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Background: The majority of patients with inherited haemochromatosis carry two mutant alleles of the recently discovered HFE gene. Individuals heterozygous for the HFE mutation could be predisposed to end-stage liver disease due to other causes. Methods: The frequencies of the HFE gene mutations C282Y and H63D were determined in DNA samples obtained from 189 liver transplant patients and 225 healthy Finnish blood donors. Results: 5% of the 189 liver transplant recipients were heterozygotes and 0.5% homozygotes for the C282Y mutation, while 16% were heterozygotes and 0.5% homozygotes for the H63D mutation. These figures were not increased in comparison to controls, of whom 11% were C282Y heterozygotes, 16% H63D heterozygotes and 0.9% H63D homozygotes. Among recipients with acute non-A-E hepatitis (n = 31), the frequency of the H63D allele was higher than in controls (21% versus 9.1%, P < 0.01). Perls' stain for iron in explanted liver specimens was positive in 28% of recipients with alcoholic cirrhosis, 26% of patients with acute non-A-E hepatitis and 14% in the rest of the recipients. The HFE genotypes did not correlate with the iron status. Conclusion: Individuals heterozygous for either the C282Y or H63D mutation of the HFE gene are not at increased risk of developing chronic endstage liver disease. However, subjects heterozygous for the H63D mutation may have an increased risk to develop fulminant non-A-E hepatitis. [ABSTRACT FROM AUTHOR]

The etiology of liver disease would expectedly affect health-related quality of life (HRQoL) and employment after liver transplantation (LT), but studies are scarce. We sent the 15D HRQoL instrument and an employment questionnaire to all 401 adult LT patients alive in Finland in 2007. The response rate was 89% (n = 353; mean of eight yr since LT). In age-adjusted analysis, patients transplanted for primary sclerosing cholangitis (PSC; n = 56), primary biliary cirrhosis (PBC; n = 72), acute liver failure (ALF; n = 76), alcoholic cirrhosis (n = 38), or liver tumor (n = 22) exhibited comparable HRQoL, whereas the combined group of miscellaneous chronic liver diseases (n = 89) exhibited significantly higher HRQoL scores (p = 0.003). Among working-aged patients (20-65 yr at LT), employment rates were highest in the PSC (56%) group and lowest in the ALF (39%) and PBC (29%) groups. In age-adjusted logistic regression, patients with PSC or alcoholic cirrhotics were 2.4- and 2.5-fold more likely to resume work after LT than patients with PBC. In conclusion, HRQoL scores late after LT were in general relatively high and comparable among disease groups. Patients with PSC or alcoholic cirrhosis were most likely to resume work after LT. The relatively low employment among patients with ALF may merit enhanced rehabilitation efforts., (© 2012 John Wiley & Sons A/S.)

Cost issues in liver transplantation (LT) have received increasing attention, but the cost-utility is rarely calculated. We compared costs per quality-adjusted life year (QALY) from the time of placement on the LT waiting list to 1 year after transplantation for 252 LT patients and to 5 years after transplantation for 81 patients. We performed separate calculations for chronic liver disease (CLD), acute liver failure (ALF), and different Model for End-Stage Liver Disease (MELD) scores. For the estimation of QALYs, the health-related quality of life was measured with the 15D instrument. The median costs and QALYs after LT were €141,768 and 0.895 for 1 year and €177,618 and 3.960 for 5 years, respectively. The costs of the first year were 80% of the 5-year costs. The main cost during years 2 to 5 was immunosuppression drugs (59% of the annual costs). The cost/QALY ratio improved from €158,400/QALY at 1 year to €44,854/QALY at 5 years, and the ratio was more beneficial for CLD patients (€42,500/QALY) versus ALF patients (€63,957/QALY) and for patients with low MELD scores versus patients with high MELD scores. Although patients with CLD and MELD scores > 25 demonstrated markedly higher 5-year costs (€228,434) than patients with MELD scores < 15 (€169,541), the cost/QALY difference was less pronounced (€59,894/QALY and €41,769/QALY, respectively). The cost/QALY ratio for LT appears favorable, but it is dependent on the assessed time period and the severity of the liver disease., (Copyright © 2011 American Association for the Study of Liver Diseases.)

