bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic Effectiveness of Serum Bile Acids in Liver Diseases as Evaluated by Multivariate Statistical Methods
Authors: Festi Davide , Labate Antonio Maria Morselli , Roda Aldo , Bazzoli Franco , Frabboni Roberto , Rucci Paola , Taroni Francesco , Aldini Rita , Roda Enrico , Barbara Luigi
Published: July 2010

The aims of this study were to determine the diagnostic effectiveness of fasting and postprandial serum bile acid determinations in liver diseases, and to compare results with those of conventional liver function tests.

In 322 patients with biopsy-proved liver disease and 93 healthy subjects, fasting and postprandial (2 hr) serum levels of cholic, chenodeoxycholic, and lithocholic acid conjugates and conventional liver function tests were evaluated. Data were subjected to variance and discriminant and factor analyses.

Fasting serum bile acids were higher in patients when compared to controls and were significantly higher in severe than in mild liver diseases. Determination of cholic plus lithocholic acid provided the highest discrimination capacity.

The percent of correct allocation was 75.4% for conventional liver function tests, 70.1% for fasting serum bile acids and increased to 79.6% when liver function tests plus serum bile acids were considered. Postprandial percentages were always lower than fasting. Factor analysis identified two factors possibly related to cytolysis and protein synthesis. The serum bile acid concentrations highly correlated with both factors.

We conclude that serum bile acid determinations increase the diagnostic and discriminant capacities of liver function tests and are more sensitive and discriminant when obtained in fasting than postprandially.
Hypouricemia and Hyperuricosuria as Expressions of Renal Tubular Damage in Primary Biliary Cirrhosis
Authors: Izumi Namiki , Hasumura Yasushi , Takeuchi Jugoro
Published: July 2010

Renal tubular damage, in particular, renal tubular acidosis is associated with primary biliary cirrhosis (PBC), but hypouricemia has not been described. We studied four patients with PBC whose serum uric acid levels were 1.4 to 1.8 mg per dl, and compared their renal and liver functions with those of 11 patients with PBC whose serum uric acid levels were normal. In the patients with PBC and hypouricemia, uric acid clearance (Cua) and the ratio of Cua and creatinine clearance (Cua/Ccr) were high enough to cause hypouricemia. Elevated Cua/Ccr was suppressed by administration of pyrazinamide, a blocker of tubular secretion of uric acid, but was not affected by probenecid; the effects of drugs on Cua/Ccr were similar to those reported in Wilson's disease. Elevation in Cua/Ccr was associated with increased serum bilirubin and urinary copper excretion. These observations indicate that hypouricemia and hyperuricosuria, which may be caused by defective postsecretory reabsorption of uric acid, are additional indicators of renal tubular damage in PBC.
Prognostic Factors in Cirrhosis Identified by Cox's Regression Model
Authors: Schlichting Poul , Christensen Erik , Andersen Per K. , Fauerholdt Lis , Juhl Erik , Poulsen Hemming , Tygstrup Niels
Published: July 2010

In a controlled clinical trial in 488 patients with chronic liver disease treated with prednisone or placebo, survival data were analyzed using Cox's proportional hazards model. A total of 162 variables were screened separately for prognostic and/or therapeutic effect by log-rank analyses, whereby 46 clinical, biochemical, serological, and histological variables were isolated. Another five variables traditionally found to be important in patients with liver disease were included. After extensively checking the assumptions of the model, the 51 variables were, by a step-wise procedure, reduced to a final model. It comprised, besides a treatment indicator, 12 variables with significant (p < 0.05) prognostic or therapeutic effect. The following eight variables had a significant prognostic effect: sex, age, prothrombin, acetylcholinesterase, eosinophil leucocytes in liver parenchyma, liver cell necrosis, inflammation in liver connective tissue, and efferent veins in parenchymal nodules. A prognostic index based on the final model is formed allowing calculation of 5 years survival probability. The usefulness of the prognostic index was tested by a cross-validation method, and no statistical significant difference was found between the estimated and observed survivorship functions.
Assessment of Prognostic Factors in Alcoholic Liver Disease: Toward a Global Quantitative Expression of Severity
Authors: Orrego Hector , Israel Yedy , Blake Joan E. , Medline Alan
Published: July 2010

