Epidemiology, Genotyping, Mutational and Phylogenetic Analysis of Hepatitis B Virus Infection in North-east India.

BACKGROUND/OBJECTIVE: Hepatitis B virus (HBV) infection is a major public health problem globally. Northeast India is home to indigenous tribes with different ethnicity and high rates of drug abuse and HIV infection. The study was designed to estimate the burden of HBV infection across various spectrums of liver diseases from this region. HBV genotypes and subgenotypes play a role in the chronicity of disease, response to treatment and its progression. As very limited data are available from this region, we tried to elucidate the role of HBV genotypes, HBV mutants and their phylogenetic analysis. METHOD: We designed a prospective multicentric study, and included 7464 liver disease cases, 7432 blood donors and 650 health care workers, who were screened for HBV infection. HBV DNA positive patients were genotyped and subjected to surface protein, precore and core mutation and phylogenetic analysis. RESULTS: The prevalence of HBV infection with respect to different types of liver diseases, blood donors and health care workers was 9.9% (1550/15,546). 49.5% (768/1550) cases were found to be HBV DNA positive. The most common genotype was found to be genotype D 74.2% (570/768), followed by genotype C 6.5% (50/768), A 4.4% (34/768) and I 0.9% (7/768). CONCLUSION: This study highlights the high hepatitis B burden in Northeast India, reflecting lacunae in health care needs of the region. Also, the different genotype distribution and presence of mutations may translate into different rates of liver disease progression, prognosis and ultimately, clinical significance. However, further prospective cohort study from Northeast India is warranted, to elucidate the clinical significance of multiple genotypes and mutation in this unique population.

Evaluation of serum alpha fetoprotein-L3 as an accuracy novel biomarker for the early diagnosis of hepatocellular carcinoma in Egyptian patients.

BACKGROUND: Most Hepatocellular Carcinomas (HCCs) are diagnosed at an advanced stage. However, HCC early diagnosis is complicated by the coexistence of inflammation and cirrhosis. The unsatisfactory sensitivity and specificity of Alpha-fetoprotien (AFP) for screening of early-stage HCC paved the way for new novel biomarkers to complement AFP such as AFP-L3. The aim of this study was the Evaluation of alpha fetoprotein-L3 (AFP-L3) as earlier marker in diagnosis of hepatocellular carcinoma in Egyptian patients. This study was conducted on 80 patients categorized into 2 groups; group 2 (40 patients with chronic active hepatitis) and group 3 (40 patients with HCC). HCC diagnosis was done by clinical, triphasic CT and positive US for focal lesion, in addition to 20 healthy individuals as controls (group 1). RESULTS: The median range of AFP and AFP-L3 were highly statistically significant difference between HCC group and other groups [p < 0.001]. In this study ALT, AST, Total & direct bilirubin and albumin results showed highly significant differences between HCC group and other groups. Serum AFP-L3 shows sensitivity 100%, specificity 100%, positive predictive value 100% and negative predictive value 100% with AUC = 1 in HCC cases. CONCLUSION: Serum AFP-L3 may serve as a diagnostic biomarker for the detection of early stage of HCC and show higher sensitivity than AFP.

Association of hepatitis B genotypes with clinical profile of patients with chronic hepatitis B.

Hepatitis B virus (HBV) infection is a common cause of chronic liver disease and is responsible for HBV-related deaths due to cirrhosis and HCC. It is well recognized that viral genotypes play an important role on the outcome of HBV infection. Ten HBV genotypes have been identified and the prevalence varies geographically. A hospital-based cross-sectional study was conducted to determine the association of HBV genotypes with the clinical profile of CHB patients. PCR-RFLP was performed to identify HBV genotypes. In this study, majority (70%) of patients were males; with ages between 22 to 67 years with a mean of 42.5 years. The ALT ranged from 23 to 111 U/L (mean 72.5 U/L). HBV DNA levels varied from less than 6 to more than 110,000,000 IU/ml. Forty-seven percent of the patients had chronic active hepatitis at the time of diagnosis. Of these, 36% were HBeAg positive while 64% were HBeAg negative. Inactive HBsAg carrier was found in 53% of cases. No significant association was established between HBV genotypes and fibrosis. PCR-RFLP analysis showed that 57%, 10%, and 13% of the samples belonged to HBV/A, HBV/B, and HBV/C, respectively and the remaining 20% had non-detectable HBV genotype. HBV/D to HBV/J were not observed in this study. Taken together, the patient's clinical profile such as sex, ALT levels, HBeAg status, HBV DNA levels and liver histology were not found to be significantly associated with HBV genotypes. A large-scale longitudinal study examining multiple HBV strains are needed to determine significant correlation of clinical profile.

