Search PubMed⌕ Search

Biomedical subjects

O Weiland

Publications and source records attributed to O Weiland.

At least 73 records · Page 4Linked to original sources

Histological outcome in patients with chronic hepatitis C given a 60-week interferon alfa-2b treatment course.

Forty patients with chronic hepatitis C virus (HCV) infection were treated with 3 MU interferon alfa-2b given subcutaneously for 60 weeks. A biochemical response with normalization of serum alanine aminotransferase (s-ALT) levels was seen in 24 patients (60%) at treatment cessation. A sustained response with continuously normal s-ALT levels during 24 weeks of follow up was seen in 15 of these 24 patients (62%), all of whom also became HCV RNA negative in serum. Histological changes in the pre- and posttreatment liver biopsies were assessed using a numerical scoring system. Biochemical responders had a significant decrease in all four scored categories: portal inflammation, piecemeal necrosis, spotty necrosis and fibrosis. Non-responders had a significant decrease in piecemeal necrosis and spotty necrosis, whereas the scores for portal inflammation and fibrosis remained unchanged. There was no significant difference in any of the scored categories in the pretreatment biopsy between responders and non-responders. We conclude that patients suffering from chronic HCV infection who responded biochemically and virologically to interferon treatment also improved their liver histology. Necroinflammatory activity decreased to some extent in biochemical non-responders, possibly giving them some benefit from the treatment, but not to the same extent as responders. No specific histological pretreatment findings were predictive of biochemical response to interferon treatment.

Alanine Transaminase↗

Hepatitis C virus replication in liver and peripheral blood mononuclear cells of interferon-alpha-treated and untreated patients with chronic hepatitis C.

Serum, liver tissue, and peripheral blood mononuclear cells (PBMC) were obtained from 72 patients with chronic hepatitis C, 19 of whom had received interferon-alpha (IFN-alpha) treatment. Hepatitis C virus (HCV) RNA was detected by polymerase chain reaction in the serum and liver of all patients with relapse after treatment and in 51 of 53 (96%) sera, 28 of 29 (97%) livers, and all of 13 (100%) PBMC from untreated patients but not in 3 patients with completely sustained responses. Minus-stranded HCV RNA was found in 5 of 14 (35%) sera, 16 of 17 (94%) livers, and 7 of 13 (53%) PBMC from untreated patients. The results indicate that HCV RNA is present not only in serum and liver but also in PBMC from the vast majority of untreated anti-HCV-seropositive patients and also in patients who respond to IFN-alpha treatment but then relapse. HCV replicates in the liver of almost all patients, but replication may possibly also occur in PBMC. By contrast, HCV RNA seems to be eradicated in patients with completely sustained responses.

Alanine Transaminase↗

Prevalence of antibodies against hepatitis C virus infection among health care workers in Stockholm.

The prevalence of hepatitis C virus (HCV) markers was investigated among health care staff with a high rate of exposure to blood or needle-stick injuries. After screening sera in pools of 10 at a time and individual testing of all reactive pools, totally 6 of 880 (0.7%; 95% confidence interval, 0.25-14.8%) were positive for anti-HCV, a figure of the same order as that found among Swedish first-time blood donors. Among the seropositives, all of five evaluable had been exposed to blood and four of five to needle-stick injuries. Our data suggest that HCV, in addition to hepatitis B virus, may constitute an occupational hazard for health care workers in Stockholm, even though the risk appears to be low, and personal risk factors such as intravenous drug abuse or blood transfusion could not be ruled out as sources of the infection.

Adolescent↗

Long-term histological outcome in patients with chronic hepatitis C treated repeatedly with interferon alpha-2b without sustained response.

