Maria Castedal

Abnormal propagation pattern of duodenal pressure waves in the irritable bowel syndrome (IBS) [correction of (IBD)].

The propagation pattern of individual pressure waves in the gastroduodenal area in IBS is unexplored. We performed antroduodenojejunal manometry on 26 patients with IBS—13 with diarrhea predominant IBS (IBS-D) and 13 with constipation predominant IBS (IBS-C)—and 32 healthy controls. Neuropathic-like motor abnormalities were found in 38% of the patients with conventional manometric evaluation. With high-resolution analysis additional abnormalities were observed in the majority of the patients, with increased frequency of retrograde pressure waves postprandially in both IBS subgroups and in phase II in IBS-D. A correlation between subjective gastrointestinal symptoms and the frequency of retrograde pressure waves in phase II in IBS-D was demonstrated. Motility indices and the number of long clusters were also higher in patients compared to controls. To conclude, an abnormal propagation pattern of individual duodenal pressure waves in IBS patients was demonstrated and found to be related to symptom severity in diarrhea-predominant IBS. High-resolution analysis adds information to standard manometry.

Long-term follow-up of patients with alcoholic liver disease after liver transplantation in Sweden: impact of structured management on recidivism.

Objective No systematic evaluation has been performed previously in the Scandinavian countries on patients transplanted for alcoholic liver disease (ALD). Data are limited on the impact of structured management of the alcohol problem on the risk of recidivism following transplantation in ALD. Material and methods A total of 103 ALD patients were compared with a control group of patients with non-alcoholic liver disease (NALD). The recidivism rates for ALD patients transplanted between 1988 and 1997 as well as after 1998 (institution of structured management) were compared. Results The median follow-up was 31 (6–60) months in the ALD group and 37 (12–63) months in the control group (NS). The overall survival rates at 1- and 5 years were, respectively, 81% and 69% for the ALD group and 87% and 83% for the non-alcoholic group. The proportion of patients with Child-Pugh C (75%) was higher in ALD patients than in NALD patients (44%) (p<0.01). Thirty-two (33%) ALD patients resumed taking some alcohol after transplantation; 17 patients (18%) were heavy drinkers. A multivariate analysis showed that: sex, age, marital and employment status, benzodiazepine use and a history of illicit drug abuse did not predict the risk of alcohol relapse post-Tx. Nineteen out of 40 (48%) patients transplanted before the start of structured management had resumed alcohol but 13 (22%) out of 58 after this intervention (p=0.002). Conclusions ALD is a good indication for liver transplantation, with similar results in the ALD patients. Structured management of the alcohol problem before and after transplantation is important in minimizing the risk of recidivism.

Dynamic FDG-PET is useful for detection of cholangiocarcinoma in patients with PSC listed for liver transplantation.

Five to 15% of patients with primary sclerosing cholangitis (PSC) develop cholangiocarcinoma (CC) with a median survival of 5 to 7 months, an outcome not significantly improved by liver transplantation. However, if CC is found incidentally during the procedure or in the explanted liver, 5‐year survival rates of 35% are reported. A noninvasive method to detect CC small enough to allow for intended curative surgery is needed. Unfortunately, computed tomography (CT) and ultrasonography (US) have poor sensitivity for detection of CC in PSC; however, positron emission tomography (PET) using 2‐[18F]fluoro‐2‐deoxy‐D‐glucose (FDG) differentiates well between CC and nonmalignant tissue. We examined whether PET findings are valid using a blinded study design comparing pretransplantation FDG‐PET results with histology of explanted livers. Dynamic FDG‐PET was performed in 24 consecutive patients with PSC within 2 weeks after listing for liver transplantation and with no evidence of malignancy on CT, magnetic resonance imaging, or ultrasonography. The PET Center staff was blinded to clinical findings, and surgeons and pathologists were blinded to the PET results. Three patients had CC that was correctly identified by PET. PET was negative in 1 patient with high‐grade hilar duct dysplasia. In 20 patients without malignancies, PET was false positive in 1 patient with epitheloid granulomas in the liver. In conclusion, dynamic FDG‐PET appears superior to conventional imaging techniques for both detection and exclusion of CC in advanced PSC. FDG‐PET may be useful for screening for CC in the pretransplant evaluation of patients with PSC. (HEPATOLOGY 2006;44:1572–1580.)