Tremella polysaccharide: The molecular mechanisms of its drug action.

Tremella fuciformis is an edible medicinal mushroom well known as "Yiner" or "Baimuer" in China and has been used as a Chinese herb for many years. T. fuciformis polysaccharide (TFPS) has been identified as a major bioactive component. Different experimental conditions can obtain different TFPS fractions, which makes TFPS a mixture of different polysaccharides with the molecular weight ranging from 5.82×105Da to 3.74×106Da. The monosaccharides detected in TFPS include mannose, xylose, fucose, glucuronic acid, glucose, and galactose. One characterized TFPS chemical structure consists of a linear (1→3)-linked α-d-mannose backbone with highly branched ß-d-xylose, α-d-fucose and ß-d-glucuronic acid as the side chains. TFPS shows multiple physiological and healthy promoting effects including immunomodulation, antitumor, anti-oxidation, anti-aging, hypoglycemic, hypolipidemic, neuroprotection, and other effects. As a result, "Tremella Polysaccharide Enteric-coated Capsules" was approved by Chinese Food and Drug Administration (SFDA) in 2002 for treating cancer patients with leukopenia induced by chemotherapy and radiotherapy. It is also used as adjuvant drug for treating chronic persistent hepatitis and chronic active hepatitis. In this chapter, 113 independent studies involving in biochemical, pharmacological, and clinical studies of TFPS during the past 46 years (1972-2018) on the base of PubMed, CNKI (China National Knowledge Infrastructure) and Wanfang database search are summarized. TFPS shows efficacy for all types of human diseases in the reported clinical studies. The structure, molecular mechanisms of the immunomodulation, antitumor, anti-oxidation, anti-aging, hypoglycemic, hypolipidemic, preclinical and clinical efficacy are discussed to provide a general picture of TFPS as a clinically used drug.

Alanine Aminotransferase as the First Test Parameter for Wilson's Disease.

Background and Aims: The liver is the first organ affected by toxic copper in the classical and severe hepatic forms of Wilson's disease (WD). Because their associated chronic liver damage is mostly asymptomatic, an intervention using a special test including serum alanine aminotransferase (ALT) activity is needed for detecting WD. Methods: Using the modified international criteria for the diagnosis of WD, 45 patients were selected from the collective databases of our institutions, and 7 infants were reviewed from the literature. Two patients had the severe hepatic form, with normoceruloplasminemia and no mutations in ATP7B. The rapid ALT change during hemolytic anemia was adjusted for a baseline. The diagnostic potential of the ALT test was assessed from the age-dependent natural course of the liver damage of WD. Results: The natural course had three stages. ALTs were still low in some infants younger than 4 years-old. They were high in all children between the ages of 4 and 8 years-old; then, they reduced to low levels in some patients over 9 years of age. The high ALT stage represents chronic active hepatitis, and the subsequent low ALT stage is due to silent cirrhosis. The hepatic copper content is a reliable but invasive test, while urinary copper secretion is an alternative, non-invasive test for copper toxicosis of WD. The serum ceruloplasmin and ATP7B analyses are subtype tests of WD. The response to anti-copper regimens is the final test result. Conclusions: ALT could be the first parameter to test to detect WD in children between the ages of 4 and 8 years.

Chronic active hepatitis induced by Pazopanib mimicking hypervascular liver metastases in a patient with recurrent soft tissue sarcoma: A case report.

