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Liver transplantation (LT) is an established therapy associated with a dramatic improvement in patients' life expectancy. With improved early-term management, current 10-year patient survival rates in many indications exceed 70%. Life-long immunosuppressive therapy may, however, be accompanied by considerable long-term toxicity: most importantly, renal dysfunction, cardiovascular disease, and cancer, which, in addition to recurrence of the primary liver disease, emerge as key contributors to late mortality. Chronic kidney disease cumulatively affects up to 28% of patients by ten years after LT. Various factors can contribute to renal impairment, but perioperative acute kidney injury, calcineurin inhibitor toxicity, hypertension, and diabetes are considered most important. LT patients demonstrate 3-fold risk for cardiovascular events, which seems to result mostly from an excess of traditional risk factors, mainly hypertension and diabetes. The cumulative cancer incidence reaches 16–42% by 20 years after LT, and cancer rates are 2- to 4-fold higher among LT patients than among matched controls. Highest rates are for nonmelanoma skin cancer (3- to 70-fold) and lymphoma (8- to 29-fold). The liver graft usually displays uncomplicated function in the long term. Most common causes for chronic graft dysfunction include disease recurrence and biliary problems. LT generally restores patients' quality of life to a level comparable with that of the general population, with only minor deficits in some areas. Thus, long-term survival after LT is impressive, and despite these long-term complications, patients' quality of life remains comparable with that of the general population.

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 Enterococcusspp. 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.

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 Enterococcusspp. 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.

Vascular adhesion protein-1 (VAP-1) has been shown to mediate lymphocyte adhesion to endothelia at sites of inflammation in vitroand in vivo. VAP-1 is also an ectoenzyme with semicarbazide-sensitive amine oxidase (SSAO) activity. In this study we investigated whether inhibition of SSAO influences the inflammatory infiltration in acute rat liver allograft rejection. BN recipients of DA liver allografts were treated with 50 mg/kg/d semicarbazide, an inhibitor of SSAO, or similar volumes of saline. 10 rats/group were followed for graft survival, and 10 rats/group were sacrificed on day 7 post-transplantation for histology and T-lymphocyte isolation. The area percentage of portal inflammatory infiltrates in the grafts was assessed from digital photomicrographs. The proportion of CD4-, CD8- and IL2-receptor positive lymphocytes in the graft was quantified with flow cytometry. On day 7, semicarbazide treatment significantly decreased the inflammatory infiltrate area in the grafts. CD4-, CD8- and IL2-receptor positive cells were equally affected. However, animal survival was not affected. Blockade of the enzymatic activity of VAP-1 has a significant effect on lymphocyte infiltration early in acute liver rejection. Later, activation of other adhesion pathways can by-pass the blockade caused by VAP-inhibition.

Survival after liver transplantation for fulminant hepatic failure has been reported to be less favorable than survival for patients with chronic liver diseases.

AbstractLiver transplantation was previously only offered to patients under 60 years of age. We have analyzed the outcome after acceptance on the waiting list and after liver transplantation of patients over 60 years old. A total of 150 patients over 60 years old were listed for a first liver transplantation during 1990‐1998. The annual number increased throughout the period. Primary biliary cirrhosis, primary sclerosing cholangitis, and acute hepatic failure were the most frequent diagnoses. A total of 119 patients received a first liver allograft. The patient 1‐year survival was 75 % and 3‐year survival 62%, which was not significantly lower (P= 0.21) than that of the younger patients. When correcting for year of transplantation, the survival was, however, moderately but significantly lower than among the younger patients. Survival among those > 65 years (n= 38) did not differ from that of patients 60‐65 years of age (n= 81). We conclude that an increasing number of patients over 60 years old can be listed for liver transplantation and receive a liver allograft with highly satisfying results.