Colorectal neoplasia in patients with primary sclerosing cholangitis undergoing liver transplantation: a Nordic multicenter study

Abstract Objective. Several studies have implicated primary sclerosing cholangitis (PSC) as an additional risk factor for colorectal neoplasia in inflammatory bowel disease (IBD). Some reports have indicated that the risk is even higher in PSC-IBD patients after liver transplantation (Ltx), but this issue is controversial. We aimed to compare the risk of colorectal neoplasia in PSC-IBD patients before and after Ltx and to identify risk factors for colorectal neoplasia post-transplant. Material and methods. In a multicenter study within the Nordic Liver Transplant Group, we assessed the risk of colorectal neoplasia by using the competing risk regression analysis. Results. Among the 439 PSC patients included, 353 (80%) had IBD at the time of Ltx and 15 (3%) patients developed de novo IBD post-Ltx. The median duration of IBD was 15 (0–50) years at the time of Ltx and follow-up after Ltx was 5 (0–20) years. Ninety-one (25%) PSC-IBD patients developed colorectal neoplasia. The cumulative risk of colorectal neoplasia was higher after than before Ltx (HR: 1.9, 95% CI: 1.3–2.9, p = 0.002). A multivariate analysis demonstrated aminosalicylates and ursodeoxycholic acid as significantly associated with an increased risk of colorectal neoplasia post-Ltx. Duration and activity of IBD did not significantly affect the risk of neoplasia. Conclusion. The even higher risk of colorectal neoplasia in PSC-IBD patients after when compared with that of before Ltx underscores the importance of regular surveillance colonoscopies post-Ltx. The association of aminosalicylates and ursodeoxycholic acid to the development of colorectal neoplasia after Ltx should be further investigated.

Immunosuppression After Liver Transplantation for Primary Sclerosing Cholangitis Influences Activity of Inflammatory Bowel Disease

BACKGROUND & AIMS Previous studies have shown conflicting results regarding the course of inflammatory bowel disease (IBD) after liver transplantation in patients with primary sclerosing cholangitis (PSC). We studied the progression of IBD in patients with PSC who have undergone liver transplantation. We also studied risk factors, including medical therapy, that could influence on IBD disease activity. METHODS In a longitudinal multicenter study, we analyzed data from the Nordic Liver Transplant Group on 439 patients with PSC who underwent liver transplantation from November 1984 through December 2006; 353 had IBD at the time of transplantation. We compared IBD activity before and after liver transplantation. Two hundred eighteen patients who had an intact colon and had undergone pretransplant and post-transplant colonoscopies were characterized further. RESULTS Macroscopic colonic inflammation was more frequent after liver transplantation than before liver transplantation (153 vs 124 patients; P < .001). The degree of inflammation decreased in 37 patients (17%), was unchanged in 93 patients (43%), and increased in 88 patients (40%) (P < .001). The rate of relapse after transplantation was higher than that before transplantation (P < .001), and overall clinical IBD activity also increased (P < .001). Young age at diagnosis of IBD and dual treatment with tacrolimus and mycophenolate mofetil were significant risk factors for increased IBD activity after transplantation, whereas combination treatment with cyclosporin A and azathioprine had protective effects. CONCLUSIONS Immunosuppression affects IBD activity after liver transplantation in patients with PSC; a shift from present standard maintenance treatment of tacrolimus and mycophenolate mofetil to cyclosporin A and azathioprine should be considered for these patients.

