24 weeks of interferon-ribavirin therapy should not routinely be given to all hepatitis C patients.
Explore the source record for details and available documents.
Antiviral Agents↗
Biomedical subjects
D J van Leeuwen
Publications and source records attributed to D J van Leeuwen.
Risk factors for acquisition of hepatitis C virus infection: a case series and potential implications for disease surveillance.
BACKGROUND: Transmission of hepatitis C virus (HCV) is strongly associated with use of contaminated blood products and injection drugs. Other "non-parental" modes of transmission including sexual activity have been increasingly recognized. We examined risk factors for acquiring HCV in patients who were referred to two tertiary care centers and enrolled in an antiviral therapy protocol. METHODS: Interviews of 148 patients were conducted apart from their physician evaluation using a structured questionnaire covering demographics and risk factors for HCV acquisition. RESULTS: Risk factors (blood products, injection/intranasal drugs, razor blades/ toothbrushes, body/ear piercing, occupational exposure, sexual activity) were identified in 141 (95.3%) of participants; 23 (15.5%) had one (most frequently blood or drug exposure), 41 (27.7%) had two, and 84 (53.4%) had more than two risk factors. No patient reported sexual activity as a sole risk factor. Body piercing accounted for a high number of exposures in women. Men were more likely to have exposure to street drugs but less exposure to blood products than women. Blood product exposure was less common in younger than older HCV patients. CONCLUSION: One and often multiple risk factors could be identified in nearly all HCV-infected patients seen in a referral practice. None named sexual transmission as the sole risk factor. The development of a more complete profile of factors contributing to transmission of HCV infection may assist in clinical and preventive efforts. The recognition of the potential presence of multiple risk factors may have important implications in the approach to HCV surveillance, and particularly the use of hierarchical algorithms in the study of risk factors.
Acute Disease↗
The imager replacing the pathologist in the diagnosis of hepatobiliary and pancreatic disease.
Advances in imaging technology, specifically cross-sectional imaging techniques (ultrasonography, computer tomography, magnetic resonance imaging), are dynamic and rapid. They have dramatically changed the management of hepatobiliary and pancreatic diseases. Although imaging is not identical to the traditional gold standard of a tissue diagnosis, it often obviates its need and provides a much better insight into clinically relevant pathology compared with a biopsy. However, this requires a thorough insight into the clinical and pathologic aspects of the disease, knowledge of limitations of imaging techniques, and insight in management implications. The clear identification of characteristic disease findings on imaging, such as a cirrhotic configuration of the liver or gallstones that match clinical findings, are most helpful. Imaging and tissue investigation often have a complementary role in patient management. Their yield is highest if they are part of a critical integration of clinical findings by a multidisciplinary team. The latter should help as much in identifying specific opportunities for treatment as preventing futile and potential harmful interventions. The contribution of imagers and pathologists to the management of patients will continue to be redefined in the new century. Noninvasive and virtual imaging will develop further. A specific and challenging role for the pathologists and clinical imagers in close cooperation with many other disciplines will be to identify sensitive molecular targets that can be used to provide noninvasive images that not only accurately provide a diagnosis, but also resolution of disease and response to specific therapy. Ann Diagn Pathol 5:57-66, 2001.
Bile Ducts↗
Tumor necrosis factor gene polymorphisms in patients with cirrhosis from chronic hepatitis C virus infection.
Pro-inflammatory cytokines including tumour necrosis factor (TNF) mediate the pathogenesis of hepatitis C virus (HCV) infection. The distribution of TNF gene polymorphisms was examined among cirrhotic and non-cirrhotic patients infected with HCV. Thirty Caucasians with cirrhosis due to chronic HCV infection and 114 HCV-infected patients histopathologically free of cirrhosis were genotyped for genetic variants in TNF, lymphotoxin alpha and TNF-receptor type I using PCR-based techniques. Variability in the progression of HCV-related cirrhosis was assessed in a multivariate model including genetic and non-genetic factors such as gender, estimated duration of infection, alcohol consumption, and viral genotype. Viral genotype and non-genetic host features were not independently related to the occurrence or rate of development of cirrhosis in the patient population. In contrast, the TNF promoter variants TNF2 (-238A) and TNF3 (-308A) conferred a 3.2-fold and 5.1-fold risk of cirrhosis respectively (P = 0.03 for both). Reciprocal effects were observed with several TNF alleles and haplotypes defined by the -238G/A and -308G/A dimorphic sequences. Polymorphisms in the TNF alpha promoter appear to be associated with variability in the histological severity of chronic hepatitis C infection.
