How Good Are Controlled Attenuation Parameter Scores from Fibroscan to Assess Steatosis, NASH, and Fibrosis?

BACKGROUND AND AIMS: The objective of our study was to determine the concordance rates of steatosis staging by controlled attenuation parameter (CAP) scores from transient elastography (TE) in comparison with liver histology in patients with chronic liver disease and to determine the optimal CAP cutoffs to predict the severity of steatosis and identify those with nonalcoholic steatohepatitis (NASH). METHODS: Patients (n = 217) who had both CAP scores and liver biopsy within a period of 90 days were retrospectively studied. Histology was graded in a blinded fashion by a single pathologist; steatosis was graded on a scale from 0 to 3. Nonalcoholic fatty liver disease activity scores (NAS) scores were calculated for all patients. Optimal CAP cut-points were selected by maximum Youden's index. RESULTS: Area under receiver operating characteristic curve (AUROC) for CAP (using cutoff value ≥ 278 dB/m) in differentiating steatosis 1-3 from 0 was 0.82 (95% CI 0.75-0.89), and 0.79 (95% CI 0.70-0.88) in differentiating steatosis 0-1 from 2 to 3 using CAP cutoff value ≥ 301 dB/m. With CAP cutoff value ≥ 301 dB/m, CAP identified NAS 3 or above with AUROC of 0.82 (95% CI 0.74-0.89). The AUROC for TE in differentiating fibrosis (cutoff 11.9 kPa) 3-4 from 0 to 2 was 0.85 (95% CI 0.77-0.92), and 0.84 (95% CI 0.74-0.93) in differentiating (cutoff 14.4 kPa) 4 from 0 to 3. CONCLUSIONS: Transient elastography is a good modality to accurately diagnose steatosis and NASH and can also differentiate advanced liver fibrosis from early stages.

The outcome of liver transplantation in patients with hepatocellular carcinoma in the United States between 1988 and 2001: 5-year survival has improved significantly with time.

PURPOSE: We hypothesized that the outcome of liver transplantation in patients with hepatocellular carcinoma (HCC) has improved over the past decade because of the application of published criteria for patient selection. In this study, we compared the outcome of liver transplantation in patients with and without HCC at different time periods using the United Network for Organ Sharing data. PATIENTS AND METHODS: We excluded children, patients with multiple organ transplantation or retransplantation, and those with incomplete survival data. The study period was arbitrarily divided into three time intervals: 1987 to 1991, 1992 to 1996, and 1997 to 2001. RESULTS: During the study period, 985 patients with HCC (HCC group), and 33,339 without HCC underwent liver transplantation (control group). Kaplan-Meier patient and graft survivals were significantly lower for the HCC group compared with the control group. Cox regression analysis (after adjusting for other confounding variables) confirmed a lower patient survival in the HCC group (1-year survival, 77.0% v 86.7%; hazard ratio [HR], 1.7; 95% CI, 1.5 to 2.0; P <.0001) compared with the control group (5-year survival, 48.2% v 74.7%; HR, 2.2; 95% CI, 1.9 to 2.4; P <.0001); HCC was an independent predictor of survival. Kaplan-Meier analysis showed a significant improvement in 5-year patient survival with time in patients with HCC (1987 to 1991, 25.3%; 1992 to 1996, 46.6%; 1997 to 2001, 61.1%; P <.0001). During the same period, there was only minimal improvement in survival among the control group. CONCLUSION: Five-year survival of patients transplanted for HCC is excellent, with a steady improvement in survival over the past decade. It is possible that the published criteria for patient selection may have contributed to the better outcome.

The effect of insulin-dependent diabetes mellitus on outcome of liver transplantation.