Nine patients with chronic hepatitis C who responded with normal or near-normal serum alanine aminotransferase (s-ALT) levels during an initial interferon alpha-2b treatment course, but who had subsequent relapses with elevated s-ALT levels after treatment cessation, were retreated once (3 patients) or twice (6 patients). The liver histological findings before the first and after the last treatment course were compared. The mean follow-up time between the initial and the follow-up assessment was 44 months (range 34-53). The histological findings were classified as chronic persistent hepatitis (CPH), chronic active hepatitis (CAH) or cirrhosis (Ci) by using a numerical scoring system assessing each portal zone separately. In the initial biopsy, 2 patients were classified as having CPH and 7 as having CAH, 2 of whom with signs of cirrhosis. According to the conventional classification, 4/9 (44%) patients improved after treatment, 3/9 (33%) remained unchanged, and 2/9 (22%) deteriorated. The mean histological scores for the necro-inflammatory parameters: portal inflammation, piecemeal necrosis, spotty necrosis and fibrosis improved, but the changes did not reach statistical significance. We conclude that repeated interferon alpha-2b treatment courses are probably beneficial in patients with chronic hepatitis C who show a non-sustained response to interferon, since studies on the natural course of chronic hepatitis C have indicated a progressive deterioration of the histological picture in many untreated patients, most marked among those with CAH.

Adult↗

Seroconversion after additional vaccine doses to non-responders to three doses of intradermally or intramuscularly administered recombinant hepatitis B vaccine.

Hospital staff members who failed to respond (anti-HBs < 10 IU/l) after 3 doses of a recombinant hepatitis B (HBV) vaccine (given either as 20 micrograms intramuscularly (n = 8) or 2 micrograms intradermally (n = 15)) received 1 or 2 additional doses by the same route as the initial vaccination. After the first additional dose, 12/23 responded with anti-HBs levels > or = 10 IU/l and after the second, another 2/5 responded, corresponding to a total response rate of 61%. No significant difference was seen in the response rate according to vaccination route, gender, age, or whether the vaccinee was a smoker or not. In this limited study some 50% of non-responders to 3 intradermal or intramuscular doses of recombinant HBV vaccine seroconverted after an additional 1-2 doses given by the same route as the initial vaccination, suggesting that additional doses can be administered by the same route as the initial one.

Adult↗

Serum hepatitis C virus RNA levels in chronic hepatitis C--importance for outcome of interferon alfa-2b treatment.

Sera from 39 out of 40 patients with chronic hepatitis C virus (HCV) infection who had been treated for 60 weeks with interferon alfa-2b proved initially HCV RNA positive by reversed transcriptase polymerase chain reaction (PCR). These patients were analysed for genotype and quantitatively for HCV RNA levels prior to treatment by using a competitive PCR method with colorimetric detection of the amplified products. HCV RNA levels were correlated to outcome of treatment, mode of acquisition, histology and HCV genotype. The median pretreatment HCV RNA level in sustained responders (n = 15) with eradication of the viremia and normalization of serum ALT levels lasting 24 weeks post treatment was significantly lower than that in the combined group of non-sustained responders (n = 9) and non-responders (n = 15), 2.52 x 10(5) vs 8.90 x 10(5) genome equivalents per ml serum, p < 0.0125, respectively. 10 out of 17 patients with HCV RNA levels lower than the median level (5.64 x 10(5) genome equivalents per ml serum) had a sustained response to interferon treatment versus only 5/22 with levels equal to or higher than the median level, p = 0.04. No significant pretreatment differences in median HCV RNA levels according to mode of acquisition, genotype, or liver histology prior to treatment were seen. It is concluded that a low pretreatment HCV RNA level seems to be indicative of a sustained response to interferon alfa-2b treatment, whereas a high level seems to be indicative of a non-sustained or non-response. In the individual patient, however, the levels varied widely irrespective of response category.

Adolescent↗

High sustained response rate and clearance of viremia in chronic hepatitis C after treatment with interferon-alpha 2b for 60 weeks.