Abstract: We studied the effect of initial graft function and acute rejection on graft survival in 1047 cadaveric renal transplantations during 1991–1997 with a constant policy of donor selection, graft allocation, and immunosuppression. The overall 1- and 5-year patient survival rates were 96 % and 88 %, and the 1- and 5-year graft survival (GS) rates were 92 % and 78 %. Delayed graft function (DGF) occurred in 31 % and there were 1.2 % never-functioning grafts. One-year GS in transplantations with early graft function (EGF) was 95 % compared to 87 % in DGF (P < 0.001). Donor age and cause of death, type of graft perfusion and cold ischemia time, and type and length of dialysis treatment were significant factors in determining the onset of graft function. These factors did not have a significant direct effect on GS. Early ( < 100 days) acute rejection occurred in 25 %. In transplantations without rejection, the 1 and 5-year GS was 93.3 % and 80.8 %. In acute rejection responding to steroids, the GS was equal to that up to 3 years, but after that a significantly worse survival rate was observed (1- and 5-year GS: 93.6 % and 73.4 %). DGF was detrimental to GS both in transplantations without rejection and in all rejection types.

To evaluate the diagnostic value of nucleic-acid-sequence-based amplification (NASBA) for the detection of cytomegalovirus (CMV) infection in transplant recipients, we compared immediate early 1 (IE1) and late pp67 mRNA detection by NASBA with the antigenemia assay, PCR and viral culture in 72 renal transplant (RTx) recipients and with antigenemia and serology in 25 liver transplant (LTx) recipients. Antigenemia, viral culture and pp67 NASBA were almost equivalent for the detection of CMV in RTx recipients. In LTx recipients, antigenemia detected more positive samples and more positive recipients compared to pp67 NASBA. In RTx recipients, PCR detected more positive samples and positive recipients compared to pp67 NASBA, antigenemia and viral culture. Also the first day of detection was slightly earlier for PCR. However, IE1 NASBA was the most sensitive test and detected 96% of all positive samples and positive transplant recipients. In addition, IE1 NASBA preceded PCR and all other positive results. This makes IE1 NASBA a very attractive screening test for the early detection of CMV infection.

Serial measurements of high‐density lipoprotein‐associated serum amyloid A protein (SAA) concentrations were carried out in 9 consecutive patients following liver transplantation. On the basis of clinical findings and repeated fine‐needle aspiration biopsies of the transplants, 11 rejection episodes were diagnosed in these patients. SAA increased significantly during all 11 rejections: peak SAA values ranged from 55 to 265 mg/1 (median 165 mg/l; SAA in healthy control subjects < 5 mg/l, range < 5 to 15 mg/l). A weak positive correlation (rs= 0.58) was found between peak cytology scores and peak SAA levels during rejections. Ten out of the 11 rejections were associated with a concentration of SAA > 80 mg/l. With this cut‐off level, and excluding the surgery‐induced SAA peak occurring on post‐transplant day 2 or 3, there were 2 false positive SAA readings with respect to rejection; 1 of these was associated with a severe septic complication. Immunoperoxidase staining for SAA of the transplant aspiration biopsies showed increased intensity in the hepatocytes during rejection episodes, suggesting that the rejection‐associated increase in SAA production occurs in the graft. The results suggest that serial measurements of SAA may be a useful, noninvasive aid in the detection of acute graft rejection episodes after liver transplantation.

Thirty-seven patients treated for severe acute pancreatitis were investigated a mean of 6·2 years after the attack; 30 were found to be in good condition and 24 were working normally. Two-thirds of previously heavy drinkers had either reduced their intake considerably or become abstainers. The main complication observed on follow-up was diabetes mellitus, which affected 20 patients and required insulin treatment in nine. Of the remaining patients, four were taking oral antidiabetic agents and seven were on a strict diabetic diet. Before severe acute pancreatitis none had been diabetic. All patients who underwent resection of the pancreas developed diabetes. In 21 of 24 patients with overt or imminent diabetes, pancreatitis had been primarily alcoholic in origin. Polyneuropathy, as diagnosed by clinical signs and/or neurophysiological tests, was observed in six patients, all of them heavy drinkers. It is concluded that patients with severe acute pancreatitis have a high chance of returning to normal activity and productive work. These results serve to encourage all those involved to persist with the exacting work involved in treating such patients.

