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Biomedical subjects

R A de Man

Publications and source records attributed to R A de Man.

At least 55 records · Page 3Linked to original sources
PubMed2001

Indications and long-term outcome of treatment for benign hepatic tumors: a critical appraisal.

HYPOTHESIS: The natural history and clinical behavior of benign hepatic tumors during long-term follow-up may not justify primary surgical treatment. DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: Two hundred eight patients diagnosed as having a benign liver tumor between January 1, 1979, and December 31, 1999. INTERVENTION: Seventy-four patients underwent hepatic surgery and 134 were managed conservatively by radiological follow-up. MAIN OUTCOME MEASURES: Symptoms and complications were assessed during management and follow-up. RESULTS: In the surgically treated population, the liver lesion was symptomatic in 47 patients (64%) and an incidental finding in 27 (36%). The operative morbidity and mortality were 27% (20 of 74 patients) and 3% (2 of 74 patients), respectively. Overall, 28 (80%) of 35 patients with complaints were asymptomatic after surgery. During observation of the tumor in the conservatively managed group, 39 (87%) of 45 patients who presented with complaints were asymptomatic during a mean follow-up of 45 months; 6 patients had mild abdominal pain considered to be unrelated to the tumor. CONCLUSIONS: Conservative management of solid benign liver lesions such as focal nodular hyperplasia and hemangioma can be performed safely, irrespective of their size. We only advise surgery for liver lesions when there is an inability to exclude malignancy or in the case of severe complaints related to the tumor. Resection is always advocated in the case of a large hepatocellular adenoma (>5 cm) to reduce the risk of rupture and malignant degeneration.

Adenoma, Liver Cell↗
PubMed2001

Administration of a human monoclonal antibody (TUVIRUMAB) to chronic hepatitis B patients pre-treated with lamivudine: monitoring of serum TUVIRUMAB in immune complexes.

A human monoclonal anti-hepatitis B antibody preparation (TUVIRUMAB) was administered 6 times over a 2-week period in a dose-escalating scheme to chronic hepatitis B patients pre-treated with lamivudine. The capacity of the TUVIRUMAB antibody to "neutralize" hepatitis B surface antigen in the circulation was investigated by means of experimental enzyme-immunoassays. Monoclonal antibody conjugates enabled the detection of HBsAg, TUVIRUMAB, and HBsAg/TUVIRUMAB complexes. The results showed that (1) TUVIRUMAB was able partially to "neutralize" in vitro and in vivo, (2) HBsAg/TUVIRUMAB complexes can be traced by assays that capture the complex at either its HBsAg or its TUVIRUMAB component, (3) the final concentration of TUVIRUMAB at the end of therapy varied greatly but seemed to be related to HBsAg production at the start of therapy, (4) for at least 14 days after discontinuation of therapy, a minimal HBsAg level could be maintained in the presence of a declining TUVIRUMAB titer in patients with less than 3 microg/ml HBsAg before the start of therapy, (5) three months after therapy, all HBsAg levels had returned to pre-treatment levels and TUVIRUMAB had disappeared.

Antibodies, Monoclonal↗
PubMed2001

A comparison of the costs and effects of liver transplantation for acute and for chronic liver failure.

Little is known about costs and cost-effectiveness of liver transplantation (LTx) for acute liver failure compared to costs and cost-effectiveness of LTx for chronic liver failure. In this study, costs of acute and of chronic LTx patients were determined in a retrospective study. Files of 100 consecutive patients who underwent LTx in 1993-1997 were studied. Costs up to 1 year after LTx were Euro 107,675 (chronic liver failure) and Euro 90,792 (acute liver failure). The difference was mainly caused by higher hospitalisation costs and higher personnel costs for chronic liver failure. Medication costs for acute liver failure were higher, due to a high administration rate of expensive anti-HBs immunoglobulin therapy in patients with viral hepatitis B. LTx for chronic liver failure is more costly and seems to be more cost-effective than LTx for acute liver failure, since 1-year survival is higher in patients who underwent transplantation for chronic liver failure.

Acute Disease↗
PubMed2001

Is combination therapy with lamivudine and interferon-alpha superior to monotherapy with either drug?

