with interferon may induce a long-term response in only a small proportion of hepatitis C virus carriers with persistently normal aminotransferase levels, and many patients develop aminotransferase-flare-up during or shortly after treatment. Thus, interferon or combination antiviral treatment of hepatitis C virus carriers with normal aminotransferase values should be avoided in clinical practice.

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.

To examine the possible involvement of MMP-9 and -2 in the development of liver diseases caused by HCV or HBV infection, serum activities of both enzymes were studied by zymograph. Eight groups of subjects (60 for each) were examined in the study: healthy control, patients with hepatoma, liver cirrhosis, chronic hepatitis B or chronic hepatitis C, and carriers positive for HBsAg, both HBsAg and HBeAg, or anti-HCV. The results showed significant changes in the MMP-9 and -2 activities in the carriers. The presence of HBeAg was accompanied by a highest activity of MMP-2 and an inversely correlated (r=-0.578, P=<0.001), lowest activity of MMP-9 among all groups. For those with active liver diseases, MMPs activities were fluctuated at each stage of pathological symptoms. Chronic hepatitis B and C patients had significant different serum MMP-2 and -9 activities. These findings imply an influence on the balance of MMPs system by the existence of virus that might influence the following progression of liver disease, and a distinction between the pathological mechanisms of HCV and HBV. Since the serum MMPs activities were significantly varied between each stage of liver disease, an individual profile of these parameters might serve as an easy accessing serum marker to monitor the progression of liver disease.

In endemic areas of hepatitis B and C, hemodialysis patients are highly exposed to these infections. So the authors studied the prevalence of hepatitis B and C viruses among chronic hemodialysis patients of CHU A. Le Dantec of Dakar in a cross study carried out from June 1996 to June 1997, in order to identify risk factors and suggest appropriate prophylaxis. The study concerned fifteen chronic hemodialysis patients in an unit of hemodialysis in Dakar. For each patient, clinical and biochemical data were collected serological markers of B and C viruses were tested and HCV-RNA in case of seropositivity to C virus. The mean age of patients were 48 years and average duration of hemodialysis was 40 months. Hepatic injury was silent in all cases. Only one patient (6.7%) was AgHBs carrier while 9 patients (60%) were positive for antibodies anti HBs without previous hepatitis B vaccine. Twelve patients (80%) were found to be HCV-antibody positive and half of them were HCV. RNA positive. Average value of alanine amino transferase was higher in HCV-viremic patients than in seropositive but non viremic patients, although normal. Genotype 2 ac was found in 3 HCV viremic patients but it could not be determined in 3 other patients. Hemodialysis duration and number of blood transfusions were found to be risk factors of HCV infection. The high prevalence of HCV seropositivity among chronic hemodialysis patients in Dakar has led to strengthen precautions in our hemodialysis unit. HCV serological screening in blood donors is advocated.

The hepatitis C virus (HCV) infects some 170 million people worldwide and is responsible for approximately 20% of cases of acute hepatitis and 70% of cases of chronic hepatitis. Acute hepatitis is icteric in only 20% of patients and is rarely severe. Eighty five per cent of the infected patients develop chronic infection which is generally asymptomatic. Among the HCV chronic carriers, 25% have persistently normal serum alanine aminotransferase (ALT) levels despite having detectable HCV-ribonucleic acid in serum, 75% have elevated ALT levels. While the majority of patients with mild chronic hepatitis have a slowly progressive liver disease, the patients with moderate or severe chronic hepatitis may develop cirrhosis within a few years. In patients with HCV-related cirrhosis, the incidence of hepatocellular carcinoma is 2-5% per year. HCV-related end-stage cirrhosis is currently the first cause of liver transplantation. Treatment with the combination of interferon-alpha and ribavirin induces a sustained virological response in roughly 40% of the patients. The virological response is associated with a biochemical response and histological improvement. It is believed that the decrease of necroinflammatory liver lesions induced by anti-viral therapy in responders, is associated with a decreased risk of development of cirrhosis and hepatocellular carcinoma