To evaluate the effect of prolonged interferon-alpha treatment on serum aminotransferase levels and hepatitis C virus RNA in serum, 40 patients with chronic hepatitis C virus infection were treated with 3 MU interferon-alpha 2b thrice weekly for 60 wk. Before treatment all patients had elevated serum ALT levels for at least 1 yr, antibodies to HCV by second-generation tests and liver histological findings consistent with chronic hepatitis C. Before treatment hepatitis C virus RNA was found in serum in 39 of 40 (97.5%) patients. Normalization of ALT levels at treatment cessation was seen in 24 of 40 (60%) patients, of whom 15 of 24 (62.5%) had sustained ALT responses up to 24 wk after treatment. At follow-up, 24 wk after treatment, hepatitis C virus RNA was cleared from serum in 17 of 40 (42.5%) patients, including all sustained responders, one nonsustained responder and one nonresponder. We conclude that 60 wk of treatment with interferon-alpha 2b seems to induce a high percentage of sustained response, which coincides with cessation of viral replication.

Adult↗

Detection of hepatitis C virus (HCV) RNA by PCR related to HCV antibodies in serum and liver histology in Swedish blood donors.

Serum samples from 103 blood donors or patients with slightly increased serum levels of liver enzymes were tested for antibodies to hepatitis C virus (anti-HCV) using second generation tests and for HCV RNA by the polymerase chain reaction (PCR). PCR was in a nested configuration, using primer pairs from the 5'-nontranslated region. The anti-HCV antibody was found by enzyme linked immunosorbent assay (ELISA) in 93 patients. The anti-HCV confirmatory second generation recombinant immunoblot assay (RIBA) was positive in 44, indeterminate in 34 and negative in 25 subjects. Histopathological examination of the liver was carried out in 51 subjects. HCV RNA was detected in serum of 39/41 (95%) RIBA positive patients, and in 7/34 (21%) RIBA indeterminate subjects, but in none of the RIBA negative subjects. All but one of the PCR positive patients with a RIBA indeterminate pattern exhibited the C22 band. HCV RNA was found in the serum of all but one patients with chronic active or persistent hepatitis, but also in one RIBA positive subject with normal liver tissue. These results imply that most patients with antibodies to two or more HCV antigens by RIBA will have a chronic replicative HCV infection associated with viraemia. HCV viraemia can also be present in some patients, who have antibodies to only one HCV antigen particularly the C22 epitope.

Adult↗

Hepatitis C viral RNA titers in serum prior to, during, and after oral treatment with ribavirin for chronic hepatitis C.

Ten patients with biopsy verified chronic hepatitis C virus (HCV) infection were treated with oral ribavirin at a dose of 1,000-1,200 mg per day in two divided doses for 12 weeks. Serum alanine aminotransferase (ALT) levels and hepatitis C viral ribonucleic acid (RNA) levels in serum were followed prior to, during, and 12 weeks posttreatment. ALT levels decreased significantly in all patients during therapy from a mean level of 3.21 mukat/l (range 1.22 to 7.79) before, to 1.25 mukat/l (range 0.78 to 2.04) at the end of treatment (P < 0.005). Hereafter, relapse to pretreatment levels was seen within 12 weeks after treatment stop. The hepatitis C viral RNA levels decreased from a mean 10 log titer of 4.1 (range 1-6) before treatment to 3.4 (range 1-5) at treatment stop. Five patients did not change their HCV RNA titers during treatment. Twelve weeks posttreatment only 3 patients had lower titers than prior to treatment. We conclude that oral ribavirin seems to reduce the viral load, at least temporarily, in some patients with chronic viremic HCV infection. Further studies are needed to evaluate fully the effect of oral ribavirin on chronic HCV infection.

Administration, Oral↗

Survival and histological resolution of fibrosis in patients with autoimmune chronic active hepatitis.

Survival and long-term clinical and histological outcome were assessed retrospectively in 33 patients treated for autoimmune chronic active hepatitis. The Mayo Clinic treatment criteria were met by 30 of 33 patients and histological signs indicating nodular fibrosis and/or cirrhosis were present in 16 of 33 (48%). An overall 10-year survival rate of 90% was found by life-table analysis. This was not significantly different from matched controls (92%). Paired liver biopsies revealed that 16 of 28 (57%) patients improved their fibrosis/cirrhosis category whereas none progressed in a follow-up biopsy performed a median of 49 months later. Furthermore, liver biopsy showed improvement in 9 of 14 patients with initial nodular fibrosis/cirrhosis and resolution of nodulation. When a semi-quantitative scoring system was applied, the median fibrosis score improved significantly. A key factor intervening in the progression of fibrosis seemed to be the reduction of inflammatory activity as a result of immunosuppressive treatment. We conclude that fibrosis may be resolved in autoimmune chronic active hepatitis following protracted and effective treatment which is initiated early in the course of the disease.

