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H L Janssen

Publications and source records attributed to H L Janssen.

32 records · Page 2Linked to original sources
PubMed1998

Graves' hyperthyroidism in a patient with primary sclerosing cholangitis. Coincidence or combined pathogenesis?

Several autoimmune disorders have been associated with the diagnosis of primary sclerosing cholangitis (PSC). We report on a 19-year-old male PSC patient with a history of ulcerative colitis who developed hyperthyroidism consistent with Graves' disease. In contrast to primary biliary cirrhosis, hyperthyroidism appears to be very uncommon in PSC patients. Nevertheless, the rarity of Graves' disease in young males, the presence of a human leucocyte antigen (HLA) phenotype often encountered in both Graves' disease and PSC and the presence of several autoantibodies suggest a common immunogenetic predisposition, rather than mere coincidence, of both diseases in this patient. Since many patients with thyroid disease exhibit mild cholestatic liver function abnormalities but few of them undergo cholangiographic examination, PSC may be underdiagnosed. Physicians should therefore be aware of the potential association between thyroid disease and PSC.

Adult↗
PubMed1995

Quantitative measurement of HBeAg in chronic hepatitis B: a comparison between a radioimmunoassay, a fluorescence ELISA and a chemiluminescence ELISA.

The presence of the hepatitis B e antigen (HBeAg) in peripheral blood of chronic hepatitis B patients is a widely accepted marker of active replication of the hepatitis B virus. HBeAg determination during interferon therapy is a useful guide for the therapeutic regimen. The aim of the study was to compare the suitability of an HBeAg radioimmunoassay (RIA, Abbott Laboratories, North Chicago, IL, USA), the IMx-HBeAg assay (IMx, Abbott Laboratories) and the HBeAg/anti-HBe Amerlite assay (Amerlite, Johnson & Johnson Clinical Diagnostics, Cardiff, UK) for semiquantitative monitoring of HBeAg during therapy. HBeAg levels in serum samples obtained before and during interferon therapy were measured using an in-house standard calibrated against the Paul Ehrlich Institute HBeAg reference preparation (PEI standard). When serial dilutions of pretreatment serum samples were assayed by the three methods, radioimmunoassay was found to be highly sensitive although it had a very limited working range (0.5 to 12 PEI U/ml). A broader linear working range was observed for Amerlite (0.5 to 50 PEI U/ml) and the IMx assay (0.5 to 100 PEI U/ml). The intra-assay and interassay variations did not differ significantly. Since the IMx assay was less susceptible to sample variation and had a broad working range, semiquantitative measurement of HBeAg in one diluted and one undiluted sample by this assay may justifiably be introduced as routine procedure. Routine semiquantitative HBeAg measurement may improve individual dose adjustments and thus the success of interferon therapy.

Chronic Disease↗
PubMed1994

Measurement of HBsAg to monitor hepatitis B viral replication in patients on alpha-interferon therapy.

HBsAg was measured quantitatively in serum samples collected serially before and after the HBeAg seroconversion date from 69 patients with HBeAg seroconversion and 17 patients with both HBeAg and HBsAg seroconversion. In patients with only HBeAg seroconversion the median HBsAg level decreased from 8.39 micrograms/ml (range 0.01-57.51) before HBeAg seroconversion to 3.53 micrograms/ml (range 0.002-68.66) after seroconversion (P < 0.001). No significant drop in HBsAg was found for the control group (18 HBeAg-positive patients without seroconversion). From 12 other patients on alpha-interferon therapy HBsAg was quantitatively assayed monthly during and after therapy; HBsAg levels were compared to the levels of HBV-DNA and HBeAg. We observed a good correlation between the HBsAg level and both the HBV-DNA (r = 0.76; P < 0.001) and the HBeAg (r = 0.70; P < 0.001) level, irrespective of the response to alpha-interferon. Quantified assessment of HBsAg appears promising as a simple and cheap method for monitoring viral replication in chronic hepatitis B in patients undergoing interferon therapy.

Hepatitis B↗
PubMed1994

Suicide associated with alfa-interferon therapy for chronic viral hepatitis.

We report on two attempted suicides and one successful suicide during or shortly after alfa-interferon therapy for chronic viral hepatitis. While on therapy, all three patients developed a psychiatric disorder leading to their suicidal behavior. In a survey of 15 European hospitals, three cases of attempted and two of successful suicide during alfa-interferon therapy for chronic viral hepatitis, were additionally reported. None of the patients had a psychiatric history. Alfa-interferon is known to lead to neuropsychiatric symptoms, and our observations strongly suggest that these mental disorders could lead to suicidal behavior. Therefore it is important that physicians, patients and their families are informed about the potential risk of the emotional and psychiatric disturbances that can occur during alfa-interferon therapy.