Because few reports have addressed infections late (≥1 year) after liver transplantation (LT), we evaluated the incidence, risk factors and pathogens involved. Infection data were from the Finnish LT registry, with starting date, type and relevant pathogens for 501 Finnish adult LT patients surviving ≥1 year post-transplant. Follow-up end points were end of study, death or retransplantation. Logistic regression to assess risk factors was adjusted for age, gender and follow-up time. With 3923 person-years of follow-up, overall infection incidence was 66/1000 person-years; 155 (31%) suffered 259 infections, and two-thirds experienced only one infection. Cholangitis (20%), pneumonia (19%) and sepsis (14%) were most common. The most frequent bacteria were Enterococcus spp. and Escherichia coli, and the most frequent viruses cytomegalovirus and varicella zoster virus. Fungal infections were rare (n = 7). With 13 fatal infections, 17% of all late deaths involved infection. Primary sclerosing cholangitis (PSC) and Roux-en-Y-type biliary anastomosis were associated with cholangitis; 18% of PSC patients suffered late cholangitis. Late acute rejection was associated with sepsis. Age, gender or cytomegalovirus did not significantly influence late infections. In conclusion, although infection risk under maintenance immunosuppression therapy is relatively low, particular vigilance regarding cholangitis, pneumonia and sepsis seems appropriate., (©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Aim: To determine the short-term cost-utility of molecular adsorbent recirculating system (MARS) treatment in acute liver failure (ALF)., Methods: A controlled retrospective study was conducted with 90 ALF patients treated with MARS from 2001 to 2005. Comparisons were made with a historical control group of 17 ALF patients treated from 2000 to 2001 in the same intensive care unit (ICU) specializing in liver diseases. The 3-year outcomes and number of liver transplantations were recorded. All direct liver disease-related medical expenses from 6 mo before to 3 years after ICU treatment were determined for 31 MARS patients and 16 control patients. The health-related quality of life (HRQoL) before MARS treatment was estimated by a panel of ICU doctors and after MARS using a mailed 15D (15-dimensional generic health-related quality of life instrument) questionnaire. The HRQoL, cost, and survival data were combined and the incremental cost/quality-adjusted life years (QALYs) was calculated., Results: In surviving ALF patients, the health-related quality of life after treatment was generally high and comparable to the age- and gender-matched general Finnish population. Compared to the controls, the average cost per QALY was considerably lower in the MARS group (64,732 euros vs 133,858 euros) within a timeframe of 3.5 years. The incremental cost of standard medical treatment alone compared to MARS was 10,928 euros, and the incremental number of QALYs gained by MARS was 0.66., Conclusion: MARS treatment combined with standard medical treatment for ALF in an ICU setting is more cost-effective than standard medical treatment alone.

Background: As opposed to most solid-organ transplant recipients, patients with acute liver failure exhibit a pretransplant health status more comparable with the general population, and any posttransplant cardiovascular risk excess should thus be more attributable to transplantation-related factors alone., Methods: This study compared the cardiovascular risk of 77 consecutive patients with acute liver failure at 5 years after liver transplantation with that of the general population using age, sex, and residence area-standardized prevalence ratios (SPR)., Results: At least one cardiovascular risk factor developed in 92% of patients. Treated hypertension, observed in 71% of patients at 5 years, was more common among patients than controls (SPR, 2.73; 95% confidence interval [CI], 2.06-3.55), whereas the 61% prevalence of dyslipidemia and 3% prevalence of impaired fasting glucose were significantly less frequent among patients (SPR, 0.69; 95% CI, 0.51-0.92 and SPR, 0.29; 95% CI, 0.04-1.00). The 5-year prevalence of diabetes (10%), overweight (32%), and obesity (13%) deviated nonsignificantly from controls (SPR 1.90, 0.85, and 0.58). Antibody therapy associated with a 1.49-fold increase in the risk of hypertension (95% CI, 1.15-1.94) and a 6.43-fold increase in the risk of diabetes (95% CI, 1.18-34.9). Immunosuppression-type, steroids, acute rejection, retransplantation, or graft steatosis revealed nonsignificant risk alterations., Conclusions: Liver transplantation and associated immunosuppression evidently cause hypertension, and possibly elicit diabetes in susceptible individuals. Conversely, the often reported transplantation-associated increased burden of overweight/obesity and dyslipidemia might relate mostly to other factors.