The prognostic significance of a battery of clinical, laboratory, and histological indicators was assessed in relation to mortality risk in a 1-year study of 253 patients with alcoholic liver disease, of whom 51 died within such time. The relative risk associated with each abnormality was calculated. A number of abnormalities was found to be statistically associated with a higher risk of death. Among the clinical abnormalities, these were: collateral circulation, edema, ascites, encephalopathy, spider nevi, anorexia, and weakness. Among the laboratory tests, these were: albumin, bilirubin, hemoglobin, abnormal prothrombin time, and alkaline phosphatase. Two hundred and sixteen of these patients had liver biopsies in which the quantifiable abnormalities were scored. Among the histological findings, the alterations significantly related to mortality were necrosis, Mallory, and inflammation, while the presence of cirrhosis per se did not influence the mortality risk. The relative risk factors for mortality associated with the histological alterations were lower than those derived from clinical or laboratory measurements. The advantage of using only clinical and laboratory items to derive a global, quantitative expression of severity is discussed. The relative mortality risks provided a means of calculating a “unit of severity” for each clinical and laboratory abnormality. A combined clinical and laboratory index (CCLI) results when these mortality-risk units are added. Such a combined index had a quasi-linear relationship with the risk of mortality for the complete population. This method compared well with severity scores derived from computerized, linear step-wise discriminant function (SDF) analysis and from a logistic regression (LR) analysis. The factors chosen to have independent prognostic significance by the SDF analysis were: encephalopathy, albumin, prothrombin time, and hemoglobin, while only encephalopathy, albumin, and hemoglobin were chosen by the LR analysis. Within a range of values, LR can provide a good discrimination in relation to mortality, similar to that observed for the CCLI in its complete range. However, there are some advantages to the CCLI method vs. the LR or SDF analyses. The CCLI is less susceptible to being unduly influenced by a nonspecific effect of treatment on the items chosen than the SDF and LR analyses, as the CCLI contains a large number of factors. Obtaining a single-severity score such as the CCLI is of value in: (a) assessing the effectiveness of treatment modalities; (b) analyzing the success of randomization; (c) separating cohorts of different severity, and (d) comparing new liver tests, histological abnormalities, or specific biological events with the severity of alcoholic liver disease.
Histologic Studies of Severe Delta Agent Infection in Venezuelan Indians
Authors: Popper Hans , Thung Swan N. , Gerber Michael A. , Hadler Stephen C. , De Monzon Mario , Ponzetto Antonio , Anzola Elias , Rivera Dalia , Mondolfi Alejandro , Bracho Ana , Francis Donald P. , Gerin John L. , Maynard James E. , Purcell Robert H.
Published: July 2010

To supplement a detailed epidemiologic study of an outbreak of viral hepatitis in Venezuelan Indians in isolated valleys, apparently resulting from delta agent infection, 10 autopsy specimens were studied histologically and immunocytochemically, and five biopsy specimens were examined. The patients were children and young adults and predominantly males. A sequence of hepatitis from focal necrosis with conspicuous small-droplet steatosis, through massive necrosis, prolonged postnecrotic collapse to early cirrhosis with massive collapse was postulated. The histologic changes tentatively suggest a cytopathic effect of the delta agent without significant indication of lympho-cytotoxicity, at least in the parenchyma. Delta agent was demonstrated in hepatocyte nuclei in moderate amounts in the focal-necrotic stage and in isolated cells in the massive-necrotic stage, but in large amounts during the transition to cirrhosis. Whether these patients, in whom neither HBcAg nor HBsAg were demonstrable in the liver, suffered exclusively from superinfection of hepatitis B virus carriers and/or coinfection of hepatitis B virus with the delta agent remains to be resolved. Delta infection may occur in isolated settings with no relation to Italian origin, drug addiction, or polytransfusion. The infection is far more widely spread than previously assumed.
Cimetidine Does Not Reduce Liver Blood Flow in Cirrhosis
Authors: Henderson Michael J. , Ibrahim Shakir Z. , Millikan William J. , Santi Michael , Warren Dean W.
Published: July 2010

Cimetidine has been shown to reduce liver blood flow, as measured by indocyanine green clearance, in normal subjects. Concern over the potential deleterious effects of such reduction in cirrhosis led to the measurement of blood flow in 14 cirrhotics receiving oral or intravenous cimetidine. Liver blood flow was measured by the clearance of galactose at steady state during infusion of 40 mg per min. In six patients receiving 300 mg cimetidine by mouth each 6 hr for 4 days, basal flow (1,019 ± 186 ml per min) was not significantly altered by cimetidine (1,087 ± 156 ml per min). Intravenous infusion of cimetidine (300 mg) did not significantly alter flow in five patients betwen the basal (1,096 ± 334 ml per min) and treatment periods (1,051 ± 383 ml per min). Hepatic extraction of galactose in three patients (82 ± 19%) was not significantly altered by cimetidine infusion (81 ± 13%). The failure to reduce liver blood flow with cimetidine in this population may be due to their diminished proportion of portal venous flow, or alternatively suggests that histamine is not an important modulator of flow via H2 receptors. At a clinical level, the use of cimetidine in this population can continue without fear of further reduction in liver blood flow.
Sex Difference in Chronic Hepatitis B Virus Infection: An Appraisal Based on the Status of Hepatitis B e Antigen and Antibody
Authors: Chu Chia-Ming , Liaw Yun-Fan , Sheen I-Shyan , Lin Deng-Yn , Huang Miau-Ju
Published: July 2010

Hepatitis B e antigen (HBeAg) and antibody (anti-HBe) were studied by radioimmunoassay in consecutive series of 145 asymptomatic hepatitis B surface antigen (HBsAg) carriers, 389 patients with HBsAg-positive chronic liver disease and 194 patients with HBsAg-positive hepatocellular carcinoma, and compared between male and female subjects. The male to female ratio increased from 1.2 in asymptomatic carriers to 6.3 in chronic liver disease and 9.8 in hepatocellular carcinoma. Abnormal SGPT was much more frequently seen in male carriers than in females (p < 0.01). Contrary to female patients with chronic liver disease, the positive rate for HBeAg in males is lower and tended to decrease with increasing age. It is postulated that male patients with chronic hepatis B virus infection might have higher HBeAg clearance ability that resulted in more frequent hepatitis B virus DNA integration and subsequent development of hepatocellular carcinoma. However, the ultimate mechanism regulating this difference awaits further study.
Immunoregulatory T Cell Subsets in Chronic Hepatitis B Virus Infection: The Influence of Homosexuality
Authors: Regenstein Fredric G. , Roodman Stanford T. , Perrillo Robert P.
Published: July 2010