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 × 105individuals in 1972 and 4·8 × 105individuals 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 105individuals, and a fall in the annual incidence of elective gastric ulcer operations, from 9·4 to 3·1 per 105individuals (P< 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 105inhabitants 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.

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.

A 61-year-old man was operated for a large tumor, 12×4 cm in size, in the lower third of the oesophagus. The tumor had the appearance of a pleomorphic rhabdomyosarcoma showing cross striations by light microscopy and typical sarcomeres by electron microscopy. This is the fifth undisputed oesophageal rhabdomyosarcoma described in the literature and the first examined using electron microscope.

Background: Biliary complications are a common problem in liver transplantation (LT). Methods: We reviewed 100 consecutive adult LTs, including 10 retransplantations. Ten patients who survived for less than 1 month or developed hepatic artery thrombosis were excluded. Biliobiliary anastomosis was performed with a T-tube (CCT) (n = 25) or without it (CC) (n = 59), or biliodigestive anastomosis (Rouxen-Y) (n = 6) was used. Results: Biliary complications (8 anastomotic strictures and 9 bile leakages) occurred in 15 LTs. Surgical treatment was needed for seven strictures and two leakages. Complications tended to be more frequent with CCT than with CC (24% versus 12%). Biliary complications were often accompanied by cytomegalovirus disease and bacterial infections. After a median follow-up time of 5.2 years, total patient survival was 71% for all 100 LTs and 81% for those with biliary complications. Conclusions: Biliary complications are rather frequent after LTs; they are often preceded by infections but can be treated and do not cause excessive mortality. T-tubes are not to be recommended.

The diagnosis of acute liver allograft rejection is difficult, as clinical signs or liver function tests are too unspecific. The diagnosis is mainly based on biopsy histology. However, the liver core biopsy may be associated with complications. The fine-needle aspiration biopsy (FNAB) method, originally developed for the monitoring of renal transplants, is a reliable and atraumatic technique to diagnose acute cellular rejection of liver allografts. FNAB makes it possible to quantity the inflammation associated with rejection, and to monitor the response to anti-rejection therapy. Additional information is received from changes in liver parenchymal cells indicating tissue damage and/or possible hepatotoxic effects of the durgs used. In addition, FNAB may be helpful in differential diagnosis of infections, cholestasis or other complications. A good correlation between FNAB findings of acute liver rejection and histology has been reported. However, histological examination is needed to diagnose chronic rejection. Several liver transplant centres now use FNAB technology as a routine diagnostic tool.

A prospective randomized study was conducted to evaluate the impact of four different conversion protocols on graft outcome in long-term follow-up. Between January 1986 and May 1987, 128 patients with first cadaveric kidnery allografts were randomized at the time of transplantation to four treatment groups of 32 patients each, to be assigned 10 weeks post-transplantation. During the first 10 weeks, all patients received triple therapy with low-dose azathioprine (Aza), cyclosporin (CyA), and methylprednisolone (MP). After 10 weeks, one group continued with triple therapy (group A) while the three other groups received different combinations of two drugs, namely, Aza and CyA (group B), Aza and MP (group C), or CyA and MP (group D). Withdrawal of MP (group B) or especially of CyA (group C) was associated with 4/29 (14%) and 10/28 (36%) acute rejection episodes, respectively, for 60 days after conversion. All rejections were mild and reversible. There were no rejections after Aza withdrawal or in the group that continued on triple therapy during the corresponding time period. The most common reason for dropping out after withdrawal, for those patients who could not continue on the originally randomized medication, was azathioprine intolerance (n=12). Five patients were switched back to triple therapy after CyA withdrawal due to rejection. Steroid intolerance was rare and CyA in low doses was very well tolerated. At 1 year there were no statistically significant differences in graft survival between groups A, B, C, and D-81%, 88%, 88%, and 88%, respecively-or in patient survival-88%, 88%, 88%, and 97%, respectively. For those patients continuing with the originally randomized treatment protocol, there were no differences in patient or graft survival either, the means being 91% and 89%, respectively. The most common cause of death after withdrawal was cardiovascular in nature, and there were no more fatal infections under triple drug treatment than with double drug regimens. There were no statistically significant differences in mean serum creatinine values at 1 year. The median serum creatinine values for groups A, B, C, and D were 112, 132, 133, and 133 µmol/l, respectively. At 1 year the mean CyA dose in the groups that continued with CyA was 3.5–4.2 mg/kg per day and CyA concentrations were equal.