Cigarette smoking has been associated with increased risk of hepatocellular carcinoma (HCC) in some epidemiological studies. Cytochrome P450 1A1 (CYP1A1) is involved in the biotransformation of tobacco-derived polycyclic aromatic hydrocarbons (PAHs) into carcinogenic metabolites. The aim of this study was to determine whether CYP1A1 polymorphisms were related to HCC risk among chronic hepatitis B virus (HBV) carriers. Genotypic variants of CYP1A1 were determined using polymerase chain reaction in 81 incident cases of HCC and 409 controls nested in a cohort study of 4841 male chronic HBV carriers. No overall association between CYP1A1 genotypes and HCC was observed. The presence of the Mspl (odds ratio (OR) 3.15, P = 0.0196) or Ile-Val (OR 1.99, P = 0.0855) variant allele of CYP1A1 increased HCC risk among smokers, but posed no increased risk among non-smokers. The smoking-related HCC risk was most pronounced among those who had a susceptible allele of the CYP1A1 and a deficient genotype of glutathione S-transferase M1, which detoxifies PAH electrophilic metabolites produced by CYP1A1. In the absence of the Ile-Val variant allele, the Mspl polymorphism was still associated with smoking-related HCC. This study suggests that tobacco-derived PAHs play a role in HCC risk among chronic HBV carriers, and CYP1A1 polymorphism is an important modulator of the hepatocarcinogenic effect of PAHs. The Mspl and Ile-Val polymorphisms of CYP1A1 may have different mechanisms for increasing susceptibility to smoking-related HCC.

Background/aims: Chronic hepatitis C virus carriers may have repeatedly normal alanine aminotransferase activity despite detectable viremia and histological hepatitis. We aimed to evaluate the effect of interferon treatment in these cases., Methodology: Twelve patients with persistently normal alanine aminotransferase levels at least 6 months before therapy were treated with recombinant interferon (IFN)alpha-2b for 6 months, totaling 840 MU in amount. Alanine aminotransferase levels were measured monthly during treatment and after treatment withdrawal, and HCV-RNA levels were measured by polymerase chain reaction before treatment, and 6 and 12 months after treatment withdrawal., Results: At treatment withdrawal, HCV-RNA levels had significantly decreased and HCV-RNA disappeared in 9 of the 12 patients by polymerase chain reaction. At 6 months after treatment withdrawal, HCV-RNA reappeared in 6 of the 9 patients whose HCV-RNA was negative at treatment withdrawal. Over all, only 4 of the 12 patients (33%) were sustained virological responders (HCV-RNA is negative more than 6 months after treatment withdrawal). Pre-treatment HCV-RNA levels in a sustained virological responder was significantly lower than that of transient and non-responders (4.9 +/- 1.6 vs. 7.7 +/- 1.6 log10[copies/ml], p < 0.05). Of 8 patients who did not achieved sustained virological response, alanine aminotransferase levels had transiently increased above normal during treatment in one patient and after treatment withdrawal in 6 patients; however, in the remaining one patient abnormal values have continued from 8 months after treatment withdrawal till now for 24 months., Conclusions: In patients with chronic hepatitis C with normal alanine aminotransferase levels, the response to interferon therapy was by no means satisfactory. However, if it would be used in cases with the lower pre-treatment HCV-RNA levels with careful attention to a transient alanine aminotransferase elevation, the more a sustained virological response might be expected.

This study was aimed to evaluate demographic, clinical, histological, and virological characteristics of 46 hepatitis C virus (HCV) carriers with persistently normal alanine transaminase (ALT) levels and to compare the results with those obtained in a group of 52 HCV-RNA-positive patients with elevated ALT levels. Subjects with normal ALT were more often females (P < .001), were more likely to be asymptomatic (P < .001), and have a lower incidence of risk factors for HCV transmission (P < .01). All patients with normal ALT had significant histological liver damage. The mean grading and staging did not differ between patients with normal and those with raised ALT concentrations. Moderate to severe hepatitis was more frequently found among subjects with normal than with elevated ALT. HCV genotype 2a was far more common in subjects with normal (43%) than with abnormal ALT levels (6%; P < .002), genotype 1b being more frequent in these latter (50% vs. 17%; P < .001). Patients with normal ALT levels had similar serum HCV-RNA titers than subjects with raised ALT. Neither HCV genotype distribution nor viral load correlated with the severity of liver damage. We conclude that significant liver disease may occur irrespective of clinical symptoms, ALT levels, HCV genotypes, and viral load.