Adolescent↗
Hepatopulmonary syndrome and venous emboli causing intracerebral hemorrhages after liver transplantation: a case report.
Increasing experience has fostered the acceptance of liver transplantation as a treatment for patients with hepatopulmonary syndrome. Morbidity and mortality is most commonly attributed to progressive arterial hypoxemia postoperatively. A cerebral hemorrhage has been reported in one patient with hepatopulmonary syndrome after transplantation. However, a postmortem examination of the brain was not performed and the pathogenesis or type of cerebral hemorrhage was undefined. We report on a patient with severe hepatopulmonary syndrome who developed multiple intracranial hemorrhages after transplantation. The intracerebral hemorrhages were most consistent with an embolic etiology on postmortem examination. We postulate that venous embolization, caused by the manipulation of a Swan Ganz catheter in a thrombosed central vein, resulted in pulmonary emboli that passed through dilated intrapulmonary vessels into the cerebral microcirculation. Special attention to central venous catheters and avoidance of manipulation may be warranted in subjects with severe hepatopulmonary syndrome after liver transplantation.
Cerebral Hemorrhage↗
Cost-effectiveness of interferon treatment for hepatitis C.
Explore the source record for details and available documents.
Antiviral Agents↗
Efficacy of interferon treatment for patients with chronic hepatitis C: comparison of response in cirrhotics, fibrotics, or nonfibrotics.
Chronic hepatitis C patients (472 patients) were treated with consensus interferon (CIFN) or interferon (IFN) alfa-2b for 6 months in a large multicenter trial. Efficacy was assessed by clearance of hepatitis C virus (HCV) RNA using reverse transcription polymerase chain reaction (RT-PCR) (<100 copies/mL), normalization of serum alanine aminotransferase (ALT), and histological improvement. The purpose of these analyses was to compare these efficacy parameters in nonfibrotics, fibrotics, and cirrhotics. Patients with chronic HCV and cirrhosis showed the same benefit from IFN treatment as noncirrhotic patients when efficacy was assessed by clearance of serum HCV RNA or by histological benefit. Sustained HCV RNA response rates were similar when measured among nonfibrotic (11%), fibrotic (13%), and cirrhotic (11%) patients. Improvement in histologic activity index (HAI) scores was noted among all 3 groups. Cirrhotic patients had a lower sustained ALT response rate (12%) than did nonfibrotic patients (23%). Ninety percent of nonfibrotics, but only 71% of fibrotics and 67% of cirrhotics, who sustained a virological response normalized their ALT. This suggests that cirrhotic patients may clear the hepatitis C virus without normalization of ALT levels. The pattern of both HCV RNA clearance over time and ALT decrease was similar among nonfibrotics, fibrotics, and cirrhotics. Tolerability to IFN therapy was similar among the 3 groups except that more cirrhotics required dose reduction because of thrombocytopenia. In patients with cirrhosis, ALT levels may be a less appropriate endpoint in the measurement of response to therapy. We conclude that liver cirrhosis should not be a reason for excluding patients from therapy because both cirrhotic and fibrotic HCV patients benefit from IFN therapy not only by clearance of virus but by improvements in liver histology.
Adult↗
Primary sclerosing cholangitis and cholangiocarcinoma as a diagnostic and therapeutic dilemma.
Differentiating primary sclerosing cholangitis (PSC) from cholangiocarcinoma (CC) can be a diagnostic challenge with major therapeutic implications. In case of advanced or symptomatic PSC, liver transplantation (OLTx) can be life saving with excellent long-term outcome. However, the outcome of CC diagnosed prior or during OLTx is dismal. PSC is a premalignant condition associated with a risk of developing cholangio- or hepatocellular carcinoma in > 15% of patients. Imaging diagnoses should be integrated into the further clinical data. It is the sudden, rapid and irreversible deterioration of the patient's condition, and the rapid progression of cholangiographic abnormalities, which may strongly point towards a malignancy or a malignant evolution in case of PSC. Brush cytology, (guided) biopsy, and tumor markers such as Ca 19.9 and CEA levels can be of some help, but confirmation of malignancy is often associated with a poor outcome and exclusion from liver transplantation. Clinical deterioration of the PSC patient and signs indicating advanced liver damage are a justification to evaluate patients for liver transplantation. Early transplantation should be considered in appropriate patients.
Bile Duct Neoplasms↗
Early hepatitis C virus-RNA responses predict interferon treatment outcomes in chronic hepatitis C. The Consensus Interferon Study Group.