In order to evaluate the effect of a short-term high-dose corticosteroid therapy on the gastric and duodenal mucosa, 30 consecutive renal transplant recipients (mean age 39.1 years, 10 women and 20 men) underwent an endoscopic examination of gastroduodenal mucosa 12 and 30 days after renal transplantation. In addition to the postoperative immunosuppressive medication (methylprednisolone and azathioprine), antacids and H2-receptor antagonists were given. Seventeen patients showed no signs of acute rejection, whereas 11 patients experienced one episode and 2 patients two episodes of rejection during endoscopic follow-up. Each rejection episode was treated with a high-dose regimen of methylprednisolone. The two groups of patients studied, i.e., those who did and those who did not experience rejection, were matched for age, sex, period of preoperative dialysis treatment, period of postoperative time elapsed from transplantation, serum creatinine level, and dose of methylprednisolone or azathioprine at the beginning of the endoscopic follow-up, as well as for ulcer prophylactic medication during follow-up. The gastroduodenal mucosa was similar in the two patient groups, both endoscopically and histologically, at the start of the study. During the observation period of 2 weeks, erosive antral gastritis increased significantly in patients who did not experience rejection, whereas in patients with acute rejection and concomitant high-dose corticosteroid therapy, the antral mucosa remained nearly unchanged. Also, the gastric corpus and the duodenum remained unaltered in both groups during follow-up. No ulcer complications occurred in the series. Thus, a high-dose short-term corticosteroid treatment does not seem to be related to grossly harmful side effects in the gastroduodenal mucosa in the immediate post-transplant phase after renal transplantation. This suggests that the current policy of active treatment of renal failure, including antiulcer prophylaxis with H2-receptor antagonists and improved immunosuppressive medication, renders the gastroduodenal mucosa resistant enough to also tolerate the acute post-transplant period well.

We have investigated the impact of triple drug immunosuppression on the occurrence of early inflammatory episodes, as detected by fine needle aspiration biopsy, and of episodes of clinical rejection during the immediate postoperative period. The prospective component of this study includes 128 consecutive first cadaveric renal transplant recipients receiving triple drug treatment consisting of azathioprine (Aza), cyclosporin (CyA) and methylprednisolone (MP). For controls we have used three historical groups: one immunosuppressed with Aza and MP (group A), another with CyA monotherapy (group B), and the third with CyA together with MP (group C) in equivalent drug dosages. On the average, 0.8 episodes of inflammation per patient were recorded during the immediate postoperative period of 30 days with triple drug treatment. This was significantly less than the 1.3 episodes in patients receiving Aza and MP (P<0.01), the 1.7 episodes in patients on CyA monotherapy (P<0.001), or the 1.6 episodes in patients receiving CyA together with MP (P<0.001). Although the first episode of inflammation commenced concurrently in each group and the peak intensity of inflammation was the same, the mean duration of inflammation was significantly shorter-2.7 days-under triple drug treatment than the 7.8–11.7 days for controls (P<0.001). The frequency of rejection episodes under triple treatment was also significantly lower-0.2 per patient-than the 0.8 per patient in controls (P<0.001). The first rejection episode occurred later in the triple drug treatment group-on the average, on day 15.2-than in the historical controls (on days 7.7–11.7). There was, however, no difference in the duration of rejection. There were no differences in patient survival between the four groups. Graft survival was 97% at 10 weeks for triple drug-treated recipients and 79%, 68%, and 87% for first grafts in groups A, B, and C, respectively. Disregarding a minor demographic bias for the triple drugtreated group with respect to preformed antibodies and preoperative dialysis treatment, the study suggests that the triple drug protocol, in the short run, is superior to any conceivable double drug combination or CyA monotherapy.