For the treatment of chronic hepatitis B (CHB) two drugs have been licensed world-wide: interferon-alpha (IFN) and lamivudine. Both drugs significantly increase the hepatitis B e-antigen (HBeAg) seroconversion rate, but a sustained treatment response occurs in less than 40% of patients. To explore whether there is an additional benefit of combining these two drugs, we reviewed the literature on lamivudine-IFN combination therapy in comparison to the two monotherapies in compensated, HBeAg-positive, CHB patients. We focussed on two clinically relevant outcome measures: HBeAg seroconversion, and change in liver histology. Candidates for lamivudine-IFN combination therapy were, previously untreated, patients with moderately elevated alanine aminotransferase (ALT). Such regimen should still be considered experimental. Viral kinetics may provide insight into how long therapy should be continued; prolongation of therapy to 52 weeks currently appears a reasonable approach. According to principles of anti-viral therapy today, simultaneously dosing of both drugs is to be preferred, since rapid maximal virus suppression is thought to be essential to prevent drug resistance and enhance seroconversion. From an immunological point of view, pre-treatment with lamivudine or IFN may alter the virus-host balance and set the stage for the other drug to enhance the effect of treatment. Further clinical research on lamivudine-IFN combination therapy appears warranted.

Antiviral Agents↗
PubMed2001

Randomized trial of lamivudine versus hepatitis B immunoglobulin for long-term prophylaxis of hepatitis B recurrence after liver transplantation.

BACKGROUND/AIMS: The long-term prophylaxis of hepatitis B after liver transplantation requires further optimization. In a randomized trial we investigated a regimen where the initially given hepatitis B immunoglobulin (HBIg) is replaced by long-term lamivudine treatment. METHODS: Twenty-four liver transplant recipients (all HBsAg-positive/HBV DNA-negative before transplantation), who had received HBIg for at least 6 months without HBV recurrence, were randomized to receive lamivudine (n = 12) or HBIg (n = 12) for 52 weeks. The efficacy criteria involved seronegativity for HBsAg and undetectable HBsAg/ HBcAg in the liver. RESULTS: Twenty-one of 24 patients completed the study without hepatitis B virus (HBV) recurrence (11 on HBIg, ten on lamivudine), while three patients became HBsAg-positive. Amongst those without HBV recurrence HBV DNA was detectable only by polymerase chain reaction, intermittently in serum and lymphocytes, and in liver specimens from six of eight patients receiving HBIg and five of seven receiving lamivudine. YMDD variant was found in four cases with no viral antigen expression. Eight patients continued lamivudine after the study and during an additional 6-22 months remained HBsAg-negative with normal graft function. CONCLUSIONS: Substitution of HBIg with lamivudine is effective for prevention of HBV recurrence in low-risk liver transplant recipients and offers a convenient and cost-effective alternative for long-term HBV prophylaxis.

Adult↗
PubMed2001

A psychometric comparison of health-related quality of life measures in chronic liver disease.

Four generic [the Sickness Impact Profile (SIP-68), Short-Form Health Survey (SF-36), EuroQol instrument (EQ-5D), COOP/WONCA charts], two domain-specific health-related quality of life measures [the sexuality scale of the HIV Overview Problems Evaluating System (HOPES), Multi-dimensional Fatigue Index (MFI-20)], and a self-developed 12-item symptom index were compared in terms of feasibility, test-retest reliability, internal consistency reliability, construct validity, and known groups validity in patients with chronic liver disease. All instruments could be completed within 10 min and exhibited a good psychometric performance in patients with chronic liver disease. The SF-36 and the MFI-20 performed relatively best in terms of reliability, construct validity, and discriminative ability. The sexuality scale of the HOPES demonstrated a relatively poor performance, as the missing value rate was higher than 5%. Further research is needed into the sensitivity to important clinical changes of the instruments.

Adolescent↗
PubMed2001

Efficacy and safety of an intravenous monoclonal anti-HBs in chronic hepatitis B patients.

BACKGROUND/AIMS: In this study the safety and efficacy of a monoclonal anti-HBs, Tuvirumab (Mab), were investigated. Tuvirumab is a human monoclonal antibody recognizing the stable 'a'-determinant of the HBsAg. METHODS: We included ten chronic hepatitis B patients: four received monotherapy, and six combination therapy with interferon alpha 2b. RESULTS: Because the development of insoluble [HBsAg-HBsAb] complexes led to adverse events, the Mab dose had to be reduced in seven patients. In nine patients treatment was stopped prematurely because of lack of efficacy, i.e. neutralization of HBsAg in serum. However, temporary HBsAg levels were reduced by at least 50% in all patients; in three patients receiving combination therapy, background levels of HBsAg in serum were reached. A loss of serum HBV-DNA was seen in three patients in the combination group, followed by HBeAg seroconversion in two patients. CONCLUSIONS: We conclude that Mab was not effective in achieving primary efficacy as assessed by neutralization of circulating HBsAg. Whether a combination of Mab with an antiviral agent that reduces the HBsAg load--and therefore minimizes the risk of adverse events--may result in clinical efficacy should be investigated.