Adolescent↗

Influenza A in immunocompromised patients.

Immunocompromised patients with influenza A were identified in Stockholm during two influenza seasons. The predominant subtypes were H3N2 during 1988-1989 and H1N1 during 1990-1991. The median age of the 25 patients was 43 years (range, 3-80 years). Twelve patients had received renal transplants and had ongoing immunosuppression. Seven patients had received bone marrow transplants between 2 days and 3 years before becoming infected with influenza virus A. Two patients were in an aplastic phase, and four had chronic graft-versus-host disease with ongoing immunosuppression. Six patients had hematologic malignancies. Two of the 25 patients had severe infections. One of these infections occurred in a bone marrow transplant recipient during an aplastic phase and was fatal; the other affected a patient who had received a renal transplant. One bone marrow transplant patient had mild but protracted infection. The remaining 22 patients had mild influenza A. We conclude that influenza A in immunocompromised patients occasionally causes severe complications but in most patients is mild and self-limiting.

Adolescent↗

Second-generation hepatitis C Elisa antibody tests confirmed by the four-antigen recombinant immunoblot assay correlate well with hepatitis C viremia and chronic liver disease in Swedish blood donors.

Seventy-three Swedish blood donors (52 men, 21 women; median age 36 years) repeatedly reactive for hepatitis C antibodies (anti-HCV C-100-3) were tested with a second-generation (2nd-gen) anti-HCV Elisa and a 4-band recombinant immunoblot assay (RIBA 2). These results were correlated to serum alanine aminotransferase (S-ALAT), liver morphology and viremia as detected by 'nested' polymerase chain reaction (PCR) based on primers from a 5'-noncoding sequence of the HCV genome. Thirty-five of 46 (76%) donors with positive 2nd-gen Elisa tests confirmed by RIBA 2 were PCR positive whereof 27 had histological findings compatible with chronic persistent hepatitis (CPH) and 7 had chronic active hepatitis (CAH). Ten of 56 (18%) 2nd-gen Elisa-positive donors were RIBA 2 negative (or indeterminate) and none of these had chronic hepatitis nor were PCR positive. Seventeen of 73 (23%) donors were 1st-gen Elisa positive but 2nd-gen Elisa negative. All of these were PCR negative and only 1 (6%) had chronic hepatitis (CPH). An elevated S-ALAT level (reference < 0.7 mu kat/l) was found in 26 2nd-gen Elisa and RIBA 2-positive donors of which 18 had CPH and 7 had CAH and all 25 were PCR positive. A normal S-ALAT level was found in 9 of 34 (26%) donors with chronic hepatitis (all had CPH) and positive PCR. We have found that blood donors with positive 2nd-gen anti-HCV Elisa tests confirmed by RIBA-2 and especially with a concomitant elevated S-ALAT are highly likely to be viremic as demonstrated by PCR and to have chronic hepatitis.

Adult↗

Outcome of acute symptomatic non-A, non-B hepatitis: a 13-year follow-up study of hepatitis C virus markers.

Thirty-nine of 61 prospectively followed patients who had had acute non-A, non-B hepatitis in 1978 were clinically reexamined in 1991 and tested for antibodies to hepatitis C virus (anti-HCV) with a second generation ELISA and RIBA and for HCV RNA by PCR. Acute hepatitis C was diagnosed in stored sera from 1978 in 24 patients, who were found still to be anti-HCV positive in 1991, and 16 of them were also HCV RNA positive. The majority of anti-HCV positive patients with or without HCV RNA had elevated serum ALT levels 13 years after onset of their acute hepatitis C. After 13 years follow-up, 1.6% of the patients had died of end-stage liver disease, 8% of anti-HCV positive patients had histologically confirmed liver cirrhosis, 79% of anti-HCV positive patients were judged to have chronic infection, whereas 21% seemed to have recovered. To conclude, we found that a majority of our patients with acute symptomatic hepatitis C continued to be viraemic 13 years after onset of hepatitis C, and that all continued to be anti-HCV positive by second-generation ELISA.