Health-related quality of life (HRQoL) is one preferable outcome measure of medical interventions such as liver transplantation (LT). The aim of this study was to compare HRQoL of LT patients with that of the general population and to assess the employment status of LT patients. HRQoL was measured with the 15D instrument, a validated, non-disease-specific, 15-dimensional, self-administered HRQoL instrument. The questionnaire was sent to all adult LT patients in Finland (401 patients) alive in June 2007. The response rate was 89% (353 patients). The results were compared to those of 6050 age-standardized and gender-standardized controls from the general population. LT patients (mean age, 55 years; range, 20-82) had slightly worse HRQoL scores than the general population (mean 15D score, 0.889 versus 0.907; P < 0.002). Survival time and retransplantation did not affect HRQoL significantly in age-adjusted and gender-adjusted analyses. HRQoL decreased with increasing age (P < 0.0001). Patients transplanted for acute liver failure (ALF) or chronic liver disease (CLD) had significantly worse HRQoL than the general population (P = 0.014 and P = 0.040). Forty-four percent of working-age patients were employed at the time of the study. Persons that were employed had significantly better HRQoL than those unemployed (15D scores, 0.934 versus 0.859; P < 0.0001). Eighty-seven percent of patients experienced improved working capacity after LT. Early retirement was the most common cause of unemployment (56% of unemployed patients), and those patients presented with worse HRQoL than patients unemployed for other reasons. In conclusion, HRQoL of LT patients is very close to that of the general population. Older age, CLD, and ALF impair HRQoL. Employment is an indicator of HRQoL., (Copyright 2008 AASLD.)

Posttransplant malignancies have become a serious long-term complication after liver transplantation. Our aim was to compare the incidence of posttransplant cancers with national cancer incidence rates. The study included all Finnish liver transplant patients transplanted at the Helsinki University Central Hospital between 1982 and 2005. The cohort was linked with the nationwide Finnish Cancer Registry. Observed numbers of cancers were compared to site-specific expected numbers based on national cancer incidence rates stratified by age, sex, and calendar time. The standardized incidence ratios (SIRs) were calculated as observed-to-expected ratios. Thirty-nine posttransplant de novo cancers and 11 basal cell carcinomas were found in the cohort of 540 patients during 3222 person years of follow-up. The overall SIR was 2.59 (95% confidence interval 1.84-3.53). SIR was higher for males (SIR 4.16) than for females (SIR 1.74), higher among children (SIR 18.1) than among adults (SIR 5.77 for ages of 17-39 years and 2.27 for ages >/= 40 years), and more elevated in the immediate posttransplant period (SIR 3.71 at < 2 years) compared to later periods (SIR 2.46 at 2-10 years and 1.53 at >10 years). The most common cancer types were nonmelanoma skin cancer (SIR 38.5) and non-Hodgkin lymphoma (SIR 13.9). Non-Hodgkin lymphoma was associated with male gender, young age, and the immediate posttransplant period, whereas old age and antibody induction therapy increased skin cancer risk. In conclusion, cancer incidence is increased among liver transplant patients compared to the general population. This study points out the importance of cancer surveillance after liver transplantation., ((c) 2008 AASLD.)