Background: The aim of this study was to evaluate the role of primary sclerosing cholangitis (PSC) as a cofactor in the dysplasia-carcinoma sequence in ulcerative colitis (UC). Methods: Forty-five patients with UC and concomitant PSC and 45 pair-matched control patients with UC only were examined for colorectal dysplasia and carcinoma. Results: The median duration of UC was 11 years in the group with UC and PSC and 15 years in the control group. Thirteen of the 45 patients (29%) with UC and PSC had colorectal neoplasia: 4, carcinoma; 2, high-grade dysplasia; and 7, low-grade dysplasia. Four of the 45 control patients (9%) had neoplastic findings: 1, carcinoma; 1, high-grade dysplasia, and 2, low-grade dysplasia (P < 0.05). Conclusion: The results suggest that the risk of colorectal dysplasia and carcinoma in patients with UC is increased by concomitant PSC.

Background: T-tube-related bacteriobilia causes infectious complications and obstruction. To prevent these, the choice of T-tube material may be of importance. Methods: Transected common bile ducts (CBDs) of 17 piglets were sutured over latex or silicone T-tubes, or without a T-tube. Results: After 6 weeks bacteriobilia was found in all of 12 CBDs with and in 1 of 5 CBDs without a T-tube (p < 0.05). By scanning electron microscopy (SEM) four of five latex and none of five silicone T-tubes had bacterial biofilms (p < 0.05). All tubes remained patent. Segments of T-tubes were incubated with five different bacterial strains. Sonication and SEM showed that 0.1-1.1% of 107 colony-forming units of inoculum adhered to T-tubes. Two to six times more bacteria adhered to latex than to silicone (p < 0.05). Conclusions: Silicone offers better long-term patency than latex. Less infectious complications occur if T-tubes are omitted.

Summary Vasopressin has been found to significantly decrease tissue pO2 in the gastrointestinal tract and the liver. The aim of this study was to find out whether 60% oxygen ventilation could prevent the tissue hypoxia.

Summary Liver oxygenation was studied with hemorrhagic hypotension and corrected using whole blood, a synthetic colloid (hydroxyethyl starch or hetastarch, HES; mol. wt. 120 000), or a crystalloid solution. Measurements were performed directly by recording pig liver tissue oxygen tension with an implanted silicone elastomer (Silastic) tube, and indirectly by calculating blood oxygen contributions. The direct method seems fairly reliable and accurately reflects different levels of bleeding and shock and their correction. Liver tissue oxygen tension (PlO2) may thus be used as an indicator of central organ response to shock management. PlO2 decreased during bleeding from 33.5 ± 0.5 to 16.0 ± 0.5 torr, and normalized rapidly after retransfusion. The baseline values were significantly exceeded after hetastarch infusion but were never reached with Ringer's solution. The correction of liver oxygen consumption was less complete after crystalloid infusion as well. On the other hand, the difference in liver oxygenation was less marked after crystalloid infusion and retransfusion, which restored perfusion to the baseline. The total amount of Ringer's solution needed to keep the animals hemodynamically stable during the 2-h follow-up period was four times higher than with hetastarch and some five times the blood volume shed. The cause of defective correction of liver oxygenation seems to be the poor response of liver blood flow to refilling in the Ringer group, in addition to apparent tissue edema after crystalloid infusion. According to our study, hemorrhagic hypotension related to liver oxygenation is more promptly and completely corrected with the colloid hydroxyethyl starch than with a crystalloid solution in the early phase of treatment.