Acute Disease↗

Serum HCV RNA levels in patients with chronic hepatitis C given a second course of interferon alpha-2b treatment after relapse following initial treatment.

10 patients with chronic hepatitis C virus (HCV) infection who previously had responded temporarily to 9 months interferon alpha-2b treatment with normalization of ALT levels during treatment but later relapse were given a second 6-month treatment course. All patients were positive for anti-HCV by a second generation ELISA confirmed by second generation RIBA and positive for HCV RNA in serum before retreatment with interferon. Serum HCV RNA titers and ALT levels were monitored before, during and after treatment. ALT levels fell significantly from mean 1.95 mu kat/l before treatment to mean 0.96 and 0.85 mu kat/l after 4 and 24 weeks treatment, respectively (p < 0.005-p < 0.009). Six patients had normal ALT levels (< 0.07 mu kat/l) at treatment stop. 12 weeks post treatment cessation, however, the mean ALT level, 2.29 mu kat/l, was not significantly changed from the pretreatment level and all patients had raised ALT levels. The mean pretreatment HCV RNA titer in serum 10(5) (range 10(7)-10(3.5)) fell in all patients to mean 10(1.3) (range 10(3)-10(0)) already after 4 weeks treatment and became undetectable at treatment cessation in 5 patients, of whom 4 had normal ALT levels. ALT levels, however, were also normal in 2/5 patients who continued to have detectable HCV RNA titers at treatment cessation. After treatment was stopped HCV RNA titers rose again and 12 weeks post treatment the mean titer was 10(4.7) (range 10(3.5)-10(5.5)).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Interferon alpha-2b treatment in an HIV-infected patient with hepatitis B virus induced nephrotic syndrome.

A 31-year-old male patient with an asymptomatic HIV infection but with a hepatitis B (HBV) related membraneous glomerulonephritis with nephrotic syndrome was given interferon alpha-2b subcutaneously 3 times weekly for 7.5 months. Zidovudine was added at the 10th week due to low CD4+ cell counts. Before the 6th week of treatment the patient reported a reduced need for diuretics to keep his lower limb edemas at a minimum. This response was partially sustained even after the 7.5 months interferon treatment course. The titers of HBV-DNA decreased markedly during the treatment with interferon but rose to pretreatment levels after discontinuation of the interferon treatment. The serum albumin increased but the proteinuria and hematuria were unaffected. Adverse reactions like fever, myalgias and anemia were tolerable and did not require dose reduction of either interferon or zidovudine. This treatment regimen, at least temporarily, improved the situation for the patient and can be worthwhile to try in HIV-infected patients with HBV related nephritis with nephrotic syndrome.

Adult↗

Prevalence of hepatitis B virus markers among intravenous drug abusers in Stockholm: impact of heterosexual transmission.

In order to study the importance of sexual transmission of hepatitis B virus (HBV) among intravenous drug abusers (IVDAs), and from IVDAs to others, we consecutively interviewed 171 IVDAs detained at the Stockholm Remand Prison during 4 months in 1990. Sexual histories revealed that 77% reported > or = 3 sexual partners during the last 3 years, 64% had had a sexual partner who did not inject drugs, and 61% reported a prior STD. The prevalence of HBV markers was 75%. In a multiple logistic regression analysis, a high risk for HBV markers was associated with an increasing duration of drug abuse, a high prevalence of hepatitis A markers, and an increasing number of drug injecting sexual partners during the last 3 years, indicating that sexual transmission, along with sharing of needles, may contribute to the high prevalence of HBV markers within this group. It is suggested that an adequate sexual history must be obtained from IVDAs with acute viral hepatitis in order to identify sexual partners who should be offered postexposure prophylaxis, and that non-immune IVDAs should be vaccinated against viral hepatitis A and B.

Adult↗