Kim Krogsgaard - Academia.edu (original) (raw)

Papers by Kim Krogsgaard

Research paper thumbnail of Glucocorticosteroids for viral hepatitis C

Cochrane Database of Systematic Reviews, Sep 6, 2000

R, et al. Pretreatment with prednisolone does not improve the e icacy of subsequent alpha interfe... more R, et al. Pretreatment with prednisolone does not improve the e icacy of subsequent alpha interferon therapy in chronic hepatitis C.

Research paper thumbnail of Ribavirin with or without alpha interferon for chronic hepatitis C

The Cochrane library, Apr 22, 2002

Hepatitis C is a major cause of liver-related morbidity and mortality. Ribavirin plus interferon ... more Hepatitis C is a major cause of liver-related morbidity and mortality. Ribavirin plus interferon combination therapy is presently considered the optimal treatment of interferon naive patients with chronic hepatitis C, but its role in relapsers and non-responders to previous interferon therapy is not established. To assess the efficacy and safety of ribavirin alone or in combination with alpha interferon in interferon naive patients, relapsers, and non-responders with chronic hepatitis C. Eligible trials were identified through searches on electronic databases: The Cochrane Hepato-Biliary Group Controlled Trials Register (August 2001), The Cochrane Controlled Trials Register on The Cochrane Library Issue 3, 2001, MEDLINE (1966 - August 2001), and EMBASE (1985 - August 2001). Manual searches of bibliographies and journals were done as well as authors of trials and pharmaceutical companies producing ribavirin or interferon were contacted. We included all randomised trials comparing ribavirin with or without alpha interferon versus no intervention, placebo, or alpha interferon for chronic hepatitis C. The primary outcome measures were the 'sustained' (six months after treatment) virological response, and morbidity plus mortality. The secondary outcome measures were the 'end of treatment' and 'sustained' biochemical response, the 'end of treatment' virologic response, histology, quality of life, and adverse events. We included eight trials in which 271 patients were randomised to ribavirin versus placebo or no intervention and 48 trials in which 6585 patients were randomised to interferon with or without ribavirin. Compared with placebo or no intervention, ribavirin monotherapy had no significant effect on the virological response or histology and only a transient effect on the biochemical response. Compared with interferon, combination therapy reduced the risk of not having a sustained virological response by 26% in naive patients (relative risk (RR) 0.74; 95% confidence interval (CI) 0.70-0.78), 33% in relapsers (RR 0.67; 95% CI 0.57-0.78), and 11% in non-responders (RR 0.89; 95% CI 0.83-0.96). There was no significant effect on morbidity plus mortality (Peto odds ratio 0.45; 95% CI 0.19-1.06). Irrespective of previous therapy, combination therapy significantly reduced the risk of not having a sustained biochemical response (RR 0.76; 95% CI 0.59-0.84) or improved histology (RR 0.67; 95% CI 0.56-0.81). Combination therapy also significantly increased the risk of treatment discontinuation (RR 1.28; 95% CI 1.07-1.52) and several types of adverse events. Combination therapy increased the number of naive patients, relapsers, and non-responders with a sustained virological, biochemical, or histological response, but also the occurrence of adverse events.

Research paper thumbnail of A systematic review on interferon-alpha with or without ribavirin for interferon naive, non-responders, and relapsers with chronic hepatitis C

Journal of Hepatology, Apr 1, 2001

Research paper thumbnail of Glucocorticosteroids for viral hepatitis B

The Cochrane library, Sep 3, 2018

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:The object... more This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:The objectives were to evaluate the evidence indicating or contraindicating glucocorticosteroid monotherapy in acute and chronic HBV infected individuals.

Research paper thumbnail of Correlation between liver morphology and haemodynamics in alcoholic liver disease

Research paper thumbnail of Published Online First

Research paper thumbnail of Exercise program for prevention of groin pain in football players: a cluster-randomized trial

Scandinavian journal of medicine & science in sports, 2010

Groin injuries cause major problems in sports and particularly in football. Exercise is effective... more Groin injuries cause major problems in sports and particularly in football. Exercise is effective in treating adductor-related groin pain, but no trials have been published regarding the specific prevention of groin pain or prevention specifically targeting overuse injuries in sport using exercise programs. We performed a cluster-randomized trial including 55 football clubs representing 1211 players. The clubs were randomized to an exercise program aimed at preventing groin injuries (n=27) or to a control group training as usual (n=28). The intervention program consisted of six exercises including strengthening (concentric and eccentric), coordination, and core stability exercises for the muscles related to the pelvis. Physiotherapists assigned to each club registered all groin injuries. Twenty-two clubs in each group completed the study, represented by 977 players. There was no significant effect of the intervention (HR=0.69, 95% CI 0.40-1.19). The risk of a groin injury was reduce...