The purposes of this study were 2-fold: (i) To enumerate peripheral immunoregulatory T cell subsets in untreated patients with chronic hepatitis B virus (HBV) infection and (ii) to examine the relationship between disturbances in the balance of lymphocyte subsets with liver disease and the presence of homosexuality. Circulating T lymphocyte subsets were evaluated by monoclonal antibodies to the following cell antigens: OKT3 (total T cells), OKT4 (helper/inducer T cells), and 0KT8 (suppressor/cytotoxic T cells). The following groups of subjects were examined: (i) 16 heterosexuals with HBV-associated chronic active hepatitis (CAHB); (ii) 10 heterosexual, healthy HBsAg carriers, and (iii) 16 male homosexuals with CAHB. Controls included 51 healthy heterosexuals and 12 healthy, noninfected male homosexuals.

We were able to demonstrate that heterosexuals with CAHB had T4/T8 ratios which did not differ from those of noninfected heterosexuals. Both healthy carriers and healthy homosexuals, however, exhibited significantly lower T4/T8 ratios than did noninfected heterosexuals (p < 0.05, p < 0.01, respectively). In addition, homosexuals with CAHB had lower (1.5 ± 0.1) T4/T8 ratios than did heterosexuals with CAHB (2.0 ± 0.2).

A possible mechanism for these findings is discussed. The data indicate that the presence of homosexuality may be an important factor to consider when evaluating immunoregulatory subsets in CAHB.
Chronic Bile Duct Ligation in the Dog: Hemodynamic Characterization of a Portal Hypertensive Model
Authors: Bosch Jaime , Enriquez Rosa , Groszmann Roberto J. , Storer Edward H.
Published: July 2010

Splanchnic and systemic hemodynamics were measured in six normal dogs and in 18 dogs that had the bile ducts ligated for a period of 8 weeks. In the bile duct-ligated dogs, there was a decrease in arterial pressure (110 ± 4 mm Hg vs. normal 136 ± 6 mm Hg; p < 0.005) and peripheral vascular resistance (4.60 ± 0.38 vs. 6.28 ± 0.38 dynes-sec-cm−5; p < 0.02), and an increase in cardiac index (129 ± 7 vs. 98 ± 9 ml per min per kg; p < 0.05). The splanchnic hemodynamic characteristics in the bile duct-ligated dogs included an increase in portal venous pressure (13.3 ± 0.6 mm Hg vs. 6.7 ± 0.5 mm Hg; p < 001) and wedged hepatic venous pressure (14 ± 1.2 mm Hg), the development of extensive portal-systemic shunting (49 ± 10 vs. 0.03 ± 0.017c; p < 0.01), and a decrease in portal venous flow (194 ± 21 ml per min vs. 427 ± 21 ml per min; p < 0.001). This study demonstrated that chronic bile duct-ligated dogs develop sinusoidal portal hypertension with extensive portal-systemic shunting and a hyperdynamic systemic circulation. These findings closely resembled hemodynamic abnormalities observed in human cirrhosis and suggest that this model is useful in physiopathological and pharmacological studies of portal hypertension.
Exudative Ascites in the Course of Acute Type B Hepatitis
Authors: Viola Carmen , Vineta Lydia , Bosch Jaime , Rodés Juan
Published: July 2010

Two patients who presented with an exudative ascites in the course of typical acute type B hepatitis are reported. In one of them, ascites was associated with an exudative pleural effusion. In both patients, the clinical course of the hepatitis was uneventful, and ascites and pleural effusion disappeared spontaneously. Portal hypertension and common causes of exudative ascites were excluded. It is suggested that the development of exudative ascites in these patients represent a hitherto unrecognized manifestation of the hepatitis itself.
Hepatic Imaging: Positron Emission Tomography, Digital Angiography, and Nuclear Magnetic Resonance Imaging†
Authors: Aisen Alex M. , Martel William , Glazer Gary M. , Carson Paul L.
Published: July 2010

Major advances in diagnostic imaging of the human body have been made in recent years. Positron emission tomography, a technique founded on advances in radiopharmaceuticals and radionuclide imaging apparatus, permits imaging regional metabolism, metabolite distribution, and flow. Thus far, its major applications have been in the study of the brain, and to a lesser extent, the heart; however, it is also finding a role in the study of the liver. Digital angiography is being applied to fluoroscopic systems which permits visualization of relatively low doses of intravascular iodinated radiographic contrast media. Imaging of the major arteries is possible using simple intravenously administered contrast media; digital techniques also increase the diagnostic yield in intraarterial studies. Nuclear magnetic resonance (NMR) imaging is an outgrowth of laboratory NMR spectroscopy; the interaction of radiofrequency signals with nuclei in strong magnetic fields permits imaging the distribution and certain chemical properties of various isotopes. Hydrogen NMR imaging is proving most useful for clinical diagnosis. The techniques used to image hydrogen are also being applied to NMR spectroscopy in vivo of various isotopes, including carbon-13, phosphorus-31, and hydrogen-1.
Recommendations for identification and public health management of persons with chronic hepatitis B virus infection #
Authors: Weinbaum Cindy M. , Mast Eric E. , Ward John W.
Published: July 2010

