Expression of S100A12 (EN-RAGE) in cystic fibrosis.

BACKGROUND: Chronic airway inflammation and recurrent infections are a core phenomenon in cystic fibrosis (CF). Diagnosing acute infectious exacerbations is difficult in the presence of chronic inflammatory processes. S100A12 exhibits proinflammatory functions via interaction with the multiligand receptor for advanced glycation end products. Blocking this interaction inhibits inflammatory processes in mice. METHODS: The expression of S100A12 in lung specimens of patients with end stage lung disease of CF was investigated, and S100A12 levels in the serum of patients with acute infectious exacerbations of CF were measured. RESULTS: Immunohistochemical studies of CF lung biopsy specimens revealed a significant expression of S100A12 by infiltrating neutrophils. High S100A12 levels were found in the sputum of patients with CF, and serum levels of S100A12 during acute infectious exacerbations were significantly increased compared with healthy controls (median 225 ng/ml v 46 ng/ml). After treatment with intravenous antibiotics the mean S100A12 level decreased significantly. There was also a significant difference between S100A12 levels in patients with acute infectious exacerbations and 18 outpatients without exacerbations (median 225 ng/ml v 105 ng/ml). CONCLUSIONS: S100A12 is extensively expressed at local sites of inflammation in CF. It is a serum marker for acute infectious exacerbations. High local expression of S100A12 suggests that this protein has a proinflammatory role during airway inflammation and may serve as a novel target for anti-inflammatory treatments.

Long-term results of the use of silicone sheets after diskectomy in the temporomandibular joint: clinical, radiographic and histopathologic findings.

The aim of the present study was to evaluate the long-term results of a group of patients who had the disk of the temporomandibular joint (TMJ) removed and permanently replaced by a silicone sheet. The study group comprised 48 patients, treated in the period from 1983 to 1993. In eight patients, the implants had to be removed after an average interval of 5.6 years and they were submitted for histopathological examination. Twenty-five of the 40 patients with silastic implants in place, and five of the 8 patients who had their implants removed, were available for long-term follow-up (mean interval of 7.0 years, SD 2.8 years). Clinical function was rated according to the Helkimo Dysfunction Index and compared to the preoperative findings. Results showed decreased tenderness of muscles and joints to palpation and increased mouth opening, but no statistically significant improvement in joint function. In 4 patients, a decrease in condylar width was found, while another 4 patients presented with thickening of the condyle by appositional bone formation. Histopathology of the failed implants showed scattered fragments of silastic material and dacron fibers with accumulation of histiocytes in immediate contact with the silicone particles and phagocytozed intracellular material. T-lymphocytes were also present in the vicinity of the silicone particles.

Recurrence patterns of hepatocellular and fibrolamellar carcinoma after liver transplantation.

PURPOSE: Tumor recurrence is the major limitation of long-term survival after liver transplantation for hepatocellular carcinoma (HCC) or fibrolamellar carcinoma (FLC). Understanding tumor-biologic characteristics is important for selection of patients and for development of adjuvant therapeutic strategies. PATIENTS AND METHODS: The study included 69 patients who underwent potentially curative liver transplantation for HCC/FLC and survived for more than 150 days; minimum follow-up was 33 months. Frequency, localization, and timing of recurrence were analyzed and compared with primary tumor and patient characteristics. RESULTS: Tumor recurrence was observed in 39 patients at 67 locations. Hematogenous spread was the major route of tumor recurrence (87%), and the most frequent sites were the liver (62%), lung (56%), and bone (18%). Parameters associated with recurrence were absence of cirrhosis, tumor size greater than 5 cm, more than five nodules, vascular infiltration, and International Union Against Cancer (UICC) stage IVA. Selective intrahepatic recurrence was found in nine patients (23%); it was associated with highly differentiated tumors, lack of vascular infiltration, and male sex. Recurrence at multiple sites was found predominantly in young patients (< or = 40 years) and for multicentric (> 5) primary tumors. Recurrences were observed within a wide time range after transplantation (43 to 3,204 days; median, 441 days); late recurrences (> 1,000 days, n = 8) were associated with highly differentiated or fibrolamellar tumors and low UICC stages. Surgical treatment was the only therapeutic option associated with prolonged survival after recurrence. CONCLUSION: In transplant recipients, hepatocellular carcinomas vary considerably in their pattern and kinetics of metastases. Tumor cells may persist in a dormant state for long time periods before giving rise to clinical metastases. Surgical treatment of recurrence should be considered whenever possible.

