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S W Schalm

Publications and source records attributed to S W Schalm.

At least 19 recordsLinked to original sources
PubMed1992

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

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

Acyclovir↗
PubMed1992

Graft regeneration and host liver atrophy after auxiliary heterotopic liver transplantation for chronic liver failure.

We studied the size of the liver graft and the host liver in six consecutive patients undergoing auxiliary heterotopic liver transplantation for chronic end-stage liver disease. In all cases, a liver reduced in size by left lateral hepatectomy was inserted. The sizes of the graft and host liver were estimated by planimetry of two-dimensional di-isopropyl iminodiacetic acid scintigrams taken 3, 7, 21, 90 and 180 days after surgery. Graft size increased from a mean of 12.2 cm2 (95% confidence interval = 10.2 to 14.1) on day 3 to a maximum of 14.8 cm2 (95% confidence interval = 13.4 to 16.1) on day 21 and remained stable thereafter; in contrast, the host liver decreased in size from 9.6 cm2 (95% confidence interval = 6.8 to 12.3) on day 3 to 3.9 cm2 (95% confidence interval = 3.0 to 4.8) at mo 6. We conclude that in patients with chronic liver failure, an auxiliary allograft reduced in size and placed adjacent to the host liver shows regenerative growth within 3 wk, whereas the host liver atrophies in 3 to 6 mo.

Adult↗
PubMed1992

Increased tissue-type plasminogen activator activity in orthotopic but not heterotopic liver transplantation: the role of the anhepatic period.

The major cause of the increased tissue-type plasminogen activator activity during orthotopic liver transplantation is still unclear. Both the lack of hepatic clearance of tissue-type plasminogen activator in the anhepatic period and increased endothelial release from the graft on reperfusion have been proposed as the major causes. Heterotopic liver transplantation avoids the resection of the host liver and is a useful model to help differentiate between these two possibilities. In this study the fibrinolytic system was evaluated in 10 orthotopic liver transplantations, 18 heterotopic liver transplantations and a control group of 10 partial hepatic resections. A marked increment in tissue-type plasminogen activator activity, from 0.2 to 5.2 IU/ml (p less than 0.02), was observed during the anhepatic period of orthotopic liver transplantation, which rapidly normalized after reperfusion. In contrast, tissue-type plasminogen activator activity levels remained normal in heterotopic liver transplantation and partial hepatic resections. In orthotopic liver transplantation and in heterotopic liver transplantation no increase occurred in tissue-type plasminogen activator activity after reperfusion. The first venous hepatic outflow after reperfusion did not contain elevated tissue-type plasminogen activator activity levels. Plasma degradation products of fibrin and fibrinogen increased during the anhepatic period of orthotopic liver transplantation (from 2.60 to 8.80 micrograms/ml [p less than 0.008] and from 0.40 to 1.60 micrograms/ml [p less than 0.04], respectively) and remained elevated thereafter. In heterotopic liver transplantation and partial hepatic resections these levels remained low. In conclusion, the lack of hepatic clearance during the anhepatic period is probably the most important factor in the evolution of increased tissue-type plasminogen activator activity during orthotopic liver transplantation.

Blood Transfusion↗
PubMed1992

Treatment of chronic viral hepatitis anno 1990.

The therapeutic efficacy of alpha-interferon therapy in chronic hepatitis is discussed in light of various international studies. Although beneficial to some extent, treatment is of limited value and is accompanied by more-or-less serious side effects. Development of complementary drugs and new therapeutic methods must therefore be continued.

Clinical Trials as Topic↗
PubMed1992

New aspects of heterotopic liver transplantation.

In this report the history and clinical results of heterotopic liver transplantation (HLT) are reviewed and some special aspects of current research on HLT are high-lighted. The first laboratory experiments on liver transplantation were performed with auxiliary heterotopic grafts. The initial clinical results of HLT, however, were disappointing and orthotopic liver transplantation (OLT) evolved to be the procedure of choice. Of all the patients who received a heterotopic graft before 1980, only two survived. Since 1980, 50 HLTs are known to have been performed on 48 patients. Results of HLTs after 1986 are clearly better than earlier ones, and survival rates come within the range of those reported for OLT. Intraoperative fibrinolysis is found in the anhepatic phase of OLT, something which is absent in HLT. Tissue-type plasminogen activator (t-PA) is said to be responsible for this phenomenon, as well as for the postreperfusion hyperfibrinolysis. Parallel to the hemostatic changes, the intraoperative hemodynamic stability may be impaired by deleterious substances that arise during liver transplantation. Furthermore, the interaction between the two livers, the effect of HLT on portal pressure and hypersplenism, and the possible role of HLT in inborn errors of hepatic metabolism are described. Special attention is given to the treatment of acute hepatic failure. OLT, in an early phase of the disease, negates the possibility of spontaneous recovery, while delay of the decision to transplant may lead to further deterioration of the patient's clinical condition. As the procedure of HLT is reversible, the decision to transplant can be made more quickly. The clinical experience with HLT for acute liver failure is reported in detail.