Early identification of persons with chronic HBV infection enables infected persons to receive necessary care to prevent or delay onset of liver disease, and enables the identification and vaccination of susceptible household contacts and sex partners, interrupting ongoing transmission. Testing has been recommended previously to enable primary prevention of HBV infection among close contacts for pregnant women, household contacts and sex partners of HBV-infected persons, persons born in countries with hepatitis B surface antigen (HBsAg) prevalence of more than 8%, persons who are the source of blood or body fluid exposures that might warrant postexposure prophylaxis (e.g., needlestick injury to a healthcare worker or sexual assault), and to enable appropriate treatment for infants born to HBsAg-positive mothers and persons infected with human immunodeficiency virus. Recently, with the increasing availability of efficacious hepatitis B treatment, the Centers for Disease Control and Prevention published new recommendations for public health evaluation and management for chronically infected persons and their contacts and extended testing recommendations to include persons born in geographic regions with HBsAg prevalence of greater than 2%, men who have sex with men, and injection drug users. Patient and provider education, developing partnerships between health departments and community organizations, and other resources will be needed to assure appropriate populations are tested and care provided for persons newly identified as HBsAg-positive. (Hepatology 2009;49:S35–S44.)
Hepatitis B and human immunodeficiency virus coinfection #
Authors: Thio Chloe L.
Published: July 2010

Coinfection with human immunodeficiency virus-1 (HIV) and hepatitis B virus (HBV) is common; worldwide, an estimated 10% of HIV-infected persons have chronic hepatitis B. Because the incidence of traditional acquired immunodeficiency syndrome–related opportunistic infections has decreased with successful anti-HIV therapy, liver disease has emerged as a leading cause of morbidity and mortality in HIV-infected individuals. HIV infection negatively impacts all phases of the natural history of hepatitis B leading to increased rates of persistent infection, higher HBV DNA levels, lower rates of hepatitis B e antigen loss, increased cirrhosis and liver-related mortality, and increased risk of hepatocellular carcinoma at lower CD4+ T cell counts. The management of hepatitis B in HIV infection is complicated by the dual activity of several nucleoside analogs, the more rapid development of lamivudine-resistant HBV in patients who are HIV-positive, and the paucity of studies in this population. Until further research emerges on the optimal treatment for this population, data from HBV monoinfected persons will need to be extrapolated to the HIV-HBV coinfected population. Further research is also needed to determine the mechanism(s) for the increased liver disease progression and optimal treatment goals. (Hepatology 2009;49:S138–S145.)
Hepatitis B virus DNA levels and outcomes in chronic hepatitis B # †
Authors: Chen Chien-Jen , Yang Hwai-I , Iloeje Uchenna H.
Published: July 2010

Serum hepatitis B virus (HBV) DNA levels can fluctuate markedly during the course of chronic HBV infection. Both case-control and cohort studies have shown a significant, dose-response association between serum HBV DNA levels measured at the time of initial evaluation and the subsequent risk of cirrhosis. A similar direct relationship has been shown for the risk of hepatocellular carcinoma (HCC) in cross-sectional, case-control, and cohort studies. Interventional studies have shown a strong correlation between the indices of disease activity seen on liver biopsy and levels of serum HBV DNA. These studies have also shown that reduction in HBV DNA levels correlate strongly with improvements in liver histology. For patients with HCC, prognosis (including risk of death, metastasis, and recurrence following surgery) is worse with higher serum HBV DNA levels. The preponderance of the evidence in the published literature demonstrates that serum HBV DNA level is an important and independent risk factor for disease progression in chronic hepatitis B. The relative importance of serial HBV DNA measurements, the loss of hepatitis B e and surface antigens, as well as the emergence of HBV mutants in the progression of chronic hepatitis B, especially in young patients, is an important need for future research. (Hepatology 2009;49:S72–S84.)
The natural history of chronic hepatitis B virus infection #
Authors: McMahon Brian J.
Published: July 2010

Chronic hepatitis B virus (HBV) infection has a complicated course. Three phases are identified: an immune tolerant phase with high HBV DNA and normal alanine aminotransferase (ALT) levels associated with minimal liver disease; an immune active phase with high HBV DNA and elevated ALT levels with active liver inflammation; and an inactive phase with HBV DNA levels < 2000 IU/mL and normal ALT levels with minimal inflammation and fibrosis on liver biopsy. Affected persons can move progressively from one phase to the next and may revert backward. The primary adverse outcomes of chronic HBV infection are hepatocellular carcinoma (HCC) and cirrhosis. Published natural history studies were reviewed and ranked by the strength of evidence regarding the study design. Factors with the highest evidence of risk for development of HCC or cirrhosis from population-based prospective cohort studies include male sex, family history of HCC, HBV DNA level above 2000 IU/mL in persons above age 40, HBV genotypes C and F, and basal core promoter mutation. Those with the next highest level of evidence include aflatoxin exposure, and heavy alcohol and tobacco use. Improved methods to identify persons at highest risk of developing HCC or cirrhosis are needed to allow intervention earlier with antiviral therapy in appropriate patients. Future studies should include prospective follow-up of established population-based cohorts as well as new cohorts recruited from multiple centers stratified by HBV genotypes/subgenotypes and clinical phase to determine the incidence of the various HBV phases, HCC, and cirrhosis. Also, nested case-control studies assessing immunological and host genetic factors among persons with active and inactive disease phases, HCC, and cirrhosis could be conducted using these types of cohorts. (Hepatology 2009;49:S45–S55.)
Monitoring during and after antiviral therapy for hepatitis B #
Authors: Andersson Karin L. , Chung Raymond T.
Published: July 2010

