Treatment Of Chronic Active Hepatitis Research Articles

Treatment of Hepatitis B Virus-Associated Membranous Nephropathy: Lamivudine Era versus Post-Lamivudine Era

Treatment of Hepatitis B Virus-Associated Membranous Nephropathy: Lamivudine Era versus Post-Lamivudine Era

Thoracic Complications of Liver Cirrhosis: Radiologic Findings

Patients with chronic liver disease exhibit various cardiovascular and pulmonary complications. Hepatopulmonary syndrome results in dyspnea due to intrapulmonary arteriovenous shunting and ventilation-perfusion mismatch. Portopulmonary hypertension occurs in patients with portal hypertension. Intrathoracic portosystemic collateral vascular pathways develop in patients with portal hypertension to allow decompression of the portal vein into the systemic circulation. Hepatic hydrothorax may develop in patients with cirrhosis and ascites. Massive necrosis of the liver from any cause may be associated with acute hypoxic respiratory failure, necessitating ventilatory support. Bacterial infection is common in cirrhotic patients because of a compromised host defense system. Hepatocellular carcinoma may produce hematogenous lung metastases, intrathoracic lymph node metastases, direct intracardiac extension, and pulmonary embolism. Interferon therapy for treatment of chronic active hepatitis C may disturb cellular immune activation in some patients and contribute to the onset and progression of sarcoidosis. Awareness of the various thoracic manifestations in chronic liver disease can be helpful for making a differential diagnosis and planning proper management.

The effect of recombinant interferon-alpha on lymphocyte subpopulations and HLA-DR expression on liver tissue of HBV-positive individuals

Interferon-alpha (IFN-alpha) has been reported to be beneficial in the treatment of chronic active hepatitis occurring as a result of hepatitis B virus (HBV) infection. Treatment with IFN-alpha has been proposed as a means of reducing the high rate of allograft infection in clinical liver transplantation in patients transplanted for HBV-related chronic active hepatitis and cirrhosis who are positive for hepatitis B surface antigen (HBsAg). We obtained resected whole livers from two groups of patients who received liver transplants. Group A consisted of 11 patients who were HBsAg+ but were not treated with IFN-alpha, and group B consisted of 10 patients who were also HBsAg+ but received IFN-alpha therapy for 29.4 +/- 5.6 days prior to orthotopic liver transplantation. No differences between the two groups existed in terms of a variety of demographic and clinical characteristics. The liver tissue was stained with monoclonal antibodies to cell surface antigens unique to different mononuclear cell populations by the avidin-biotin-immunoperoxidase technique to determine the effect of IFN-alpha on the lymphocyte subsets as well as HLA antigen expression on liver-infiltrating mononuclear cells. The number of HLA-DR+ lymphocytes in the liver was significantly increased (P less than 0.005) within the portal areas in group B compared with that found in group A (84 +/- 14 versus 33 +/- 5 per one high-power field). Moreover, the intensity of the HLA-DR antigen expression on lymphocytes in the portal areas (P less than 0.02) and in the hepatic lobule (P less than 0.05) was greater in group B than in group A. The number of natural killer (NK) cells was increased in the portal areas (P less than 0.05) of group B compared with group A. These alterations in the lymphocyte and NK cell populations present in the liver in response to IFN-alpha therapy presumably reflect an IFN-alpha-induced enhancement of the immune response to virus-infected cells.

Persistence of acute infection with hepatitis B virus genotype A and treatment in Japan

Among the 97 adult patients with acute hepatitis B who were admitted to the Toranomon Hospital in Metropolitan Tokyo during 28 years from 1976 to 2003, 31 (32%) were infected with hepatitis B virus (HBV) genotype A, nine (9%) with genotype B, 44 (45%) with genotype C, one (1%) each with genotypes E and F. HBV in the remaining 11 (11%) patients were untypeable. All the 31 patients with acute hepatitis B caused by HBV genotype A infection were male with a median age of 31 years, and 16 (52%) contracted infection through extramarital sexual contacts. The baseline HBV DNA level was higher in the seven (23%) patients in whom infection with HBV genotype A persisted than the remaining 24 (77%) with spontaneous resolution (median: >8.7 vs. 6.0 log genome equivalents/ml, P = 0.004). Persistent infection was more frequent in patients with maximum alanine aminotransferase <500 IU/L than > or =500 IU/L (83% [5/6] vs. 4% [1/25], P = 0.0001). Of the six patients with persistent HBV genotype A infection who received interferon and/or lamivuidine for treatment of chronic active hepatitis, three (50%) responded with the loss of hepatitis B e antigen (HBeAg); hepatitis B surface antigen (HBsAg) was cleared from serum in one patient who received interferon and lamivudine in sequence. HBV genotype A persisted along with HBeAg in the remaining three patients given antiviral therapy as well as another who was not treated. In conclusion, infection with HBV genotype A prevails in patients with acute hepatitis B in Japan where genotypes B and C are common, is often contracted sexually (16/31 [52%]) and tends to persist (7/31 [23%]). Infection was cleared in only one of the six (17%) patients who received antiviral therapy.