Fifty percent of healthy hepatitis B surface antigen carriers may have histologically proven chronic hepatitis. Our aim was to study the benefit of interferon-alpha in healthy patients. Twenty-nine hepatitis B surface antigen carriers with normal liver enzymes and with serum hepatitis B virus DNA were randomized into two groups: Group I, 14 patients treated with 9 megaunits of interferon alpha-2a thrice weekly for six months, and Group II, 15 control patients. A liver biopsy was obtained from each patient at study initiation. A second biopsy was available in nine treated patients and six controls. During treatment, a significant increase in alanine amino transferase levels was observed in treated patients as compared with the controls (P < 0.05). After treatment, transaminase levels decreased to normal values. No differences between treated and control patients were observed in clearance of hepatitis B virus markers. A significant increase in the total histological activity index between base line and final liver biopsies was observed in treated patients (P < 0.05). It is concluded that interferon alpha treatment may induce a biochemical and histological activation of liver disease. Accordingly, interferon alpha should not be administered to healthy hepatitis B surface antigen carriers, at least with the schedule used in this work.

This study was carried out to elucidate the effect of glutathione S-transferase (GST) Ml and Tl polymorphisms on the aflatoxin-related hepatocarcinogenesis among chronic carriers of hepatitis B surface antigen (HBsAg). A total of 32 newly diagnosed hepatocellular carcinoma (HCC) cases and 73 age-matched controls selected from a cohort of 4,841 chronic HBsAg carriers who had been followed for 5 years were studied. The level of aflatoxin B1 (AFB1)-albumin adducts in their serum samples collected at the recruitment was examined by competitive enzyme-linked immunosorbance assay, and genotypes of GST M1 and T1 were determined by PCR. There was a dose-response relationship between serum level of AFB1-albumin adducts and risk of HCC. The biological gradients between serum AFB1-albumin adducts level and HCC risk were observed among chronic HBsAg carriers who had null genotypes of GST M1 and/or T1 but not among those who had non-null genotypes. The multivariate-adjusted odds ratios of developing HCC for those who had low and high serum levels of AFB1-albumin adducts compared with those who had a undetectable adduct level as the referent (odds ratio = 1.0) were 4.1 and 12.4, respectively, for HBsAg carriers with null GST M1 genotype (P < .01, on the basis of the significance test for trend); 0.7 and 1.4 for those with non-null GST Ml genotype (P = .98); 1.8 and 10.2 for those with null GST T1 genotype (P < .05); and 1.3 and 0.8 for those with non-null GST T1 genotype (P = .93). The interaction between serum AFB1-albumin adduct level and polymorphisms of GST M1 and T1 was at marginal statistical significance levels (.05 < P < .10).

The hepatitis B surface antigen (HBsAg) carrier state is associated with changes in hepatocellular function involving the cytochrome P450 (CYP) system. Among this system, CYP1A2 enzyme plays an important role in chemical carcinogenesis and in the metabolism of several drugs. We have thus investigated CYP1A2 function using two 14C-caffeine breath tests (3-methyl-14C; C3BT and 7-methyl-14C caffeine; C7BT) in 12 HBsAg healthy carriers and 8 healthy volunteers matched for 14C-aminopyrine breath test values. HBsAg carriers exhibited lower C3- and C7BT values than normal controls. This difference, however, did not reach statistical significance except for C7BT values normalised for aminopyrine breath test values. Our data thus do not support the association between viral presence and CYP1A2 dysfunction.

