ABO incompatible (ABO-In) liver transplant remains a controversial solution to acute liver failure in adults. Adult liver recipients with acute liver failure or severely decompensated end-stage disease, intubated and/or in the intensive care unit, were grouped as ABO-In (n = 14), ABO-compatible (n = 29, ABO-C) and ABO-identical (n = 65, ABO-Id). ABO-In received quadruple immunosuppression with antibody-depleting induction agents (except two), calcineurin inhibitors, antimetabolites and steroids. No significant difference of patient and graft survivals was observed among ABO-In, ABO-C and ABO-Id: graft survivals were 64%, 62% and 67%, respectively, in 1 year and 56%, 54% and 60%, respectively, in 5 years; patient survivals 86%, 69% and 67%, respectively, in 1 year and 77%, 61% and 62%, respectively, in 5 years. Three ABO-In grafts were lost (one hyper-acute rejection and two hepatic artery thrombosis). Surgical and infectious complications were similarly distributed between groups, except the hepatic artery thrombosis, more frequent in ABO-In (2, 14%) than ABO-I (1, 1.5%, P
We have recently found that allogeneic intrabone marrow-bone marrow transplantation (IBM-BMT) + donor lymphocyte infusion (DLI) using CD4(+) cell-depleted spleen cells (CD4(-) cells) can prevent graft-versus-host disease (GvHD) but suppress tumor growth (Meth A: fibrosarcoma) in mice. In the present study, we show that allogeneic IBM-BMT + DLI using CD4(-) cells also has suppressive effects on the growth of colon cancer cells implanted not only in the skin but also in the liver of rats. First, we examined the effects of allogeneic IBM-BMT + DLI on the subcutaneously inoculated ACL-15 (rat colon cancer cell line). Lethally irradiated Fischer rats (F344 rats) were transplanted with T-cell-depleted bone marrow cells (BMCs) from Brown Norway (BN) rats. Simultaneously, DLI was performed using whole spleen cells (whole cells), CD4(+) cell-depleted spleen cells (CD4(-) cells) or CD8(+) cell-depleted spleen cells (CD8(-) cells) of BN rats. Although allogeneic IBM-BMT + DLI suppressed tumor growth, a considerable number of rats treated with allogeneic IBM-BMT + DLI using whole cells or CD8(-) cells died due to GvHD. In contrast, allogeneic IBM-BMT + DLI using CD4(-) cells also suppressed tumor growth, but there was no GvHD. Based on these findings, we next examined the effects of allogeneic IBM-BMT + DLI using CD4(-) cells on the cancer cells implanted in the liver. Allogeneic IBM-BMT + DLI using CD4(-) cells via the portal vein significantly prolonged the survival. These results suggest that allogeneic IBM-BMT + DLI using CD4(-) cells could become a new strategy for the treatment of solid tumors.
To prospectively follow the evolution of hepatobiliary diseases in a population-based cohort of patients with inflammatory bowel diseases.
Between 2005 and 2009, 790 incident cases of ulcerative colitis and Crohn's disease were registered in the Uppsala Health Region, corresponding to an average incidence of 20.0 and 9.9 new cases/100?000 inhabitants/year, respectively. Liver function tests were analyzed in 97.1% and the results of ensuing investigations were summarized.
Seventeen patients with primary sclerosing cholangitis were diagnosed corresponding to an overall prevalence of 2.2% (ulcerative colitis 1.7% and Crohn's disease 3.0%, respectively). The median age at diagnosis was 25 years (interquartile range: 17.0-34.0). Among the 92 patients below 17 years of age, three had autoimmune hepatitis and three primary sclerosing cholangitis, summing up to a prevalence of 6.5% immune-mediated hepatobiliary diseases among the pediatric patients. Three patients have undergone liver transplantation and one died of colonic carcinoma. Ten patients have demonstrated persistent elevation of alkaline phosphatases but had a normal magnetic resonance cholangiopancreatography (two patients) or refused further investigation (one patient).
