A recent mandate emphasizes severity of liver disease to determine priorities in allocating organs for liver transplantation and necessitates a disease severity index based on generalizable, ...verifiable, and easily obtained variables. The aim of the study was to examine the generalizability of a model previously created to estimate survival of patients undergoing the transjugular intrahepatic portosystemic shunt (TIPS) procedure in patient groups with a broader range of disease severity and etiology. The Model for End-Stage Liver Disease (MELD) consists of serum bilirubin and creatinine levels, International Normalized Ratio (INR) for prothrombin time, and etiology of liver disease. The model's validity was tested in 4 independent data sets, including (1) patients hospitalized for hepatic decompensation (referred to as “hospitalized” patients), (2) ambulatory patients with noncholestatic cirrhosis, (3) patients with primary biliary cirrhosis (PBC), and (4) unselected patients from the 1980s with cirrhosis (referred to as “historical” patients). In these patients, the model's ability to classify patients according to their risk of death was examined using the concordance (c)-statistic. The MELD scale performed well in predicting death within 3 months with a c-statistic of (1) 0.87 for hospitalized patients, (2) 0.80 for noncholestatic ambulatory patients, (3) 0.87 for PBC patients, and (4) 0.78 for historical cirrhotic patients. Individual complications of portal hypertension had minimal impact on the model's prediction (range of improvement in c-statistic: <.01 for spontaneous bacterial peritonitis and variceal hemorrhage to ascites: 0.01-0.03). The MELD scale is a reliable measure of mortality risk in patients with end-stage liver disease and suitable for use as a disease severity index to determine organ allocation priorities. (HEPATOLOGY 2001;33:464-470.)
BACKGROUND & AIMS: Long-term ursodeoxycholic acid (UDCA) therapy slows the progression of primary biliary cirrhosis. This study examined the effect of UDCA therapy on survival free of liver ...transplantation in a large group of patients.
METHODS: Data from three clinical trials were combined in which patients with primary biliary cirrhosis were randomly assigned to receive UDCA (n = 273) or placebo (n = 275). After 2 years, patients from French and Canadian studies received UDCA for up to 2 years. Patients from the American study remained on their assigned treatment for up to 4 years.
RESULTS: Survival free of liver transplantation was significantly improved in the patients treated with UDCA compared with the patients originally assigned to placebo (P < 0.001; relative risk, 1.9; 95% confidence interval, 1.3-2.8). Subgroup analyses showed that survival free of liver transplantation was significantly improved in medium- and high-risk groups (serum bilirubin level, 1.4 to 3.5 or > 3.5 mg/dL; P < 0.0001 and P < 0.03, respectively) and histological stage IV subgroup (P < 0.01).
CONCLUSIONS: Long-term UDCA therapy improves survival free of liver transplantation in patients with moderate or severe disease. An effect in patients with mild disease is probably not found because they do not progress to end-stage disease in 4 years. (Gastroenterology 1997 Sep;113(3):884-90)
The epidemiology of primary sclerosing cholangitis (PSC) in the United States is unknown. We report the incidence, clinical spectrum, and outcomes of PSC in Olmsted County, Minnesota.
Using the ...Rochester Epidemiology Project, a medical records linkage system in Olmsted County, Minnesota, we identified county residents with PSC, and the diagnosis was confirmed according to clinical, biochemical, radiographic, and histologic criteria.
Twenty-two patients met diagnostic criteria for PSC in 1976–2000. The age-adjusted (to 2000 U.S. whites) incidence of PSC in men was 1.25 per 100,000 person-years (95% CI, 0.70 to 2.06) compared with 0.54 per 100,000 person-years (95% CI, 0.22 to 1.12) in women. The prevalence of PSC in 2000 was 20.9 per 100,000 men (95% CI, 9.5 to 32.4) and only 6.3 per 100,000 women (95% CI, 0.1 to 12.5). Seventy-three percent of cases had inflammatory bowel disease, the majority with ulcerative colitis. Survival among PSC patients was significantly less than expected for the Minnesota white population of similar age and gender (
P < 0.001).
These data represent the first population-based estimates of the incidence and prevalence of PSC in the United States. The incidence and prevalence of PSC were approximately one third of those previously described for primary biliary cirrhosis in the same population. Our data suggest that the prevalence of PSC in the United States, with its attendant medical burdens, is significantly greater than previously estimated.