To determine when the precore mutation at the 83rd nucleotide occurs, leading to the formation of a stop codon in the hepatitis B virus genome in carriers, which would indicate the presence of antibody to hepatitis B e antigen (anti-HBe), we investigated this mutation by direct sequencing and subcloning in 22 young hepatitis B antigen (HBeAg) (+) carriers. These subjects were 7-17 years old and were found during a survey for hepatitis B surface antigen (HBsAg) in three elementary schools, a junior high, and a senior high school. None of these carriers had clinical manifestations, although one-third of them had elevated serum alanine aminotransferase levels. All were HBeAg-positive by radioimmunoassay (RIA), and 6 of them had preserved titers of anti-HBe at the same time. Precore mutations were found in 4 subjects (18.2%), with predominance of the wild type. Although 3 of these 4 had preserved titers of HBeAb, the other had no HBeAb titers. In an other 3 subjects with preserved titers of HBeAb, the precore mutation was not detected, even after the subcloning of viral DNA. The remaining 15 subjects with HBeAg showed no precore mutation. Subjects with ALT levels exceeding 100 IU/l were all HBeAg-positive without the mutation. It was clear that the precore mutation itself occurred in the subjects at an early age during the course of infection. However, the chronological relationship between the emergence of the precore mutation and the onset of hepatitis requires further study.

To study steroid sulfatase activity in women in the field of obstetrics and gynecology, especially to differentiate carrier women with steroid sulfatase deficiency (recessive X-linked ichthyosis, RXLI) from normal women, steroid sulfatase activity was assayed in peripheral blood leukocytes from normal nonpregnant women, pregnant women, patients with RXLI, carriers of RXLI and in other normal males of different age. Steroid sulfatase activity in pmol/mg protein/min was significantly lower in patients with RXLI than in the other groups and significantly higher in the 3rd trimester pregnant women than in nonpregnant women and adult men. In addition, sulfatase activity was significantly higher in the 3rd trimester pregnant women than in fetuses. However, it was difficult to differentiate carrier women with RXLI from normal women because of considerable overlap between the two groups. The biochemical control mechanism of steroid sulfatase is the subject of further research.

Studies were undertaken to investigate whether interferon therapy could induce hepatitis C virus (HCV) carriage with normal serum alanine aminotransferase (ALT) values using an assay that combined reverse transcription and polymerase chain reaction. The subjects studied were 53 patients with chronic active hepatitis C who received interferon (alpha, 33 cases; beta, 20 cases) therapy. All were seropositive for HCV RNA prior to therapy. In all 22 complete responders, whose ALT levels fell to normal during therapy and for at least 24 weeks after therapy, HCV RNA became persistently negative except in two cases. The two had sustained viremia on treatment and for 1.0-1.5 years of follow-up, although their biochemical tests were normal. In 15 patients with a transient response in whom the disease recurred when interferon was stopped, HCV RNA was undetectable in 80% of the cases at the end of therapy, but the virus reappeared with subsequent elevation of ALT in all patients. However, 3 patients in this group had normal enzyme levels with viremia for 2.1-2.8 years of follow-up after acute deterioration of illness. In 16 patients who did not respond to interferon, HCV RNA was persistently positive during and after therapy. These findings suggest that interferon therapy induces a long-term carrier state of HCV infection with normal ALT levels in some patients.

This study followed 314 children who were carriers of hepatitis B virus for 2 to 4 years and compared them with noncarriers, matched for age and sex, from the same community. No confirmed carrier lost hepatitis B surface antigen. Hepatitis B e antigen (HBeAg) was lost at a rate of 10.6% per year; the rate of decay was not affected by age or gender. Liver enzymes were higher in HBeAg-positive than in HBeAg-negative carriers and loss of HBeAg was usually followed by return to values in the normal range. There was evidence, however, of persistent mild liver dysfunction in carriers even after development of antibody to HBeAg. Serum alanine aminotransferase concentrations above twice the upper limit of normal were observed in 7% of carriers on at least one occasion but persisted for more than 1 year in less than 1% and clinical manifestations were rare. The hepatitis B carrier state was uncomplicated during the course of this study. However, risks of subsequent serious disease in adult life may be significant and continued surveillance of carriers is important for individual protection and to determine adverse prognostic features.