Beta 1 integrin expression in adenocarcinoma of Barrett's esophagus.

BACKGROUND/AIMS: In vitro and in vivo studies did not show that beta 1 integrin expression is associated with malignant transformation or that it is of prognostic value in some malignant tumors. There are no data on the expression or prognostic value of beta 1 integrins in adenocarcinoma of Barrett's esophagus. METHODOLOGY: We assessed the expression pattern and the prognostic impact of beta 1 integrins in paraffin-embedded specimens of 41 patients with adenocarcinoma of Barrett's esophagus by immunochemistry. At the time of investigation, neither histomorphological parameters nor the survival time were known. RESULTS: There was no correlation between histomorphological parameters and the expression of beta 1 integrins. The expression of beta 1 integrins had no influence on long- term survival. There was a relationship between the prognosis and the following histopathological parameters: pT, pN and pM category, the UICC stage, the presence of lymphangiosis, and the DNA content of the tumor cells. CONCLUSIONS: The preliminary results obtained in this study did not show that the expression of beta 1 integrins was of prognostic value in patients with adenocarcinoma of Barrett's esophagus. Further studies in a larger number of patients are required to confirm the results obtained in this investigation.

Prognostic value of immunohistochemical expression of beta-1 integrin in pancreatic carcinoma.

BACKGROUND: Prognostically relevant factors based on the histological assessment of the resected pancreas are known. However, the knowledge of additional factors associated with the prognosis is helpful in planning the therapy for an individual patient. beta1 Integrin expression is known to have a prognostic influence in some malignant tumors. No data are, however, available on the prognostic value of beta1 integrins in pancreatic carcinoma. METHOD: We investigated paraffin-embedded specimens of 19 patients undergoing surgical treatment for periampullary carcinoma and of 42 patients for ductal pancreatic carcinoma by immunohistochemistry to assess the expression pattern and the prognostic impact of beta1 integrins. Neither histomorphological parameters nor the survival time of the patients were known at the time of the investigation. RESULTS: No correlation was established between histomorphological parameters and beta1 integrin expression in periampullary or ductal pancreatic carcinoma, respectively. Patients with periampullary carcinoma and beta1 integrin overexpression had a significantly poorer prognosis than patients without overexpression of beta1 integrins (median survival: 18.3 vs. 58.4 months). In ductal pancreatic carcinoma beta1 integrin expression had no influence on prognosis. CONCLUSION: beta1 Integrins exert an influence on prognosis in periampullary carcinoma but not in ductal pancreatic carcinoma. However, further investigations in larger patient samples are required to confirm these results.

[Xanthoma disseminatum with marked mucocutaneous involvement]. / Xanthoma disseminatum mit ausgeprägter mukokutaner Beteiligung.

HISTORY AND CLINICAL FINDINGS: When aged 23 years, a now 36-year-old man was first diagnosed as having xanthomas on the upper arms and shoulders. Xanthomas then progressed, affecting both the skin and the laryngo-pharyngeal mucosa. They were so marked that several laser-surgical interventions for their removal in the phayngo-laryngeal tract were necessary to ensure unimpaired breathing. There were also extensive confluent symmetrical cutaneous xanthomas over the upper and lower arms, the face, neck and trunk. Xanthomas and scars in the pharynx and larynx necessitated marked nasal breathing. INVESTIGATIONS: There was no laboratory evidence of abnormal lipid metabolism. The concentrations of cholesterol, triglycerides, lipoprotein (a), apolipoprotein A-1, apolipoprotein B, apolipoprotein E phenotype and steroles were all normal. The biochemical composition of LDL, VLDL and HDL particle was also unremarkable. Histological examination of resected xanthomas revealed dense infiltrations of the interstitial spaces by foam-cell histiocytes with multiple lipid vacuoles, typical of xanthoma disseminatum. TREATMENT AND COURSE: Neither probucol nor cholesterol synthesis enzyme inhibitors nor glucocorticoid medication influenced the xanthomas. The only effective treatment was removal of the most unsightly or obstructing lesions. But the sars left removal in the mucocutaneous regions caused obstruction in the laryngopharyngeal tract. CONCLUSION: The cause of xanthoma disseminatum remains unknown. Skeletal muscle can also be extensively infiltrated. This case shows similarities to Erdheim-Chester disease, another are xanthomatous condition.