Important innovations, such as hepatitis B immune globulin (HBIG) and lamivudine, have been introduced to the care of patients undergoing liver transplantation (OLT) for viral hepatitis B (HBV) (over ...the last 15 years). We analyzed survival of OLT recipients with HBV in the United States to examine the effect of these innovations. A retrospective analysis was conducted based on data collected prospectively by the United Network for Organ Sharing in all adult (older than 18) patients undergoing primary OLT in the United States between 1987 and 2002. OLT recipients with HBV were identified by the principal diagnosis of acute or chronic HBV or positive results on HBV markers. Patients were divided into Era 1 (1987‐1991), Era 2 (1992‐1996), and Era 3 (1997‐2002). Era 1 consisted of 6,708 patients (675 with HBV), Era 2 consisted of 13,995 patients (1,005 with HBV), and Era 3 consisted of 20,730 patients (1,723 with HBV). More recent patients were older and had less advanced liver disease and shorter ischemic time. The survival of patients with HBV was significantly better for Era 2 than for Era 1 (P < .01) and for Era 3 than for Era 2 (P < .01). There was no difference in survival between patients with HBV and all other diagnoses for Era 3 (P = .14). In the multivariable analysis, the effect of these eras persisted when other variables such as recipient and donor age, warm ischemic time, pre‐OLT disease severity, and hepatocellular carcinoma (HCC) were taken into account. Unlike previous reports, fulminant disease and Asian race had no effect on patient survival. In conclusion, these data underscore the effectiveness of therapeutic innovations that have occurred in the past two decades and indicate timely and widespread adoption of these measures by transplant centers nationwide. (Liver Transpl 2004;10:968–974.)
The usual method of estimating survival probabilities, namely the Kaplan-Meier method, is suboptimal in the analysis of deaths on the transplant waiting list. Death, transplantation, and withdrawal ...from list must all be considered. In this analysis, we applied the competing risk analysis method, which allows evaluating these end points individually and simultaneously, to compare the risk of waiting list death across era, blood types, liver disease diagnosis, and severity (Model for End-stage Liver Disease; MELD). Of 861 patients registered on the waiting list at Mayo Clinic Rochester between 1990 and 1999, 657 (76%) patients underwent transplantation, 82 (10%) died while waiting, 41 (5%) withdrew from the list, and 81 (9%) patients were still waiting as of February 2002. The risk of death at 3 years was 10% by the competing risk analysis. During the study period, the median time to transplantation increased from 45 to 517 days. In univariate analyses, there was no significant difference in the risk of death by era of listing (P = .25) or blood type (P = .31), whereas the risk of death was significantly higher in patients with alcohol-induced liver disease and those with higher MELD score (P < .01). A multivariable analysis showed that after adjusting for MELD, blood type, and diagnosis, patients listed in the latter era had higher mortality. In conclusion, the competing risk analysis method is useful in estimating the risk of death among patients awaiting liver transplantation.
To describe a natural history model for primary sclerosing cholangitis (PSC) that is based on routine clinical findings and test results and eliminates the need for liver biopsy.
Using the Cox ...proportional hazards analysis, we created a survival model based on 405 patients with PSC from 5 clinical centers. Independent validation of the model was undertaken by applying it to 124 patients who were not included in the model creation.
Based on the multivariate analysis of 405 patients, a risk score was defined by the following formula: R = 0.03 (age y) + 0.54 loge (bilirubin mg/dL) + 0.54 loge (aspartate aminotransferase U/L) + 1.24 (variceal bleeding 0/1) - 0.84 (albumin g/dL). The risk score was used to obtain survival estimates up to 4 years of follow-up. Application of this model to an independent group of 124 patients showed good correlation between estimated and actual survival.
A new model to estimate patient survival in PSC includes more reproducible variables (age, bilirubin, albumin, aspartate aminotransferase, and history of variceal bleeding), has accuracy comparable to previous models, and obviates the need for a liver biopsy.
Background/Aims
: To identify indicators of osteoporosis and to determine the rate of bone loss in patients with primary biliary cirrhosis (PBC).
Methods
: Bone mineral density of the lumbar spine ...and hip was measured at annual intervals over 7 years of follow-up in 176 patients with PBC.
Results
: Osteoporosis (
t
-score below −2.5) was found in 20% of patients and occurred 32.1 times more frequently in patients with PBC than expected. Patients with histologic stage 3 or 4 disease had a 5.4-fold increased risk of osteoporosis compared to patients with stage 1 or 2. Age, body mass index, advanced stage (3 or 4), and history of fractures were the only independent indicators of osteoporosis. After 3 years of follow up, the rate of bone loss in patients with stage 1 or 2 increased and equaled that seen in patients with stage 3 or 4. Serum bilirubin level was the only variable independently associated with the rate of bone loss over time.