Research paper thumbnail of Outpatients' knowledge about and attitude towards clinical research and randomized clinical trials. The INFO Trial Group

Danish medical bulletin, 1998

To investigate the knowledge about randomized clinical trials and the attitude towards clinical r... more To investigate the knowledge about randomized clinical trials and the attitude towards clinical research among Danish outpatients and to examine the relationships between outpatient demographic variables and knowledge and attitude. Outpatients (n = 415) were recruited from four departments at a university hospital in Copenhagen. The participants answered an 18 item multiple choice test evaluating knowledge about randomized clinical trials and a 32 item Likert format questionnaire evaluating attitudes towards clinical research in general and randomized clinical trials. Assessment of scales for knowledge and attitudes was performed using Rasch analysis and Cronbach's alpha. Associations between demographic variables, knowledge score and attitude score were examined using analysis of variance. Mean age for all outpatients was 46 years (range 18-88 years); 251 (60%) were females. A total of 27 outpatients (7%) had previously participated in a randomized clinical trial. Mean knowledg...

Research paper thumbnail of Glucocorticosteroids for viral hepatitis B

Reviews, 2001

The editorial group responsible for this previously published document have withdrawn it from pub... more The editorial group responsible for this previously published document have withdrawn it from publication.

Research paper thumbnail of Glucocorticosteroids for viral hepatitis C

Cochrane Database of Systematic Reviews, 2004

R, et al. Pretreatment with prednisolone does not improve the e icacy of subsequent alpha interfe... more R, et al. Pretreatment with prednisolone does not improve the e icacy of subsequent alpha interferon therapy in chronic hepatitis C.

Research paper thumbnail of Ribavirin with or without alpha interferon for chronic hepatitis C

Cochrane Database of Systematic Reviews, 2002

Hepatitis C is a major cause of liver-related morbidity and mortality. Ribavirin plus interferon ... more Hepatitis C is a major cause of liver-related morbidity and mortality. Ribavirin plus interferon combination therapy is presently considered the optimal treatment of interferon naive patients with chronic hepatitis C, but its role in relapsers and non-responders to previous interferon therapy is not established. To assess the efficacy and safety of ribavirin alone or in combination with alpha interferon in interferon naive patients, relapsers, and non-responders with chronic hepatitis C. Eligible trials were identified through searches on electronic databases: The Cochrane Hepato-Biliary Group Controlled Trials Register (August 2001), The Cochrane Controlled Trials Register on The Cochrane Library Issue 3, 2001, MEDLINE (1966 - August 2001), and EMBASE (1985 - August 2001). Manual searches of bibliographies and journals were done as well as authors of trials and pharmaceutical companies producing ribavirin or interferon were contacted. We included all randomised trials comparing ribavirin with or without alpha interferon versus no intervention, placebo, or alpha interferon for chronic hepatitis C. The primary outcome measures were the 'sustained' (six months after treatment) virological response, and morbidity plus mortality. The secondary outcome measures were the 'end of treatment' and 'sustained' biochemical response, the 'end of treatment' virologic response, histology, quality of life, and adverse events. We included eight trials in which 271 patients were randomised to ribavirin versus placebo or no intervention and 48 trials in which 6585 patients were randomised to interferon with or without ribavirin. Compared with placebo or no intervention, ribavirin monotherapy had no significant effect on the virological response or histology and only a transient effect on the biochemical response. Compared with interferon, combination therapy reduced the risk of not having a sustained virological response by 26% in naive patients (relative risk (RR) 0.74; 95% confidence interval (CI) 0.70-0.78), 33% in relapsers (RR 0.67; 95% CI 0.57-0.78), and 11% in non-responders (RR 0.89; 95% CI 0.83-0.96). There was no significant effect on morbidity plus mortality (Peto odds ratio 0.45; 95% CI 0.19-1.06). Irrespective of previous therapy, combination therapy significantly reduced the risk of not having a sustained biochemical response (RR 0.76; 95% CI 0.59-0.84) or improved histology (RR 0.67; 95% CI 0.56-0.81). Combination therapy also significantly increased the risk of treatment discontinuation (RR 1.28; 95% CI 1.07-1.52) and several types of adverse events. Combination therapy increased the number of naive patients, relapsers, and non-responders with a sustained virological, biochemical, or histological response, but also the occurrence of adverse events.