[Expression of CD44 and isoforms v4, v5, v6, v7, v10--new prognostic parameters in ductal pancreatic carcinoma?]. / Expression von CD44 und seiner Isoformen v4, v5, v6, v7, v10--neue prognostische Parameter beim duktalen Pankreascarcinom?

UNLABELLED: Prognostically relevant factors based on the histological assessment of the resected pancreas are known. However, additional parameters, such as biological staging of the intrinsic malignant potentiality of the tumor, would be useful. There has been no uniform finding of a relationship between CD44 variant expression and tumor progression. METHOD: We assessed the expression pattern and prognostic impact of CD44 standard and CD44 isoforms v4, v5, v6, v7 and v10 in 40 ductal pancreatic carcinomas by immunochemistry on paraffin-embedded tumor material in patients after tumor resection. At the time of the investigation neither histomorphological parameters nor the survival time were known. RESULTS: There was no correlation between the histomorphological parameter and the expression of CD44 splice variants. CD44 splice variants v4-v10 were almost only expressed in tumor tissue. In ductal pancreatic carcinoma, patients with an overexpression of CD44 splice variants had a worse prognosis. However, because of the small number of cases this was statistically not significant. CONCLUSION: CD44 splice variants may have an influence on prognosis in ductal pancreatic carcinoma. However, further investigation on a larger number of patients is necessary to confirm these results.

Carcinoma of the ampulla of vater: determinants of long-term survival in 94 resected patients.

This retrospective study details 94 patients after surgical resection of carcinoma of the ampulla of Vater to determine prognostic factors. The tumour was limited to the ampulla of Vater in 32%, invaded the duodenal wall in 34%, infiltrated 2 cm or less into the pancreas in 22%, and invaded more than 2 cm into the pancreas and/or other adjacent structures in 11%. Curative resection was accomplished in 97% of cases. After exclusion of perioperative deaths the 1-, 5- and 10-year survival rates were 79.6%, 38.2%, and 31.6%, respectively with a median survival of 3.68 years. 26 patients survived more than five and 15 patients more than ten years. In an univariate analysis advanced tumour size, poor tumour grading, lymph node metastases and advanced UICC stage significantly decreased survival. Comparison of short and long survivors confirmed tumour size, lymph node status and UICC stage as significant prognostic factors. In a multivariate analysis (Cox model), only tumour size was a statistically independent predictor of prognosis. The survival probability increased with each year a patient survived after resection. When a patient had already survived five years after resection, the probability to survive another five years was 83%. Careful clinicopathologic staging is important for the prognosis after resection.

Lipoprotein-X in patients with cirrhosis: its relationship to cholestasis and hypercholesterolemia.

Lipoprotein-X (Lp-X) is an abnormal low-density lipoprotein frequently found in liver disease. It is regarded as the most sensitive and specific biochemical parameter for the diagnosis of intra- and extrahepatic cholestasis. Moreover, Lp-X is supposed to contribute to the development of hypercholesterolemia in cholestatic liver disease, because it fails to inhibit de novo cholesterol synthesis. This investigation will focus on the relationship between the presence of Lp-X and serum lipid concentrations in cirrhosis. The significance of Lp-X in the diagnosis of cholestasis, compared with alkaline phosphatase (AP), gamma-glutamyl transferase (GGT), and bilirubin levels, will be assessed as well. The present cross-sectional study includes 212 patients with histopathologically proven cirrhosis. The detection of Lp-X and the quantification of -, beta-, and pre-beta-cholesterol was based on agar gel electrophoresis and polyanion precipitation. For the characterization of liver function, the concentrations of albumin and bilirubin, the activities of liver enzymes, and coagulation times were assessed. In a subgroup of 40 individuals, liver biopsies were re-evaluated to confirm or exclude intrahepatic cholestasis. As a result, there was no association between the appearance of Lp-X and total cholesterol concentrations. While all patients with Lp-X showed intrahepatic cholestasis (predictive value of the positive test = 1), only 16 of 28 patients with cholestasis formed Lp-X (sensitivity = 0.57). The activities of AP and of GGT, as well as the concentrations of bilirubin, were strongly elevated in most patients, with and without cholestasis. The predictive values of AP, GGT, and bilirubin were 0.77, 0.69, and 0.74 for the positive test and 0.5, 0, and 0.6 for the negative test, respectively. We conclude that Lp-X is not related to hypercholesterolemia in cirrhosis. The positive, but not the negative, Lp-X test has high predictive value for the diagnosis of cholestasis in cirrhosis. The biochemical parameters traditionally used for the assessment of extrahepatic cholestasis, AP, GGT, and bilirubin, do not support the diagnosis of intrahepatic cholestasis caused by cirrhosis.