BACKGROUND: It is not known whether there was a difference in outcome between insulin-dependent diabetes mellitus (type 1) and non-insulin dependent diabetes mellitus (type 2) after liver transplantation. METHODS: The outcome of liver transplantation in adult patients with type 1 (n=1,629) and type 2 (n=1,618) was compared to those without diabetes mellitus (DM) (nondiabetics, n=17,974) using the United Network for Organ Sharing database from 1994 to 2001, after excluding patients who had living donor or multiple organs or who underwent retransplantation, and those with incomplete data. RESULTS: Cryptogenic cirrhosis, hypertension, and coronary artery disease (CAD) were two to three times more common in types 1 and 2 compared with nondiabetics. Five-year patient and graft survivals by Kaplan-Meier analysis were significantly lower for type 1 (P <0.0001) compared with type 2 or nondiabetics; only patient survival was lower for type 2 ( P=0.04). Cox regression survival analysis, after adjusting for confounding variables, showed a lower 1-year, 2-year, and 5-year patient and graft survival in patients with type 1 compared with nondiabetics; however, type 2 was not an independent predictor of survival. Preexisting CAD, and not hypertension, was also an independent predictor of poor 5-year survival. Patients who had both DM and CAD had a lower survival compared with those with either DM or CAD. CONCLUSIONS: Type 1 and CAD are both independent predictors of poor outcome after liver transplantation. Liver transplant recipients with type 1 or CAD have approximately 40% lower 5-year survival compared with patients without DM or CAD.

Trends in post-liver transplant survival in patients with hepatitis C between 1991 and 2001 in the United States.

It has been suggested that the post-liver transplantation (LT) survival rate of patients with hepatitis C virus infection (HCV) has declined in recent years. To compare the outcome of LT in patients with HCV at various time intervals between 1991 and 2001, we used United Network for Organ Sharing data to compare the post-LT survival of adult patients (age >18 years) with HCV with those without HCV. Of the 37,101 patients who underwent LT during the study period, 28,193 patients (HCV 7,459 and 20,734 non-HCV) were eligible for the study. On the basis of the time of transplantation, patients were divided into 3 groups: 1991-1993 (period 1), 1994-1997 (period 2), and 1998-2001 (period 3). The patient and graft survival rates were adjusted for other known confounding variables that influenced outcomes. The 3-year patient survival rate was lower in HCV patients compared with non-HCV recipients (78.5% vs. 81.4%, hazard ratio 1.14, 95% confidence interval 1.05-1.23, P = 0.001). The graft (72.8%, 71.0%, and 69.8%) and patient (77.4%, 79.6%, and 78.5%) survival of HCV patients remained unchanged during study periods 1-3, respectively. However, the graft and patient survival rates of non-HCV recipients improved markedly during study periods 2 and 3 compared with period 1. The graft and patient survival has remained unchanged between 1991 and 2001 in HCV recipients, but during the same period, there was a great improvement in survival among non-HCV recipients.

Short-term postliver transplant survival after the introduction of MELD scores for organ allocation in the United States.

BACKGROUND: It has been suggested that the introduction of model for end-stage liver disease (MELD) for organ allocation may reduce overall graft and patient survival since elevated serum creatinine is an important predictor of poor outcome after liver transplantation. OBJECTIVE: In this study, we determined the outcomes of liver transplantation before (PreMELD group, 1998-February, 2002) and after (MELD group, March-December, 2002, n = 4642) the introduction of MELD score, and examined the impact of MELD scores on the outcome in the United States (US). PATIENTS & METHODS: After excluding patients for a variety of reasons (children, live-donor, fulminant liver failure, patients with hepatoma and others who received extra MELD points, multiple organ transplantation, re-transplantation, incomplete data), there were 3227 patients in the MELD group. These patients were compared with 14,593 patients in the preMELD group after applying similar exclusion criteria. The survival was compared using Kaplan-Meier survival analysis and Cox regression survival analysis. RESULTS: There was no difference in short-term (up to 10 months) graft and patient survival between MELD and preMELD groups. However, graft and patient survival was lower in patients with MELD score > or = 30 when compared with those with MELD score <30 after adjusting for the confounding variables. CONCLUSION: Introduction of MELD score for organ prioritization has not reduced the short-term survival of patients, but patients with MELD score of 30 or higher had a relatively poor outcome.