AbstractHuman herpesvirus 6 (HHV‐6) infection has been recently reported in liver transplant patients. HHV‐6 is closely related to cytomegalo‐virus (CMV), and some interaction between the viruses has been suggested. In this study, the post‐transplant HHV‐6 antigenemia was investigated in relation to symptomatic CMV infections in adult liver transplant patients. CMV infections were diagnosed by the pp65 antigenemia test and by viral cultures. HHV‐6 infections were demonstrated by the HHV‐6 antigenemia test and by serology. Significant symptomatic CMV infection was diagnosed in 42 of 75 patients during the first 6 months after transplantation. All CMV infections were successfully treated with ganciclovir. Concurrent HHV‐6 antigenemia was detected in 21 (50%) of 42 patients with CMV infection. All HHV‐6 infections were reactivations. HHV‐6 also responded to the antiviral treatment, but with less clear effect. In conclusion, HHV‐6 reactivation is often associated with CMV infection in liver transplant patients. The results support the suggestion that CMV and HHV‐6 may have interactions.

Abstract Human herpesvirus 6 (HHV-6) infection has been recently reported in liver transplant patients. HHV-6 is closely related to cytomegalo-virus (CMV), and some interaction between the viruses has been suggested. In this study, the post-transplant HHV-6 antigenemia was investigated in relation to symptomatic CMV infections in adult liver transplant patients. CMV infections were diagnosed by the pp65 antigenemia test and by viral cultures. HHV-6 infections were demonstrated by the HHV-6 antigenemia test and by serology. Significant symptomatic CMV infection was diagnosed in 42 of 75 patients during the first 6 months after transplantation. All CMV infections were successfully treated with ganciclovir. Concurrent HHV-6 antigenemia was detected in 21 (50 %) of 42 patients with CMV infection. All HHV-6 infections were reactivations. HHV-6 also responded to the antiviral treatment, but with less clear effect. In conclusion, HHV-6 reactivation is often associated with CMV infection in liver transplant patients. The results support the suggestion that CMV and HHV-6 may have interactions.

Seven patients with end‐stage primary biliary cirrhosis were evaluated both before and 1 and 2 years after liver transplantation using a clinical psychiatric interview and the self‐rating questionaire SCL‐90. Neuro‐psychological tests were done before and 1 year after operation. Preoperatively, all patients had a poor general condition and overall quality of life. Flattening of emotions and reactions, regression, disturbances of verbal memory and cognitive function, and dependence on close relatives were observed. One year after transplantation, 6 patients had a much better overall quality of life, and with five patients it improved still further during the 2nd year, but only 2 patients felt that their life situation had fully stabilised. However, nearly all of them experienced phases of moderate or even severe depression or anxiety during those 2 years. On neuropsychological tests patients appeared to be near their normal level. The only patient who died during this follow‐up (some months after transplantation) had in her life history a prominent sense of insecurity and mistrust. It seems to take more than a year for the majority of patients to give up the regressive mode of experience and turn to adult interests in life again, as well as psychologically experience the new liver as part of oneself.

Intercellular adhesion molecule 1 (ICAM‐1) induction on hepatocytes was investigated in relation to immune activation of acute liver allograft rejection. Twelve liver recipients undergoing an episode of acute rejection were monitored by frequent fine needle aspiration biopsy (FNAB) study. All episodes were reversible, and the lymphocyte and lymphoid blast predominated with a high peak of inflammation (6.9 ± 4.0 corrected increment units). The rejections were treated with a high dose of steroids, and the inflammation subsided within 1 week. ICAM‐1 was demonstrated from FNAB preparations by a monoclonal antibody and immunoperoxidase staining. ICAM‐1 was not detected on the hepatocytes immediately after transplantation but was always seen during rejection. ICAM‐1 appeared 1–5 days before the onset of inflammation in the FNAB. The intensity of ICAM‐1 expression increased towards the peak of inflammation and subsided thereafter. ICAM‐1 induction on hepatocytes appears to be linked with a very early phase of immune activation and can be considered an early marker for acute liver allograft rejection in the FNAB.

The effect of intravesically applied antibiotic solution in the prevention of infectious complications of renal transplantation was evaluated in a prospective, randomized study. The bladder was filled preoperatively with saline solution containing cephalotin in the test group, and with saline solution only in the controls. Both groups of patients received IV doses of cephamandole during, and once after, surgery. Two hundred consecutive patients were randomly allocated to the study groups. The overall incidence of urinary tract infection was 10.4% during the first 4 postoperative weeks; that of wound infections was 1.6% and of septicemia 3.3%. The addition of cephalotin to the bladder irrigation fluid did not have any effect on the overall incidence of infectious complications.