Antiproteinuric efficacy of fosinopril after renal transplantation is determined by the extent of vascular and tubulointerstitial damage.

BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors have been successfully used for treatment of proteinuria after renal transplantation (RTx). Factors possibly responsible for the great inter-patient variance of the antiproteinuric effect (APE) have not yet been investigated in renal-transplanted patients. METHODS: 28 patients after RTx with a persistent proteinuria of more than 1.25 g/d were treated prospectively with does of fosinopril (10-15 mg/d) which were not effective on systemic arterial blood pressure. Prior to initiation of fosinopril, renal graft biopsy was performed in all patients and renal graft artery stenosis was excluded by duplex ultrasound. Serum creatinine and proteinuria were measured prior to, as well as 3 and 8 months after initiation of ACE inhibition, mean arterial pressure was controlled via 24-h measurement and repeated spot measurements. Reduction of proteinuria was correlated with renal histology, serum creatinine, creatinine clearance, mean arterial blood pressure, sodium excretion before therapy and the relative changes of these parameters during therapy respectively. RESULTS: Therapy had to be stopped in 8/28 patients due to side effects including rise of serum creatinine (n = 4). Three patients were excluded due to non-compliance. In the remaining patients (n = 17) proteinuria was reduced from 2.94 +/- 1.66 to 1.82 +/- 1.39 and 2.48 +/- 3.05 g/d after 3 and 8 months respectively, in the mean +/- SD. There was a significant inverse correlation between the APE and the extent of benign nephrosclerosis, interstitial fibrosis and tubular atrophy. No correlation of the APE to any of the other parameters could be demonstrated. CONCLUSIONS: Fosinopril can be administered effectively in a subgroup of proteinuric renal transplant recipients. However, because of a high proportion of patients developing side effects, careful monitoring is obligatory. Our results show that the lesser the degree of chronic morphological injury, the greater is the antiproteinuric effect. Thus, the degree of pre-existing histologically proven damage of the graft may serve as an indicator for the antiproteinuric efficacy of ACE inhibitor therapy after RTx.

Expression of CD44 variant proteins in adenocarcinoma of Barrett's esophagus and its relation to prognosis.

BACKGROUND: None of the commonly used staging criteria accurately determine the prognosis of a patient with adenocarcinoma of Barrett's esophagus. The authors therefore assessed the expression pattern and prognostic impact of CD44 standard and CD44 isoforms CD44v4, v5,v6,v7, and v10 in adenocarcinoma of Barrett's esophagus. METHODS: Specimens from 41 patients with adenocarcinoma of Barrett's esophagus who underwent esophageal resection were embedded in paraffin and studied immunohistochemically to determine the expression of CD44 splice variants. Histomorphologic parameters and survival time were not known at the time of the investigation. RESULTS: Correlations between favorable clinical or histomorphologic parameters and CD44s or any of the split variants could not be established. Down-regulation of CD44s and the split variant v10 was significantly correlated with pT classification. Furthermore, down-regulation of CD44v10 and up-regulation of CD44v7 were significantly correlated with ploidy. There was a significant correlation between CD44s and split variants in tumorous and nontumorous tissue from the same patient. Down-regulation of CD44s and CD44v4 had a significant influence on prognosis in that it was associated with shortened life expectancy. Multivariate analysis revealed that the expression of CD44v4 was an independent factor in prognosis. CONCLUSIONS: The results obtained for this small patient sample suggest that CD44v4 is a new independent prognostic parameter for adenocarcinoma of Barrett's esophagus that can be determined preoperatively by biopsy. It may therefore be helpful in planning therapy by allowing the identification of patients who may benefit from esophageal resection as well as those who are at high risk for morbidity and mortality even when the tumor is otherwise resectable. Further studies of larger patient samples are required to validate the results of the current study.