Recent studies suggest that long-term suppression of viral replication is critical to reducing the complications of chronic hepatitis B virus (HBV) infection. Monitoring for continued virological response during and after treatment is essential because current treatment options have limited success in achieving durable endpoints, and antiviral resistance may emerge during long-term therapy. Methods of monitoring treatment response include tests for serum aminotransferase levels, HBV DNA level, hepatitis B e antigen (HBeAg) and antibody (anti-HBe), hepatitis B surface antigen (HBsAg) or antibody (anti-HBs), and liver histology. Virological suppression and loss of HBeAg or HBsAg with or without seroconversion play a prominent role in decision-making regarding the success and duration of antiviral therapy. Guidelines recommend that testing for serum markers be repeated every 12-24 weeks during antiviral therapy and every 6-12 months afterward. Recent data also suggest that serum HBV DNA levels should be assessed at weeks 12 and 24 of therapy, because early viral response may predict the likelihood of sustained response and antiviral resistance. The use of serum HBV DNA levels for this purpose requires an assay with a wide range of quantification, such as real-time polymerase chain reaction assays, which have a 7-8 log10 dynamic range. Newer, investigational methods for monitoring treatment response include quantitative measurement of HBsAg, HBeAg, and intrahepatic covalently closed circular DNA. Conclusions: Better methods for defining durable treatment endpoints are needed. Other areas requiring further research include the optimal treatment duration and the establishment of the optimal use of early viral kinetics for decision-making during antiviral therapy. (Hepatology 2009;49:S166–S173.)
Antiviral resistance and hepatitis B therapy #
Authors: Ghany Marc G. , Doo Edward C.
Published: July 2010

The management of chronic hepatitis B currently rests with long-term therapy using oral nucleoside analogs. The major limitation of long-term therapy is antiviral resistance. Antiviral resistance is due to the high rate of mutations that can occur during hepatitis B virus (HBV) replication and the selection of these mutants due to a replication advantage in the presence of the antiviral agent. Indeed, high rates of antiviral resistance have been found with long-term use of lamivudine, in up to 76% of patients treated for 5 years or more. Rates of antiviral resistance are lower with adefovir therapy, ˜30% at 5 years. Newer more potent nucleoside analogs (tenofovir and entecavir) have proven to have much lower rates of antiviral resistance (<1% after 2 years in treatment-naïve subjects), but the long-term rates of resistance have yet to be fully defined. The appearance of these viral mutations (genotypic resistance) is usually followed by rises in HBV DNA levels (virological breakthrough) and then by rises in serum aminotransferase levels (biochemical breakthrough). The appearance of antiviral resistance can be accompanied by a transient but occasionally severe exacerbation of the underlying liver disease which in some instances has led to acute liver failure. Combinations of nucleoside analogs may offer an approach to preventing antiviral resistance, but the efficacy and safety of this approach have yet to be shown. A future research priority is to identify new agents active against HBV that target different steps in the viral life-cycle and might provide effective means to circumvent the antiviral resistance of nucleoside analogs. (Hepatology 2009;49:S174–S184.)
Benefits and risks of nucleoside analog therapy for hepatitis B #
Authors: Dienstag Jules L.
Published: July 2010

Five oral agents have been approved for the treatment of chronic hepatitis B, ranging in virological potency, clinical efficacy, barrier to resistance, and side-effect profile. The degree of histological, biochemical, and serological improvement with therapy generally corresponds to the degree of suppression of serum hepatitis B virus (HBV) DNA achieved with therapy. Conversely, for agents with a low barrier to resistance, the profundity of HBV DNA suppression in individual patients correlates inversely with the likelihood of resistance. The durability of hepatitis B e antigen (HBeAg) responses after a consolidation period of an additional 6–12 months of therapy is ˜80% in western populations, lower in Asian populations. Loss of hepatitis B surface antigen (HBsAg) during a year of oral-agent therapy is limited, except with the most potent agents, but extending therapy for a second year and beyond can yield frequencies of HBsAg responses close to those reported in trials of interferon-based therapy. The oral agents are approved for 1–2 years of therapy, but treatment is continued indefinitely in the majority of patients (except for the ˜20% of patients who are HBeAg-reactive who achieve a durable HBeAg response). HBeAg responses and virological/biochemical benefit continue to be maintained and to increase with continued therapy beyond the first year. Data continue to accumulate supporting the link between long-term HBV DNA suppression and reduction in hepatic fibrosis, hepatic decompensation, and liver-related mortality. All the benefits of a single year of injectable peginterferon therapy can be achieved with the newer, low-resistance oral agents continued beyond the first year, without interferon side effects. Future studies are needed to develop drug regimens that are even more effective in achieving clinical endpoints, that are not hampered by resistance, and that are more confined in treatment duration but are more durable. (Hepatology 2009;49:S112–S121.)
Clinical outcomes in adults with chronic hepatitis B in association with patient and viral characteristics: A systematic review of evidence # †
Authors: Taylor Brent C. , Yuan Jian-Min , Shamliyan Tatyana A. , Shaukat Aasma , Kane Robert L. , Wilt Timothy J.
Published: July 2010