Cyclosporin A (CsA) is metabolized principally by the hepatic cytochrome P 450‐dependent microsomal enzyme system and eliminated virtually entirely as metabolites, mainly in the bile [1, 4, 6]. Only less than 1% of the oral dose is excreted unmetabolized in the urine or bile [5, 7]. Metabolites account for 50–70% of the total CsA in whole blood [3, 5, 8]. Some of the metabolites have been shown to possess an immunosuppressive and even toxic effect but the role of this effect remains uncertain [2, 9]. In order to evaluate the effect of liver and kidney failure on the metabolism of CsA, we studied twelve patients who had undergone liver transplantation. The samples were collected during the first 4 postoperative weeks. The aim of the study was threefold: to evaluate (1) whether an impairment of liver function, as measured by standard biochemical liver function tests, decreased the metabolism or excretion of CsA; (2) whether an induction of either the CsA metabolites or the parent compound took place in the first postoperative period; and (3) whether kidney failure, as measured by serum creatinine, correlated with blood levels of CsA or its metabolites.

AbstractAs a pilot series on the frequency of gastroduodenal cytomegalovirus (CMV) involvement after liver transplantation, we examined forceps biopsies of 13 consecutive patients who underwent esophagogastroduodenoscopy during the first 3 months after transplantation. CMV was demonstrated in frozen sections by monoclonal antibody and immunoperoxidase staining. In parallel, peripheral blood was examined for CMV pp65 antigenemia. CMV antigens were detected in biopsies of ten patients, in ten cases in the duodenum and in four in the stomach. At the time of endoscopy, sic patients had CMV antigenemia, five of them had a simultaneous positive finding in the duodenum. Although all ten patients with the positive biopsy finding had some gastrointestinal symptoms, only one had severe enteritis. In liver transplant patients, CMV was commonly detected in leukocytes located in the mucosa of the upper gastrointestinal tract, especially in the duodenum. Further investigation is needed to determine the significance of positive CMV findings in the biopsies and their association with the development of severe gastrointestinal symptoms.a

The histological changes in renal allografts are usually studied when graft function has already deteriorated. The early results of renal allografts have improved dramatically during the last two decades, but the half‐life of renal cadaveric allografts has remained unchanged at approximately 7 years [1]. The mechanism of chronic rejection, and how to prevent it, is not known. We studied the histology of renal allografts under four different immunosuppressive regimens 2 years after transplantation. The aim of this study was to investigate whether histopathological changes exist in the renal allografts with relatively good and stable graft function. We also investigated whether there were differences in allograft histology between four immunosuppressive treatment groups 2 years after transplantation.

After 1987 10 RSOLT and one OLT have been performed in 10 pts at a mean age of 4.3y (range 0.6-14.2); in 3 pts over the ABO barrier. The diagnoses were: biliary atresia (4 pts), tyrosinemia (3 pts), alpha-1-antitrypsin deficiency, liver adenoma and hepatoblastoma. Triple immunosupression (MP, Az and CyA) with constant i.v. CyA infusion (B-CyA-spes=500-600 ug/L) for 2 w and MP+CyA after 2 mo. Two arterial thromboses were seen; one led to re-OLT and the other cleared with local i.v. streptokinase infusion for 2d. Five pts had one rejection 5-21d (mean 12) after OLT and responded to 3 mg/kg/d p.o. MP for 5d. There was no rejection in the 3 pts were the ABO barrier was crossed. CMV viremia with clinical symptoms was seen in 5 pts and treated with gancyclovir.After a mean follow-up time of 0.8y (range 0.3-2.5y) all pts are at home with a functioning graft. Psychomotor development and growth (catch-up growth after 6 mo) are normal, mean SGPT is 30 U/L, gamma GTP 26 U/L and creatinine 49 umol/L.