[Adult giant cell hepatitis with fatal outcome. Clinicopathologic case report and reflections on pathogenesis]. / Adulte Riesenzellhepatitis mit tödlichem Verlauf. Klinisch-pathologischer Fallbericht und Uberlegungen zur Pathogenese.

The occurrence of plasmodial giant cells in the liver is probably a morphological reaction pattern with the most diverse causes. In babies and infants, these changes occur in particular in neonatal hepatitis and intrahepatic and extrahepatic bile duct atresia. Viral infections and/or autoimmune reactions are discussed etiologically in giant cell hepatitis in adults (adult gaint cell hepatitis, AGCH), which is much rarer. In some of the cases, there were conspicuously high titers against paramyxoviruses. Giant cell hepatitis can occur in the course of HIV infection. These both indicate an infectious cause. However, the disease cannot be transmitted to chimpanzees. Apart from our case, only one further case is described in the literature in which a completed hepatitis A infection could be demonstrated serologically. In addition, the titer of antinuclear antibodies was raised in our patient. This autoimmune phenomenon is probably of crucial pathogenetic significance in our patient, especially since a hepatitis A infection on its own does not afford an adequate etiological explanation for the form of chronic and active hepatitis with consecutive cirrhotic transformation observed here.

Ovarian-like stroma in an invasive mucinous cystadenocarcinoma of the pancreas positive for inhibin. A hint concerning its possible histogenesis.

A female patient with a mucinous cystadenocarcinoma originating from a mucinous cystadenoma of the pancreas is presented. The cystic tumour was diagnosed 3 years before and was treated with interventional external and internal surgical drainage before radical resection was accomplished by left hemipancreatectomy. Histology showed simultaneous occurrence of mildly dysplastic and invasive malignant epithelium. Immunohistology revealed inhibin-positive cells in the ovarianlike stroma of the tumour. The demonstration of ovarian-like stroma positive for inhibin suggests that this could be a hamartoma with dispersed sex-cord stroma, which would explain the predominance of the female gender in mucinous cystic tumours of the pancreas.

[Diagnostic and therapeutic strategies in hepatocellular adenoma]. / Diagnostische und therapeutische Strategie beim hepatozellulären Adenom.

While liver hemangioma and focal nodular hyperplasia are not considered an indication for surgery in asymptomatic patients resection has been recommended for hepatocellular adenoma because of the risk of rupture and malignant transformation. Problems arise from differential diagnosis and the appropriate surgical radicality including the indication for liver transplantation. This retrospective analysis deals with 58 patients who underwent surgery for hepatocellular adenoma: resection of different extension: n = 54, liver transplantation n = 4. In 39.6% of the patients the tumor was an incidental finding. In 62.0% of the character of the lesion was unclear prior to surgery. Tumor rupture and bleeding occurred in 17.2%, malignant transformation in 6.9%. Surgical morbidity was 27.6%, mortality 5.2% with the transplant patients alive for 1.5, 7, 9 and 10 years. Two and five years after resection 2 patients developed hepatocellular carcinoma in the liver remnant. The results confirm the indication for surgery in hepatocellular adenoma. Diagnostic approach for solid liver tumors without serum increase of tumor markers should rule out FNH and hemangioma. In all other patients surgery should be considered whenever possible with the radicality of malignant disease. Liver transplantation can be discussed even in asymptomatic patients with multiple adenoma.

Benign giant-cell tumor of the patellar ligament.

We report the symptoms, clinical findings, and treatment of a patient with an extra-articular benign giant-cell tumor of the patellar ligament. Between the years 1966 and 1996 no similar case has been found to be documented by a Medline search. On palpation, a soft, mobile lesion, the size of a pigeon's egg, was felt in the lateral region of the patellar ligament. There was no set of laboratory values to determine the diagnosis. In addition, there were no typical findings in diagnostic imaging procedures and it seems that the most important fact is that the clinician is aware of this type of synovial tumor. A clear diagnosis is only possible by means of a pathological investigation. The choice of therapy for giant-cell tumors is local excision. Arthroscopy is recommended exclusively for the diagnosis and therapy of a localized intra-articular giant-cell tumor.

Mutations of the DPC4/Smad4 gene in biliary tract carcinoma.

