Asymmetrical Dimethylarginine Levels in Hepatitis B Virus-Positive Patients

BACKGROUND: High asymmetrical dimethylarginine (ADMA) levels have been associated with endothelial dysfunction and contribute to the development of several diseases. However, data on the relationship between hepatitis B virus (HBV) and ADMA are limited. The aim of our study was to explore the relationship between ADMA and HBV by comparing the ADMA levels in patients with chronic active hepatitis B (CHB), inactive HBV carriers (carriers), and healthy volunteers (controls). METHODS: The participants were divided into three groups: 90 patients with CHB, 90 HBV carriers, and 90 controls. Serum ADMA levels were quantified using an ELISA kit (Cusabio, Wuhan, China). The data were analyzed using an ANOVA or the Kruskal-Wallis test as appropriate, with P<0.05 considered significant. RESULTS: Serum ADMA levels were significantly higher in patients with CHB (228.35±91.10 ng/mL) than in HBV carriers (207.80±75.80 ng/mL) and controls (207.61±89.10 ng/mL) (P=0.049). The clinical scores of the patients were positively correlated with ADMA levels. CONCLUSIONS: The elevated serum ADMA levels in patients with CHB confirm that HBV plays a role in vasculitis. Further investigation of the mechanisms contributing to the high levels of ADMA in CHB may contribute toward development of new treatment modalities.

Application Study on the Combined Detection of Serum HCY and Liver Function Indicators in Liver Disease Diagnosis / 现代检验医学杂志

Objective To investigate the serum homocysteine (HCY)levels of patients with various liver diseases,and discuss the clinical value of combined detection of HCY and other liver function indicators in liver disease diagnosis.Methods Se-lected 123 cases of inpatients with different liver diseases (79 cases of male,44 cases of female),including 39 cases of chronic active hepatitis,52 cases of cirrhosis and 32 cases of primary hepatic cancer from Department of Gastroenterology,and 90 ca-ses of healthy persons as control group from Out-patient Health Examination Center of Shaanxi Provincial People’s Hospi-tal.Detected serum HCY and some indicators of liver function (TBIL,ALT,GGT and TBA)in different liver disease groups and normal control group with Roche MODUALR automatic biochemical analyzer,and did statistic analysis.Results The serum HCY levels of chronic active hepatitis,liver cirrhosis and primary hepatic cancer were 16.25± 3.98μmol/L,20.89± 4.26μmol/L and 22.92 ± 6.08μmol/L respectively,and significantly higher than those in normal control group (8.16 ± 4.03μmol/L,t=5.352~9.021,P<0.01).The serum HCY levels of liver cirrhosis and primary hepatic cancer group were higher than that of chronic active hepatitis group (P<0.05).Serum levels of HCY were obviously lower after treatment than that before treatment (P<0.05)for three groups of liver diseases.The positive rate of HCY was higher than those of other liver function indicators (P<0.05).Conclusion Serum homocysteine may be as one of the most important indexes of liver damage,and the combined detection of other liver function indicators may have important clinical value for liver disease diagnosis,differential diagnosis,treatment and prognosis.

A reduced grade of liver fibros-steatosis after raltegravir, maraviroc and fosamprenavir in an HIV/HCV co-infected patient with chronic hepatitis, cardiomyopathy, intolerance to nelfinavir and a marked increase of serum creatine phosphokinase levels probably related to integrase inhibitor use / Grado reducido de fibroesteatosis tras la administración de raltegravir, maraviroc y fosamprenavir en un paciente co-infectado de VIH/VHC con hepatitis crónica, cardiomiopatía, intolerancia al nelfinavir y un aumento pronunciado de los niveles de creatina fosfoquinasa sérica probablemente debido al uso del inhibidor de la integrasa

The use of new antiretroviral drugs in HIV infection is particularly important in patients with intolerance or resistance to other antiretroviral agents. Raltegravir and maraviroc represent new, important resources in salvage regimens. A reduced grade of liver fibro-steatosis after a combination of raltegravir and maraviroc (second-line) has not been studied and the mechanism by which these new drug classes induced a marked reduction of grade of liver diseases is currently unknown. In the present case report, nested in an ongoing multicentre observational study on the use of new antiretroviral inhibitors in heavy treatment-experienced HIV patients, we evaluated the correlation between a "short therapeutic regimen" raltegravir, maraviroc and fosamprenavir and liver diseases. The aim of this report is to describe the use of a three-drug regimen based on two novel-class antiretroviral agents (raltegravir and maraviroc) plus the protease inhibitor fosamprenavir, in an experienced HIV-infected patient with chronic progressive hepatitis C complicated by liver fibrosis; an overwhelming increased serum creatine kinase level occurred during treatment, and is probably related to integrase inhibitor administration. At present no information is available regarding this correlation.