Graft and patient survival after adult live donor liver transplantation compared to a matched cohort who received a deceased donor transplantation.

Live donor liver transplantation (LDLT) has become increasingly common in the United States and around the world. In this study, we compared the outcome of 764 patients who received LDLT in the United States and compared the results with a matched population that received deceased donor transplantation (DDLT) using the United Network for Organ Sharing (UNOS) database. For each LDLT recipient (n = 764), two DDLT recipients (n = 1,470), matched for age, gender, race, diagnosis, and year of transplantation, were selected from the UNOS data after excluding multiple organ transplantation or retransplantation, children, and those with incomplete data. Despite our matching, recipients of LDLT had more stable liver disease, as shown by fewer patients with UNOS status 1 or 2A, in an intensive care unit, or on life support. Creatinine and cold ischemia time were also lower in the LDLT group. Primary graft nonfunction, hyperacute rejection rates, and patient survival by Kaplan-Meier analysis were similar in both groups (2-year survival was 79.0% in LDLT vs. 80.7% in case-controls; P = .5), but graft survival was significantly lower in LDLT (2-year graft survival was 64.4% vs. 73.3%; P < .001). Cox regression (after adjusting for confounding variables) analysis showed that LDLT recipients were 60% more likely to lose their graft compared to DDLT recipients (hazard ratio [HR] 1.6; confidence interval 1.1-2.5). Among hepatitis C virus (HCV) patients, LDLT recipients showed lower graft survival when compared to those who received DDLT. In conclusion, short-term patient survival in LDLT is similar to that in the DDLT group, but graft survival is significantly lower in LDLT recipients. LDLT is a reasonable option for patients who are unlikely to receive DDLT in a timely fashion.

Portal Hypertensive gastropathy.

Portal hypertensive gastropathy (PHG), a term used to describe the endoscopic appearance of gastric mucosa with a characteristic mosaic-like pattern with or without red spots, is a common finding in patients with portal hypertension. Current classification systems that describe the severity of PHG have many limitations, but it appears that simple grading systems have better inter- and intraobserver agreement. The wide variation in the reported prevalence of PHG is probably related to selection bias, absence of uniform criteria and classification, and more importantly, the differences in inter- and intraobserver variation. Pathogenesis of PHG is not clearly defined, but there is a very close relationship between portal hypertension and development of PHG. GAVE is a separate entity from PHG, but patients with severe PHG may have a GAVE-like appearance in the gastric antrum. Acute bleeding from PHG, seen usually in the presence of severe PHG, is often mild and self-limiting. Currently, the only treatment that could be recommended for prophylaxis of bleeding from PHG is nonselective B-blockers.

Long-term outcome of liver transplantation in patients with PSC: a comparative analysis with PBC.

BACKGROUND: Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are reported to have the best outcomes after liver transplantation. Based on excellent 5-yr survival results after transplantation, it has been suggested that PSC patients may benefit from "preemptive" transplantation to reduce the risk of cholangiocarcinoma. In this study, we compared 10-yr survival of patients with PSC and PBC using a large database after adjusting for other confounding risk factors. METHODS: The United Network for Organ Sharing (UNOS) database of all patients who had liver transplantation from 1987 to 2001 was used for analysis after excluding patients with multiple organ transplantation, children, and incomplete data. RESULTS: Patients with PSC (n = 3,309) were younger than those with PBC (n = 3,254). Retransplantation rate was high in PSC (12.4%vs 8.5%; p< 0.01), and PSC was an independent predictor for retransplantation on multivariate analysis. Cox regression analysis showed that PSC patients had significantly lower graft and patient survival compared to PBC patients after adjusting for other risk factors. Lower survival in PSC became apparent 7 yr after transplantation. CONCLUSIONS: Patients with PSC had a higher retransplantation rate and lower survival when compared to PBC. Based on this analysis, we do not recommend preemptive liver transplantation for patients with PSC.