Postprandial peristalsis in the human duodenum

MMC‐related retroperistalsis is a cyclical phenomenon in the duodenum linked to phase III. The aim of this study was to elucidate the direction of propagation of juxtapyloric duodenal pressure waves in the postprandial state in healthy humans and to compare with the contractions in the interdigestive phase II. Antroduodenal manometry was performed in 11 healthy subjects. Individual pressure waves propagating along a 6‐cm duodenal segment were analysed with respect to the proportions of antegrade and retrograde propagation in the four duodenal subsegments (D1–D2) to (D4–D5), each subsegment being 15 mm. A test meal was given 30 min after a phase III had passed and motility recording continued for 60 min after the meal. During both the first and the second 30‐min period of postprandial recording the proportion of retrograde pressure waves was larger just distal to the pylorus, (D1–D2), 40% (23–68) and 50% (23–68), respectively, compared to the distal part, (D4–D5), of the duodenal segment, 29% (12–30) and 10%(10–24), respectively (P < 0.05 and 0.01). In contrast, during late phase II of the interdigestive state antegrade pressure waves predominated in all four duodenal subsegments. We conclude that in the postprandial state a high proportion of the duodenal pressure waves (40–50%) is retrograde in the immediate juxtapyloric area while antegrade contractions predominate at a distance 5–6 cm distal to the pylorus. These manometric data together with recent observations of postprandial transpyloric liquid flow, indicate that retrograde duodenogastric propelling of contents may be an important determinant for the gastric emptying rate.

Liver transplantation in the Nordic countries – An intention to treat and post-transplant analysis from The Nordic Liver Transplant Registry 1982–2013

Abstract Aim and background. The Nordic Liver Transplant Registry (NLTR) accounts for all liver transplants performed in the Nordic countries since the start of the transplant program in 1982. Due to short waiting times, donor liver allocation has been made without considerations of the model of end-stage liver disease (MELD) score. We aimed to summarize key outcome measures and developments for the activity up to December 2013. Materials and methods. The registry is integrated with the operational waiting-list and liver allocation system of Scandiatransplant (www.scandiatransplant.org) and accounted at the end of 2013 for 6019 patients out of whom 5198 were transplanted. Data for recipient and donor characteristics and relevant end-points retransplantation and death are manually curated on an annual basis to allow for statistical analysis and the annual report. Results. Primary sclerosing cholangitis, acute hepatic failure, alcoholic liver disease, primary biliary cirrhosis and hepatocellular carcinoma are the five most frequent diagnoses (accounting for 15.3%, 10.8%, 10.6%, 9.3% and 9.0% of all transplants, respectively). Median waiting time for non-urgent liver transplantation during the last 10-year period was 39 days. Outcome has improved over time, and for patients transplanted during 2004–2013, overall one-, five- and 10-year survival rates were 91%, 80% and 71%, respectively. In an intention-to-treat analysis, corresponding numbers during the same time period were 87%, 75% and 66%, respectively. Conclusion. The liver transplant program in the Nordic countries provides comparable outcomes to programs with a MELD-based donor liver allocation system. Unique features comprise the diagnostic spectrum, waiting times and the availability of an integrated waiting list and transplant registry (NLTR).

Factors related to fatigue in patients with cirrhosis before and after liver transplantation.

BACKGROUND & AIMS We performed a prospective study to evaluate fatigue and identify potential determinants among patients with cirrhosis. We also studied the effects of liver transplantation on fatigue in these patients. METHODS A total of 108 patients with cirrhosis being evaluated before liver transplantation completed the fatigue impact scale (FIS), the hospital anxiety and depression (HAD) scale, and the short-form 36 (SF-36). Results were compared with controls from the general population. Fasting serum levels of insulin and glucose were measured in all patients. Levels of serum thyrotropin, free T(3) and T(4), cortisol, free testosterone, dehydroepiandrosterone sulfate, estradiol, interleukin-6, and tumor necrosis factor-α were measured in a subgroup of 80 patients. Transplant recipients were followed for 1 year. RESULTS Compared with controls, patients with cirrhosis had more pronounced fatigue, on the basis of higher FIS domain and total scores (P < .05), which were related to all SF-36 domains (r = -0.44 to -0.77, P < .001). All FIS scores improved significantly after liver transplantation, although physical fatigue levels remained higher than in controls (P < .05). In multivariate analysis, pretransplant FIS scores were only related to depression, anxiety, cirrhosis severity, and low serum levels of cortisol (P < .05 for all). Impaired renal function and anemia were independent predictors of physical fatigue (P < .05). CONCLUSIONS Fatigue is common among patients with cirrhosis and associated with impaired quality of life. Psychological distress, severity of cirrhosis, and low levels of cortisol determine general fatigue, whereas anemia and impaired renal function also contribute to physical fatigue. Physical fatigue remains of concern for patients who have received liver transplants for cirrhosis.