Research paper thumbnail of A systematic review on interferon-alpha with or without ribavirin for interferon naive, non-responders, and relapsers with chronic hepatitis C

Journal of Hepatology, 2001

Research paper thumbnail of Localisation of immunoglobulin on the liver cell surface in primary biliary cirrhosis

Journal of Clinical Pathology, 1981

Direct immunofluorescence studies were performed on isolated liver cells in order to detect surfa... more Direct immunofluorescence studies were performed on isolated liver cells in order to detect surface localisation of IgG in acute and chronic hepatitis and primary biliary cirrhosis. Membrane-bound IgG was demonstrated in nine patients. Six of eight patients with primary biliary cirrhosis showed granular fluorescence on their liver cell surfaces suggesting that an antibody or immune complex-mediated cytotoxicity might be involved in the pathogenesis of this disease.

Research paper thumbnail of Characterisation of Liver membrane autoantibodies determined by indirect immunofluorescence

Journal of Clinical Pathology, 1982

Indirect immunofluorescence studies were performed using sera and IgG-Fab2 fragments from patient... more Indirect immunofluorescence studies were performed using sera and IgG-Fab2 fragments from patients with chronic active hepatitis (CAH) who were positive for a liver membrane antibody (LMA). The specificity was investigated using hepatocytes from humans as well as rabbit, rat, guinea pig and monkey. Only sera also positive for smooth muscle antibody gave staining of lymphocytes and absorption with F-actin from rabbit muscle abolished this as well as all other smooth muscle staining without influencing LMA. It was concluded that LMA, routinely detected by indirect immunofluorescence using rabbit hepatocytes, represents specific binding to non-species-specific membrane antigens which are normal constituents of human hepatocytes. The antigen is separately located, and not cross-reactive with F-actin.

Research paper thumbnail of Temporal relation of antigenaemia and loss of antibodies to core antigens to development of clinical disease in HIV infection

BMJ, 1987

A total of 276 sequential serum samples from 34 men with antibodies to the human immunodeficiency... more A total of 276 sequential serum samples from 34 men with antibodies to the human immunodeficiency virus (HIV) followed up for two to seven years were analysed for HIV antigen and antibodies to the viral core and envelope proteins. Results were correlated with clinical outcome and CD4 T lymphocyte count. Both antigenaemia and the disappearance of antibodies to the core protein were associated with development of the acquired immune deficiency syndrome (AIDS) or AIDS related complex and depletion of CD4 cells. Thus AIDS or AIDS related complex developed in eight out of 16 patients with antigenaemia compared with one out of 18 patients without antigenaemia. Low counts of CD4 cells (<OU5x 109/l) were found in 14 of the 16 patients with antigenaemia and five of the 18 without antigenaemia. Nine patients seroconverted to HIV during the study; two of these developed antigenaemia 14 and 16 months after the estimated time of seroconversion. These results show that the late stages of HIV infection are characterised by increased production of antigen and a decrease in antibodies directed against the core protein. Antigenaemia indicates a poor prognosis; and as the antigen test is simple to do and interpret, it may therefore be useful for selecting patients for antiviral treatment.

Research paper thumbnail of Sexual transmission of hepatitis C virus: cohort study (1981-9) among European homosexual men

BMJ, 1990

Objective-To determine the prevalence, incidence, and persistence of positivity for antibodies to... more Objective-To determine the prevalence, incidence, and persistence of positivity for antibodies to hepatitis C virus (anti-HCV) and the potential for sexual transmission of the virus. Design-A cohort analysis covering 1981-9 comparing estimated cumulative incidences of and seroconversion rates for anti-HCV with those of hepatitis B core antibody (anti-HBc) and antibodies to the human immunodeficiency virus (anti-HIV). Setting-Copenhagen and Aarhus, Denmark. Subjects-259 Male members of a Danish homosexual organisation. Main outcome measures-Correlations of prevalence and incidence with a wide range of sexual lifestyle variables. Results-Only four (1-6%) subjects were positive for anti-HCV in 1981. The estimated cumulative incidence of positivity for anti-HCV was 41% in 1984 (seroconversion rate during 1981-4 (2-5%)) and remained at 4-1% in 1989 (seroconversion rate nil during 1984-9). In contrast, positivity for anti-HBC rose from 44 0% in 1981 to 52-7% in 1984 (seroconversion rate 15-5%) and 58-8% in 1989 (serconversion rate 12-9%), and that for anti-HIV rose from 8-8% to 24-0% (seroconversion rate 16-7%) and 30-1% (seroconversion rate 8.0%) respectively. Three anti-HCV positive patients seroreverted three to five years later. None of the anti-HCV positive subjects had had a transfusion and only one gave a past history of intravenous drug use. Variables in sexual lifestyle correlated with the presence of anti-HBc but not with that of anti-HCV. Conclusions-In contrast with hepatitis B virus and HIV, sexual transmission of hepatitis C virus seems to be a rare event. Furthermore, antibodies to the virus may become undetectable after several years.