El uso de nuevos medicamentos antiretrovirales para la infección por VIH es particularmente importante en los pacientes con intolerancia o resistencia a otros agentes antiretrovirales. Raltegravir (RTV) y maraviroc (MRV) representan nuevos e importantes recursos en las terapias de salvamento. Un grado reducido de fibroesteatosis hepática después de una combinación de raltegravir y maraviroc (terapia de segunda línea) no ha sido estudiado, y el mecanismo por el cual estas nuevas clases de droga indujeron una marcada reducción de grado de las enfermedades hepáticas se desconoce hasta el momento. Como parte de la realización en curso de un estudio observacional multicentro acerca del uso de nuevos inhibidores antiretrovirales en pacientes de VIH altamente experimentados en el tratamiento, en el presente reporte de caso se evalúa la correlación entre un "régimen terapéutico corto" (raltegravir, maraviroc y fosamprenavir) y las enfermedades del hígado. El objetivo de este reporte es describir el uso de un régimen de tres medicamentos - basado en dos agentes antiretrovirales de nuevo tipo (raltegravir y maraviroc) además del fosamprenavir inhibidor de la proteasa - en un paciente de VIH experimentado. El paciente también sufre de hepatitis C evolutiva, progresiva, crónica, complicada por fibrosis hepática. Durante el tratamiento, se produjo un aumento extraordinario del nivel de creatina quinasa sérica, el cual probablemente esta relacionado con la administración del inhibidor de la integrasa. Actualmente no hay información disponible con respecto a esta correlación.

Clinical & molecular characterization of human TT virus in different liver diseases.

Background & objectives: TT virus (TTV) is a newly discovered non-enveloped, single stranded DNA virus of high genotypic variability, found frequently in patients with acute or chronic hepatitis of non A-G aetiology. This study was carried out to look for the presence of TTV and its genotypes in patients with different types of liver diseases from northern India. Methods: A total of 262 serum samples from patients of acute viral hepatitis (AVH; n=72), fulminant hepatic failure (FHF; n=49), chronic active hepatitis (CAH; n=93) and liver cirrhosis (LC; n=48), were analyzed for hepatitis A-G viral markers. TTV DNA was detected in all cases by nested polymerase chain reaction (PCR) using the primers from N22 and untranslated (UTR) region. TTV-DNA was also tested in 150 volunteer blood donors. Direct nucleotide sequencing of N22 amplicons were carried out to look into the prevalent TTV genotypes. Results: TTV-DNA was detected in 73.6, 59.2, 21.5 and 29.1 per cent cases with AVH, FHF, CAH and cirrhosis, respectively. In AVH and FHF groups, TTV showed co-infection with all A-G hepatitis cases whereas in CAH and cirrhosis groups, TTV co-infection observed with HBV, HCV and HGV. TTV-DNA was detected in 45.3 per cent volunteer blood donors. No statistically significant difference was observed amongst the mean liver function profile of UTR PCR positive and negative cases in different liver disease groups except AVH cases, in whom the various biochemical parameters between TTV positive and TTV negative patients were marginally significant. However, no significant evidence of biochemical or histological deterioration of the liver was observed in TTV positive cases amongst FHF, CAH and cirrhosis. Predominance of genotype 1a was observed in all the cases from north India. Interpretation & conclusions: TTV is a frequent virus isolated from patients with various types of liver diseases as well as in healthy individuals from northern India. TTV has no effect on biochemical markers of associated liver diseases. Genotype 1a was the most predominant type in different liver disease groups. The occurrence of TTV did not further influence the course of the disease.

T cell subsets in chronic hepatitis B and the effect of prednisolone withdrawal and interferon alpha-2b