In this first large prospective population-based cohort of 526 patients with ulcerative colitis (UC) and 264 with Crohn's disease, 17 cases of primary sclerosing cholangitis were found, among whom three (17%) so far have been liver transplanted and one has died of colon carcinoma. The average age of those affected by primary sclerosing cholangitis is considerably lower than usually reported. Ten patients had or have had elevated alkaline phosphatase without confirmed liver or biliary disease.
To determine the outcomes of Canadian children with biliary atresia.
Health records of infants born in Canada between January 1, 1985 and December 31, 1995 (ERA I) and between January 1, 1996 and December 31, 2002 (ERA II) who were diagnosed with biliary atresia at a university center were reviewed.
349 patients were identified. Median patient age at time of the Kasai operation was 55 days. Median age at last follow-up was 70 months. The 4-year patient survival rate was 81% (ERA I = 74%; ERA II = 82%; P = not significant [NS]). Kaplan-Meier survival curves for patients undergoing the Kasai operation at age 90 days showed 49%, 36%, and 23%, respectively, were alive with their native liver at 4 years (P
Between June 1, 1976 and June 30, 1989 The Regional Trauma Unit at Sunnybrook Medical Centre in Toronto, Ontario, Canada received 3730 patients. Of these 335 (9%) sustained a liver injury, 95% being due to blunt trauma. Open peritoneal lavage was performed on 80% of liver trauma patients (267/335), 99% being true positive. A laparotomy was performed on 97% of patients (324/335). Major surgical treatment was required in 132 patients (41%) and minor treatment in 192 patients (59%). The remaining 11 patients were treated conservatively (n = 3) or died during resuscitation (n = 8). Morbidity directly related to the liver injury was seen in 29 of 249 surviving patients (11%) although overall morbidity was 27% (67/249). Reoperation was required in 6% (14/249) with abscess or hematoma accounting for 11 of 14 operations. The overall mortality rate was 26% (86/335). Eighty two percent of patients (n = 276) had a grade I, II or III liver trauma according to Moore's classification with a mortality of 12% (n = 32). The remaining 18% of patients (n = 59) had a grade IV or V liver trauma with a mortality of 44% (n = 26). Of the 86 deaths, head injury accounted for 48 (56% of deaths); liver hemorrhage for 17 (20%), liver sepsis for 1 (1%) and other causes for 20 deaths (23%). Thus death due to the liver injury itself (hemorrhage and sepsis) occurred in 18 out of 335 patients (5% overall). Head injury accounted for the death of 48 out of 335 patients (14% overall). Over the past 13 years a trend has occurred at our institution whereby we are seeing less liver trauma in our population of multiply injured patients from 12% (1976-1983) down to 7% (1985-1989); with a gradual decline in overall mortality from 32% (1976-1983) to 19% (1985-1989), whereas the percentage of deaths due to head injuries and liver injury have increased.
The analyses presented in this chapter are a subset of the yearly audit of organ donation and transplantation in Canada published in the CORR Annual Report. They represent the collaborative efforts and the voluntary contributions of many of the transplant physicians, surgeons, nurses and coordinators in Canada. In Canada, organ donation has remained static at approximately 14 per million population. Despite many local and provincial as well as corporate initiatives, this rate is approximately half the current rate in many regions of the U.S.A. and Spain. The modest increases in transplant activity represent an increase in the use of living donors, reassessment of the traditional donor risk factors (including age) and expansion of the potential donors for each organ. Analysis of the renal transplant activity has determined that the likelihood of being transplanted during the first year on the list was less than 40%. A graft loss rate of 4% per year after the first year was observed for a cadaveric kidney, compared with graft loss rates of 3% and 2% per year for living-related and living-unrelated donor kidneys, respectively. Cox regressional analysis identified that the major determinants of patient survival were the transplant year, the region where the transplant was performed, the presence of diabetes, the recipient's age, and whether the kidney was from a living donor. Liver transplantation has increased each year at the transplant centers in Vancouver, Edmonton, London, Toronto, Montreal, and Halifax. Patient and graft survival rates have improved since 1985 and the most significant determinant of patient survival following transplantation was the patient's medical status at the time of transplantation. Living-related liver donor transplant programs have begun in London and Toronto. Pancreas transplantation remains limited across Canada, but with the development of new pancreas programs in Toronto and Halifax, an increase in the availability of this therapy for Type 1 diabetics is anticipated. Heart transplantation has recovered from a decline in 1991-1992 to approximately 6 hearts per million population. There has been a trend towards better one- and 3-year patient survival rates since 1985. With the development of a lung transplantation program in Winnipeg, lung transplantation has increased. This likely reflects increased utilization of the available donor lungs. A particular increase in double-lung transplants was noted.