Research paper thumbnail of Widespread use of condoms and low prevalence of sexually transmitted diseases in Danish non-drug addict prostitutes

Research paper thumbnail of Would you trust a surrogate respondent?

The Lancet, 1997

from the 1960s to the 1980s, roughly 2-8% per year. This increase is seen in countries with a fai... more from the 1960s to the 1980s, roughly 2-8% per year. This increase is seen in countries with a fair-skinned population (UK, USA, Scandinavia, and Australia). 6 Known risk factors for the development of NHL include chronic immunosuppression (in transplant patients, oncology patients, and those on chronic steroid therapy), chronic renal disease, infections with HIV, HTLV-I, and Epstein-Barr virus, and petrochemical and agrochemical exposure. None of these risk factors, however, is able to account for the striking increase in incidence of NHL. 6,7 On the basis of this epidemiological evidence, there has been speculation that the rise in NHL may also be explained by an immunosuppressed state resulting from chronic sunlight exposure. 5,7-9 Sunlight has been shown experimentally to have profound effects on the immune system, contributing to an altered host resistance and the development of skin cancer. Sunlight exposure in susceptible people produces UV-induced damage, which triggers a cascade of events leading to a state of antigenspecific, T-lymphocyte-mediated immunosuppression. 10 With such additional evidence for the deleterious effects of excessive sunlight exposure, efforts to educate the public about these dangers should be intensified. Patients with basal-cell carcinoma, squamous-cell carcinoma, or malignant melanoma need to be examined regularly for skin cancers , as well as NHL, leukaemia, cancer of the lip, salivary glands, mouth, lungs, breast, kidney, and testis.

Research paper thumbnail of Sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone for HBeAg-positive chronic hepatitis B

Reviews, 2005

Chronic hepatitis B has serious effects on morbidity and mortality. Alfa interferon has been show... more Chronic hepatitis B has serious effects on morbidity and mortality. Alfa interferon has been shown to increase the rates of HBeAg-clearance as well as seroconversion to anti-HBe, but response rates are unsatisfactory. Glucocorticosteroid pretreatment may increase the response to alfa interferon. The objectives were to assess the effects of the sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone in hepatitis B &#39;e&#39; antigen positive chronic hepatitis B on mortality, virological response, biochemical response, liver histology, quality of life, and adverse events. Electronic searches of the controlled trial registers of The Cochrane Hepato-Biliary Group and The Cochrane Library, MEDLINE, BIOSIS, and EMBASE were combined (May 2000). Reading the bibliography of retrieved articles identified further trials. Alfa interferon-manufacturing companies were approached in order to inquire about any published and unpublished randomised trials. The analyses included randomised trials comparing identical alfa interferon treatment regimens with and without glucocorticosteroid pretreatment for hepatitis B &#39;e&#39; antigen positive chronic hepatitis. The trials could be open, single blinded, or double blinded. No patient exclusion criteria were applied. Three reviewers independently selected the trials and one extracted the data, which were validated. Assessments of the outcome measures were performed at the end of treatment and at six months and at maximal follow up after the end of treatment with alfa interferon. A total of 13 randomised trials including 790 patients were included. Loss of hepatitis B &#39;e&#39; antigen (OR 1.41, 95% confidence interval 1.03 to 1.92, P = 0.03) and hepatitis B virus DNA (OR = 1.51, 95% confidence interval 1.12 to 2.05, P = 0.008) were significantly more frequent among patients treated with the sequential combination of glucocorticosteroids and alfa interferon than among patients treated with alfa interferon alone. Glucocorticosteroid pretreatment did not significantly influence seroconversion from hepatitis B &#39;e&#39; antigen to antibodies to hepatitis B &#39;e&#39; antigen, loss of hepatitis B surface antigen, normalisation of alanine aminotransferase/aspartate aminotransferase activities, and severity of adverse events. Glucocorticosteroid pretreatment did not significantly affect mortality and adverse events. The effect of glucocorticosteroid pretreatment on liver histology and quality of life could not be assessed due to insufficient data. Pretreatment with glucocorticosteroids before treatment with alfa interferon in patients with hepatitis B &#39;e&#39; antigen positive chronic hepatitis B may be more effective than treatment with alfa interferon alone with regard to loss of hepatitis B &#39;e&#39; antigen and hepatitis B virus DNA, but evidence for effect on clinical outcomes is lacking.