OBJECTIVES: The evaluations of the pathogenetic roles of cell mediated immunity and of the preventive effect for disease progression with interferon(IFN) treatment in patients with chronic active hepatitis-B(CAH-B) are the objectives of this study. METHODS: Thirty-two patients with CAH-B were treated with interferon alpha-2b(IFN alpha-2b) with prednisolone withdrawal and 30 control patients were treated with conventional hepatotonics for 6 months. Peripheral total T cell fractions and T cell subsets of the patients with CAH-B, treated with IFN alpha-2b with prednisolone withdrawal, were examined 1 month before administration of prednisolone, and compared with 12 normal controls for assessing the potential role of cellular immunity in the development of CAH-B. To estimate the effectiveness of IFN therapy for the patients with CAH-B, levels of various liver function tests, HBsAg, anti-HBs, HBeAg, anti-HBe, HBV DNA, anti-HCV and others were assessed for the treatment group and compared with control patients at pre- and post-treatment period each. RESULTS: The value of CD4 was significantly lower in patients with CAH-B than normal controls (36.3 +/- 7.7% vs 42.1 +/- 5.7%, p < 0.05) and the value of CD8 was significantly higher in patients with CAH-B than normal controls (30.6 +/- 10.3% vs 24.3 +/- 5.2%, p < 0.05) before prednisolone administration. The patients in responder group (n = 26) had significantly lower CD4 cells compared with normal controls, but non-responders (n = 6) did not have. The levels of liver function test(LFT) in the patients with IFN alpha-2b treatment with prednisolone withdrawal were not different from the control patient group at pretreatment, but significantly lower than control patient group's after treatment, regardless of response to IFN alpha-2b treatment with prednisolone withdrawal. CONCLUSIONS: The cellular immunity of the host may have a potential role in the pathogenesis of chronicity of hepatitis B infection. IFN alpha-2b treatment with prednisolone withdrawal may be regarded as one of the effective treatment modalities for the inhibition of disease progression in patients with CAH-B.

The Comparison of Adverse Effect and Short-term Effect of Different Dosage of Recombinant Interferon Alpha-2b Treatment in Patients with Chronic Active Hepatitis Type B / 대한간학회지

BACKGROUND/AIMS: The efficacy and adverse effects of two different dosages of recombinant a2b interferon were studied in 45 patients with chronic active hepatitis B from March 1991 to December 1996. METHODS: The 19 patients received in a dose of 3MU thrice weekly for 16 weeks, the 14 patients received in a dose of 5MU thrice weeldy for 16 weeks and the 12 patients received conservative management. We evaluated serologic examination and adverse effects. Results 1) The rate of improvement in aminotransferase was significantly higher in interferon treated group (75.0%) compared to control group (16.7%) and it tended to be higher in 5MU group (85.6%) than 3MU group (68.4%) but, the latter had no statistical signifcance (P=0.27). 2) The disappearance rate of HBV-DNA was significantly higher in interferon treated group (72.7%) compared to control group (0%) and it tend to be higher in 3MU group (78.5%) than 5MU group (62.5%) but, the latter had no stastical significance (P=037). 3) The loss rate of HBeAg was significantly higher in interferon treated group (50.0%) compared to control group (O%) and it tend to be higher in 5MU group (66.7%) than 3MU group (37.5%) but, the latter had no stastical significance(P=0.13). 4) Fever (75.8%), leukopenia (41.2%), headache (30.3%), myalgia (18.2%), thrombocytopenia (17.6%), anorexia (11.8%) were noted and fever was significantly higher in 5MU group compared to 3MU group (P=0.02). Conclusion The effective improvement of liver function test and disappearance rate of HBeAg tended to be higher in 5MU group than 3MU group, but it was not stastistically significant. Fever was significantly higher in 5MU group compared to 3MU group.

A Case of Chronic Active Hepatitis Developed in Patient with Psoriasis after Long-term Methotrexate Treatment / 대한간학회지

Methotrexate (MTX) has been widely used in the treatment of psoriasis and rheumatoid arthritis. But prolonged use of MTX can induce hepatic fibrosis and even cirrhosis. To date, in Korea, there have been very few reports on hepatotoxicity due to MTX, and no report on biopsy-proven chronic active hapatitis. We report one patient who developed chronic acitve hepatitis while taking long-term daily dose of MTX(10mg per day) for psoriasis for a prolonged period.

Methotrexate Induced Chronic Active Hepatitis: A report of two cases

Although methotrexate(MTX) has been known to have many side effects, especially toxicity on the hemopoietic cells and the liver, it has been used as a potent anticancer drug and for the treatment of psoriasis or rheumatoid arthritis. The severity of hepatotoxicity varies from mild fatty change to chronic active hepatitis(CAH) and cirrhosis. We experienced two cases of MTXinduced CAH in patients with psoriasis, which prompted us to report in view of the absence of biopsy proven MTX hepatotoxicity in the Korean literature. Microscopically, the liver showed a distorted lobular architecture with portal fibrous expansion, piecemeal necrosis and bridging necrosis/fibrosis. The hepatic lobules revealed fatty changes of hepatocyte, focal hepatocytolysis, delicate collagen deposits along the space of Disse and the characteristically marked polyploid nuclear change of hepatocytes.