The acetylcholinesterase (AChE) activity was measured in human serum from persons infected with the filarial parasite Wuchereria bancrofti. The asymptomatic microfilaremic serum showed five times increase in AChE-activity as compared with normal serum, whereas only little difference was observed in serum from patients with elephantiasis. Similar results were obtained when the enzyme activity was measured in the immune complexes precipitated with polyethyleneglycol. Further, the effect of the antifilarial drug diethylcarbamazine (DEC), on the AChE activity of infected and normal serum was studied in in vivo and in vitro experiments. In vitro, DEC was found to be effective only with respect to AChE from asymptomatic microfilaremic serum where 75% decrease in enzyme activity was observed at 100 mumol. The oral administration of DEC (5 mg/kg of body weight/day) effected the activity of AChE from microfilaremic serum as shown after 1 hr, 1 and 3 weeks. A regular decrease in enzyme activity of asymptomatic microfilaremic serum was observed. By increasing time periods and after three weeks the level of AChE reaches the normal value. In vitro and in vivo the same concentration of DEC has negligible effect on the normal serum suggesting that in case of asymptomatic microfilaremic serum the increased activity of AChE is different in nature than the host acetylcho-[abstract incomplete in journal]

The aim of the study was to test the clinical value of HBV DNA polymerase (DNAp) determination in patients with various forms of HBV infection, namely: acute hepatitis, chronic hepatitis, cirrhosis and healthy HBV carriers. The determination of DNAp was found to be particularly useful in patients with chronic HBV infection with active virus replication (HBeAg+) independent of histopathological changes.

Four healthy calves were inoculated with Pasteurella haemolytica serotype 1 by instillation of a broth culture into the middle nasal meatus of the left nostril. Four weeks later, calves were exposed to infectious bovine rhinotracheitis virus by aerosol into both nostrils. All calves became ill, from approximately day 3 through day 10 after virus exposure, and shed increased amounts of nasal mucus. Two calves were induced to shed P haemolytica by the virus infection, and 2 calves required reinoculation with P haemolytica for nasal passages to become actively colonized. Elastase activity in nasal mucus increased about 15-fold within 3 days and peaked about 60-fold over baseline by 7 days after virus exposure. Activity of N-acetyl-beta-D-glucosaminidase, a measure of cell damage and serum leakage, increased slightly by day 3 and reached plateau on day 5, almost threefold over baseline activity. Protein and carbohydrate content increased at a rate similar to that of N-acetyl-beta-D-glucosaminidase activity with about 12-fold and sixfold increases, respectively. None of the variables returned to baseline by 19 days after virus exposure. Increased elastase activity preceded colonization by P haemolytica and decreasing elastase activity preceded decreasing P haemolytica concentration in the nasal secretions. A causal relation between elastase activity and P haemolytica colonization could be mediated by cleavage of epithelial cell surface fibronectin and exposure of receptors.

Immunohistochemical analysis was performed in 21 patients with acute and chronic dysentery, in 32 patients with different forms of salmonellosis in comparison with the cytoenzymatic status (CES) of immunocytes in the mucous membrane of the large intestine. It has been revealed that for acute dysentery the activation of the cellular and humoral links of local immunity is typical, but for salmonellosis--mainly of the humoral one. The chronic processes in dysentery and salmonellosis are connected with the increase in the subpopulation of T8-suppressors. Immunohistochemical data correlate completely with CES of immunocytes and that allows one use them with prognostic purposes.

Serum deoxythymidine kinase (TK) was measured in 15 patients with the acute type of adult T-cell leukemia (ATL), in 4 with chronic ATL, in 10 with lymphoma type ATL, in 9 with pre-ATL, in 11 with human T-cell leukemia virus type I (HTLV-I) associated with myelopathy (HAM) and in 19 HTLV-I carriers. All these patients were positive for anti-HTLV antibody. The level of TK in pretreatment serum was highest in acute ATL (15.6-1600 U/l, median 107 U/l). It was elevated in chronic ATL (5.4-55.0 U/l, median 37.6 U/l) and lymphoma ATL (6.8-316 U/l, median 16.8 U/l) but normal in pre-ATL (1.8-4.7 U/l, median 2.8 U/l), HAM (1.2-6.0 U/l, median 3.0 U/l) and HTLV-I carriers (1.1-4.6 U/l, median 2.3 U/l). Statistical examination revealed a significant difference between the levels of acute ATL and chronic ATL/lymphoma ATL. In the patients of this series, a close correlation between the level of TK and lactic dehydrogenase (LDH) was statistically present (p less than 0.01). These facts indicate that TK level is a useful indicator of the aggressiveness of ATL cells.