Research paper thumbnail of Widespread use of condoms and low prevalence of sexually transmitted diseases in Danish non-drug addict prostitutes

Research paper thumbnail of Glucocorticosteroids for viral hepatitis C

Cochrane Database of Systematic Reviews, Sep 6, 2000

R, et al. Pretreatment with prednisolone does not improve the e icacy of subsequent alpha interfe... more R, et al. Pretreatment with prednisolone does not improve the e icacy of subsequent alpha interferon therapy in chronic hepatitis C.

Research paper thumbnail of Ribavirin with or without alpha interferon for chronic hepatitis C

The Cochrane library, Apr 22, 2002

Hepatitis C is a major cause of liver-related morbidity and mortality. Ribavirin plus interferon ... more Hepatitis C is a major cause of liver-related morbidity and mortality. Ribavirin plus interferon combination therapy is presently considered the optimal treatment of interferon naive patients with chronic hepatitis C, but its role in relapsers and non-responders to previous interferon therapy is not established. To assess the efficacy and safety of ribavirin alone or in combination with alpha interferon in interferon naive patients, relapsers, and non-responders with chronic hepatitis C. Eligible trials were identified through searches on electronic databases: The Cochrane Hepato-Biliary Group Controlled Trials Register (August 2001), The Cochrane Controlled Trials Register on The Cochrane Library Issue 3, 2001, MEDLINE (1966 - August 2001), and EMBASE (1985 - August 2001). Manual searches of bibliographies and journals were done as well as authors of trials and pharmaceutical companies producing ribavirin or interferon were contacted. We included all randomised trials comparing ribavirin with or without alpha interferon versus no intervention, placebo, or alpha interferon for chronic hepatitis C. The primary outcome measures were the &#39;sustained&#39; (six months after treatment) virological response, and morbidity plus mortality. The secondary outcome measures were the &#39;end of treatment&#39; and &#39;sustained&#39; biochemical response, the &#39;end of treatment&#39; virologic response, histology, quality of life, and adverse events. We included eight trials in which 271 patients were randomised to ribavirin versus placebo or no intervention and 48 trials in which 6585 patients were randomised to interferon with or without ribavirin. Compared with placebo or no intervention, ribavirin monotherapy had no significant effect on the virological response or histology and only a transient effect on the biochemical response. Compared with interferon, combination therapy reduced the risk of not having a sustained virological response by 26% in naive patients (relative risk (RR) 0.74; 95% confidence interval (CI) 0.70-0.78), 33% in relapsers (RR 0.67; 95% CI 0.57-0.78), and 11% in non-responders (RR 0.89; 95% CI 0.83-0.96). There was no significant effect on morbidity plus mortality (Peto odds ratio 0.45; 95% CI 0.19-1.06). Irrespective of previous therapy, combination therapy significantly reduced the risk of not having a sustained biochemical response (RR 0.76; 95% CI 0.59-0.84) or improved histology (RR 0.67; 95% CI 0.56-0.81). Combination therapy also significantly increased the risk of treatment discontinuation (RR 1.28; 95% CI 1.07-1.52) and several types of adverse events. Combination therapy increased the number of naive patients, relapsers, and non-responders with a sustained virological, biochemical, or histological response, but also the occurrence of adverse events.

Research paper thumbnail of A systematic review on interferon-alpha with or without ribavirin for interferon naive, non-responders, and relapsers with chronic hepatitis C

Journal of Hepatology, Apr 1, 2001

Research paper thumbnail of Glucocorticosteroids for viral hepatitis B

The Cochrane library, Sep 3, 2018

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:The object... more This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:The objectives were to evaluate the evidence indicating or contraindicating glucocorticosteroid monotherapy in acute and chronic HBV infected individuals.

Research paper thumbnail of Correlation between liver morphology and haemodynamics in alcoholic liver disease

Research paper thumbnail of Published Online First

Research paper thumbnail of Exercise program for prevention of groin pain in football players: a cluster-randomized trial

Scandinavian journal of medicine & science in sports, 2010

Groin injuries cause major problems in sports and particularly in football. Exercise is effective... more Groin injuries cause major problems in sports and particularly in football. Exercise is effective in treating adductor-related groin pain, but no trials have been published regarding the specific prevention of groin pain or prevention specifically targeting overuse injuries in sport using exercise programs. We performed a cluster-randomized trial including 55 football clubs representing 1211 players. The clubs were randomized to an exercise program aimed at preventing groin injuries (n=27) or to a control group training as usual (n=28). The intervention program consisted of six exercises including strengthening (concentric and eccentric), coordination, and core stability exercises for the muscles related to the pelvis. Physiotherapists assigned to each club registered all groin injuries. Twenty-two clubs in each group completed the study, represented by 977 players. There was no significant effect of the intervention (HR=0.69, 95% CI 0.40-1.19). The risk of a groin injury was reduce...