Adult↗
PubMed1993

Quantitative assessment of hepatitis B virus DNA in chronic hepatitis B: comparison of two solution hybridization assays.

We compared two solution hybridization assays, the AffiProbe assay (Orion Corporation) and the Abbott HBV-DNA assay (Abbott), for quantitative measurement of hepatitis B virus (HBV) DNA in serum samples obtained from chronic hepatitis B surface antigen (HBsAg) carriers. Forty transversally collected (group 1) and 83 serially collected (group 2) serum samples from chronic hepatitis B patients were tested with both assays. The serial serum samples were obtained from 6 patients who underwent alpha-interferon therapy with different outcomes (nonresponse, hepatitis B e antigen [HBeAg] seroconversion, HBeAg and HBsAg seroconversion). In group 1 a good correlation (r = 0.91; P < 0.001) was found between the HBV-DNA results of the two assays. Two samples (5%) were HBV-DNA positive according to the Abbott but negative according to the AffiProbe assay; for all other samples the HBV-DNA status corresponded. In group 2 the assays gave colinear HBV-DNA results during follow-up of 5 of the 6 patients (correlation for the total group: r = 0.90; P < 0.001). Nevertheless, in both groups the AffiProbe assay yielded about 5-10 times higher HBV-DNA levels than the Abbott HBV-DNA assay (P < 0.001). These discordant results were most probably due to standardization differences of the positive control samples of the two test systems. This observation underlines the need for international standardization of HBV-DNA and uniform reference panels.

Chronic Disease↗
PubMed1993

Repeated courses of alpha-interferon for treatment of chronic hepatitis type B.

In chronic hepatitis B transition from active replication to viral latency (HBeAg seroconversion) usually leads to remission of the disease. alpha-Interferon (IFN) therapy induces HBeAg seroconversion in about one-third of the patients, thus leaving the majority of patients with persistent disease. Eighteen chronic hepatitis B patients who did not respond (HBeAg seroconversion and clearance of HBV-DNA) to an initial 16-week course of IFN subsequently received IFN again after at least 6 months of no therapy. The repeated therapy consisted of 1.5-5 MU lymphoblastoid IFN daily for 16 weeks. Treatment effects were monitored by quantitative measurement of HBeAg and HBV-DNA. To analyze whether the results were related to patient characteristics known to affect the response to initial treatment, a predicted response rate, based on pre-treatment factors, was determined. After a follow-up of 52 weeks, 2 of the 18 patients (11%) had responded to therapy. Two additional patients became HBV-DNA-negative with sustained HBeAg positivity. All patients remained HBsAg-positive. According to the pre-treatment parameters, a response was predicted for 9 of the 18 patients (50%). This predicted response rate was significantly higher than the actual response rate (p = 0.03). In conclusion, this pilot study with moderate dosages of IFN suggests that the HBeAg seroconversion rate after repeated IFN treatment is low for previous non-responders and probably is not related to important clinical characteristics that influence the response to initial IFN treatment. A large controlled trial with higher doses of IFN is desirable to further evaluate the benefits of retreatment.

Adult↗
PubMed1993

Interferon-alpha and zidovudine combination therapy for chronic hepatitis B: results of a randomized, placebo-controlled trial.

Interferon-alpha therapy leads to HBeAg seroconversion in only one third of patients with chronic hepatitis B. In an attempt to increase the seroconversion rate, we investigated the combination of interferon-alpha and zidovudine in a subset of patients with presumably low response rates for interferon-alpha monotherapy. In a double-blind, controlled trial, 24 HBeAg-positive patients were randomized to receive lymphoblastoid interferon-alpha in subcutaneous doses increasing to 5 MU daily, combined with zidovudine given orally in doses increasing from 500 to 1,000 mg/day or with placebo for 16 wk. Treatment effects were monitored by quantitative assessment of HBV DNA, HBeAg and HBV DNA polymerase. Six months after termination of therapy, 1 of 12 (8%; 95% confidence interval = 2% to 39%) patients treated with interferon-alpha plus zidovudine and 2 of 12 (17%; 95% confidence interval 2% to 48%) patients from the control group exhibited responses (HBeAg seroconversion). All patients remained HBsAg positive. The only responder of the interferon-alpha-zidovudine group relapsed after cessation of therapy, so none of the zidovudine-treated patients were HBeAg negative at the end of follow-up. No significant difference in AST level or in any of the virological markers was observed between the two groups during the course of the study. Adverse effects (anemia, leukopenia) necessitated reduction in the dose of zidovudine in 50% and of interferon-alpha in 42% of the patients treated with interferon-alpha plus zidovudine; in the control group these rates were 0% for placebo and 8% for interferon-alpha. In conclusion, the antiviral effect of interferon-alpha in chronic hepatitis B was not enhanced by additional zidovudine treatment. The combination therapy induced considerable side effects leading to dose reduction for both zidovudine and interferon-alpha. For combination therapy with interferon-alpha, oral nucleoside analogs with more potent antiviral effects and less toxicity than zidovudine should be developed.