Acute liver failure (ALF) is a medical emergency. Molecular adsorbent recirculating system (MARS), an artificial liver support system, can partly compensate for the detoxifying function of the liver by removing toxins from blood. To analyze the efficacy of MARS treatment, the outcomes of 113 ALF patients, treated with MARS between 2001 and 2007, were compared with a historical control group of 46 ALF patients treated without MARS between 1995 and 2001. Overall survival of transplanted patients was 94% in the MARS group and 77% in the control group (P=0.06). Without transplantation, survival was 66% and 40% (P=0.03), respectively. However, the etiological distribution of ALF differed significantly between the groups. In ALF patients with unknown etiology, groups were comparable at baseline; 91% and 69% of transplanted patients survived the MARS and control groups and the native liver recovered in 20% and 8% of the patients, respectively. Of the originally nonencephalopathic patients of unknown etiology, 36% underwent liver transplantation in the MARS group compared to 100% in the control group. Interpretation of the results was difficult in toxic etiology patients on account of differing baseline statuses. MARS treatment might partly explain the trend toward increased survival of ALF patients with unknown etiology.

The results of solid organ transplantation have improved during the last decade. Five-year patient survivals over 80% and graft survivals over 70% are common in many transplant centers. Also, quality-of-life assessments show that not only adults but even small children have a good quality of life after successful organ transplantation. Furthermore, transplantation programs have proved to be cost-effective. However, the organ shortage is a worldwide problem, which has in many countries led to prolonged waiting times, deaths on the waiting list, increased living related donations, acceptance of lower-quality organs, and in some instances even commercialization of the organ supply. Thus, it is extremely important to find strategies that increase the number of cadaveric organs for donation. In Finland organ transplantation is concentrated in one center with about 250 transplantations of different organs performed annually. The number of patients needing a new cadaveric organ is steadily increasing, but the number of donors has remained the same during the last decade. To improve cadaveric organ procurement the Donor Action (DA) program, which consists of a Hospital Attitude Survey and a medical records review performed by the donor hospital, has proved to increase the number of cadaveric donors. We introduced the DA program in Finland in 2000. Here in we report the results of this program in terms of its impact on the availability of cadaveric donors.

Background: Liver transplantation has become an established therapeutic option for patients with life-threatening liver disease. The aim of the present study was to analyse the results of and developments in liver transplantation in the Nordic countries during a 15-year period., Methods: Data on all patients receiving a liver allograft in the Nordic countries during 1982-98 and waiting list data for all patients listed for a liver transplantation after 1989 were obtained from the Nordic Liver Transplantation Registry., Results: A total of 1485 first liver transplantations were performed during 1982-98. The annual number of first liver transplantations increased steadily up to 1993, thereafter remaining around 150-170 per year. There are major differences between countries both in the number of transplants adjusted to populations performed per year, with more than twice as many performed in Sweden as in Norway, and in the relative distribution of patients in accordance with diagnosis. The number of patients more than 60 years old increased and comprised 13%-14% of the total patient population during 1996-98. Primary biliary cirrhosis, primary sclerosing cholangitis, acute hepatic failure, malignant liver disease, and alcoholic cirrhosis are the five most frequent diagnoses. The over-all 1-year patient survival probability has increased from 66% among patients receiving a transplant in 1982-89 to 83% in 1995-1998. The waiting time remains stable, with a median waiting time of 35 days during 1990-98. The mortality of patients while on the waiting list is 7.4% and is not increasing., Conclusion: Results of liver transplantation in the Nordic countries are very similar to those obtained in other countries. Waiting time and mortality remain low. There are, however, major differences between the countries both as to the number of transplantations performed and as to distribution of diagnoses.

The Nordic collaboration in organ transplantation was initiated nearly 30 years ago in the frame of Scandiatransplant. With a recent formalization of its structure, Scandiatransplant has become a modern organ exchange organization. The increasing activities of Scandiatransplant clearly reflect the continuously growing need for a close and firm Nordic collaboration in the transplantation field, for the benefit of the numerous patients waiting for an organ transplant.