Fibrinolysis↗
PubMed1992

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

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

Adult↗
PubMed1992

Zidovudine inhibits hepatitis B virus replication.

Hepatitis B virus DNA polymerase is a viral enzyme that can use viral DNA as well as viral RNA as a template for DNA synthesis. Since both activities are essential for the production of new virus particles, blocking of this enzyme should reduce viral replication. In the present study the in vitro effect of zidovudine triphosphate on hepatitis B virus DNA polymerase activity and the in vivo effect of zidovudine on viral replication in chronic HBsAg-positive patients are investigated. Zidovudine triphosphate inhibited in vitro DNA polymerase activity by 50% at a concentration of 0.3 microM. Serum DNA polymerase activity was significantly reduced in 7 patients who received zidovudine (200 mg orally 4 times daily) for one week. A dose-response effect was suggested by the results found for 6 patients who received 100 mg, 200 mg and 300 mg orally 4 times daily for one week with 2 drug-free weeks between each course. We conclude that zidovudine may be of value for non-responders to alpha-interferon therapy or patients with high initial levels of viral replication prior to the start of interferon treatment.

Administration, Oral↗
PubMed1992

Serial determination of type III procollagen amino propeptide serum levels in patients with histologically progressive and non-progressive primary biliary cirrhosis.

We examined the value of serum procollagen III amino propeptide (PIIIP) for predicting the histological progression of primary biliary cirrhosis (PBC). Serial PIIIP measurements were obtained for nine patients with histologically progressive PBC and nine patients with histologically stable early disease, assessed by repeated liver biopsies and followed for up to 13 years. The means of the follow-up PIIIP concentrations were elevated in 39% of the cases; moreover, PIIIP levels were elevated at least once during follow-up in 72% of the cases. Mean follow-up PIIIP concentrations did not differ significantly between progressive and non-progressive patients. In addition, in the progressive group, histological progression was not reflected by PIIIP levels. No difference was found between the serum PIIIP levels corresponding to the histological stages I, II and III. The individual coefficients of the correlation between serum PIIIP and biochemical variables (bilirubin, alkaline phosphatase, ASAT, albumin) and histology showed a wide distribution without a consistent trend towards positive or negative. Treatment with cyclosporin A or cyclosporin A combined with prednisone did not influence serum PIIIP levels. Treatment with penicillamine combined with prednisone, however, resulted in a significant decrease in PIIIP concentrations (p less than 0.05). We conclude that serum PIIIP measurements are of no value for predicting the histological progression of PBC.

Adult↗
PubMed1992

Course of hepatitis B and D virus infection in auxiliary liver grafts in hepatitis B-positive patients. A light-microscopic and immunohistochemical study.

Four patients who received an auxiliary partial liver graft for decompensated liver cirrhosis due to hepatitis B (HBV), associated in two cases with hepatitis D virus (HDV) superinfection, were studied. The sequential appearance of hepatitis B and D antigens in the grafts was investigated in serial liver biopsies by immuno-histochemical methods and compared with the viral antigenic profiles of the host livers. The histological changes in the liver grafts were studied in relation to the viral expression patterns. One week after transplantation, expression of HBsAg was already apparent in two grafts. HBcAg was found in the graft of the only patient with HBcAg in the host liver. HDAg was expressed in the grafts of both patients with HDV superinfection; in one of these cases HDAg was present without HBsAg. At 3 months, viral antigen expression was maximal. Expression of HBsAg and HBcAg in the grafts of the two HDV-positive patients was, however, less extensive than in the two HBV-positive patients. All patients developed a mild lobular hepatitis, histologically demonstrated between the 47th and 107th posttransplantation day. In the two HBV-positive, HDV-negative patients, cirrhotic transformation of the graft occurred within 1 year. In the HDV-positive patients only a mild chronic active hepatitis with slight or moderate fibrosis was observed after 1 year. We conclude that recurrence of HBV and HDV infection in auxiliary liver grafts is demonstrable within 1-3 weeks. HBV infection in liver grafts may be a rapidly progressive disease. Coinfection with HDV does not aggravate the acute hepatitis and may even suppress the progression of chronic HBV.