Adult↗
PubMed2001

Suppression of hepatitis B virus replication mediated by hepatitis A-induced cytokine production.

BACKGROUND: Acute hepatitis A virus (HAV) infection can cause severe hepatitis especially in patients with underlying chronic liver disease. In patients with pre-existing chronic hepatitis B (HBV) acute HAV infection can suppress HBV replication. The exact mechanism of HBV suppression during acute HAV infection is still a subject of debate. One mechanism may be the production of HAV infection-induced cytokines leading to suppression of HBV replication and viral clearance. AIM: To evaluate cytokine production and HBV-specific lympho-proliferative responses (LPR) during acute HAV infection in a patient with chronic HBV infection-clearing markers of active HBV replication. DESIGN: Early detection of a case of acute HAV infection in an HBeAg-positive, HBV DNA-positive chronic HBV patient treated with lamivudine. RESULTS: At the time of HAV infection a sharp peak in the gamma-interferon (IFN-gamma) level occurred just before the rise in serum transaminase activity. This was subsequently followed by a decrease in HBV DNA and HBeAg below the limit of detection of the assay. However the HBV-specific T-cell response was not modified. After resolution of the acute HAV infection and withdrawal of antiviral therapy HBV replication relapsed. CONCLUSION: The sharp rise in IFN-gamma production mediated by the acute HAV infection may be pivotal in the suppression of HBV replication in chronic hepatitis B.

Acute Disease↗
PubMed2001

Treatment of ruptured hepatocellular adenoma.

BACKGROUND: As the morbidity and mortality rates associated with emergency resection in patients with a ruptured hepatocellular adenoma are high, the authors have favoured initial non-operative management in haemodynamically stable patients. METHODS: A retrospective study was performed to evaluate the treatment of ruptured hepatocellular adenoma. RESULTS: Over a 21-year interval, 12 patients presented with a ruptured hepatocellular adenoma. Haemodynamic observation and support was the initial management in all 12 patients. Three underwent urgent laparotomy and gauze packing because of haemodynamic instability; no emergency liver resection was necessary. Eight patients had definitive surgery; three developed postoperative complications but none died. Regression of the tumour was observed in three of four patients treated conservatively. CONCLUSION: The initial management of a ruptured hepatocellular adenoma should be haemodynamic stabilization. Definitive resection is required for rebleeding or for tumours exceeding 5 cm in diameter. A conservative approach may well be justified in case of regression of an asymptomatic adenoma.

Adenoma, Liver Cell↗
PubMed2001

Safety and efficacy of oral entecavir given for 28 days in patients with chronic hepatitis B virus infection.

Entecavir is an oral antiviral drug with selective activity against hepatitis B virus (HBV). We conducted a randomized, placebo-controlled, dose-escalating study in patients with chronic hepatitis B infection in which we evaluated the efficacy and safety of entecavir given for 28 days. Follow-up was 24 weeks. All doses of entecavir (0.05 mg, 0.1 mg, 0.5 mg, and 1.0 mg) showed a pronounced suppression of replication of the HBV with a 2.21, 2.29, 2.81, and 2.55 mean log(10) reduction of viral load, respectively. Approximately 25% of patients on entecavir showed a decline of HBV DNA below the limit of detection of the Chiron HBV-DNA assay (<0.7 MEq/mL). In the postdosing follow-up period patients who were treated with 0.5 and 1.0 mg of entecavir showed a considerably slower return in their HBV DNA levels to baseline compared with those patients treated with lower dosages (P <.05). All doses of entecavir were well tolerated with no significant difference between treated patients and those receiving placebo. No significant changes in alanine transaminase (ALT) levels within the dose groups and the placebo group between baseline and the end of treatment were observed. Three patients (9%) (1 each in the 0.05-, 0.1-, and 0.5-mg groups) experienced asymptomatic hepatitis flares 16 weeks (2 patients) and 24 weeks (1 patient) after withdrawal of entecavir. In conclusion, in this 28-day study of entecavir a pronounced decrease of HBV DNA was observed and there were no significant side effects in entecavir patients in comparison with placebo-treated patients.