Research paper thumbnail of Outpatients' knowledge about and attitude towards clinical research and randomized clinical trials. The INFO Trial Group

Danish medical bulletin, 1998

To investigate the knowledge about randomized clinical trials and the attitude towards clinical r... more To investigate the knowledge about randomized clinical trials and the attitude towards clinical research among Danish outpatients and to examine the relationships between outpatient demographic variables and knowledge and attitude. Outpatients (n = 415) were recruited from four departments at a university hospital in Copenhagen. The participants answered an 18 item multiple choice test evaluating knowledge about randomized clinical trials and a 32 item Likert format questionnaire evaluating attitudes towards clinical research in general and randomized clinical trials. Assessment of scales for knowledge and attitudes was performed using Rasch analysis and Cronbach's alpha. Associations between demographic variables, knowledge score and attitude score were examined using analysis of variance. Mean age for all outpatients was 46 years (range 18-88 years); 251 (60%) were females. A total of 27 outpatients (7%) had previously participated in a randomized clinical trial. Mean knowledg...

Research paper thumbnail of Glucocorticosteroids for viral hepatitis B

Reviews, 2001

The editorial group responsible for this previously published document have withdrawn it from pub... more The editorial group responsible for this previously published document have withdrawn it from publication.

Research paper thumbnail of Glucocorticosteroids for viral hepatitis C

Cochrane Database of Systematic Reviews, 2004

R, et al. Pretreatment with prednisolone does not improve the e icacy of subsequent alpha interfe... more R, et al. Pretreatment with prednisolone does not improve the e icacy of subsequent alpha interferon therapy in chronic hepatitis C.

Research paper thumbnail of Ribavirin with or without alpha interferon for chronic hepatitis C

Cochrane Database of Systematic Reviews, 2002

Hepatitis C is a major cause of liver-related morbidity and mortality. Ribavirin plus interferon ... more Hepatitis C is a major cause of liver-related morbidity and mortality. Ribavirin plus interferon combination therapy is presently considered the optimal treatment of interferon naive patients with chronic hepatitis C, but its role in relapsers and non-responders to previous interferon therapy is not established. To assess the efficacy and safety of ribavirin alone or in combination with alpha interferon in interferon naive patients, relapsers, and non-responders with chronic hepatitis C. Eligible trials were identified through searches on electronic databases: The Cochrane Hepato-Biliary Group Controlled Trials Register (August 2001), The Cochrane Controlled Trials Register on The Cochrane Library Issue 3, 2001, MEDLINE (1966 - August 2001), and EMBASE (1985 - August 2001). Manual searches of bibliographies and journals were done as well as authors of trials and pharmaceutical companies producing ribavirin or interferon were contacted. We included all randomised trials comparing ribavirin with or without alpha interferon versus no intervention, placebo, or alpha interferon for chronic hepatitis C. The primary outcome measures were the &#39;sustained&#39; (six months after treatment) virological response, and morbidity plus mortality. The secondary outcome measures were the &#39;end of treatment&#39; and &#39;sustained&#39; biochemical response, the &#39;end of treatment&#39; virologic response, histology, quality of life, and adverse events. We included eight trials in which 271 patients were randomised to ribavirin versus placebo or no intervention and 48 trials in which 6585 patients were randomised to interferon with or without ribavirin. Compared with placebo or no intervention, ribavirin monotherapy had no significant effect on the virological response or histology and only a transient effect on the biochemical response. Compared with interferon, combination therapy reduced the risk of not having a sustained virological response by 26% in naive patients (relative risk (RR) 0.74; 95% confidence interval (CI) 0.70-0.78), 33% in relapsers (RR 0.67; 95% CI 0.57-0.78), and 11% in non-responders (RR 0.89; 95% CI 0.83-0.96). There was no significant effect on morbidity plus mortality (Peto odds ratio 0.45; 95% CI 0.19-1.06). Irrespective of previous therapy, combination therapy significantly reduced the risk of not having a sustained biochemical response (RR 0.76; 95% CI 0.59-0.84) or improved histology (RR 0.67; 95% CI 0.56-0.81). Combination therapy also significantly increased the risk of treatment discontinuation (RR 1.28; 95% CI 1.07-1.52) and several types of adverse events. Combination therapy increased the number of naive patients, relapsers, and non-responders with a sustained virological, biochemical, or histological response, but also the occurrence of adverse events.