Adult↗
PubMed1992

Failure of acyclovir to enhance the antiviral effect of alpha lymphoblastoid interferon on HBe-seroconversion in chronic hepatitis B. A multi-centre randomized controlled trial.

Serum HBeAg levels and HBe-seroconversion were investigated in patients with chronic HBeAg-positive hepatitis who were randomized to receive either alpha lymphoblastoid interferon (5 megaunits subcutaneously daily for 16 weeks) plus acyclovir (2 g intravenously daily during weeks 1 and 2 and weeks 9 and 10) (n = 49) or no treatment (n = 48). HBeAg levels in serial dilutions of patient serum were assessed quantitatively by radioimmunoassay and compared with the values found for negative control serum. One year after the start of therapy 44 treated patients and 43 control patients were available for follow-up. A complete response (HBe-seroconversion) occurred in 11 treated patients (25%) and six controls (14%) (difference: 11%, 95% CI-5-28%). A partial response (HBeAg less than 50% of initial level) was found significantly more often for treated patients (n = 13, 30%) than for controls (n = 2, 5%) (difference: 25%, 95% CI 10-40%). During acyclovir-interferon combination therapy the decrease in HBeAg level was similar to that achieved during therapy with interferon alone. We conclude that acyclovir does not enhance the effect of interferon on serum HBeAg levels. Since HBeAg levels continue to decline during interferon treatment and rebound thereafter to pretreatment levels, prolongation of therapy may yield a higher response rate.

Acyclovir↗
PubMed1992

Oral pharmacokinetics of cyclosporin in patients with primary biliary cirrhosis and patients with skin diseases.

The pharmacokinetics of cyclosporin after oral administration were studied in seven patients with non-end stage primary biliary cirrhosis (PBC) without previous cyclosporin treatment (Group I), a control group of nine patients with skin diseases (mainly psoriasis; Group II) and six patients with PBC after prolonged cyclosporin treatment (Group III). Whole blood concentrations of cyclosporin were measured using a non-specific (N) radioimmunoassay (RIA) and--in a majority of the cases--also by a RIA specific (S) for the parent drug. No difference in cyclosporin absorption was observed between patients with PBC and those with a skin disease. The mean values for the area under the blood concentration-time curve for the first 6 h after the test dose (AUC0-6) and the maximal blood concentrations (Cmax) were significantly higher for Group I compared with Group II patients (P = 0.007 and 0.03, respectively), but the time to maximal blood concentrations (tc,max) did not differ. There was a trend toward higher mean AUC0-6 (P = 0.08) and Cmax (P = 0.08) values for Group III compared with Group I patients. Tc,max values were not influenced by prolonged cyclosporin treatment. The ratio of cyclosporin whole blood concentrations measured by the non-specific and specific RIA's (N/S ratio) increased with time without obvious differences between the three groups. These data suggest that cyclosporin absorption and its biotransformation in the liver are not impaired in patients with non-end stage PBC and that neither is affected by prolonged treatment.

Administration, Oral↗
PubMed1992

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

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

Adolescent↗
PubMed1992

[Premature infants and hepatitis B vaccination. Study Group Prevention Neonatal Hepatitis B].

Since 1986 health authorities in the Netherlands advise to vaccinate preterm infants at similar age as term infants, without correction for their shortened gestational age. This advice was based on a study, which showed comparable immune responses after DTP vaccination in preterm and term infants. To assess the immunogenicity of hepatitis B vaccination not corrected for gestational age in preterm infants, we compared the antiHBs titer after hepatitis B vaccination in 44 preterm infants with the antiHBs titer in 829 term infants. More than 95% of the preterm infants developed an adequate immune response (> 10 IU/l antiHBs), irrespective the vaccination scheme which varied in vaccine dose, the number of vaccinations and the onset of the first vaccination. The percentage preterm infants with an antiHBs titer > 10 IU/l (98%) was not different of the corresponding percentage of term infants (98%). Similarly, no difference between preterm and term infants was observed when an antiHBs value of 100 IU/l was considered a positive response, neither when active immunisation started at month 0 or month 3. The geometric mean titre at 12 months of age was considered.

Gestational Age↗