The cytochemical study of lymphocytes and neutrophils isolated from fractionated blood of diphtheria patients and carriers has revealed that a decrease in the activity of lymphocyte succinic dehydrogenase and myeloperoxidase can be observed at all periods of the disease and in all its forms. A decrease in the activity of lymphocyte nonspecific esterase has been noted only in patients with toxic and subtoxic diphtheria and a decrease in the activity of neutrophil alkaline phosphatase, in carriers. The analysis of correlations between the parameters of five enzymes under study (lymphocyte succinic dehydrogenase, lymphocyte acid phosphatase, lymphocyte non-specific esterase, myeloperoxidase, neutrophil alkaline phosphatase) and enzymatic rosette parameters has been made. The analysis has revealed an essential increase in the number of correlations in comparison with donors, changes in the qualitative nature of these correlations and sometimes the reversion of the correlations. Carriers have shown the greatest number of correlations. By the end of the terms of observations no restoration of normal correlations has been observed.

Alanine transaminase (ALT) levels in healthy hospital personnel were studied. ALT levels in pre and post vaccinated sera were compared. In this study, all sera showed normal values of ALT, lower than 36 IU/L. Hepatitis B vaccination did not cause any change.

Twenty-six patients, positive for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B virus (HBV)-deoxyribonucleic acid (DNA), and DNA polymerase activity, were treated with human lymphoblastoid interferon (IFN-alpha) or human fibroblast interferon (IFN-beta) after enoxolone glycoside (glycyrrhizinic acid), given for four weeks and then withdrawn. The interferons were given continuously for four weeks. Four months after the treatment, six of 12 patients treated with IFN-alpha were both HBeAg-negative and HBV-DNA-negative while three of 14 patients treated with IFN-beta were HBV-DNA-negative and one was HBeAg-negative. None of the ten untreated control patients became negative for either HBeAg or HBV-DNA. All patients studied remained HBsAg-positive. Both interferons were generally well tolerated. A persistent low-grade fever was reported by more patients in the IFN-beta group and hair and weight loss were more common in the IFN-alpha group. The results indicate that the combination of enoxolone glycoside withdrawal and IFN-alpha treatment reduces HBV replication more effectively than does interferon alone.

A soluble DNA polymerase was purified 8,000-fold from hepatitis B surface antigen positive serum. The molecular weight of the enzyme by gel filtration was about 1.60 X 10(5), the sedimentation coefficient was 5.5S, the apparent Km for dTTP was 4 micrometer, the optimum pH in the presence of Mg2+ was 9.2, and the pl was 4.7. The enzyme was found in HBsAg-positive sera and required an external primer for activity. The properties of the DNA polymerase were different from hepatitis B virus particle enzyme and from vertebrate and bacterial DNA polymerases. The prevalence of this enzyme did not correlate with HBeAg or particle DNA polymerase in HBsAg-positive sera.

A new commercially available radioimmunoassay (RIA) (Abbott-HBeTM) was used for determination of hepatitis B e-antigen (HBeAg) and its antibody (anti-HBe). Serial serum samples from 20 transiently HBsAg-positive patients with acute hepatitis were tested. In nearly all patients HBeAg could be shown for a short period with subsequent development of anti-HBe. From 24 chronic HBsAg carriers serial serum samples collected during several years were tested. In 18 of 19 initially HBeAg-positive patients the HBeAg was lost after 6 months to 6 years; in 14 anti-HBe developed. A correlation was seen between the seroconversion and normalization of elevated alanine transferase levels. From another 22 chronic HBsAg carriers single serum samples were assayed. These samples were selected because neither HBeAg nor anti-HBe could be detected by the immunodiffusion (ID) technique. They had previously been examined for HBV-associated DNA-polymerase activity. In 20 patients HBeAg or anti-HBe could be detected by RIA. Those who were DNA-polymerase negative had anti-HBe, and 3 of 4 who were DNA-polymerase positive had HBeAg. When compared to earlier results by ID in these materials a higher frequency of HBeAg and, in particular, anti-HBe was detected by the RIA. By this test, HBeAg or anti-HBe was found in nearly all patients. The usefulness of HBeAg/anti-HBe in the evaluation of infectivity and prognosis in hepatitis B has been limited by the low sensitivity of the earlier test systems. Thus, this new RIA is a valuable addition to the diagnostic tests for patients with hepatitis B.