Efficacy of treatment with lamivudine in patients with chronic active E-minus variant hepatitis B virus infection: A nonrandomized, open-label study

Abstract Objective The aim of the present study was to assess the efficacy of lamivudine in the treatment of chronic active hepatitis B virus (HBV) infection in patients with the e-minus variant (HBeAb-HBV DNA positive). Background Lamivudine is a nucleoside analogue that inhibits the synthesis of DNA. Its efficacy in the treatment of chronic HBV infection of the wild type and the e-minus variant has recently been demonstrated. Methods The study patients, all of whom were nonresponders to previous therapy with interferon alfa, were assigned to receive oral lamivudine (group A; n = 10) or placebo (group B; n = 8). Eleven patients had chronic active hepatitis and 7 had cirrhosis; the average histologic score was 13. The treatment period lasted 52 weeks. Results All patients completed the study. At week 52, 7 of 10 patients showed evidence of clearance of HBV DNA and 6 of 10 had normal serum alanine aminotransferase (ALT) levels. At the end of the 12-month follow-up period, only 2 patients still showed both the virologie and biochemical response, whereas the other patients had relapsed. The histologic test at the end of the follow-up period showed a sustained response in 2 patients—a reduction of ≥2 points in the necroinflammatory score. No significant differences in response were noted between the 2 groups. Conclusions Lamivudine 100 mg/d administered orally for 52 weeks may be effective in normalizing serum ALT levels and HBV DNA negativity in patients with chronic active e-minus variant HBV infection who do not respond to antiviral therapy with interferon alfa. The long-term results were modest, however, with frequent relapses, even considering the difficult type of patients included in our study (ie, interferon alfa nonresponders).

Interferon treatment of chronic active hepatitis C during therapy of acute lymphoblastic leukemia

Due to concerns that antineoplastic therapy produces prolonged decrease in immune function, interferon treatment of chronic active hepatitis C (CAHC) has been used only at one year or longer after the end of cancer therapy. We report the experience of an 11-year-old who developed symptomatic CAHC at the start of maintenance therapy for testicular relapse of acute lymphoblastic leukemia (ALL). Significant dose reduction of maintenance therapy did not improve the tolerance of antileukemic treatment. In an effort to improve his liver disease and to deliver effective antileukemic therapy, interferon alpha and an alternative maintenance therapy regimen for ALL were initiated. The patient tolerated the combined therapy well. Interferon therapy was continued for 27 months, which was three months from the end of antineoplastic therapy. At that time serum transaminase values were normal, and no HCV viral genome was detectable. Viral genome was detected 10 months later. The combined effects of interferon and antineoplastic therapy resulted in myelosuppression requiring dose reduction of both treatments. The patient remains asymptomatic and with no evidence of recurrent leukemia more than six years from diagnosis of relapse. The effect on the status of this patient's CAHC was similar to that reported among leukemic patients who underwent an interferon course more than one year from the end of antineoplastic therapy. Interferon treatment of CAHC can be given concomitantly with antineoplastic therapy. Am. J. Hematol. 61:130–134, 1999. © 1999 Wiley-Liss, Inc.

Thymic hormones reduce replication of hepatitis B virus (HBV) in a course of treatment of chronic active hepatitis B (CAHB)

Thymic hormones reduce replication of hepatitis B virus (HBV) in a course of treatment of chronic active hepatitis B (CAHB)

Combining IgG and interferon alpha-2b in chronic hepatitis C virus infection

Treatment of chronic active hepatitis C virus (HCV) liver disease remains unsatisfactory. Interferon alpha2b (IFN) has shown favorable though often unsustained effects. Besides its antiviral properties, IFN is a recognized immune modulator. We present data showing the favorable evolution of a case treated with IFN and IgG. Besides the antibody repertoire, the influence of IgG on the immune network is increasingly considered. The complex interactions resulting from combining drugs with immunomodulatory properties, such as IFN and different IgG preparations, may sound confusing. However, it might provide an insight into the outcome of chronic HCV infection, in which, evidently, immune components are heavily implicated. Prolonged treatment, with high-dose intravenous immunoglobulin (IVIG) seemed to be effective, either independently or by potentiating IFN.

