Biomedical subjects

J W Rasenack

Publications and source records attributed to J W Rasenack.

7 recordsLinked to original sources

PubMed2001

Specific cellular immune response and cytokine patterns in patients coinfected with hepatitis C virus and Schistosoma mansoni.

Patients coinfected with hepatitis C virus (HCV) and Schistosoma mansoni show high incidence of viral persistence and accelerated fibrosis. To determine whether immunological mechanisms are responsible for this alteration in the natural history of HCV, the HCV-specific peripheral CD4(+) T cell responses and cytokines were analyzed in patients with chronic hepatitis C monoinfection, S. mansoni monoinfection, or HCV and S. mansoni coinfection. An HCV-specific CD4(+) proliferative response to at least 1 HCV antigen was detected in 73.3% of patients infected with HCV, compared with 8.6% of patients coinfected with HCV and S. mansoni. Stimulation with HCV antigens produced a type 1 cytokine profile in patients infected with HCV alone, compared with a type 2 predominance in patients coinfected with HCV and S. mansoni. In contrast, there was no difference in response to schistosomal antigens in patients infected with S. mansoni alone, compared with those coinfected with HCV and S. mansoni. These findings suggest that the inability to generate an HCV-specific CD4(+)/Th1 T cell response plays a role in the persistence and severity of HCV infection in patients with S. mansoni coinfection.

Adult↗

PubMed2001

Acute hepatitis C without and with schistosomiasis: correlation with hepatitis C-specific CD4(+) T-cell and cytokine response.

BACKGROUND & AIMS: Immune responses during the first few months of acute hepatitis C virus (HCV) infection seem crucial for viral control, but the relationship of these responses to natural history is poorly characterized. METHODS: This prospective study investigated the HCV-specific CD4(+) and cytokine responses in patients with acute HCV hepatitis with or without Schistosoma mansoni coinfection, a parasitic infection with T helper (Th) 2 immune bias. HCV-specific CD4(+) proliferative responses and cytokine production in peripheral blood mononuclear cells were correlated with liver biopsy results at 6 months and at the end of follow-up. RESULTS: Whereas 5 of 15 patients with HCV alone recovered from acute HCV, all (17 of 17) patients with S. mansoni coinfection progressed to histologically proven chronic hepatitis. Coinfected patients had either absent or transient weak HCV-specific CD4(+) responses with Th0/Th2 cytokine production. The magnitude of the HCV-specific CD4(+) response at week 12 was inversely correlated with the fibrosis progression rate in chronically infected patients. CONCLUSIONS: Patients with acute hepatitis C and schistosomiasis coinfection cannot clear viremia and show rapid progression once chronic infection is established. This rapid progression is associated with a strong Th2 response in peripheral immune responses, suggesting that early development of vigorous Th1 responses not only facilitates clearance but delays disease progression.

Acute Disease↗

PubMed2000

[Hepatitis C--standard therapy].

Infection with the hepatitis C virus leads to chronic hepatitis in the majority of patients. Diagnosis is based on the presence of anti-HCV antibodies and confirmed by positive HCV RNA. The natural course of the disease is slow. Cirrhosis is found in a minority of patients two decades post infection. Nevertheless, cirrhosis is much more frequently observed than in patients with hepatitis B infection. Treatment of choice is interferon-alpha. Today combination with ribavirin is recommended for most patients. In combination therapy the sustained response rate six months after stop of treatment is about 40% in naive patients with respect to virus elimination. In patients treated with high doses of interferon-a for one year the sustained response rate is comparable. The response rate is higher in patients with HCV infections of non-1 genotype and in patients with lower virus titers, e.g. less than 2 Mill. genome equivalents per ml. Interferon-a treatment also leads to an improvement of liver histology. Necro-inflammatory scores are reduced. It has also an antifibrogenic effect. Progression of fibrosis is reduced. The antiproliferative effect of interferon-a leads a lower rate of hepatocellular carcinomas, which has been demonstrated in several retrospective studies. In patients with Child A cirrhosis the time till decompensation is delayed. Because of the slow progression, the relatively low response rate and the adverse events of interferon-a and ribavirin treatment should be instituted on an individual base depending on host factors such as age, co-morbidity and stage of liver disease.

Antiviral Agents↗

PubMed2000

Clinical, virological and histopathological features: long-term follow-up in patients with chronic hepatitis C co-infected with S. mansoni.