The effects of prolonged treatment in children with chronic hepatitis B with combination of alpha-interferon and acyclovir

This study was conducted to evaluate the effect of prolonged treatment in children with chronic hepatitis B with combination of alpha-interferon and acyclovir. The study population consisted of 7 patients with chronic hepatitis B who showed histological findings compatible with chronic active hepatitis (4 cases) or chronic persistent hepatitis (3 cases) on liver biopsy and had elevated AST and ALT with positive HBsAg, HBeAg and HBV-DNA for more than 6 months. Recombinant interferon-alpha-2 was given in a dose of 3 million IU/m2 daily for 3 months with acyclovir in a dose of 15mg/Kg of body weight every 12 hours for 7 days of each month for 3 months. Then, the same dose of interferon was given thrice a week for 9 more months. One patient who had vertically transmitted hepatitis B from her mother had received only 6 months of treatment in total as she did not show any effect after 6 months of treatment. Among 6 patients who had positive HBV-DNA on entry to the study, 4 patients (66.7%) showed conversion of HBV-DNA to negative. HBeAg was converted to negative in 3 patients (42.9%). AST and ALT became normal in 6 cases but HBsAg remained positive in all cases. prolonged treatment in children with chronic hepatitis B with combination of alpha interferon and acyclovir seems to be beneficial but the proper dosage and duration of therapy need to be determined with further and controlled study.

Effect of polyadenylic.polyuridylic acid on cellular responses of peripheral blood mononuclear cells from patients with chronic active hepatitis B

We have investigated in vitro proliferative responses of peripheral blood mononuclear cells and productions of interferon-gamma and soluble interleukin-2 receptors by these cells from 6 patients with chronic active hepatitis B immediately before and 24 hours after a single intravenous injection of 100 mg of polyadenylic.polyuridylic acid. Cell proliferations were assessed by the technique of tritiated-thymidine incorporation and productions of interferon-gamma and soluble interleukin-2 receptors were measured by enzyme-linked immunosorbent assay. The administration of polyadenylic.polyuridylic acid to the patients has resulted in significant increases of in vitro proliferations of their peripheral blood mononuclear cells as well as productions of interferon-gamma by these cells. However, in vitro productions of soluble interleukin-2 receptors were not changed significantly. These results suggest that the enhanced cellular responses by polyadenylic.polyuridylic acid might be due to the increased sensitivity rather than the increased expression of cellular interleukin-2 receptor.

Two Cases of Oral Lichen Planus Associated with Chronic Liver Disease

We present two cases of oral lichen planus associated with chronic liver diseases. One patient was a 56-year-old man that had advanced liver cirrhosis with hepatitis B viral infection, and the other, a daughter of patient 1, was identified as chronic active hepatitis with hepatitis B viral infection. Clinical and histopathological features of oral lesions were consistent with lichen planus in both cases.

Liver in Systemic Lupus Erythematous: Clinicopathological analysis of 8 cases

Hepatic changes in eight cases of systemic lupus erythematosus(SLE), were studied to evaluate the nature of hepatic injury of SLE and its relation to lupoid hepatitis. Common histologic changes of the liver in SLE included intralobular necro-inflammatory activities, fatty change, canalicular bile stasis and mild perivenular and Disse space fibrosis. The fatty change and intralobular fibrosis were thought not to be due to SLE itself but associated with steroid administration or chronic alcoholic consumption. The necro-inflammatory changes were usually mild and features of chronic active hepatitis with periportal destruction occured in one case. Symptoms related to the involvement of many other organs than the liver appeared much frequently in patients with SLE than lupoid hepatitis, suggesting that the SLE involving liver and the lupoid hepatitis are different diseases.

Hepatic Piecemeal Necrosis under Electron Microscope / 昆明医科大学学报

It was observed under an electron microscope that in the hepatic piecemeal necrotic area of CAH patients,there were T lymphocytes,plasma cells,monocytes,fatstoring cells and proliferating Hering's tubules.The more severe the patient's condition was,the much more the sorts and numbers of these cells were.We consider that the above observations by electron microscopy afford valuable morphological information about the severity of CAH.

A Case of Allergic Vasculitis Associated with Chronic Active Hepatitis / 대한피부과학회지

Hepatitis B virus is of growing clinical importance. This virus not only produces acute and chronic liver disease but also produces a variety of dermatologic syndromes. A 77-year-old man with erythematous urticarial-like papulonodules had a chronic active hepatitis. And microscopic findings were compatible with allergic vasculitis. We reported a case of allergic vasculitis associated with chronic active hepatitis and reviewed literatures briefly.