A model to predict survival at one month, one year, and five years after liver transplantation based on pretransplant clinical characteristics.

Reliable models that could predict outcome of liver transplantation (LT) may guide physicians to advise their patients of immediate and late survival chances and may help them to optimize organ use. The objective of this study was to develop user-friendly models to predict short and long-term mortality after LT in adults based on pre-LT recipient characteristics. The United Network for Organ Sharing (UNOS) transplant registry (n = 38,876) from 1987 to 2001 was used to develop and validate the model. Two thirds of patients were randomized to develop the model (the modeling group), and the remaining third was randomized to cross-validate (the cross-validation group) it. Three separate models, using multivariate logistic regression analysis, were created and validated to predict survival at 1 month, 1 year, and 5 years. Using the total severity scores of patients in the modeling group, a predictive model then was created, and the predicted probability of death as a function of total score then was compared in the cross-validation group. The independent variables that were found to be very significant for 1 month and 1 year survival were age, body mass index (BMI), UNOS status 1, etiology, serum bilirubin (for 1 month and 1 year only), creatinine, and race (only for 5 years). The actual deaths in the cross-validation group followed very closely the predicted survival graph. The chi-squared goodness-of-fit test confirmed that the model could predict mortality reliably at 1 month, 1 year, and 5 years. We have developed and validated user-friendly models that could reliably predict short-term and long-term survival after LT.

Relationship of the model for end-stage liver disease (MELD) scale to hepatic encephalopathy, as defined by electroencephalography and neuropsychometric testing, and ascites.

OBJECTIVE: It has recently been suggested that the Model for End-Stage Liver Disease (MELD) is a better and a more objective predictor of mortality in patients with end-stage liver disease. The aim of our study was to determine the relationship of the MELD score to hepatic encephalopathy (HE), as determined by electroencephalography (EEG) and clinical and neuropsychometric examination, and ascites. METHODS: A total of 66 patients underwent EEG, a neuropsychometric screening by Mini-Mental State Examination, Trails Making Tests, Rey-Osterreith Complex Figure, and Hopkins Verbal Learning Tests, and a clinical assessment for HE. The MELD score was calculated as previously described by using serum creatinine, bilirubin, and international normalized ratio. Subclinical HE was diagnosed if clinical examination did not detect HE but neuropsychometric tests and EEG were abnormal. RESULTS: Sixteen patients had no HE, 28 had subclinical HE, and 22 had clinical HE. Age, sex, race, and cause of liver disease were similar in all three groups. Child-Turcotte-Pugh score was significantly higher in patients with clinical HE compared with the other two groups. There was only a modest correlation (r = 0.5) between Child-Turcotte-Pugh and the MELD scores. The distribution and mean MELD scores were similar in patients with or without HE as determined by clinical or neuropsychometric examination and EEG. Approximately 90% of patients with clinical HE or abnormal EEG and neuropsychometric tests had a MELD score less than 25. Similarly, the MELD score was not affected by the severity of ascites. CONCLUSION: The MELD score does not correlate well with severity of HE or ascites. Patients with HE and ascites might not receive liver transplantation in a timely manner if MELD scores were to be used exclusively for organ allocation.

Retransplantation of liver: primary graft nonfunction and hepatitis C virus are associated with worse outcome.