Background and Aims: The ominous prognosis of primary gallbladder cancer is well-known. This study assesses whether the prognosis has improved, and whether the substantial development in the radiologic imaging techniques is reflected in the survival of these patients., Material and Methods: The series consisted of 122 patients operated on for primary cancer in the gallbladder in the Helsinki City area between 1970 and 1990., Results: The mean age of the patients was 68.6 years and did not change during the period, but there was a significant proportional increase in male patients. Only 2% of patients had a localized disease at the time of diagnosis, and there was no improvement in the diagnostic sensitivity during the observation period. Yet, the number of unexpected postoperative cancer diagnoses increased from 4% to 15% during the two decades. The primary mortality decreased from 21% to 13%, the one-year survival increased from 7% to 13%, whereas the five-year survival remained unchanged., Conclusions: During the past two decades the frequency of surgery for primary gallbladder cancer has increased significantly among males in the Helsinki City area. Regardless of the improved immediate survival the long-term survival has remained poor. The marked development in radiologic techniques is not reflected in the prognosis of these patients. Even under conditions in which the potential for the diagnosis of a malignant gallbladder disease is available, the opportunities for radical surgery are not utilized maximally, which is a cause for concern.

Scandiatransplant is an organ exchange organisation founded in 1969. It serves a population of 23 million inhabitants in the five Nordic countries; Iceland, Norway, Sweden, Finland and Denmark. Scandiatransplant maintains a common central waiting list for all Nordic patients waiting for necro-organ transplantation. The waiting lists are maintained on a central computer by each of the eleven transplant centres in the organisation. The number of necro-organ donors in Scandiatransplant is about 340-375 yearly, corresponding to 15-16 donors per million population (PMP) per year. Since the foundation, a total of 14,500 necro-kidney transplants have been performed, and the number of transplants with extrarenal organs is steadily increasing. Presently, about 7-8 liver transplants PMP are being performed, and the heart transplant activity amounts to about 5 PMP. The supreme authority of Scandiatransplant is the Council of Representatives, in which each transplant centre is represented by one or more professionals who are clinically active in organ transplantation. The responsibility for day-to-day operations lies with the Board which has one member appointed by each of the five Nordic countries and a chairman elected by the Council. The activities of Scandiatransplant are financed exclusively by the participating centres.

During triple-drug immunosuppression, consisting of azathioprine, steroids, and cyclosporine, the number of acute rejections was low. Close monitoring of the patient and the graft during the early posttransplant weeks with regular cytological and histological analyses was the cornerstone of early diagnosis and a favorable outcome of acute rejection. Genetic homogeneity of our patient population, third-party transfusion program, and use of well HLA-matched kidney grafts may have been additional factors behind the low rate of acute rejection. Acute rejection within the first three postoperative months did not predispose the renal graft to chronic rejection in the long term. The histologically determined allograft damage index was a reliable predictor of future graft survival. Recipients with systemic diseases such as diabetes and amyloidosis, as well as elderly patients, could be transplanted safely with results only slightly inferior to those achieved with primary kidney disease. Results in diabetic recipients have steadily improved, encouraging the continuation of critical evaluation of the patients' pretransplant status and the preference for cadaveric transplants. Renal transplantation in small children yielded superior patient and graft survival rates. We consider the use of living donors justifiable in these cases. The five million population of Finland offers an ideal size for a transplant center. Continuous education of medical personnel and the general public is crucial for the cadaver transplant program.