Immunological aspects in patients with chronic active hepatitis--cellular immune responses

We studied host immune parameters which might be related to the activity and the pathogenetic mechanism of chronic active hepatitis. The subjects consisted of 45 cases with hepatitis B virus surface antigen (HBsAg)-positive chronic active hepatitis (CAH), 44 HBsAg-negative CAH, 22 with inactive chronic hepatitis, and 45 cases of normal persons, hepatitis B virus (HBV) carriers, or the patients with acute myocardial infarction. The in vitro assay for the in vivo activated lymphocytes was performed by measuring spontaneous thymidine uptake (SLT) of lymphocytes isolated from peripheral blood. SLT was significantly (p less than 0.001) elevated in cases with HBsAg-positive (1227 +/- 806 cpm) and-negative CAH (1017 +/- 559 cpm) compared to the patients with inactive chronic hepatitis (347 +/- 79 cpm) and to the control group (320 +/- 106 cpm). SLT values observed in 7 cases with active disease (group I and II), in which remission and relapsing phase could be assessable, were elevated from 648 +/- 121 cpm in remission phase to 1548 +/- 606 cpm one to two weeks before the appearance of biochemical evidence (SGPT) of relapse. This pattern of SLT elevation, however, was not observed in patients with inactive hepatitis. Neither the abnormal distribution of T-celi subsets nor the presence of conventional HBV markers were related to the elevated SLT value. Our findings may therefore indicate that SLT might be useful in assessment of the disease activity in patients with CAH.

Histopathological and Ultrastructural Observations on Liver Biopsy Specimens from Patients with Chronic Active Hepatitis / 第三军医大学学报

Seventy-five liver biopsy specimens taken from patients with chronic active hepatitis(CAH) were studied with light microscopy, and 22 of the 75 with electron microscopy as well. The pathological changes of CAH could be divided into mild, moderate and severe types according to the severity and extent of the liv-e'r lesions. Piecemeal necrosis was an outstanding feature of this series of cases. Ultrastructttrally, the ballooning degeneration of hepatocytes could be distinguished into 3 forms; rough endoplasmic reticulum(RER) dilatation, RER dilatation associated with mitochondrial swelling, and edema of cytosol. The last one was considered as one of the features of the severe type of CAH.Particular attention was paid to the changes of the cell membtane. Ultra-structurally, generalized thickening of the cell membrane was demonstrated in two forms, that is, (1) there was fibrillarv substance interposed between the membranes of 2 adjacent cells, and (2) the cell membrane became thickened, adhered with each other, or twisted, forming the so-called "chain-ring-like structure" , which was considered as another prominent feature of the severe type of CAH.According to our observation, the accuracy of diagnosis is chiefly dependent on the histopathological findings.

BIOCHEMICAL ANALYSIS OF CHRONIC HEPATIC INJURY MODEL INDUCED BY TEF / 西安交通大学学报(医学版)

Chronic hepatic injury animal model induced by TEF was made with carbontetrachloride, ethyl alcohol and a high-fat feed. An increase in serum GPT, LDH_5 and r-globulin, a decrease in serum albumin and a remarkable increase in hepatic collagen were found. The results indicated that all biochemical data obtained in this model is similar to those in patients with chronic active hepatitis.

A STUDY ON HBV DNA IN PATIENTS WITH SERUM HBsAg-NEGATIVE AND POSITIVE CHRONIC ACTIVE HEPATITIS / 解放军医学杂志

HBV DNA was detected by in situ hybridization using a biotin labelled probe and HBV antigens (including HBsAg and HBcAg) and by avdin-biotin-peroxidase complex technique in liver sections from 34 patients negative for serum HBsAg and 30 patients positive for HBsAg of chronic active hepatitis.The incidence of intrahepatic HBV DNA,HBcAg and HBsAg in 34 patients negative for serum HBsAg were 23.5%,23.5% and 32.4%,and that in 30 patients positive for serum HBsAg were 63.3%,56.7% and 83.3%,respectively.In a few patients negative for HBsAg,though positive for HBV antibody (even for anti-HBs) or negative for HBV antiboody,HBV DNA and HBV antigens could still be detected in liver tissue.In these patients who showed positive HBsAg,no matter positive for serum HBeAg,or positive for anti-HBe,or negative for HBeAg,all of them had high incidence of HBV DNA positivity in liver,which were 68.8%,60.0% and 55.5%,respectively.Intrahepatic HBcAg was associated closely with the presence of HBV DNA in hepatocytes,suggesting that it could be considered as an index to reflect HBV DNA synthesis.