It is not known whether the outcome of liver retransplantation (re-LT) is dependent on the indication for re-LT or cause of liver disease. In this study, our aim is to compare the outcome of re-LT in adults with that of primary liver transplantation (PLT) and determine whether the outcome of re-LT is dependent on its indication. United Network for Organ Sharing data from 1988 to 2001 were used for the study. Of 34,267 patients who met our inclusion criteria, 761 patients underwent re-LT for primary graft nonfunction (PGNF; group 1), 3,428 patients underwent re-LT for other reasons (group 2), and 30,078 patients underwent PLT (group 3). There was a greater incidence of PGNF (9.4% v 4.0%; P <.001) and regrafting (23.1% v 7.4%; P <.001) in the re-LT groups compared with the PLT group. Kaplan-Meier analysis and Cox regression analysis, after adjusting for confounding risk factors, showed significantly lower short- and long-term patient and graft survival in the re-LT groups compared with the PLT group. Kaplan-Meier survival showed lower patient and graft survival in group 1 compared with group 2. However, only graft, not patient, survival was lower in group 1 by Cox regression analysis when adjusted for other risk factors. Patients with hepatitis C virus (HCV) infection who underwent re-LT had lower patient and graft survival compared with those without HCV infection, and HCV was an independent predictor of mortality after re-LT. Re-LT was associated with a greater rate of complications and lower patient and graft survival compared with PLT. Re-LT for PGNF and HCV infection was associated with lower patient and graft survival compared with re-LT for other causes.

The effect of donor body mass index on primary graft nonfunction, retransplantation rate, and early graft and patient survival after liver transplantation.

Previous studies have suggested that moderate donor liver steatosis is associated with an increased incidence of primary graft nonfunction (PGNF), delayed graft function, early graft loss, and retransplantation rates. The objective of our study was to determine the effect of donor body mass index (dBMI), after adjusting for other known confounding variables, on PGNF, early graft failure, retransplantation rate, and patient survival. The United Network for Organ Sharing (UNOS) database (1987 to 2001) of 22,303 adult patients, excluding patients of pediatric age (age less than 18 years) and those with multiple organ transplantations, living donors, and retransplantations, was used for this study. Based on the BMI (kg/m(2)) of the organ donor, transplant recipients were divided into four groups as follows: BMI < 25 (group 1, n = 11,660), 25 to 29.9 (group 2, n = 7418), 30 to 34.9 (group 3, n = 2301), and > or = 35 (group 4, n = 924). Information on donor liver histology was available for 1603 patients who underwent transplantation after 1999, and this subgroup was divided into three groups based on severity of steatosis (group A, < 20%; group B, 20% to 35%; group C, > 35%). Incidence of PGNF and early retransplantation rates were similar in groups 1 to 4 and in groups A, B, and C. Logistic regression analysis showed that dBMI or severity of steatosis was not a predictor of PGNF and early retransplantation. Cox regression analysis, after adjusting for confounding variables, showed similar patient and graft survival at 1 month and 1, 2, and 5 years for groups 1 to 4, and at 1 month and 6 months for groups A, B, and C. Severe donor obesity or moderate steatosis did not influence short-term and long-term outcome of liver transplantation.

Prevalence of transaminase abnormalities in asymptomatic, healthy subjects participating in an executive health-screening program.

The objective of this study was to characterize the prevalence of asymptomatic liver transminase (LT) abnormalities in a healthy, low-risk adult population and identify associated risk factors. We reviewed 2340 completed medical records of participants in our Executive Health Program, which provided screening medical evaluations for executives. LT (alanine aminotransferase and aspartate aminotransferase) were considered abnormal if they above normal range for our laboratory. Subjects were excluded if they had a history of viral hepatitis, nonviral liver disease, or an identifiable cause of LT elevation. Of the 2340 subjects 2294 met inclusion criteria and all had AST recorded, but only 1309 had ALT recorded. In all, 341 subjects (14.9%) were found to have abnormal LT and in those who had less than 3 drinks per day, 13.9% had elevated LT and 3.6% had LT twice the upper limit of normal. Of the 1309 subjects in whom both AST and ALT were measured, 20.8% had abnormal LT and 6.3% had LT twice the upper limit of normal. On univariate analysis age < 60 (P = 0.005), male sex (P < 0.0001), body mass index > or = 30 (P < 0.0001), cholesterol > or = 200 mg/dl (P = 0.018), and triglycerides > or = 200 mg/dl (P < 0.0001) were associated with abnormal LT; all these variables except cholesterol were significant by logistic regression analysis. The odds ratio of abnormal LT and LT 2 times normal was 1.79 (CI 1.20-2.68) and 2.50 (CI 1.04-6), respectively, in subjects with one risk factor, and 2.80 (CI 1.07-7.34) and 4.73 (CI 0.91-24.5), respectively, in subjects with four risk factors. In conclusion, there is a high prevalence of LT abnormalities in this healthy population. Subjects with multiple risk factors should be considered for screening.