In previous studies employing interferons (IFNs) in the treatment of chronic hepatitis C, there have been few reliable predictors of sustained responses. We retrospectively evaluated the predictive value of hepatitis C virus (HCV)-RNA measurements in the first few months during consensus interferon (CIFN) treatment using a sensitive reverse-transcriptase polymerase chain reaction assay to determine sustained responses. Data from two large treatment trials, one of IFN-naive patients and one of retreated relapsers and nonresponders, were used, including serum samples at 2-week intervals in the naive study and 8-week intervals in the retreatment study. Patients received initial CIFN (9 microgram) treatment for 6 months and were assessed 6 months after treatment. There were 28 sustained viral responders of 232 CIFN-treated patients. Of the sustained responders, 48% had already cleared HCV RNA from serum (<100 copies/mL) by week 2, 78% by week 4, 81% by week 6, and 96% by week 12. Patients with early HCV-RNA clearance were more likely to have sustained responses than those who responded later. Early clearance of HCV from serum was also associated with greater likelihood of a sustained response to 48 weeks of retreatment with 15 microgram CIFN. Ninety-five percent of the sustained responders were HCV-RNA-negative by week 8 of retreatment. Early assessment of HCV RNA may help in the prediction of sustained responses to IFN and allow the value of continued treatment to be determined early in the course of IFN therapy.
Antiviral Agents↗
Gastric transit and pharmacodynamics of a two-millimeter enteric-coated pancreatin microsphere preparation in patients with chronic pancreatitis.
It has been suggested that enteric-coated pancreatin microsphere (ECPM) preparations with sphere sizes larger than 1.7 mm pass through the stomach at a slower rate than a meal and therefore may be less efficacious in restoring pancreatic enzyme activity than preparations with smaller sphere sizes. The aim of this study was to investigate the gastric transit profile of a 2-mm ECPM preparation in relation to that of a solid meal and to simultaneously measure enzyme activities in eight patients with pancreatic exocrine insufficiency due to chronic pancreatitis. Gastric transit was assessed by double-isotope scintigraphy. A pancake was labeled with 99mTc. A 2-mm ECPM preparation was labeled with 171Er. Intraluminal pancreatic enzyme activities were assessed during a 6-hr period with the cholesteryl-[14C]octanoate breath test (for carboxyl ester lipase activity) and the N-benzoyl-L-tyrosyl-p-aminobenzoic acid/p-aminosalicylic acid (NBT-PABA/PAS) test (for chymotrypsin activity). The ECPM preparation passed through the stomach more rapidly (median 24 min) than the pancake (median 52 min, P < 0.05). During ECPM therapy, mean cumulative 14CO2 outputs rose significantly from 30% to 70% (P < 0.05), but remained below outcomes in healthy volunteers. Mean cumulative plasma PABA concentrations rose significantly from 46% to 87% (P < 0.05) and were not significantly different from outcomes in healthy volunteers. In chronic pancreatitis, a 2-mm ECPM preparation does not pass through the stomach more slowly than a solid meal, but in fact faster. Digestion of ester lipids and proteins showed an improvement to subnormal and normal levels, respectively.
4-Aminobenzoic Acid↗
Relationship between biochemical and virological responses to interferon therapy in chronic hepatitis C infection. Consensus Interferon Study Group.
We have investigated the relationship between serum alanine aminotransferase (ALT) and hepatitis C virus (HCV) RNA in the assessment of responses to interferon (IFN) therapy in chronic HCV infection. Data from 704 patients with HCV infection who were randomized to receive consensus IFN-alpha (CIFN) 3 micrograms (n = 232 patients) or 9 micrograms (n = 232 patients), or IFN-alpha 2b 3 million units (MU) (n = 240 patients), were used for these analyses. All patients were treated three times weekly. Hepatitis C viral RNA (HCV RNA) was determined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) with a lower limit of detection of 100 copies ml-1. Of patients with normal serum ALT concentrations, 53% (120/225) had undetectable HCV RNA at the end-of-treatment period and 47% (51/109) had undetectable HCV RNA at the end of the post-treatment observation period. In contrast, of the patients with undetectable HCV RNA, 75% (120/161) and 84% (51/61) had normal serum ALT activities at the end-of-treatment and post-treatment observations periods, respectively. The majority of patients with undetectable HCV RNA had normal ALT values. In contrast, only half of the patients with normal ALT values were negative for HCV. End-of-treatment HCV RNA response also better predicted sustained virological response than did end-of-treatment ALT response.
Adult↗
Placebo controlled trial of enteric coated pancreatin microsphere treatment in patients with unresectable cancer of the pancreatic head region.