Conclusions
: Severity of the liver disease contributes significantly to the severity of bone disease in PBC. PBC patients who are older, thinner and have more advanced liver disease may have the most benefit from bone density measurements and treatment for their osteoporosis.
We examined whether consideration of repeated model for end‐stage liver disease (MELD) measurements for patients listed for liver transplantation improves predictive value beyond current MELD alone. ...Clinical data were extracted for all adult primary liver transplantation candidates from our institution who were listed with the United Network for Organ Sharing (UNOS) between 1990 and 1999. Serum creatinine, bilirubin, and international normalized ratio (INR) were obtained from an institutional laboratory database. Cox models were constructed using current MELD, change in MELD (Delta), and number of MELD scores to predict survival on the waiting list. Eight hundred and sixty‐one patients met inclusion criteria, 639 underwent transplantation, and 80 died while waiting. A one‐unit increment in current MELD imparted significant hazard ratios ranging from 1.12 to 1.19 in all models. Delta MELD was predictive of mortality univariately, but less predictive when current MELD was included, and not predictive when considered with both current and number of MELD scores. Overall, current MELD is the single most important determinant of mortality risk on the waiting list. Delta MELD is predictive of death only within 4 d of the event; however, part of this correlates with the dying process itself, thus limiting Delta MELD's utility in survival prediction models.
Background and Aims The pathogenesis of primary biliary cirrhosis (PBC) is unknown. The role of cytokines such as tumor necrosis factor‐α (TNF‐α) and transforming growth factor‐β (ΤGF‐β), and the ...effect of ursodeoxycholic acid (UDCA) in modifying the cytokine environment in patients with PBC has remained largely unstudied. Our aims were to determine: (i) the relationship between serum levels of TNF‐α and TGF‐β and the severity of PBC; and (ii) the effects of UDCA therapy on TNF‐α and TGF‐β levels in patients with PBC.
Methods We studied 90 patients who had been treated with UDCA (53 patients) or placebo (37 patients) for 2 years as part of a randomized, double‐blind, controlled trial. Patients were divided into histological stage I/II or stage III/IV disease. Serum TNF‐α and TGF‐β levels were quantified by enzyme‐linked immunoabsorbent assay.
Results Baseline levels of TNF‐α were significantly greater in patients with stage III/IV compared to stage I/II disease. After 2 years of treatment with UDCA, patients showed a significantly greater decrease in TNF‐α levels and progression risk score compared to placebo‐treated patients. TNF‐α and TGF‐β levels were significantly reduced compared to baseline levels in the UDCA‐treated group after 2 years, while there was no significant change in the levels of placebo‐treated patients.
Conclusions Serum TNF‐α and TGF‐β levels may reflect severity of disease in patients with PBC. The beneficial effects of UDCA therapy may be explained by lowering serum levels of these two cytokines.
Ursodeoxycholic acid (UDCA) is a safe and effective medical therapy for most patients with primary biliary cirrhosis (PBC). However, some patients show an incomplete response to UDCA therapy. ...Treatment with corticosteroids may be of benefit although at the expense of systemic side effects. Budesonide, a corticosteroid with an extensive first‐pass hepatic metabolism appeared promising for the treatment of PBC. The aim of this study was to evaluate the safety and estimate the efficacy of budesonide in patients with PBC, who have shown a suboptimal response to UDCA. Twenty‐two patients with PBC, 16 women, median age of 50 who had been on UDCA (13‐15 mg/kg/d) for a mean of 46 months (range 6‐108 months) and had shown a persistent elevation of alkaline phosphatase activity at least 2 times the upper limit of normal were enrolled. Oral budesonide, 9 mg daily was administered for 1 year and patients continued on the same dosage of UDCA. There was a significant, but transitory improvement in serum levels of total bilirubin (P
= .001) and a significant, but marginal improvement in serum alkaline phsophatase (P = .001) with combination therapy. The Mayo risk score increased significantly (P = .02) and there was a significant loss of bone mass (P < .001) of the lumbar spine. Budesonide‐induced hyperglycemia and cosmetic adverse effects were noted in 2 patients. In conclusion, oral budesonide appears to add minimal, if any, additional benefit to UDCA, and it is associated with a significant worsening of osteoporosis in patients with PBC.
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