Control of alkaline reflux esophagitis after total gastrectomy by a percutaneous jejunostomy tube.

Postoperative alkaline reflux esophagitis is a potentially devastating complication after total gastrectomy. The advent of the Roux-en-Y reconstruction has significantly decreased the incidence of this complication. However, when reflux esophagitis occurs, it is often refractory to medical treatment. Even though surgical revision of the Roux-en-Y anastomosis is the management option of choice, affected patients (especially those with advanced metastatic cancers) are often poor surgical candidates. We describe a novel treatment of refractory alkaline reflux esophagitis in a patient after radical total gastrectomy with Roux-en-Y reconstruction for advanced gastric carcinoma. Radiologic placement of a percutaneous jejunostomy tube into the proximal jejunal limb resulted in significant symptomatic relief by external diversion of the pancreaticobiliary drainage, and the procedure was associated with minimal discomfort. Nonsurgical pancreaticobiliary diversion should be considered in those patients with refractory alkaline reflux esophagitis that occurs after total gastrectomy.

Socioeconomic status does not affect the outcome of liver transplantation.

The outcome of liver transplantation is dependent on many factors. It was suggested that racial disparities in outcome may be related to differences in socioeconomic status (SES). In this retrospective study, we analyzed the effect of SES on graft and patient survival. Two hundred seventy-six adult patients who underwent liver transplantation at our institution from July 1988 to June 2001 were included in the analysis. Educational and occupation statuses were coded using established criteria (Hollingshead Index of Social Status [HI]). SES then was calculated using the HI formula: SES = education level x 3 + occupation x 5, and categorized into four groups: group 1, score less than 29 (n = 71); group 2, score of 29 to 42 (n = 82); group 3, score of 42 to 53 (n = 69); and group 4, score greater than 53 (n = 54). Kaplan-Meier analysis was used for graft and patient survival, and Cox regression analysis was used to determine the effect of confounding factors. Demographics of all four groups were similar. One-, 2-, and 5-year graft and patient survival did not differ significantly across groups by Kaplan-Meier and Cox regression survival analysis. In conclusion, SES did not predict graft and patient survival after liver transplantation.

Accuracy and reliability of the endoscopic classification of portal hypertensive gastropathy.

BACKGROUND: There is no consensus regarding the endoscopic classification of the severity of portal hypertensive gastropathy. This study compared the accuracy and reproducibility of the 2-category classification system (2-CCS) with the 3-category classification system (3-CCS). METHODS: Ninety-eight endoscopic pictures of portal hypertensive gastropathy and 22 of nonspecific gastritis were selected. Eight duplicate sets were generated, each in a different random order. These were shown to 6 experienced endoscopists during 2 sessions 1 week apart with 4 slide sets at each session. Each picture was scored by using either the 2-CCS or 3-CCS. Kappa statistics and percent agreement were used to estimate the reproducibility and agreement. RESULTS: The mean percentage agreement among the 4 separate readings for each observer was significantly lower for the 3-CCS compared with the 2-CCS (mean [standard deviation] = 33.5% [8.9%] vs. 64.9% [9.1%]; p = 0.0001). The mean (SD) interobserver kappa values were 0.44 (0.03) for the 3-CCS and 0.52 (0.04) for the 2-CCS (p = 0.02), and the respective intraobserver kappa values were 0.43 (0.1) and 0.63 (0.06) (p = 0.002). CONCLUSIONS: Even though both the 2-CCS and 3-CCS have substantial limitations with regard to specificity and reliability, there were better agreement and reproducibility with the simpler classification system for portal hypertensive gastropathy.