BACKGROUND: Impeded flow of pancreatic juice due to mechanical obstruction of the pancreatic duct in patients with cancer of the pancreatic head region causes exocrine pancreatic insufficiency with steatorrhoea and creatorrhoea. This may contribute to the profound weight loss that often occurs in these patients. AIMS: To investigate whether pancreatic enzyme replacement therapy prevents this weight loss. PATIENTS: Twenty one patients with unresectable cancer of the pancreatic head region with suspected pancreatic duct obstruction, a biliary endoprosthesis in situ, and a Karnofsky performance status greater than 60. METHODS: Randomised double blind trial of eight weeks with either placebo or high dose enteric coated pancreatin enzyme supplementation. All patients received dietary counselling. RESULTS: The mean difference in the percentage change of body weight was 4.9% (p = 0.02, 95% confidence interval for the difference: 0.9 to 8.9). Patients on pancreatic enzymes gained 1.2% (0.7 kg) body weight whereas patients on placebo lost 3.7% (2.2 kg). The fat absorption coefficient in patients on pancreatic enzymes improved by 12% whereas in placebo patients it dropped by 8% (p = 0.13, 95% confidence interval for the difference: -6 to 45). The daily total energy intake was 8.42 MJ in patients on pancreatic enzymes and 6.66 MJ in placebo patients (p = 0.04, 95% confidence interval for the difference: 0.08 to 3.44). CONCLUSIONS: Weight loss in patients with unresectable cancer of the pancreatic head region and occlusion of the pancreatic duct can be prevented, at least for the period immediately after insertion of a biliary endoprosthesis, by high dose enteric coated pancreatin enzyme supplementation in combination with dietary counselling.
Aged↗
Comparative effects of enteric-coated pancreatin microsphere therapy after conventional and pylorus-preserving pancreatoduodenectomy.
BACKGROUND: A comparative study was performed between patients with exocrine pancreatic insufficiency after conventional pancreatoduodenectomy (Whipple's procedure) and pylorus-preserving pancreatoduodenectomy (PPPD). In these patients the pharmacodynamics of 2-mm enteric-coated pancreatin microspheres (ECPMs) and their gastric transit time in relation to that of a solid meal were investigated. The efficacy of ECPM preparations may differ after Whipple's procedure compared with PPPD, because the latter procedure does not include gastrectomy. METHODS: Gastric transit was assessed by double-isotope scintigraphy. A pancake meal was labelled with 99mTc. ECPMs were cold-labelled with 170Er and neutron activated shortly before ingestion to enable imaging with a gamma camera. Intraluminal pancreatic enzyme activity was assessed during a 6-h period with two indirect tests: the cholesteryl [14C]octanoate breath test and the N-benzoyl-L-tyrosyl-p-aminobenzoic acid-p-aminosalicylic acid (NBT-PABA-PAS) test. RESULTS: In patients who had Whipple's procedure, the gastric transit time of ECPMs and of the pancake meal was not significantly different. The outcome of the indirect pancreatic function tests during enzyme supplementation was comparable, and not significantly different, from that in healthy volunteers. In patients who had PPPD, however, the gastric transit time of microspheres was greatly delayed compared with that of the pancake meal (P < 0.05). Improvement in the outcome of the indirect pancreatic function tests during enzyme supplementation was much less and remained well below that of healthy volunteers (P < 0.05). CONCLUSION: In cases of exocrine pancreatic insufficiency after Whipple's procedure, 2-mm ECPM treatment adequately restores pancreatic enzyme activity. Following PPPD, however, ECPM treatment is often ineffective because the microspheres are retained in the stomach. In these patients, use of conventional powdered pancreatin enzyme preparations may improve the efficacy of treatment.
4-Aminobenzoic Acid↗
Piperacillin to prevent cholangitis after endoscopic retrograde cholangiopancreatography. A randomized, controlled trial.