OBJECTIVES: Autoimmune hepatitis (AIH) is a liver disease which, if untreated, may lead to liver cirrhosis and hepatic failure. Limited data exist regarding factors predicting the long-term outcome. The aims of this study were to investigate symptoms at presentation, prognostic features, management and treatment in relation to long-term outcome of AIH. MATERIAL AND METHODS: A cohort of 473 Swedish patients with AIH was characterized regarding initial symptoms and signs, factors predicting death and future need for liver transplantation. Survival and causes of death were retrieved from Swedish national registers. RESULTS: At diagnosis, fatigue was a predominant symptom (69%), 47% of the patients were jaundiced and 30% had liver cirrhosis. Another 10% developed cirrhosis during follow-up. Markedly elevated alanine aminotransferase levels at presentation were correlated with a better outcome. A high international normalized ratio (INR) at diagnosis was the only risk factor predicting a need for later liver transplantation. Histological cirrhosis, decompensation and non-response to initial treatment were all factors that correlated with a worse outcome. Overall life expectancy was generally favourable. However, most deaths were liver-related, e.g. liver failure, shock and gastrointestinal bleeding. CONCLUSIONS: Cirrhosis at diagnosis, a non-response to initial immune-suppressive treatment or elevated INR values were associated with worse outcome and a need for later liver transplantation. In contrast, an acute hepatitis-like onset with intact synthetic capacity indicated a good response to treatment and favourable long-term prognosis. Lifetime maintenance therapy is most often required.
OBJECTIVE: Patients with liver cirrhosis, portal hypertension and oesophageal varices are known to have high morbidity and mortality. The knowledge of incidence, aetiology and outcome in Sweden in recent years is limited. MATERIAL AND METHODS: All patients with oesophageal varices diagnosed for the first time at Sahlgrenska University Hospital during the 6-year period 1994-1999 were retrospectively studied. Information about the aetiology of liver cirrhosis and oesophageal varices, as well as about the proportion of bleeding and non-bleeding varices, endoscopic and pharmacological treatment and outcome, was analyszed. RESULTS: 312 patients were retrieved, 297 with liver cirrhosis (197 diagnosed before first bleeding (P), 92 after bleeding (B) and 8 at autopsy) and 15 with portal vein thrombosis without cirrhosis. Fifty-four percent had alcoholic liver disease. Fifty-five percent in group B and 13% in group P had at least one bleeding episode during follow-up (p
Transarterial chemoembolization (TACE) is used as palliative treatment of hepatocellular carcinoma (HCC). Most publications are from HCC patient populations where viral hepatitis is the primary cause of liver disease. In the Nordic countries, most patients have either alcohol-induced cirrhosis or are noncirrhotic. The aim of this single-center study was to evaluate patient characteristics, survival, and side effects of TACE in a Danish referral center for HCC treatment.
Fifty-nine consecutive patients with HCC, treated with TACE, either chemoembolization with drug-eluting beads or conventional-TACE with Lipiodol, were included in the study. Their medical records were retrospectively reviewed, computed tomography images analyzed, and biochemical markers recorded. The primary endpoint was overall survival. Analyses were by intention to treat.
Thirty-five patients (59 %) had HCC on a background of liver cirrhosis most often caused by alcohol (60 % of cirrhotics or 35 % overall). Before the first chemoembolization, the patients had a median Child-Pugh score of 6 (5-7) and a median MELD score of 10 (6-21). Median survival after chemoembolization was 18.9 months (13.1-24.7). TACE patients were hospitalized for an average of 3 days (2-30). Prolonged stay was most often due to side effects-eg. pain (31 %), fever (14 %), nausea (10 %), and infection (10 %). Thirty-three patients (56 %) did not have any side effects.
In this cohort, we observed an acceptable survival following TACE without significant side effects.