Pazopanib is the first multitargeted tyrosine-kinase inhibitor approved for the treatment of patients with advanced non-adipocytic soft tissue sarcoma (STS). It has been demonstrated to improve progression-free survival without impairing health-associated quality of life. However, Pazopanib is associated with several adverse side effects associated with inhibition of the vascular endothelial growth factor receptor. These include hepatotoxicity, as manifested by abnormal liver function tests. To the best of our knowledge, the current study presents the first case of a patient with recurrent STS who developed biopsy proven Pazopanib-induced chronic active hepatitis and whose previous computed tomography examination demonstrated multiple hypervascular liver lesions. These lesions were indistinguishable from metastases and to the best of our knowledge, have not been described previously. These lesions therefore appear to be a novel finding of Pazopanib-induced chronic active hepatitis. It is crucial to be aware of this unusual finding within a clinical setting, to avoid overstaging and early discontinuation of effective treatment.

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.

Histological and Serological Epidemiology of Hepatitis Delta Virus Coinfection among Patients with Chronic Active Hepatitis B Virus in Razavi Khorasan Province, Northeastern Iran.

BACKGROUND: Hepatitis delta virus (HDV), as well as hepatitis B virus (HBV), are regarded as one of the main public health issues in developing countries. This retrospective study described histological and serological features of HDV coinfection patients with chronic active HBV in Northeastern Iran. METHODS: The frequency of HDV seropositivity and its impact on serum liver enzyme levels and pathological features were investigated by reviewing clinical and laboratory data. This study contained chronic active HBV-infected patients having admitted the department during 2009 and 2014. RESULTS: The rate of HDV coinfection in chronic active carriers was 21.84%, with a male predominance. HDV seropositive carriers showed significantly higher concentrations of liver enzyme than chronic active HBV monoinfection. Moreover, there was a strong association between degrees of inflammation with HDV-positive patients' enzyme levels. CONCLUSION: The HDV seroprevalence in northeastern Iran was higher than that reported from elsewhere in Iran while comparable to some regions in Middle East, which, in turn, requires more comprehensive tools for diagnosing and screening the blood.

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.

Unmasking of myasthenia gravis during pegylated Alfa 2 a interferon and ribavirin therapy for chronic hepatitis C.

Over last few decades, hepatitis C has emerged as a serious infection that has threatened the health and budgets of millions in the world. The objective of health professionals to treat it with recommended therapy of Alfa interferon and Ribavirin combination presents certain risks. One of the alarms is the ability of interferon to stimulate the production of autoantibodies in the body resulting in expression of autoimmune diseases in few who develop these antibodies. The case presented here is about unmasking of myasthenia gravis in a patient who received alfa interferon therapy for her chronic hepatitis C. Alfa interferon probably plays an important role in manifestation of the diseases in susceptible patients and all autoimmune diseases cannot be taken as mere side effects of the therapy. Clinicians need to be alert to pick up these diseases earlier so that the prompt management is possible.

Loss of hepatitis B surface antigen in a real-life clinical cohort of patients with chronic hepatitis B virus infection.

BACKGROUND & AIMS: Hepatitis B surface antigen (HBsAg) clearance is the main indicator of viral cure in patients infected with the hepatitis B virus (HBV). We sought to identify the parameters associated with HBsAg loss in a well-characterized real-life clinical cohort of chronically HBV-infected patients. METHODS: Patients with chronic HBV infection were prospectively included, classified according to the disease stage, and followed up to determine parameters associated with HBsAg clearance. RESULTS: In total, 315 patients were followed up for a mean of almost 6 years. At study entry, 109 (34.6%) were inactive HBsAg carriers, 204 (64.8%) had chronic active hepatitis (CAH), and two (0.6%) were immune-tolerant carriers. During follow-up, 128 (62.7%) of the 204 patients with CAH received antiviral therapy. Sixty-nine had HBeAg-positive CAH: 55 (79.7%) were treated and 14 (20.3%) untreated. One hundred thirty-five had HBeAg-negative CAH: 73 (54.1%) were treated and 62 (45.9%) untreated. Inactive carriers showed an annual HBsAg clearance incidence rate of 23.4 cases per 1000 persons-years, which was higher than that of CAH groups. The clearance incidence rates (in cases per 1000 persons-years) of CAH groups were: treated HBeAg-positive (20.7), untreated HBeAg-positive (19.1), treated HBeAg-negative (10.1), and untreated HBeAg-negative (8.1). Older age (P = 0.001) and inactive carrier status (P = 0.019) were independent predictors of HBsAg clearance. CONCLUSION: In a well-characterized real-life clinical cohort of chronically HBV-infected patients in various disease phases, older age, and inactive HBsAg carrier status were the only predictors of HBsAg clearance, whereas anti-HBV therapy only marginally increased annual incidence of HBsAg loss.