Diagnostic Performance of Five Assays for Anti-Hepatitis E Virus IgG and IgM in a Large Cohort Study

ABSTRACT Determination of anti-hepatitis E virus (anti-HEV) antibodies is still enigmatic. There is no gold standard, and results obtained with different assays often diverge. Herein, five assays were compared for detection of anti-HEV IgM and IgG. Serum samples from 500 Swedish blood donors and 316 patients, of whom 136 had suspected HEV infection, were analyzed. Concordant results for IgM and IgG with all assays were obtained only for 71% and 70% of patients with suspected hepatitis E, respectively. The range of sensitivity for anti-HEV detection was broad (42% to 96%); this was reflected in the detection limit, which varied up to 19-fold for IgM and 17-fold for IgG between assays. HEV RNA was analyzed in all patients and in those blood donors reactive for anti-HEV in any assay, and it was found in 26 individuals. Among all of the assays, both anti-HEV IgG and IgM were detected in 10 of those individuals. Twelve had only IgG and, in 7 of those 12, IgG was only detected with the two most sensitive assays. Three of the HEV-RNA-positive samples were negative for anti-HEV IgM and IgG in all assays. With the two most sensitive assays, anti-HEV IgG was identified in 16% of the blood donor samples and in 66% of patients with suspected HEV infection. Because several HEV-RNA-positive samples had only anti-HEV IgG without anti-HEV IgM or lacked anti-HEV antibodies, analysis for HEV RNA may be warranted as a complement in the laboratory diagnosis of ongoing HEV infection.

Differences in long‐term survival among liver transplant recipients and the general population: A population‐based nordic study

Dramatic improvement in first‐year outcomes post‐liver transplantation (LT) has shifted attention to long‐term survival, where efforts are now needed to achieve improvement. Understanding the causes of premature death is a prerequisite for improving long‐term outcome. Overall and cause‐specific mortality of 3,299 Nordic LT patients (1985‐2009) having survived 1 year post‐LT were divided by expected rates in the general population, adjusted for age, sex, calendar date, and country to yield standardized mortality ratios (SMRs). Data came from the Nordic Liver‐Transplant Registry and WHO mortality‐indicator database. Stagnant patient survival rates >1 year post‐LT were 21% lower at 10 years than expected survival for the general population. Overall SMR for death before age 75 (premature mortality) was 5.8 (95% confidence interval [CI] 5.4‐6.3), with improvement from 1985‐1999 to 2000‐2010 in hepatitis C (HCV) (SMR change 23.1‐9.2), hepatocellular carcinoma (HCC) (SMR 38.4‐18.8), and primary sclerosing cholangitis (SMR 11.0‐4.2), and deterioration in alcoholic liver disease (8.3‐24.0) and acute liver failure (ALF) (5.9‐7.6). SMRs for cancer and liver disease (recurrent or transplant‐unrelated disease) were elevated in all indications except primary biliary cirrhosis (PBC). Absolute mortality rates underestimated the elevated premature mortality from infections (SMR 22‐693) and kidney disease (SMR 13‐45) across all indications, and from suicide in HCV and ALF. SMR for cardiovascular disease was significant only in PBC and alcoholic liver disease, owing to high mortality in the general population. Transplant‐specific events caused 16% of deaths. Conclusion: standardized premature mortality provided an improved picture of long‐term post‐LT outcome, showing improvement over time in some indications, not revealed by overall absolute mortality rates. Causes with high premature mortality (infections, cancer, kidney and liver disease, and suicide) merit increased attention in clinical patient follow‐up and future research. (Hepatology 2015;61:668‐677)