Research paper thumbnail of A systematic review on interferon-alpha with or without ribavirin for interferon naive, non-responders, and relapsers with chronic hepatitis C

Journal of Hepatology, 2001

Research paper thumbnail of Localisation of immunoglobulin on the liver cell surface in primary biliary cirrhosis

Journal of Clinical Pathology, 1981

Direct immunofluorescence studies were performed on isolated liver cells in order to detect surfa... more Direct immunofluorescence studies were performed on isolated liver cells in order to detect surface localisation of IgG in acute and chronic hepatitis and primary biliary cirrhosis. Membrane-bound IgG was demonstrated in nine patients. Six of eight patients with primary biliary cirrhosis showed granular fluorescence on their liver cell surfaces suggesting that an antibody or immune complex-mediated cytotoxicity might be involved in the pathogenesis of this disease.

Research paper thumbnail of Characterisation of Liver membrane autoantibodies determined by indirect immunofluorescence

Journal of Clinical Pathology, 1982

Indirect immunofluorescence studies were performed using sera and IgG-Fab2 fragments from patient... more Indirect immunofluorescence studies were performed using sera and IgG-Fab2 fragments from patients with chronic active hepatitis (CAH) who were positive for a liver membrane antibody (LMA). The specificity was investigated using hepatocytes from humans as well as rabbit, rat, guinea pig and monkey. Only sera also positive for smooth muscle antibody gave staining of lymphocytes and absorption with F-actin from rabbit muscle abolished this as well as all other smooth muscle staining without influencing LMA. It was concluded that LMA, routinely detected by indirect immunofluorescence using rabbit hepatocytes, represents specific binding to non-species-specific membrane antigens which are normal constituents of human hepatocytes. The antigen is separately located, and not cross-reactive with F-actin.

Research paper thumbnail of Temporal relation of antigenaemia and loss of antibodies to core antigens to development of clinical disease in HIV infection

BMJ, 1987

A total of 276 sequential serum samples from 34 men with antibodies to the human immunodeficiency... more A total of 276 sequential serum samples from 34 men with antibodies to the human immunodeficiency virus (HIV) followed up for two to seven years were analysed for HIV antigen and antibodies to the viral core and envelope proteins. Results were correlated with clinical outcome and CD4 T lymphocyte count. Both antigenaemia and the disappearance of antibodies to the core protein were associated with development of the acquired immune deficiency syndrome (AIDS) or AIDS related complex and depletion of CD4 cells. Thus AIDS or AIDS related complex developed in eight out of 16 patients with antigenaemia compared with one out of 18 patients without antigenaemia. Low counts of CD4 cells (<OU5x 109/l) were found in 14 of the 16 patients with antigenaemia and five of the 18 without antigenaemia. Nine patients seroconverted to HIV during the study; two of these developed antigenaemia 14 and 16 months after the estimated time of seroconversion. These results show that the late stages of HIV infection are characterised by increased production of antigen and a decrease in antibodies directed against the core protein. Antigenaemia indicates a poor prognosis; and as the antigen test is simple to do and interpret, it may therefore be useful for selecting patients for antiviral treatment.

Research paper thumbnail of Sexual transmission of hepatitis C virus: cohort study (1981-9) among European homosexual men

BMJ, 1990

Objective-To determine the prevalence, incidence, and persistence of positivity for antibodies to... more Objective-To determine the prevalence, incidence, and persistence of positivity for antibodies to hepatitis C virus (anti-HCV) and the potential for sexual transmission of the virus. Design-A cohort analysis covering 1981-9 comparing estimated cumulative incidences of and seroconversion rates for anti-HCV with those of hepatitis B core antibody (anti-HBc) and antibodies to the human immunodeficiency virus (anti-HIV). Setting-Copenhagen and Aarhus, Denmark. Subjects-259 Male members of a Danish homosexual organisation. Main outcome measures-Correlations of prevalence and incidence with a wide range of sexual lifestyle variables. Results-Only four (1-6%) subjects were positive for anti-HCV in 1981. The estimated cumulative incidence of positivity for anti-HCV was 41% in 1984 (seroconversion rate during 1981-4 (2-5%)) and remained at 4-1% in 1989 (seroconversion rate nil during 1984-9). In contrast, positivity for anti-HBC rose from 44 0% in 1981 to 52-7% in 1984 (seroconversion rate 15-5%) and 58-8% in 1989 (serconversion rate 12-9%), and that for anti-HIV rose from 8-8% to 24-0% (seroconversion rate 16-7%) and 30-1% (seroconversion rate 8.0%) respectively. Three anti-HCV positive patients seroreverted three to five years later. None of the anti-HCV positive subjects had had a transfusion and only one gave a past history of intravenous drug use. Variables in sexual lifestyle correlated with the presence of anti-HBc but not with that of anti-HCV. Conclusions-In contrast with hepatitis B virus and HIV, sexual transmission of hepatitis C virus seems to be a rare event. Furthermore, antibodies to the virus may become undetectable after several years.