Association of human leukocyte antigen DQB1 and DRB1 alleles with chronic hepatitis B.

AIM: To investigate the effect of human leukocyte antigen (HLA) DRB1 and DQB1 alleles on the inactive and advanced stages of chronic hepatitis B. METHODS: Patient records at a single institution's hepatology clinic were reviewed. Demographic data, laboratory results, endoscopy results, virological parameters, biopsy scores and treatment statuses were recorded. In total, 355 patients were eligible for the study, of whom 226 (63.7%) were male. Overall, 82 (23.1%) were hepatitis B early antigen (HBeAg) positive, 87 (24.5%) had cirrhosis, and 66 (18.6%) had inactive disease. The presence of DQB1 and DRB1 alleles was determined by polymerase chain reaction with sequence-specific primers. The distribution of the genotyped alleles among patients with cirrhosis and patients with chronic active hepatitis was analyzed. RESULTS: The most frequent HLA DQB1 allele was DQB1*03:01 (48.2%), and the most frequent HLA DRB1 allele was DRB1*13/14 (51.8%). DQB1*05:01 was more frequent in patients with active disease than in inactive patients (27% vs 9.1%; P = 0.002, Pc = 0.026). DRB1*07 was rare in patients with cirrhosis compared with non-cirrhotics (3.4% vs 16%; P = 0.002, Pc = 0.022). Older age (P < 0.001) and male gender (P = 0.008) were the other factors that affected the presence of cirrhosis. In a multivariate logistic regression analysis, DRB1*07 remained a significant negative predictor of cirrhosis (P = 0.015). A bioinformatics analysis revealed that a polymorphic amino acid sequence in DRB1*07 may alter interaction with the T-cell recognition site. CONCLUSION: This study demonstrates that HLA alleles may influence cirrhosis development and disease activity in Turkish chronic hepatitis B patients.

Increased levels of IL-21 responses are associated with the severity of liver injury in patients with chronic active hepatitis B.

Interleukin-21 (IL-21) participates in tissue damage in various immune-mediated diseases. Its role in the pathogenesis of chronic active hepatitis B (CAHB) has not been clarified. The frequency of circulating IL-21(+) T cells and the levels of serum and intrahepatic IL-21 have been characterized in 70 CAHB patients, 32 inactive carrier (IC), 18 chronic hepatitis C (CHC) and 20 healthy controls (HC). Their potential association with liver injury was analysed. The percentages of IL-21(+) CD3(+) CD8(-) and IL-21(+) CD3(+) CD8(+) T cells and the levels of serum IL-21 in CAHB patients were significantly higher than that in the IC, CHC patients and HC (P < 0.001) and were correlated positively with the levels of serum alanine aminotransferase (ALT, r = 0.424, P < 0.001; r = 0.392, P = 0.001) and aspartate aminotransferase (AST, r = 0.388, P = 0.001; r = 0.329, P = 0.005) in CAHB patients, respectively. The levels of IL-21 expression in the liver tissues were associated significantly with increased degrees of inflammation and fibrosis in CAHB patients (P < 0.01 or P < 0.05). Our findings suggest that aberrant IL-21 responses may be associated with the progression of CHB.

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.

Autoimmune hepatitis induced by nitrofurantoin. The importance of the autoantibodies for an early diagnosis of immune disease.

Nitrofurantoin has been in use since 1953 as an effective agent for the prevention of recurrent urinary tract infection. It is associated with a wide range of adverse drug reactions. Chronic active hepatitis has increasingly been observed and many cases have been reported with case fatalities. We present a case of nitrofurantoin induced chronic active hepatitis and briefly review the serology and clinico pathological features of 57 similar cases reported in English literature. The consistent presence of antinuclear antibody, anti smooth muscle antibody, elevated immunoglobulin and pathological feature suggests an immunologic mechanism. Complete recovery is possible in most cases if medication is discontinued in time. Steroids may play a role in management if no improvement occurs despite discontinuation of medication. We suggest all patients who are on prolonged nitrofurantoin therapy be followed up with anti nuclear antibody, anti smooth muscle antibody, serum immunoglobulin and hepatic panel every three months.

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.