We systematically reviewed the literature on the extent to which population characteristics or clinical features predict groups of individuals likely to develop advanced liver disease or die from chronic infection with hepatitis B virus (HBV). We searched Medline to include studies with reported cirrhosis, liver failure, liver cancer, or death outcomes after at least 1 year of follow-up from the measurement of predictive factors (age, age at infection, geographic location, race/ethnicity, sex, positive family history, presence of coinfections, HBV viral level, change in hepatitis B e antigen [HBeAg] status, genotype, HBV mutations, nonalcoholic fatty liver disease, alcohol consumption, liver enzymes, and liver biopsy finding). Evidence from 41 included articles suggested that cirrhosis, higher HBV viral level, and male sex were consistently associated with significantly increased risk of death and liver cancer. Evidence about the role of HBV genotype, HBeAg status, age and duration of infection, coinfections with hepatitis C virus, human immunodeficiency virus, hepatitis delta virus, and alanine aminotransferase levels were limited and inconsistent, but were deemed promising to identify patients at higher risk of clinical outcomes. Adults with chronic hepatitis B had increased risk for poorer health outcomes compared to the general population; however, the magnitude of risk varied greatly depending on baseline patient and disease characteristics, and typically clinical outcomes required many years to become manifest. Many adults with chronic hepatitis B had low absolute risks of clinical outcomes and likely would not benefit from immediate treatment. Baseline patient and disease characteristics provide important information about the risk of clinical outcomes and should be incorporated into monitoring or treatment decisions. (Hepatology 2009;49:S85–S95.)
Liver biopsy findings in chronic hepatitis B #
Authors: Mani Haresh , Kleiner David E.
Published: July 2010

Liver biopsy plays a central role in treatment algorithms in patients with hepatitis B and remains the gold standard for evaluating hepatic pathology. The pathology of hepatitis B is diverse and reflects the natural history of infection. An acute hepatitic pattern with lobular disarray is seen in acute infection, during acute flares of disease, and with acute hepatitis D superinfection. In chronic hepatitis B, inflammation is less pronounced in the immune-tolerant phase and is prominent during immune-mediated viral clearance. Active inflammation appears to be the driving force for development of fibrosis. Inflammatory grades and fibrosis stage are assigned as is done for hepatitis C. Although current management guidelines recommend liver biopsies only in select patients based on age, viral levels, and hepatitis B e antigen status, these clinical and biochemical parameters do not show consistent correlations with liver histology. Liver biopsy also helps identify preneoplastic lesions including large cell and small cell change. Unlike in other causes of chronic hepatitis, immunostains are widely used and can help determine the phase of infection. Liver biopsies can also identify additional pathology that may contribute to liver disease such as steatohepatitis, iron overload, autoimmune hepatitis, and drug-induced injury. Thus, liver biopsy can play an important role in staging and grading chronic hepatitis B and should be more widely used in assessing the need for therapy. (Hepatology 2009;49:S61–S71.)
Epidemiology of hepatitis B in the United States #
Authors: Kim Ray W.
Published: July 2010

Hepatitis B virus (HBV) remains an important cause of acute and chronic liver disease globally and in the United States. An encouraging trend is that the incidence of acute hepatitis B in the United States declined as much as 80% between 1987 and 2004, attributable to effective vaccination programs as well as universal precautions in needle use and in healthcare in general. Although encouraging, these decreases in acute infections have not translated into diminished prevalence or burden of chronic HBV infection. The prevalence for HBV in the United States has been estimated to be approximately 0.4%. However, these estimates have been based on surveys conducted in samples in which population groups with high prevalence of HBV infection, namely foreign-born minorities, were underrepresented. Voluntary screening data indicate prevalence in excess of 15% in some of these groups. Recent immigration trends suggest a substantial increase in the number of Americans with chronic HBV infection. This trend is reflected in the health and economic burden associated with HBV infection. The number of outpatient visits and hospitalizations for a HBV-related diagnosis increased several-fold during the 1990s. Similarly, the total charges for hospitalizations have been estimated to have increased from $357 million in 1990 to $1.5 billion in 2003. Most recent data indicate that death and liver transplant waitlist registration for HBV-related liver disease, which had been increasing, have now reached a plateau or started to decline. This encouraging trend might be attributable to recent advances in treatment for HBV infection; however, to the extent that the number of Americans living with chronic HBV is growing, careful clinical monitoring and continued epidemiologic surveillance remain important. (Hepatology 2009;49:S28–S34.)
Evaluation of the patient with hepatitis B #
Authors: Rotman Yaron , Brown Thomas A. , Hoofnagle Jay H.
Published: July 2010

