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Biomedical subjects

R A de Man

Publications and source records attributed to R A de Man.

At least 19 recordsLinked to original sources
PubMed2006

Determinants of quality of life in chronic liver patients.

BACKGROUND AND AIM: Health-related quality of life of patients with chronic liver disease has been shown to be impaired in numerous studies. However, the factors which influence health-related quality of life in treated chronic liver patients are not quite known. This is the first study to assess the impact of physical and psychosocial determinants on a weighted score of health-related quality of life in patients with chronic liver disease. METHODS: The data of 1175 chronic liver patients were used to assess the relationship between items of the disease-specific Liver Disease Symptom Index 2.0 and the Short Form (SF)-6D weighted utility score by means of linear regression analyses. RESULTS: Health-related quality of life was most strongly related to disease severity (B = -0.029) and joint pain (B = -0.023). Depression (B = -0.014), pain in the right upper abdomen (B = -0.014), decreased appetite (B = 0.014) and fatigue (B = -0.013) were also strongly related to health-related quality of life. In hepatitis C virus patients, disease severity (B = -0.037) and depression (B = -0.030) were strong determinants of health-related quality of life. CONCLUSIONS: This study shows that health-related quality of life in chronic liver patients is clearly determined by disease severity, joint pain, depression, decreased appetite and fatigue. These patients may benefit most from interventions aimed at improving adaptation to the symptoms described.

Activities of Daily Living↗
PubMed2006

[Hepatic hydrothorax].

Hepatic hydrothorax was diagnosed in four patients with liver cirrhosis, three men aged 65, 41, and 48 and a woman aged 48. They presented with either right-sided or bilateral pleural-fluid accumulations in the absence of cardiopulmonary disease. In the first man with no concurrent ascites, the disorder was missed, resulting in prolonged chest tube drainage, multiple severe complications and death. In the 41-year-old man chest tube drainage was also associated with complications including renal failure and encephalopathy. Pleurodesis was effective in the woman while in the remaining man hepatic hydrothorax was only a temporary, asymptomatic finding. Pleural effusions in cirrhotic patients should be considered and managed as hepatic hydrothorax unless diagnostic studies reveal a different aetiology. Absence of ascites is not uncommon and should not delay the correct diagnosis. The gradient between pleural and serum albumin concentration is typically more than 11 g/l. Prolonged chest tube drainage is dangerous and should be avoided. In cases refractory to salt restriction and diuretic therapy, transjugular introduction of an intrahepatic portosystemic shunt is the treatment of choice. Recently, pleurodesis combined with thoracoscopic repair ofdiaphragmatic defects has been reported as a potentially effective form of therapy.

Adult↗
PubMed2006

Wild type and YMDD variant of hepatitis B virus: no difference in viral kinetics on lamivudine/tenofovir therapy in HIV-HBV co-infected patients.

Prolonged lamivudine therapy has been identified as the major risk for the development of resistance in HBV, with rates of 90% after 4 years of treatment. Tenofovir disoproxil fumarate showed activity against both wild type and lamivudine resistant HBV in HIV-HBV co-infected patients. In order to compare the efficacy of lamivudine/tenofovir treatment we investigated detailed HBV kinetics in 13 HIV-HBV co-infected patients with either wild type HBV or lamivudine resistant HBV. The viral strains in both patient groups showed a biphasic viral decline pattern. Only in the first phase of viral decay, which reflects the clearance rate of the free virus from plasma, there was a statistically significant response in favor of the wild type group. After the first phase we observed a similar viral decline till 24 weeks of both groups. This is reassuring for many pretreated co-infected patients harbouring mutant viruses.

Adenine↗
PubMed2006

Case-orientated approach to the management of hepatocellular adenoma.

BACKGROUND: Treatment of suspected hepatocellular adenoma (HA) remains controversial. The aim of this study was to evaluate the management of HA at a time when magnetic resonance imaging (MRI) and computed tomography (CT) are highly sensitive methods for diagnosing HA. METHODS: Between January 2000 and January 2005, data from 48 consecutive women with HA (median age 36 years) were prospectively collected. The protocol for diagnostic work-up consisted of multiphasic MRI or CT. Management was observation if the tumour was smaller than 5 cm and surgical intervention if it was 5 cm or larger. RESULTS: The median follow-up was 24 (range 3-73) months. Sixteen (33 per cent) patients had invasive procedures because of tumour size 5 cm or larger, malignant characteristics or haemorrhage. The remaining 32 patients (67 per cent) were observed; haemorrhage and malignant degeneration did not occur and none of the lesions showed enlargement after withdrawal of oral contraceptives. Multiple HAs were found in 32 (67 per cent) patients; liver steatosis was significantly more common in these patients than in those with a solitary lesion (59 versus 19 per cent; P = 0.008). CONCLUSION: Observation of adenomas smaller than 5 cm is justified because of improved radiological reliability. Resection should be reserved for patients with malignant tumour characteristics or with single lesions 5 cm or larger.