BACKGROUND: Cholangitis does not often occur after endoscopic retrograde cholangiopancreatography (ERCP), but it can be a serious complication of this procedure. Antibiotic prophylaxis is therefore frequently used in patients having ERCP, but existing data are insufficient to allow evaluation of the effectiveness of this practice. OBJECTIVE: To determine the efficacy of single-dose antibiotic prophylaxis with piperacillin for ERCP-induced cholangitis. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: Tertiary referral center for ERCP. PATIENTS: Patients who had ERCP for suspected biliary tract stones or distal common bile duct stricture were eligible. Major exclusion criteria were previous ERCP within 7 days, biliary endoprosthesis in situ, and use of antimicrobial agents or presence of fever within 7 days before the procedure. INTERVENTION: Piperacillin, 4 g, or placebo was given intravenously approximately 30 minutes before ERCP. MEASUREMENTS: Duration of follow-up was 1 week. Acute cholangitis was diagnosed if a patient had a body temperature greater than 38 degrees C, a clinically apparent need for antibiotic treatment, and no symptoms indicating infection outside of the biliary tree. RESULTS: 551 consecutive patients were enrolled. During ERCP, stones were found in 147 patients, malignant distal strictures were found in 203 patients, other pathologic findings were seen in 88 patients, and normal biliary tracts were seen in 113 patients. Seventeen of the 281 patients who received placebo (6.0%) and 12 of the 270 patients who received piperacillin (4.4%) developed acute cholangitis (relative risk, 0.73 [95% CI, 0.36 to 1.51]). The absolute risk reduction was 1.6% (CI, -5.3% to 2.1%). All cases of cholangitis (with the exception of one case seen in a patient in the piperacillin group) were mild or moderate in severity. CONCLUSION: Single-dose prophylaxis with piperacillin is not associated with a clinically significant reduction in the incidence of acute cholangitis after ERCP in patients suspected of having biliary tract stones or distal common bile duct stricture.
Adult↗
Do serum ALAT values reflect the inflammatory activity in the liver of patients with chronic viral hepatitis?
A retrospective study was carried out in 40 patients with chronic viral hepatitis, to assess whether serum alanine aminotransferase reflects the inflammatory process in the liver. Twenty liver biopsy specimens were included for each disease. Five histological aspects were scored: periportal inflammation, lobular inflammation, ballooning, Councilman bodies and lymphocyte follicles. Logarithmic values of alanine aminotransferase were correlated with each aspect using the Spearman correlation coefficient. For the hepatitis B cohort a statistical significant correlation was found between alanine aminotransferase and periportal inflammation (p = 0.0001), lobular inflammation (p = 0.0002) and Councilman bodies/area (p = 0.003). In the hepatitis C study population alanine aminotransferase correlates with both periportal inflammation (p = 0.007) and lymphocyte follicles/Area (p = 0.02). In conclusion, these results suggest that alanine aminotransferase can be used as an indicator of inflammatory activity. A prospective study is needed, to further analyze the use of alanine aminotransferase, as a monitor of disease activity in patients with chronic viral hepatitis.
Adult↗
Biliary excretion of ciprofloxacin and piperacillin in the obstructed biliary tract.
Biliary excretion of ciprofloxacin and piperacillin was determined in cholestatic patients who had undergone endoscopic cholangiography. The median concentration of ciprofloxacin (n = 9) was 2.36 micrograms/ml (range, 0.29 to 19.8 micrograms/ml) in bile compared with 1.66 micrograms/ml (range, 0.73 to 2.69 micrograms/ml) in serum. The median concentration of piperacillin (n = 7) was < 5 micrograms/ml (range, < 5 to 26) in bile compared with 14.3 micrograms/ml (range, 5.3 to 80) in serum. Ciprofloxacin, but not piperacillin, can be actively excreted into bile in the presence of a biliary tract obstruction.
Adult↗
Results of pancreaticoduodenectomy for ampullary carcinoma and analysis of prognostic factors for survival.
BACKGROUND: Results of pancreaticoduodenectomy for ampullary carcinoma were evaluated, and prognostic factors for survival were analyzed. METHODS: During the period from 1984 to 1992 67 patients underwent subtotal or total pancreaticoduodenectomy for ampullary carcinoma. All clinicopathologic data and their influence on survival were studied. RESULTS: Subtotal pancreaticoduodenectomy was performed in 62 of 67 patients with a mortality of 6% and a morbidity of 65%; the remaining five patients underwent total pancreaticoduodenectomy. Intraabdominal infection was the most important complication. Resection margins were tumor free in 75% of 67 patients. The overall 5-year survival was 50%. Survival was significantly influenced by the involvement of resection margins. After resection with involved margins 5-year survival was 15% and 60% after resection with free margins (p < 0.001). Tumor size, lymph node involvement, and differentiation grade had limited and not significant influence on survival. CONCLUSIONS: Subtotal pancreaticoduodenectomy is the type of resection of first choice for ampullary carcinoma. Involvement of resection margins was the strongest prognostic factor for survival. Patients with a tumor size larger than 2 cm, with lymph node involvement, or with a poorly differentiated tumor still had a 5-year survival rate greater than 40%. Patients with involved margins might be candidates for studies on adjuvant therapy.
Adenocarcinoma↗
Liver biopsy in the mid-1990s: questions and answers.
Explore the source record for details and available documents.
Biopsy↗