Research paper thumbnail of Widespread use of condoms and low prevalence of sexually transmitted diseases in Danish non-drug addict prostitutes

Research paper thumbnail of Would you trust a surrogate respondent?

The Lancet, 1997

from the 1960s to the 1980s, roughly 2-8% per year. This increase is seen in countries with a fai... more from the 1960s to the 1980s, roughly 2-8% per year. This increase is seen in countries with a fair-skinned population (UK, USA, Scandinavia, and Australia). 6 Known risk factors for the development of NHL include chronic immunosuppression (in transplant patients, oncology patients, and those on chronic steroid therapy), chronic renal disease, infections with HIV, HTLV-I, and Epstein-Barr virus, and petrochemical and agrochemical exposure. None of these risk factors, however, is able to account for the striking increase in incidence of NHL. 6,7 On the basis of this epidemiological evidence, there has been speculation that the rise in NHL may also be explained by an immunosuppressed state resulting from chronic sunlight exposure. 5,7-9 Sunlight has been shown experimentally to have profound effects on the immune system, contributing to an altered host resistance and the development of skin cancer. Sunlight exposure in susceptible people produces UV-induced damage, which triggers a cascade of events leading to a state of antigenspecific, T-lymphocyte-mediated immunosuppression. 10 With such additional evidence for the deleterious effects of excessive sunlight exposure, efforts to educate the public about these dangers should be intensified. Patients with basal-cell carcinoma, squamous-cell carcinoma, or malignant melanoma need to be examined regularly for skin cancers , as well as NHL, leukaemia, cancer of the lip, salivary glands, mouth, lungs, breast, kidney, and testis.

Research paper thumbnail of Sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone for HBeAg-positive chronic hepatitis B

Reviews, 2005

Chronic hepatitis B has serious effects on morbidity and mortality. Alfa interferon has been show... more Chronic hepatitis B has serious effects on morbidity and mortality. Alfa interferon has been shown to increase the rates of HBeAg-clearance as well as seroconversion to anti-HBe, but response rates are unsatisfactory. Glucocorticosteroid pretreatment may increase the response to alfa interferon. The objectives were to assess the effects of the sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone in hepatitis B &#39;e&#39; antigen positive chronic hepatitis B on mortality, virological response, biochemical response, liver histology, quality of life, and adverse events. Electronic searches of the controlled trial registers of The Cochrane Hepato-Biliary Group and The Cochrane Library, MEDLINE, BIOSIS, and EMBASE were combined (May 2000). Reading the bibliography of retrieved articles identified further trials. Alfa interferon-manufacturing companies were approached in order to inquire about any published and unpublished randomised trials. The analyses included randomised trials comparing identical alfa interferon treatment regimens with and without glucocorticosteroid pretreatment for hepatitis B &#39;e&#39; antigen positive chronic hepatitis. The trials could be open, single blinded, or double blinded. No patient exclusion criteria were applied. Three reviewers independently selected the trials and one extracted the data, which were validated. Assessments of the outcome measures were performed at the end of treatment and at six months and at maximal follow up after the end of treatment with alfa interferon. A total of 13 randomised trials including 790 patients were included. Loss of hepatitis B &#39;e&#39; antigen (OR 1.41, 95% confidence interval 1.03 to 1.92, P = 0.03) and hepatitis B virus DNA (OR = 1.51, 95% confidence interval 1.12 to 2.05, P = 0.008) were significantly more frequent among patients treated with the sequential combination of glucocorticosteroids and alfa interferon than among patients treated with alfa interferon alone. Glucocorticosteroid pretreatment did not significantly influence seroconversion from hepatitis B &#39;e&#39; antigen to antibodies to hepatitis B &#39;e&#39; antigen, loss of hepatitis B surface antigen, normalisation of alanine aminotransferase/aspartate aminotransferase activities, and severity of adverse events. Glucocorticosteroid pretreatment did not significantly affect mortality and adverse events. The effect of glucocorticosteroid pretreatment on liver histology and quality of life could not be assessed due to insufficient data. Pretreatment with glucocorticosteroids before treatment with alfa interferon in patients with hepatitis B &#39;e&#39; antigen positive chronic hepatitis B may be more effective than treatment with alfa interferon alone with regard to loss of hepatitis B &#39;e&#39; antigen and hepatitis B virus DNA, but evidence for effect on clinical outcomes is lacking.

Research paper thumbnail of Widespread use of condoms and low prevalence of sexually transmitted diseases in Danish non-drug addict prostitutes