Combining IgG and interferon alpha-2b in chronic hepatitis C virus infection

Treatment of chronic active hepatitis C virus (HCV) liver disease remains unsatisfactory. Interferon alpha2b (IFN) has shown favorable though often unsustained effects. Besides its antiviral properties, IFN is a recognized immune modulator. We present data showing the favorable evolution of a case treated with IFN and IgG. Besides the antibody repertoire, the influence of IgG on the immune network is increasingly considered. The complex interactions resulting from combining drugs with immunomodulatory properties, such as IFN and different IgG preparations, may sound confusing. However, it might provide an insight into the outcome of chronic HCV infection, in which, evidently, immune components are heavily implicated. Prolonged treatment, with high-dose intravenous immunoglobulin (IVIG) seemed to be effective, either independently or by potentiating IFN.

Interferon-α 2b treatment of chronic active hepatitis C in patients co-infected with the human immunodeficiency virus (HIV): HCV viremia quantified by B-DNA and genotypic analysis: [formula omitted]1[formula omitted]1[formula omitted]1[formula omitted]1[formula omitted]2[formula omitted]2[formula omitted]1. Dept. of Gastroenterology 1 and Hematology 2, Hospital Geral de Santo António, Oporto, Portugal

Interferon-α 2b treatment of chronic active hepatitis C in patients co-infected with the human immunodeficiency virus (HIV): HCV viremia quantified by B-DNA and genotypic analysis: [formula omitted]1[formula omitted]1[formula omitted]1[formula omitted]1[formula omitted]2[formula omitted]2[formula omitted]1. Dept. of Gastroenterology 1 and Hematology 2, Hospital Geral de Santo António, Oporto, Portugal

Interferon Treatment of Chronic Active Hepatitis C in Patients with End-Stage Chronic Renal Failure

Alpha interferon has been shown to be effective in the treatment of chronic hepatitis C virus infection. We studied the efficacy of alpha 2a-interferon in chronic active hepatitis C patients with end-stage chronic renal failure (CRF). Thirteen patients with CRF and 12 patients with a normal renal function were included in the study. The patients received interferon 3 million units three times a week subcutaneously for 6 months. All patients with CRF and 6 patients without CRF had a complete response, defined as a decline in serum alanine aminotransferase levels to the normal range. One patient had a decrease in alanine aminotransferase of more than 50%, and 5 patients were nonresponders. A relapse was observed in 4 patients with and in 4 without CRF. Three patients had renal transplantation, and the alanine aminotransferase levels were normal after 12-14 months. This preliminary study shows that interferon is effective in the treatment of patients with chronic hepatitis C and CRF.

Iron removal as premedication for treatment of chronic active hepatitis C

Iron removal as premedication for treatment of chronic active hepatitis C

Efficacy of polyadenylic.polyuridylic acid in the treatment of chronic active hepatitis B

In order to assess whether polyadenylic. polyuridylic acid [poly(A).poly(U)] can be used as a new therapeutic agent for the treatment of chronic hepatitis B, 19 patients with histologically proven chronic active hepatitis B were injected intravenously with 100–150 mg of poly(A).poly(U) weekly for six weeks. Changes in alanine aminotransferase (ALT) levels, 2′.5′-olidoadenylate synthetase (2.5′.5′-AS) activities and HBV markers were sequentially checked during and after treatments. Serum ALT levels were decreased gradually and 2′.5′-AS activities were significantly increased after initiation of poly(A).poly(U) injections. At the end of this trial (24th week) we have observed the normalizations of elevated ALT levels in 14 (73.7%), negative conversion of HBeAg in 11 (57.9%) and loss of HBV-DNA in 12 out of 19 patients (63.1%). Complete responses which had both normalization of ALT levels and negative conversion of HBeAg were noted in 11 patients (57.9%) and partial responses showing either normalization of ALT levels or negative conversion of HBeAg alone were in four out of 19 patients (21.1%). No notable adverse effects were observed during the treatments and follow-up period. It can be concluded that poly(A).poly(U) seems to be effective in the treatment of chronic active hepatitis B and has an advantage of being free of significant side effects.