This report covers 7-year follow-up studies on 35 HBs Ag carriers whose anti-HBc titer levels were 10 (log 2) or more and who had normal liver functions at the start of the studies, when 9 of them (25.7%) were HBe Ag positive, 24 (68.6%) anti-HBe positive and 2 (5.7%) negative to both. 1. There was no significant difference in the incidence of abnormal SGPT levels as a whole between HBe Ag positives and anti-HBe positives. But abnormally high SGPT levels of 100 KU or more were observed at a higher percentage among HBe Ag positives (4/9. 44.4%) than among anti-HBe positives (1/24. 4.2%. p less than 0.02). 2. Based on the results of the 7-year studies, all cases were classified into six clinical stages. HBe Ag positives were divided into three groups by the stage with different SGPT levels: 5 cases (15.2%) whose SGPT leves never rose above 50 KU were classified as Stage 1; 3 cases with chronic active hepatitis (9.6%) whose highest SGPT levels were over 200 KU (2 new cases and 1 case with a relapse of chronic inactive hepatitis) as Stage 2 and 1 case (3.0%) seroconverted to anti-HBe positive following an acute relapse of chronic inactive hepatitis as Stage 3. Anti-HBe positives were divided into another three groups similarly according to their mean HBs Ag titer levels: 6 cases (18.2%) whose mean HBs Ag titer levels ranged from 10 to 13 (log 2) were classified as Stage 4; 13 cases (39.4%) whose mean HBs Ag titer levels ranged from 6 to 9 as Stage 5 and 5 cases (15.2%), including 2 cases turned negative to HBs Ag, whose mean HBs Ag titer levels were below 5 as Stage 6. The average age of each group increased wth its clinical stage, namely, 32.6 in Stage 1, 34.3 in Stage 2, 33.0 in Stage 3, 34.5 in Stage 4 and 37.0 in Stage 5, but the average age in Stage 6 was 29.0. 3. All HBe Ag positives showed fluctuations in HBs Ag titer levels. The fluctuations were particularly noteworthy among cases with chronic active hepatitis in Stage 2 during an acute relapse. The HBs Ag titers rose just before the acute relapses in a case of chronic active hepatitis when SGPT levels went over 200 KU. This suggested a proliferation of the virus. On the other hand, in anti-HBe positives, a decrement of the virus was suggested by the fact that an increasing proportion of cases showed their HBs Ag titer levels to fluctuate or to become lower with the progress of stages (p less than 0.05) and two cases turned negative to HBs Ag as plotted in Stage 6. And the proportion of cases with abnormal SGPT levels decreased with the progress of stages (p less than 0.05). One case whose SGPT level was 125 KU, highest among anti-HBe positives, followed the clinical course of chronic inactive hepatitis and lowered in HBs Ag titer. 4. Between HBe Ag and anti-HBe cases, there were considerable differences in the occurrence of liver disturbances and their clinical courses...

HBeAg/anti-HBe and Dane particle-associated DNA polymerase activity were detected in serum samples from 358 HBsAg asymptomatic carriers found during normal routine screening of 11,200 blood donors (HBsAg prevalence 3.1%). Since virus specific DNA polymerase activity and HBeAg seem to be associated in some way with hepatitis B virus infectivity and liver damage, 5% of the HBsAg carriers examined, as detected by the presence of HBeAg, and 9.5%, as shown by DNA polymerase activity, can be expected to have liver damage and a potential risk of transmitting hepatitis B to contacts. On the other hand, 48% of subjects were theoretically healthy and non-infective because of the presence of anti-HBe in their blood. The differentiation of groups of asymptomatic HBsAg carriers, on the basis of these serological markers, may have important clinical and epidemiological implications.