The initial evaluation of a patient with hepatitis B virus infection should attempt to assess the disease activity and stage in the context of the known natural history of this infection and to properly assess the needs for treatment and surveillance. In addition to a medical history and focused physical examination, the initial evaluation usually requires serological, biochemical, and virological tests to confirm the diagnosis as well as an imaging study to establish a baseline for future monitoring. A liver biopsy is generally not needed but can provide useful information on prognosis, need for surveillance for hepatocellular carcinoma (HCC), and whether to recommend therapy. Follow-up monitoring is aimed at determining disease progression, development of complications, and reassessing the need for treatment. Monitoring frequency should be determined based on the activity and stage of disease. Initiation of screening for HCC should be based on age, race, sex, family history, and stage and duration of disease. The current recommended method of screening and surveillance for HCC is by ultrasonography and alpha-fetoprotein measurements every 6–12 months. Prospective studies are needed to evaluate the role of longitudinal application of noninvasive assays of fibrosis, such as serum fibrosis markers and transient elastography. Better biomarkers and imaging modalities are needed for early detection of HCC. Finally, studies are needed to better refine the indications and to balance the risks and benefits of antiviral therapy. (Hepatology 2009;49:S22–S27.)
The mechanical properties of films. II. The glass/rubber transition temperature
Authors: Holt T. , Bridge L. , Simpson W.
Published: July 2010

A mechanical method of investigating transitional behaviour is described in which the stress developed in supported polymer films is observed as a function of temperature. The method has given information on transition temperatures which has been useful in work involving the dynamic elastic properties of the polymers and the WLF equation. The method is not sufficiently sensitive to resolve all the transitions observed dilatometrically and an empirical method of ‘averaging’ the latter gave results consistently 10–15°c higher than the ‘mechanical’ value.
The loss of mercury from fungicidal paints
Authors: Taylor C. G.
Published: July 2010

Reports have indicated that the use of mercury compounds as fungicides in paints may lead to poisoning of persons spending long periods in proximity to these paints. The loss of mercury from a typical fungicidal paint has been measured over a three‐month period by a radioactive tracer technique. Results indicate that, although loss occurs, its rate is not likely to cause, in a normal sized, adequately ventilated room, a concentration of mercury greater than the maximum accetable level for adult exposure.
Reactions of benzene in a microwave discharge reactor
Authors: Brooks B. W. , Sambrook R. M.
Published: July 2010

A study has been made of the reactions of benzene in a continuous‐flow microwave‐discharge reactor. The distribution of reaction products was found to depend on the reactor pressure and flow‐rate. By accounting for all reaction products (solid, liquid and gas) an overall mass balance was obtained. The reactions are not the result of simple pyrolysis.

The insertion of nickel wire into the reactor enhanced the reactions which proceed via a radical—radical mechanism. The addition of carbon dioxide to the benzene feed appeared to retard reactions which involve highly energetic ionisation processes. Thus, the presence of carbon dioxide changed the reaction selectivity. The carbon dioxide did not react chemically.

Comparison with other work with benzene shows that the behaviour of this reactor system is significantly different from the behaviour of reactors which operate at a lower frequency. It is suggested that the distribution of electron energies in the microwave discharge is narrower than the energy distributions which are encountered in lower‐frequency and d.c. discharges.
Kinetics of benzene hydrogenation by supported nickel at low temperature
Authors: Kehoe J. P. G. , Butt J. B.
Published: July 2010

A study of the kinetics of benzene hydrogenation at low temperatures is described which confirms and completes the present fragmentary information available in the literature. Such analysis may also be useful for the purposes of using the reaction as a model system in studies of reaction engineering problems.

The results are consistent with a Rideal mechanism for the hydrogenation, proceeding via the molecular addition of hydrogen to adsorbed benzene. The very strong adsorption and the range of conditions over which zero order kinetics with respect to benzene are found support the π‐bonding theory for benzene chemisorption.
Continuously synchronised growth
Authors: Dawson P. S. S.
Published: July 2010

The advent of cell synchrony as a refinement in technique for cultivating microbes has given new dimensions to the study of microbial growth.

By wedding synchrony to continuous culture, it becomes possible to convert and resolve the invariant (steady state) performance of asynchronous growth in a chemostat into a recognisable pattern of (cell cycle) activity, which repeats continually and occupies the mean doubling time periods of the cells growing in synchrony in a continuously synchronised culture. In this way, microbial growth and metabolism in a culture can be considered in terms of the individual cell instead of being related to the statistical mean of the cell population.

Growth, continuous growth and continuously synchronised growth are considered in relation to these developments and an approach is made to account for the “physiological state”.
Kinetics of the vapour‐phase dehydrogenation of cyclohexane over palladium catalyst in a continuous stirred tank reactor
Authors: Rouleau D. , Klvana D. , Sang J.
Published: July 2010

The catalytic vapour‐phase dehydrogenation of cyclohexane has been investigated over a surface coated palladium catalyst in a continuous stirred tank reactor between 482 and 644°F and at different partial pressures (0 to 2 atm) of cyclohexane. The rate data obtained have been analysed by the Hougen—Watson method. Non‐linear least squares analyses combined with other statistical considerations were used to discriminate among rival models. The following Hougen—Watson type rate equation has been proposedThe constants in the rate equation have been expressed as functions of temperature.
Blistering in bituminous coatings
Authors: Biloen P. , Bonn R. , Marys P. D. , Spoon W. A.
Published: July 2010

Thermodynamical arguments together with the solutions of some diffusion equations lead to the theory that one of the causes of blistering of bituminous coatings is the variation in gas pressure; for instance the blistering of a coating that covers the inside of hydrophore installations. This theory has been confirmed by some experiments. A model is discussed that gives a quantitative description of the blistering. Laboratory results are discussed in view of the model predictions. A procedure is proposed to extrapolate the experimental results under laboratory conditions to practical conditions, i.e. simple laboratory experiments can be performed with a given type of bituminous coating that will show whether or not blistering will occur in practice.
Viscosity of methanol + benzene mixtures
Authors: Medani M. S.
Published: July 2010

The viscosity of pure methanol and benzene have been determined at 35, 40, 45, 50 and 55°C in a Canon—Fenske viscometer. Values of the viscosity coefficients were fitted to De Guzman's equation, i.e.

where it was shown that both A and Evisc for the two compounds are functions of temperature.