To evaluate the effects of improvements in medical therapy on the incidence of, indications for and operative methods used in peptic ulcer surgery, all cases of primary peptic ulcer surgery among adults in the city of Helsinki in the years 1972, 1977, 1982 and 1987 were analysed. There was a total of 565 such cases in a population which consisted of 5.2 X 10(5) individuals in 1972 and 4.8 X 10(5) individuals in 1987. The introduction of H2-receptor antagonists in 1979 was associated with a fall in the annual incidence of elective duodenal ulcer operations, from 15.5 to 6.7 per 10(5) individuals, and a fall in the annual incidence of elective gastric ulcer operations, from 9.4 to 3.1 per 10(5) individuals (P less than 0.05). The decrease was greatest among males with duodenal ulcer. In contrast, the annual incidence of emergency surgery for ulcer haemorrhage and perforation (all types of ulcers) remained relatively stable, varying from 7.2 to 10.2 per 10(5) inhabitants over the observation period (n.s.). The mean age of patients undergoing elective surgery remained essentially unchanged. The mean age of patients undergoing emergency surgery increased. The decrease in the annual incidence of elective duodenal ulcer surgery occurred mainly in relation to proximal gastric vagotomy. There was a concomitant relative increase in the incidence of gastric resection. The types of operative procedures used in cases of pyloric, prepyloric and gastric ulcer remained unchanged over the years 1972 to 1987.

To determine the effect of modern drug treatment on the incidence and type of ulcer operations, a retrospective survey was made of ulcer surgery performed on adult Helsinki residents during the years 1972, 1977, 1982 and 1987, with regard to indications and types of surgery. The introduction of H2-receptor blockers in 1979 was followed by a marked reduction in the incidence of elective ulcer surgery. On a population basis, the annual incidence of duodenal ulcer (DU) operations diminished by 50 per cent over the period 1972-1987, and that of operations for gastric ulcer by about two thirds, the falling trend being most marked among male DU patients. Figures for emergency surgical intervention in cases of haemorrhage or perforation remained unchanged during the period, as did the mean age of patients admitted for elective surgery, though the mean age of patients undergoing emergency surgery manifested a rising trend. The number of patients undergoing elective surgery for DU diminished, a trend first and foremost attributable to the fact that proximal selective vagotomy was performed more rarely, while the number of resections increased. The incidence of surgical treatment of pyloric and gastric ulcers remained unchanged during the period.

Somatostatin (ST) and vasopressin (VP) infusions were compared in the treatment of actively bleeding esophageal varices. Fifty-four patients with liver cirrhosis were included in the study. Thirty-two were given ST 4.2 micrograms/min, and 22 patients were given VP 0.4 IU/min for 72 h after endoscopic diagnosis. The role of alcoholic cirrhosis was similar in both groups. Initial control of bleeding was achieved significantly more often (p = 0.0281) when ST was used (84.4%) than during VP treatment (57.1%). Rebleeding occurred in 18.8% and 4.8%, respectively. Side effects of treatment were significantly more common when VP was used than during ST treatment (p = 0.0021). Overall mortality was high in both groups, being 34% in the ST group and 36% in the VP group. ST infusion seems to be more effective and safer than VP in the treatment of acute variceal bleeding. However, the high frequency of rebleeding during ST treatment means that, after primary hemostasis with ST infusion, other methods, such as surgery or sclerotherapy, are needed to prevent the serious complications of rebleeding.

Until December 1988, 38 patients with primary biliary cirrhosis (PBC) had been transplanted in the Nordic countries. The observed survival probability in accordance with Kaplan-Meier analysis was around 75% 2-3 months after surgery, with few deaths during the next 3 years. The observed survival curve was compared with the expected survival calculated from the experience of a recent English PBC transplant series; the patterns are very similar. Secondly, the observed survival was compared with the expected survival curve, calculated from the survival experience of an international trial of medical treatment--that is, the expected survival had the patients not been transplanted; after the first 2-3 months the observed survival stayed better than the expected survival. Finally, the merits of transplantation for each particular patient was evaluated by means of the ratio of probability of survival when transplanted to probability of survival when medically treated 3, 6, and 8 months after surgery. The ratio increased with time, indicating a relative increase in the benefit of transplantation with time after surgery.