Adolescent↗
PubMed1992

[Alpha-interferon antiviral treatment in 100 patients with chronic hepatitis B].

In a retrospective study we investigated the antiviral effect of alpha-interferon in 100 patients with chronic hepatitis B who were treated in controlled trials conducted in Rotterdam (1985-1990). The aim of the treatment was to induce viral latency as indicated by HBeAg seroconversion. Alpha-interferon was administered in a dose of 5 mega-units per day subcutaneously. Sixty-two patients received alpha-interferon for 16 weeks combined with a second antiviral agent (acyclovir or descyclovir) while the other 38 patients were treated with alpha-interferon monotherapy during 20 to 34 weeks. Follow-up continued until 1 year after the start of therapy. Thirty-eight per cent of the patients exhibited an HBeAg seroconversion and 9% exhibited an HBsAg seroconversion indicating a complete eradication of the virus. After 1 year transaminase levels were normalised in 70% of the patients with HBeAg seroconversion compared with 22% in those without seroconversion (p less than 0.05). The combination therapy for 16 weeks and the alpha-interferon monotherapy of longer duration resulted in HBeAg seroconversion rates of 29% and 53%, respectively (p less than 0.05). The predominant adverse effects were fatigue, flue-like illness and leukopenia. Serious side effects such as seizures, psychosis and peripheral neuropathy occurred in seven patients. Side effects led to a dose reduction in 26% of the patients. Alpha-interferon is effective in terminating the virus replication in chronic hepatitis B. However, both the common mild and the uncommon major side effects necessitate intensive patient monitoring during alpha-interferon treatment.

Acyclovir↗
PubMed1992

Survival and prognostic indicators in hepatitis B surface antigen-positive cirrhosis of the liver.

To evaluate indications for new therapies such as liver transplantation and antiviral therapy, survival of histologically proven hepatitis B surface antigen (HBsAg)-positive cirrhosis of the liver was assessed in a cohort of 98 patients followed up for a mean of 4.3 years. The overall survival probability was 92% at 1 year, 79% at 3 years, and 71% at 5 years. Variables significantly associated with the duration of survival were age, serum aspartate aminotransferase levels, presence of esophageal varices, and all five components of the Child-Pugh index (bilirubin, albumin, coagulation factors, ascites, encephalopathy). Multivariate analysis showed that only age, bilirubin, and ascites were independently related to survival. Survival of patients with decompensated cirrhosis (determined by the presence of ascites, jaundice, encephalopathy, and/or a history of variceal bleeding) and those with compensated cirrhosis at 5 years was 14% and 84%, respectively. For patients with compensated liver cirrhosis, hepatitis B e antigen (HBeAg) positivity was also a prognostic factor with a 5-year survival of 72% for HBeAg-positive cirrhosis and 97% for HBeAg-negative cirrhosis; the risk of death was decreased by a factor of 2.2 when HBeAg seroconversion occurred during follow-up. It is concluded that liver transplantation should be considered for patients with decompensated HBsAg-positive liver cirrhosis and antiviral therapy for patients with HBeAg-positive compensated cirrhosis.

Adult↗
PubMed1992

Antiviral effect of prolonged intermittent lymphoblastoid alpha interferon treatment in chronic hepatitis B.

In a European multicentre study 40 patients with HBeAg positive chronic hepatitis B virus (HBV) infection were treated with 5 mega units of lymphoblastoid alpha-interferon daily according to the following regimen: a four week primer course, four weeks of rest and a second course lasting 16 to 30 weeks. After 52 weeks of follow up, a response (HBeAg seroconversion and HBV-DNA negativity) was observed in 22 patients (55%). HBsAg seroconversion occurred in five patients (12.5%). One patient exhibited a relapse for serum HBeAg and HBV-DNA after cessation of treatment. According to a response prediction model, the observed response rate was not related to the selection of patients likely to respond. The initial interferon course induced a reduction of the serum HBV-DNA and HBeAg levels of 87% and 18%, respectively, leading to a significantly lower level of viral replication activity at the start of the second longterm course compared with baseline. After 24 weeks of follow up (week 16 of the second course), 19 (48%) patients exhibited a response, 13 (32%) a partial response (HBeAg < 50% of initial level or HBV-DNA negative) and 8 (20%) no response. For eight of the 13 partial responders treatment was stopped at week 24 and viral replication rebounded to pretreatment values. In the last five partial responders prolongation of therapy up to week 38 led to a definite response and HBsAg seroconversion in three of the five patients. The results of this study suggest that a short primer course and prolongation of therapy may help to enhance the response rate of alpha-interferon therapy for chronic hepatitis type B.

Adolescent↗