Administration, Oral↗
PubMed2001

Nucleoside analogues for chronic hepatitis B.

Hepatitis B virus replicates inside the hepatocyte through an intermediate step of reverse transcription mediated by the viral polymerase. We describe five nucleoside/nucleotide analogues that interfere with the replication mechanisms of the hepatitis B virus. The resemblance of nucleoside analogues to natural nucleosides may lead to direct cytotoxicity. Therefore, antiviral activity should always be interpreted in the light of cellular toxicity. In addition, prolonged therapy with a nucleoside analogue may induce mutations in the viral polymerase, causing structural and configurational changes of the polymerase resulting in a decreased affinity for the nucleoside analogue. Subsequently, the mutated virus is capable of renewed replication during continued antiviral pressure of the nucleoside analogue. The best antiviral strategy in the future is probably combination therapy, either with several nucleoside analogues or with a nucleoside analogue and interferon.

2-Aminopurine↗
PubMed2000

[Acute liver failure ascribed to nefazodone: importance of 'postmarketing surveillance' for recently introduced drugs].

A 50-year-old man developed acute liver failure 7 months after nefazodone treatment was initiated. There was no evidence of any aetiology apart from the exposure to the antidepressant drug nefazodone, while the results of repeated histological examinations of the liver were compatible with serious progressive drug-induced hepatitis. This diagnosis was initially disregarded because in the literature no patients with nefazodone-induced hepatitis were reported. However, the drug had only recently been introduced, which meant that relatively infrequent adverse drug reactions might not have been published. Further analyses of databases of the marketing pharmaceutical industry and of the World Health Organization revealed more cases of liver toxicity ascribed to nefazodone, which showed that liver failure may indeed be associated with nefazodone use. Consequently, prescribing doctors have been warned by the pharmaceutical company about this possible adverse drug reaction.

Adverse Drug Reaction Reporting Systems↗
PubMed2000

[Treatment of non-resectable liver tumors with percutaneous interstitial laser coagulation while interrupting blood circulation to the liver].

OBJECTIVE: To evaluate, in patients with hepatocellular carcinoma or colorectal carcinoma disseminated to the liver, treatment with interstitial laser coagulation (ILC) during temporary occlusion of vascular inflow in the liver: feasibility, complications and initial tumour response. DESIGN: Prospective, descriptive. METHODS: Patients were included if their tumours were surgically irresectable and smaller than 4 cm in diameter and did not exceed a number of 3. ILC was performed under general anaesthesia, basically via a percutaneous approach. Vascular inflow was occluded during laser treatment. Twenty-four hours after ILC a triphasic spiral CT was performed to assess the result of the treatment. RESULTS: In 10 patients 14 hepatic tumours were lasered in 12 treatment sessions (10 percutaneous and 2 at laparotomy). After 5 treatment sessions, complications were observed of which pain at the insertion site of the catheters was the most frequent. For 6 out of the 10 patients with percutaneous procedures, discharge was within 24 hours after ILC. Nine out of the 14 tumours (65%) were completely coagulated. CONCLUSION: ILC with vascular inflow occlusion is a safe and feasible technique that can be performed during a short hospital stay. Initial tumour response is 65% and these results justify determination of duration of response in a larger group of patients.

Aged↗
PubMed2000

Anti-HBs characteristics after hepatitis B immunisation with plasma-derived and recombinant DNA-derived vaccines.

Hepatitis B surface antigen derived from chronic hepatitis B carriers has been replaced almost completely by recombinant DNA-derived HBsAg for use as hepatitis B vaccine. Similarly, recombinant DNA-derived HBsAg is replacing plasma-derived HBsAg in standard anti-HBs assays. We analysed the influence of a change from plasma-derived HBsAg to recombinant DNA-derived HBsAg on antigen presentation in immunoassays and the characteristics of the anti-HBs antibodies after immunisation. Antigens and/or antibodies were subjected to three types of experiments: (a) binding of 'a'-loop specific monoclonal (anti-S) antibody conjugates to immobilised vaccine-HBsAg; (b) binding of post-vaccination anti-HBs to immobilised (vaccine-)HBsAg and (c) inhibition of HBsAg binding to immobilised monoclonal anti-HBs after pre-incubation with post-vaccination antibodies. Our results show that, in both antigen presentation and anti-HBs binding properties, yeast recombinant HBsAg and related antibodies could be clearly distinguished from plasma-derived HBsAg and related antibodies. Divergent results were also obtained in the inhibition assay with recombinant DNA-derived HBsAg but not with serum HBsAg from the vaccine HBsAg subtype. It is concluded that both antigen presentation in vaccines and in anti-HBs assays can markedly influence the quantitation anti-HBs response. It is suggested that a challenge with an heterologous hepatitis B virus may encounter reduced efficacy of vaccine antibodies.