A candidate tumor suppressor gene, DPC4, located at 18q21.1, has recently been shown to be inactivated in half of pancreatic adenocarcinomas. The close developmental relationship of the pancreas and biliary tract prompted us to determine the role of DPC4 in the multistep carcinogenesis of biliary tract carcinoma. A search for mutations in the genomic sequence of the highly conserved COOH-terminal domain of DPC4 (exons 8-11) was performed by single-strand conformational polymorphism analysis. Five of 32 (16%) primary biliary tract carcinomas had point mutations in the DPC4 sequence. Interestingly, inactivation of DPC4 was especially common in carcinomas originating from the common bile duct (four of eight specimens analyzed), suggesting an important role for DPC4 in the development of this subtype of biliary tract tumor.

Oxytocin and vasopressin receptors in human and uterine myomas during menstrual cycle and early pregnancy.

The purpose of this study was to determine the specificity and concentration of oxytocin (OT) and arginine vasopressin (AVP) binding sites in non-pregnant (NP) human and rhesus monkey endometrium, myometrium and fibromyomas, and to determine the cellular localization of OT receptor (OTR). Besides [3H]AVP, [125I]LVA, a specific VP1 receptor subtype antagonist, was used to determine vasopressin receptor (VPR) concentrations. Samples were obtained from 42 pre-menopausal and three pregnant women (5, 13 and 35 weeks gestation), and several NP and pregnant monkeys. Specificity of binding was assessed in competition experiments with unlabelled agonists and antagonists of known pharmacological potency. Cellular localization of OTR was determined by immunohistochemistry. In NP human uterine tissues, [3H]AVP was bound with higher affinity and greater binding capacity than [3H]OT, whereas in pregnant women and in NP and pregnant rhesus monkeys, uterine OT binding capacity was greater. OT and AVP binding sites discriminated very poorly between OT and AVP; [125I]LVA binding sites were more selective than [3H]AVP. Their ligand specificity and binding kinetics indicated the presence of two distinct populations of binding sites for OT and AVP in primate uterus. Endometrium of NP women and monkeys had low OTR and VPR concentrations. Myometrial and endometrial OTR and VPR were down-regulated in midcycle and in early human pregnancy, they were up-regulated in the secretory phase and second half of pregnancy. Immunoreactive OTR in NP uterus was localized in patches of myometrial muscle cells and small numbers of endometrial epithelial cells.

[De novo hepatitis B infection after liver transplantation--evidence for the need of active hepatitis B vaccination of liver transplantation candidates]. / Hepatitis-B-de-novo-Infektion nach Lebertransplantation--Evidenz der Notwendigkeit für die aktive Hepatitis-B-Impfung von Lebertransplantationskandidaten.

BACKGROUND: Liver transplantation (LTX) is a generally accepted therapy in the treatment of acute and chronic end-stage liver diseases. Recurrent and de-novo hepatitis B and C virus infection following liver transplantation have been shown. PATIENTS AND METHODS: We analyzed retrospectively the course of patients treated at our transplant center between 01.01.1992 and 31.12.1997, who does not show any markers of an active hepatitis B (HBV) infection prior to liver transplantation but developed replicative HBV infection afterwards. During this period 544 liver transplantations were performed in 452 patients, 395 of whom were HBs-Ag negative prior to transplantation. RESULTS: Six patients were identified who underwent LTX for non-hepatitis B-induced liver disease, and who subsequently developed a highly replicative de-novo HBV-infection six to twelve months (mean 8.5 months) after LTX. In each of the patients HBV de-novo infection showed clinically and biochemically a mild but chronic course without evidence of liver failure during a maximum follow-up period of 14 to 37 months (mean 26 months). Liver biopsies taken in four patients nine to 22 months after LTX showed chronic active hepatitis (n = 2), chronic portal hepatitis (n = 1), and a mild rejection (n = 1). The source of de-novo HBV infections remained unclear, but inapparent infection of patients pre-LTX was ruled out so that the donor livers or postoperative infection appear to be the likely source. CONCLUSION: In our center the number of HBV de-novo infections (1.5%, 6/395) following liver transplantation was comparable to the results published by other centers, but in our center no inapparent infection of patients prior to LTX was observed. For further minimization of HBV de-novo infection following LTX active HBV immunization of patients awaiting LTX is recommended.