Adenoma, Liver Cell↗
PubMed2006

Hepatitis B virus (HBV) DNA levels and the management of HBV-infected health care workers.

Different guidelines exist for the management of hepatitis B virus (HBV)-infected health care workers (HCWs). Various HBV DNA levels are used as a cutoff level to determine whether an HBV-infected HCW is allowed to perform exposure-prone procedures (EPPs) or not. In this paper we discuss the factors that determine HBV DNA levels and the implications of different HBV DNA cutoff levels for EPP performing HCWs. If the level of HBV DNA in the serum of HCWs is used to determine acceptability for the conduct of EPPs, it is necessary to take into account the variability in time of HBV DNA levels in HBV carriers and the reliability and reproducibility of the molecular diagnostic test involved. The issue of standardization has to be addressed, before a universal, maximum level of viraemia for EPP performing HCWs can be introduced.

DNA, Viral↗
PubMed2006

Quantitative HBV DNA levels as an early predictor of nonresponse in chronic HBe-antigen positive hepatitis B patients treated with interferon-alpha.

To reduce unnecessary exposure to treatment, physicians must decide at an early stage whether continuation of treatment has a reasonable chance of success for the individual patient. The objectives of our study were to evaluate the previously described quantitative hepatitis B e antigen (HBeAg) measurements vs quantitative hepatitis B virus (HBV) DNA measurements for prediction of nonresponse and response in interferon (IFN)-alpha treated HBeAg positive chronic HBV patients. Serum HBV DNA and HBeAg levels were assessed at baseline and weeks 8 and 12. For each test (HBV DNA level at baseline, HBV DNA decrease between baseline and weeks 8 and 12, or the combination of these two, as well as HBeAg level at baseline, HBeAg decrease between baseline and weeks 8 and 12, and the combination of these two), we calculated the positive predictive value, negative predictive value, sensitivity and specificity. Monitoring with quantitative HBV DNA levels (area under ROC 0.87) was superior to monitoring with quantitative HBeAg levels (0.76, P < 0.05). Step-wise logistic regression identified HBV DNA at baseline and decrease in HBV DNA from baseline to week 12, as independent predictors of response. The overall test performance of predicting nonresponse (predictive value 100%) was best for log HBV DNA testing at week 12 compared with testing at week 8 due to a better prediction of sustained response (46%vs 38%) and lower misidentification of nonresponse (39%vs 54%). This study showed that quantitative HBV DNA testing at baseline in combination with a decrease between baseline and week 12 has a high predictive value for identifying patients who have virtually no chance of reaching a sustained response with IFN therapy.

Adolescent↗
PubMed2005

Flares in chronic hepatitis B patients induced by the host or the virus? Relation to treatment response during Peg-interferon {alpha}-2b therapy.

BACKGROUND AND AIMS: Flares are a well known phenomenon during antiviral treatment for chronic hepatitis B. Little is known about the effect of flares on response. We investigated the timing and characteristics of flares, in relation to treatment response (hepatitis B e antigen loss). PATIENTS: A total of 266 patients, participating in a global randomised controlled study, were assigned to 52 weeks of 100 mug pegylated (Peg)-interferon alpha-2b weekly, combined with either daily lamivudine 100 mg or placebo. RESULTS: Sixty seven patients (25%) exhibited 75 flares, with 38 (51%) flares in the combination therapy and 37 (49%) in the monotherapy groups. Overall, 30% of patients with and 38% of patients without a flare responded to therapy (p = 0.25). In 24 patients (36%) the flare was followed by a decrease in hepatitis B virus (HBV) DNA (host induced flare). In 25 (38%) patients the flare was preceded by an increase in HBV DNA (virus induced flare). In 17 (26%) patients the flare did not meet one of these criteria (indeterminate flare). Of patients with host induced flare, 58% responded whereas only 20% of patients with virus induced flares responded (p = 0.008). Hepatitis B surface antigen loss (n = 8) was exclusively seen in patients experiencing a host induced flare. Multivariate logistic analysis showed that host induced flares was an independent predictor of response (p = 0.043). CONCLUSION: Flares are not more common in responders than in non-responders to Peg-interferon alpha-2b therapy. Virus induced flares, which occur after an increase in HBV DNA level, and most probably are indicative for increased expression of viral antigens, did not lead to treatment response. In contrast, host induced flares which were followed by a HBV DNA decrease were highly associated with treatment response.