BACKGROUND/AIMS: Infection with Schistosoma mansoni is endemic in Egypt leading to hepatic schistosomiasis and eventually portal hypertension. The prevalence of antibodies against hepatitis virus C among Egyptians is 14-51%. The aim of the present study was to investigate the influence of schistosomiasis on chronic hepatitis C with respect to the natural course of the disease, immunology, virology and histology. PATIENTS AND METHODS: One hundred and twenty-six Egyptian patients classified into three groups: group A: chronic hepatitis C (n=33); group B: chronic schistosomiasis (n=30) and group C: chronic hepatitis C and chronic schistosomiasis (n=63) were enrolled and prospectively followed for 62.7 +/- 22 months. Patients infected with other hepatic viruses and/or parasites were excluded. Detailed history, clinical examination, CD4+ and CD8+ lymphocyte counts in blood, hematological and blood chemical values, abdominal ultrasonography, upper endoscopy, HCV RNA titer by RT/PCR, genotype and histological activity index in the liver biopsy were determined. RESULTS: Thirty patients (48%) with HCV and schistosomiasis had liver cirrhosis and Child-Pugh class C vs. five (15%) in HCV patients and none in the schistosomal group. HCV RNA levels ranged between 0.07 and 13 x 10(5) copies/ml in group A, and between 1 and 25 x 10(5) copies/ml in group C. HCV genotype 4 was detected in 58 patients with co-infection (92%) and 21 patients with HCV alone (64%). Patients with coinfection showed higher grading and staging scores in their liver biopsies. Hepatocellular carcinoma was detected only in patients with coinfection. During follow-up, the mortality rate was 12%, 3% and 48% in group A, B and C, respectively. CONCLUSIONS: Patients with concomitant HCV and schistosomiasis infection were characterized by more advanced liver disease, higher HCV RNA titers, predominance of HCV genotype 4, higher histologic activity, higher incidence of cirrhosis and hepatocellular carcinoma as well as a much higher mortality rate.

Adult↗

PubMed1997

[Hepatitis B virus mutants--clinical significance].

Hepatitis B virus (HBV) mutants have recently been identified in patients with acute or fulminant as well as chronic infections. Naturally occurring mutations have been identified in all viral genes and regulatory elements, most notably in the genes coding for the structural envelope and nucleocapsid proteins. Mutations in the gene coding for the hepatitis B surface antigen (HBsAg) may result in infection or viral persistence despite the presence of antibodies against HBsAg (anti-HBs) ("vaccine escape" or "immune escape"). Mutations in the gene encoding the pre-core/ core protein (pre-core stop codon mutant) result in a loss of hepatitis B e antigen (HBeAg) and seroconversion to antibodies to HBeAg (anti-HBe) with persistence of HBV replication (HBeAg minus mutant). Mutations in the core gene may lead among others to an "immune escape" due to a T cell receptor antagonism. Mutations in the gene coding for the polymerase/reverse transcriptase can be associated with viral persistence or resistance to nucleoside analogues. Thus, HBV mutations may affect the natural course of infection, viral clearance and response to antiviral therapy. Apart from the precore/core stop codon mutations, the exact contribution of specific mutations to diagnosis and therapy of HBV infection as well as patient management in clinical practice remain to be established.

Antibody Formation↗

PubMed1996

Immunosuppressive therapy and hepatitis C virus infection: the clinical course of liver disease.

In a retrospective long-term follow-up study the clinical course of liver disease was examined in renal allograft recipients with hepatitis C virus (HCV) infection and negative hepatitis B surface antigen under immunosuppressive therapy. We compared 42 anti-HCV antibody (anti-HCV) positive patients (study group) to 213 anti-HCV negative patients (control group). All patients received immunosuppressive therapy. Measurements were made of the following: aminotransferases, bilirubin, albumin, gammaglobulins, ascites, spleen diameter, HCV RNA, and anti-HCV antibody. We found all but four anti-HCV positive patients to be HCV RNA positive prior to transplantation. There were no differences in overall mortality or mortality secondary to liver disease or sepsis. Normal liver enzymes were found in 13 (31%) anti-HCV positive and in 137 (64%) anti-HCV negative patients during the whole mean observation period of 65 months (range 10-215). Aminotransferase activity decreased in anti-HCV positive and negative patients during the observation period. Liver function with regard to synthesis and excretion was normal in anti-HCV negative and anti-HCV positive patients. No signs of portal hypertension were observed in the anti-HCV positive group. Neither the different immunosuppressive regimens nor the antirejection therapy led to differences between anti-HCV positive and negative groups with respect to liver function and did not alter the clinical course. We conclude that HCV infection in patients under immunosuppressive therapy causes only a mild liver disease, as determined by clinicochemical and clinical parameters, and that mortality rate is not increased.

Adolescent↗

PubMed1995

Hepatitis B virus infection without immunological markers after open-heart surgery.

Post-transfusion hepatitis is still an important problem, despite the screening of blood donors for hepatitis B (HBV) and C virus infections. We assessed whether HBV DNA might be detected by PCR in prospectively collected serum samples of patients with unexplained post-transfusion hepatitis but no immunological HBV markers. We found HBV DNA in 4 (20%) of 20 patients with unexplained post-transfusion hepatitis and in 5 patients with mildly increased aminotransferases. The clinical course of these HBV infections was usually mild and self-limiting. Thus we found that low-titre, immunologically negative HBV infections do exist and might represent a significant cause of post-transfusion hepatitis.

Alanine Transaminase↗