The cost effectiveness of alpha interferon in the treatment of chronic active hepatitis C

To model the costs and effects of alpha interferon in the treatment of chronic active hepatitis C. A Markov modelling process to simulate the costs and outcomes in hypothetical cohorts of patients treated with and without alpha interferon. Costs per life saved and per life-year gained. On the basis of assumptions formulated about the disease processes and response to treatment, treatment with alpha interferon results in a discounted cost per life-year gained of $33,230 in patients with cirrhosis at the start of treatment and $71,950 in patients without advanced liver disease. The result is sensitive to the assumptions made about the long term effectiveness of alpha interferon. Alpha interferon is an expensive drug. Its effectiveness is clouded by uncertainty about the long term impact of the drug on the natural history of the disease. If adopted, its use should be monitored to allow the long term cost effectiveness of the drug to be evaluated properly.

Exacerbation of psoriasis due to alpha interferon (INF-α) treatment of chronic active hepatitis C (CAHC)

Exacerbation of psoriasis due to alpha interferon (INF-α) treatment of chronic active hepatitis C (CAHC)

Pilot study of interferon $alpha;-2B treatment of chronic active hepatitis C in patients co-infected with the human immunodeficiency virus 6HIV-19

Pilot study of interferon $alpha;-2B treatment of chronic active hepatitis C in patients co-infected with the human immunodeficiency virus 6HIV-19

Interferon treatment of chronic active hepatitis B: effect of a six month treatment regimen.

In this study of 17 patients with chronic active hepatitis B, the loss of hepatitis B virus DNA, the return to normal of alanine aminotransferase activities, and histological improvement after six months' treatment with 3 million units three times weekly with interferon alfa-2b, was achieved in 40% of hepatitis B e antigen (HBeAg) positive/anti HBe negative patients, and 41.66% of HBeAg negative/anti HBe positive patients. The reappearance of hepatitis B virus DNA was seen in most patients when treatment was stopped, although a higher percentage of HBeAg positive/anti HBe negative patients (20%) had a sustained loss of hepatitis B virus DNA, return to normal alanine aminotransferase activities, and histological improvement compared with HBeAg negative/anti HBe positive patients (8.3%).

Significance and relevance of serum preS1 antigen detection in wild-type and variant hepatitis B virus (HBV) infections.

These studies assessed whether the serum expression of preS1 antigen could be a useful HBV marker for monitoring the progress of antiviral therapy in the treatment of chronic active hepatitis B (CAH-B) virus infections. Our findings indicate that: 1) the rearrangements we observed in the preS region of mutated HBV DNA molecules during chronic infection did not effect the preS1 sequence (21-47) critical for HBV infectivity; 2) the persistence or even the rebound of preS1 antigen expression during follow-up in responders to antiviral therapy may indicate virus persistence, suggesting the possibility of relapse through wild-type HBV or the emergence of HBV variants following the immunoelimination phase.

To treat or not to treat?: The judicious use of interferon-α-2a for the treatment of chronic hepatitis B

Based on results from extensive clinical research, interferon-alpha-2a (IFN-alpha-2a, Roferon-A, F. Hoffmann-LaRoche Ltd., Switzerland) and other interferons have been registered for the treatment of chronic active hepatitis B. The officially recommended dose regimen is 4.5 MIU (or 2.5 MIU/m2) thrice weekly for 6 months. To present guidelines for the optimization of treatment for individual patients, 3 major controlled trials from our worldwide research program with a total of 416 patients were reviewed in a meta-analysis. Before deciding whether to treat or not, the history, prognosis and chances of treatment success for a given patient must be carefully assessed. Liver histology and repeated quantitative measurements of markers for viral replication (HBV-DNA, HBeAg) and biochemical markers for liver disease such as ALT are valuable indicators. After the decision to treat, monthly quantitative measurements of these markers make it possible to monitor therapeutic success. Depending on the course they run, treatment can continue unchanged, be adjusted in dose or duration until a full response is achieved, or be terminated early in case of evidence of non-response.

Chronic liver disease. The scope of causes and treatments.

Evaluation of chronic liver disease begins with a carefully taken history, thorough physical examination, and standard laboratory tests. Often, however, other studies are required, such as a viral hepatitis panel, serologic tests for autoimmune markers, tests for antimitochondrial antibodies, measurement of serum iron and ceruloplasmin levels, liver biopsy, and imaging studies of the extra-hepatic bile ducts. Medical treatment of chronic active hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis remains unsatisfactory. Early treatment of hemochromatosis and Wilson's disease can prevent cirrhosis and liver failure. Liver transplantation is now a viable procedure for patients with end-stage chronic liver disease.