Adult↗
PubMed2005

[Fever as a sign of inflammatory syndrome in a female patient with hepatic haemangioma].

A 41-year-old patient presented with fever, night sweats, general malaise, abdominal pain, and substantial weight loss. Laboratory analysis suggested an inflammatory process. Diagnostic imaging revealed a hepatic haemangioma with a diameter of 20 cm. Because such giant haemangiomas of the liver can lead to inflammatory syndrome, the tumour was surgically removed. Pathological analysis confirmed the clinical diagnosis and evidence of extensive thrombosis and other vascular defects was found. Following treatment, the symptoms resolved without further complications. In patients with a giant haemangioma in the liver who present with an inflammatory syndrome, the haemangioma should be considered as the causal factor. For these patients, resection is the treatment of choice.

Abdominal Pain↗
PubMed2005

The safety of pegylated interferon alpha-2b in the treatment of chronic hepatitis B: predictive factors for dose reduction and treatment discontinuation.

BACKGROUND: Treatment with interferon-alpha has been shown to be effective in one-third of hepatitis B e antigen-positive chronic hepatitis B patients, but is clinically associated with relevant adverse events. AIM: To investigate the safety of pegylated interferon alpha-2b in 300 hepatitis B e antigen-positive patients with compensated liver disease. METHODS: Patients were treated with pegylated interferon alpha-2b for 52 weeks combined with either lamivudine 100 mg/day or placebo. Pegylated interferon alpha-2b was administered for 100 microg once a week for 32 weeks; thereafter, the dose was reduced to 50 microg once a week. Adverse events and their effect on study medication were reported at monthly visits in a standardized way. RESULTS: The most frequently reported side-effects were flu-like syndrome (68%), headache (40%), fatigue (39%), myalgia (29%) and local reaction at the injection site (29%). These symptoms typically occurred within the first month of therapy and subsided during the course of therapy. Neutropenia and thrombocytopenia induced by pegylated interferon alpha-2b increased the risk of infections and bleeding complications, but these complications were rare and mild. The frequency of all side-effects was not different between patients treated with pegylated interferon alpha-2b combined with lamivudine or placebo. In 69 (22%) patients the dose of pegylated interferon alpha-2b was reduced prematurely. Of these dose reductions, 36 (52%) were because of neutropenia. Therapy was discontinued in 28 (8%) patients. The most frequent reasons for early discontinuation were psychiatric side-effects (depression, psychosis) and flu-like symptoms. Multivariate Cox regression analysis showed that low neutrophil count at baseline and cirrhosis were independent predictors of dose reduction or therapy discontinuation. CONCLUSION: We conclude that in patients with chronic hepatitis B and compensated liver disease prolonged pegylated interferon alpha-2b therapy is safe, and that pre-existent cirrhosis and neutropenia are the most important predictors of dose reduction or early treatment discontinuation.

Adult↗
PubMed2005

Viral dynamics during tenofovir therapy in patients infected with lamivudine-resistant hepatitis B virus mutants.