Antigen Presentation↗
PubMed2000

Molecular cytogenetic evaluation of virus-associated and non-viral hepatocellular carcinoma: analysis of 26 carcinomas and 12 concurrent dysplasias.

The worldwide incidence of hepatocellular carcinoma (HCC) is approximately one million cases a year. This makes HCC one of the most frequent human malignancies, especially in Asia and Africa, although the incidence is increasing also in the western world. HCC is a complication of chronic liver disease, with cirrhosis as the most important risk factor. Viral co-pathogenesis makes cirrhosis due to hepatitis B (HBV) and hepatitis C virus (HCV) infection a very important factor in the development of HCC. As curative therapy is often ruled out due to the late detection of HCC, it would be attractive to find parameters which predict malignant transformation in HBV- and HCV-infected livers. This study has used comparative genomic hybridization (CGH) to analyse 26 HCCs (11 non-viral, nine HBV, six HCV) and 12 concurrent dysplasias (five non-viral, five HBV, two HCV). Frequent gain (> or =25% of all tumours) was detected, in decreasing order of frequency, on 8q (69%), 1q (46%), 17q (46%), 12q (42%), 20q (31%), 5p (27%), 6q (27%), and Xq (27%). Frequent loss (> or =25% of all tumours) was found, in decreasing order of frequency, on 8p (58%), 16q (54%), 4q (42%), 13q (39%), 1p (35%), 4p (35%), 16p (35%), 18q (35%), 14q (31%), 17p (31%), 9p (27%), and 9q (27%). Minimal overlapping regions could be determined at multiple locations (candidate genes in parentheses). Minimal regions of overlap for deletions were assigned to 4p14-15 (PCDH7), 8p21-22 (FEZ1), 9p12-13, 13q14-31 (RB1), 14q31 (TSHR), 16p12-13.1 (GSPT1), 16q21-23 (CDH1), 17p12-13 (TP53), and 18q21-22 (DPC4, DCC). Minimal overlapping amplified sites could be seen at 8q24 (MYC), 12q15-21 (MDM2), 17q22-25 (SSTR2, GH1), and 20q12-13.2 (MYBL2, PTPN1). A single high level amplification was seen on 5q21 in an HBV-related tumour. Aberrations appeared more frequent in HBV-related HCCs than in HCV-associated tumours (p=0.008). This was most prominent with respect to losses (p=0.004), specifically loss on 4p (p=0.007), 16q (p=0.04), 17p (p=0.04), and 18q (p=0.03). In addition, loss on 17p was significantly lower in non-viral cancers than in HBV-related HCC (p<0.001). Furthermore, loss on 13q was more prevalent in HCCs in non-cirrhotic livers (p=0.02), thus suggesting a different, potentially more aggressive, pathway in neoplastic progression. A tendency (p=0.07) was observed for loss on 9q in high-stage tumours; no specific changes were found in relation to tumour grade. A subset of the HCC-associated genetic changes was disclosed in the preneoplastic stage, i.e. liver cell dysplasia. This group of dysplasias showed frequent gain on 17q (25%) and frequent loss on 16q (33%), 4q (25%), and 17p (25%). The majority of the dysplasias with alterations revealed genetic changes that were also present in the primary tumour. In conclusion, firstly, this study has provided a detailed map of genomic changes occurring in HCC of viral and non-viral origin, and has suggested candidate genes. Loss on 17p, including the TP53 region, appeared significantly more prevalent in HBV-associated liver cancers, whereas loss on 13q, with possible involvement of RB1, was distinguished as a possible genetic biomarker. Secondly, CGH analysis of liver cell dysplasia, both viral and non-viral, has revealed HCC-specific early genetic changes, thereby confirming its preneoplastic nature. Finally, genes residing in these early altered regions, such as CDH1 or TP53, might be associated with hepatocellular carcinogenesis.

Adult↗