The viscosity of 10 different concentration levels of methanol + benzene mixtures have also been measured at 35, 40 and 45°C. Points of maximum and minimum viscosities were shown to exist, the compositions of which vary with temperature.

Estimates of the viscosity coefficients of methanol + benzene mixtures at 100, 120, 160 and 200°C have been made from the vapour‐liquid equilibrium data of this system. It was found that points of minimum viscosity still exist while points of maximum viscosity have disappeared. These phenomena are discussed in terms of the dissociation of methanol “polymers” and the formation of benzene + methanol complexes.
Pyrolysis of methane in a single pulse shock tube
Authors: Napier D. H. , Subrahmanyam N.
Published: July 2010

The thermal decomposition of methane has been studied in a chemical shock tube at pressures up to 20 atm over a temperature range of between 1750 and 2700 K and for reaction times up to 2.5 ms. Attention is drawn to some of the experimental features of the shock tube and to the fact that reaction temperatures were measured.

Optimum conditions for the production of acetylene from methane are suggested, and the relatively small effect of pressure on the acetylene yields is noted.

Values for activation energy (93.6 kcal/mol) and frequency factor (3.8 × 1013 s−1 for methane decomposition are given. The experimental results obtained are discussed in connection with suggested mechanisms of decomposition. In the discussion attention is drawn to the difficulty of predicting acetylene yields arising from the incomplete understanding of the mechanism of acetylene decomposition and of “carbon” formation under the conditions employed.
Optimisation of a liquid extraction process
Authors: Jeffreys G. V. , Mumford C. J. , Herridge M. H.
Published: July 2010

A mathematical model of a solvent extraction process has been developed which has been arranged into a form suitable for optimising the process by the indirect optimisation procedure and by the direct method developed by Hooke and Jeeves. These optimisation procedures have been compared by analysing an extraction process in which solvent recovery is by distillation.
A semi‐automatic method for the production of primary cell suspensions
Authors: Belton F. C. , Garriock D. J.
Published: July 2010

A method is described for the production of primary chick embryo cell suspensions that allows the processing of from 200 to several thousand embryos daily at a significantly lower cost than with other methods. Special apparatus enables high yields of cells, free of microbial contamination to be produced under controlled conditions with the minimum of supervision.
The application of an infrared absorption technique to the measurement of moisture content of building materials
Authors: Cornell J. B. , Coote A. T.
Published: July 2010

The principles underlying the use of differential infrared absorption for measuring moisture contents are explained and it is shown how a commercial moisture recorder of this type, intended for measuring the moisture content of paper, may be adapted for the measurement of the moisture content of the surface and interior of some building materials. Encouraging results are obtained with mortars and aerated concrete, but the results with bricks are inexplicably erratic. The results are substantially independent of changes in the soluble salt concentration in the moisture. The method seems to merit further investigation though the present high cost of the apparatus will restrict its use.
The effect of various alkali metal fluoride solutions on the brushite—fluoroapatite transformation
Authors: Duff Edward J.
Published: July 2010

The brushite—fluoroapatite transformation reaction has been examined in 10−1 M solutions of NaF, KF, RbF, CsF and NH4F at room temperature. The nature of the alkali metal ion has no effect on the fluoride‐diffusion‐controlled reaction, although the incorporation of the cation into the apatite structure is dependent the nature of the alkali metal cation.
The concentration of mammalian cells in a tangential flow filtration unit
Authors: Radlett P. J.
Published: July 2010

A tangential flow filtration unit is described through which cell suspension is continuously recycled. A pressure drop is incurred across the filter which forces liquid through the filter sheet, and cells in the remaining suspension are thus concentrated. The unit described has been used to concentrate 4 1 of cell suspension containing at least 2 × 106 cells/ml 12‐to 23‐fold in 2 to 4 h, with 94% viable cell recovery and little loss of viability. The filter is amenable to scale‐up and a pilot scale version is under test in this laboratory.
Concentration of the virus of foot‐and‐mouth disease in a tangential flow ultrafiltration unit
Authors: Morrow A. W.
Published: July 2010

Ultrafiltration by means of a thin channel tangential flow unit was used to concentrate suspensions of inactivated foot‐and‐mouth disease virus. When 5 to 7 1 batches were filtered, the liquid volume was reduced by approximately 98 % with little loss of antigen and good separation from nitrogenous compounds of low molecular weight.
The effects of some esters on friction with particular reference to railway locomotion. II
Authors: Dyson R. W. , Himatsinghani G. V.
Published: July 2010

Work previously described has been extended by the use of an electron microscope. Examination with this instrument of variously treated rail steel surfaces has been correlated with friction measurements. The results are reported and discussed, and a tentative theory has been proposed in outline.