Tenofovir, an antihuman immunodeficiency virus (HIV) drug, has activity against lamivudine-resistant hepatitis B virus (HBV) mutants. To describe the efficacy of tenofovir in patients with lamivudine-resistant hepatitis B we applied two investigative approaches based on mathematical models of viral dynamics: the individual nonlinear fitting and the mixed-effect group fitting approaches. Eleven chronic HBV patients on lamivudine for a median of 176 weeks (range: 72-382) with YMDD mutation-related HBV-DNA breakthrough received 'add-on' tenofovir 300 mg once-daily, while maintaining their existing therapy. Sequential sera were taken at day 1 (t = 0 and t = 8 h), days 2, 4, 7, 10, 14, 21, 28 and every 4 weeks thereafter, and HBV-DNA levels were assessed using a validated quantitative polymerase chain reaction (PCR) assay. Median baseline log HBV-DNA was 8.62 (range: 6.48-9.76 log HBV-DNA). Tenofovir treatment resulted in a mean (+/-SD) log HBV-DNA decline of 1.37 +/- 0.51 in the first phase, 2.54 +/- 0.91 after 4 weeks, and 4.95 +/- 0.90 log HBV-DNA after 24 weeks. The median effectiveness of blocking viral replication in the individual fit model was 93% (range: 73-99) for eta = 0 and 93% (range: 59-99) for eta = 1. There was only a small difference between the efficacy parameter 'epsilon' of the individual nonlinear fitting and mixed-effect group fitting on the biphasic exponential model. These data show that tenofovir has good efficacy in blocking viral replication in HBV patients with lamivudine-induced drug-resistant HBV mutants, but effectiveness varies greatly among individuals. Both models can be used to describe viral decay during tenofovir therapy.

Adenine↗
PubMed2005

Hepatitis B immunoglobulins inhibit dendritic cells and T cells and protect against acute rejection after liver transplantation.

The efficacy of anti-viral intravenous immunogobulins (anti-HBs Ig and anti-CMV Ig) in preventing acute rejection after liver transplantation was assessed in a retrospective analysis, and correlated to their effects on immune cells in vitro. HBs Ag-positive liver graft recipients (n = 40) treated prophylactically with anti-HBs Ig had a significantly lower incidence of acute rejection compared with recipients without viral hepatitis (n = 147) (12% vs. 34%; p = 0.012), while the incidence of rejection in HCV-positive recipients (n = 29) was similar to that in the control group. Treatment with anti-CMV Ig (n = 18) did not protect against rejection. In vitro, anti-HBs Ig suppressed functional maturation of and cytokine production by human blood-derived dendritic cells (DC) at concentrations similar to the serum concentrations reached during anti-HBs Ig treatment of liver graft recipients. In addition, anti-HBs Ig inhibited allo-antigen- and lectin-stimulated proliferation of peripheral T cells. Anti-CMV Ig suppressed functional DC-maturation and alloantigen-stimulated T-cell proliferation, but not lectin-driven T-cell proliferation. In conclusion, anti-HBs Ig protects against acute rejection after liver transplantation, probably by functional inhibition of the two principal immune cells involved in allograft rejection, DC and T cells.

Adult↗
PubMed2004

[Liver transplantation in a HIV-positive patient receiving potent antiretroviral therapy; the first case in The Netherlands].

In a 49-year-old woman infected with HIV who was receiving highly-active antiretroviral treatment (HAART), terminal liver failure developed. She also had an acute exacerbation of hepatitis B. She was treated by means of liver transplantation and was in good condition two years later. At that time she was treated with tacrolimus, lamivudine, tenofovir, nelfinavir and hepatitis-B immunoglobulin. HIV-RNA and the DNA of hepatitis-B virus could not be detected, her CD4-count was not abnormal and the liver transplant functioned well. No opportunistic infections had developed. HIV infection has long been considered an absolute contraindication to solid organ transplantation, due to the increased risk of infection and rapid progression to AIDS. With HAART, restoration of immune function is possible. Currently, international experience with liver transplantation for HIV-positive patients that are not infected with hepatitis C has shown promising results. Specifically, the risks of transplant rejection, opportunistic infections and progression to AIDS are not increased. Therefore, criteria have been defined for solid organ transplantation in HIV-positive recipients.

Antiretroviral Therapy, Highly Active↗
PubMed2004

Hepatocellular carcinoma in the Netherlands incidence, treatment and survival patterns.

To examine recent trends of hepatocellular carcinoma (HCC) in an unselected patient population in the Western world, cancer registration data of HCC in the Netherlands were analysed. Trends in incidence, mortality, treatment and survival, according to gender, age, stage of disease and period of diagnosis were studied. Age-standardised incidence of HCC in the Netherlands did not rise from 1989 to 2000. In men older than 75 years, there was a significant increase. Mortality due to primary liver cancer increased from 1989 to 2000. There was no change in the treatment pattern (1989-1998), whereas 73% of patients with HCC received no cancer-related therapy during this period of analysis. Twelve percent of the patients underwent either a partial liver resection or orthotopic liver transplantation. This low percentage suggests that patients with HCC must be analysed and discussed in specialised centres to minimise the number of patients not receiving possible curative therapy.

Adult↗
PubMed2004

Doctor-to-patient transmission of hepatitis B virus: the potential of antiviral therapy for prevention.

Hepatitis B virus (HBV)-infected health-care workers (HCWs) have infected patients during medical procedures. In many countries HBV-infected HCWs are restricted in performing exposure prone procedures based on either HBeAg status or serum HBV DNA level. To prevent loss of skilled HCWs and to minimize transmission risk, highly viraemic HCWs can be offered antiviral therapy. Nucleoside analogues have proven to be effective in reducing transmission of HIV and HBV in the setting of vertical mother-to-infant transmission. Following the same rationale, suppression of viral load in HBV-infected HCWs could minimize the risk of doctor-to-patient transmission to such an extent that job modifications are no longer indicated. To limit the risk of drug resistance, the use of combination therapy is advocated. We describe two chronic HBV-infected HCWs treated with antiviral therapy, eventually leading to well-tolerated and highly effective combination therapy with lamivudine and tenofovir, with continuation of medical practice.

Antiviral Agents↗
PubMed2004

A randomised study on the efficacy and safety of an automated Tru-Cut needle for percutaneous liver biopsy.

BACKGROUND: We studied whether the theoretical advantages of a spring-loaded liver biopsy needle exist in clinical practice and if so if they are dependent upon the experience of the physician performing the biopsy. METHODS: In a stratified randomised study we enrolled 215 consecutive patients to compare the safety and efficacy of a new automatic biopsy gun (Acecut) with that of a standard Tru-Cut needle. RESULTS: A total of 464 biopsies were performed. The endpoints of the study were number of needle passes needed per patient, tissue yield of each needle pass and post-biopsy complications. The performance of the automatic needle was superior and more consistent with respect to tissue yield compared with the Tru-Cut needle (median yield 100% and 80%, respectively; p < 0.001). The difference was most marked for inexperienced physicians. There was no difference between the two needles in the number of passes needed. More post-biopsy pain and post-biopsy use of analgesics were observed in the automatic needle group (p = 0.04). CONCLUSION: The automatic Tru-Cut needle offers an advantage, particularly for physicians with no or limited experience in liver biopsies. However more post-biopsy pain and post-biopsy use of analgesics were observed in the automatic needle group.

Adult↗
PubMed2003

Good outcomes after resection of large hepatocellular carcinoma in the non-cirrhotic liver.

BACKGROUND: The results of partial liver resection of hepatocellular carcinoma (HCC) in non-cirrhotic livers are not well known. Therefore a retrospective study was conducted. METHODS: The medical records of 180 patients with HCC were reviewed. In 40 patients (22%), HCC occurred in a non-cirrhotic liver. A detailed analysis of these patients was performed. The diagnosis HCC was based on imaging and/or percutaneous ultrasound-guided biopsy. A biopsy of the remaining liver and peroperative findings documented the absence of cirrhosis. RESULTS: Twenty-two patients underwent partial liver resection. There was no surgical mortality. The median tumour diameter in the operated patients was 10 cm. Survival rates for operated patients at 1 and 5 years were 96 and 68%, respectively. Significant factors reducing survival were portal vein thrombosis, positive lymph nodes, microscopic vascular invasion and tumour recurrence. Tumour size at the initial moment of diagnosis was not of predictive value. After surgery with curative intent disease-free interval at 1 and 5 years were 86 and 56%, respectively. CONCLUSION: In selected patients without cirrhosis, HCC can be treated successfully by surgical resection, independent of the tumour diameter, with a 5-year survival rate of 68%.

Adult↗
PubMed2003

[The treatment of hepatitis C].

The recent advances in the antiviral therapy of hepatitis C have significantly lowered the threshold for offering such therapy to patients. Sustained virological response rates of 42-46% are achieved after 48 weeks of combination therapy with peginterferon alpha and ribavirin in patients with genotype 1 infection. In patients with a genotype 2 or 3 infection, 24 weeks of combination therapy leads to a sustained response rate of almost 80%. The U.S. National Institutes of Health consensus states that every patient with hepatitis C should be considered for antiviral therapy. Identification of the patients, selection for therapy, the provision of good information, guidance of the patient during therapy and a successful management of side effects lead to better treatment compliance and are of paramount importance in obtaining maximal therapeutic efficacy. Supportive guidance during substance abuse withdrawal programmes and the adequate use of selective serotonin reuptake inhibitors should be part of these measures.

Antiviral Agents↗