The Impact of Metabolic Health and Obesity on Liver Transplant Candidates and Recipients.

Poor metabolic health and obesity have significant impacts on the outcomes of patients suffering from chronic liver disease, particularly those with metabolic dysfunction-associated steatotic liver disease. Patients with such comorbidities who require liver transplant evaluation for advancing liver disease or liver failure require special consideration due to increased risk of cardiovascular disease, renal dysfunction, sarcopenic obesity, and cancer. Those who have had a history of prior bariatric surgery pose specific anatomical constraints and may also be at increased risk of alcohol use disorder. Pre-operative risk assessment as well as strict control of metabolic risk factors are essential to reduce intra-operative and post-liver transplant complications. As immunosuppressive therapy exacerbates metabolic dysfunction and risk for cancer, post-liver transplant care must focus on balancing the need to prevent rejection and the impact of progressive metabolic dysfunction in this unique, but growing, patient population.

Model for End-Stage Liver Disease and Sodium Velocity Predicts Overall Survival in Nonmetastatic Hepatocellular Carcinoma Patients.

Background & Aims: The significance of short-term changes in model for end-stage liver disease and Sodium (MELD-Na) following hepatocellular carcinoma (HCC) diagnosis is unknown. In this report, we explore the value of the rate of short-term changes in MELD-Na as an independent predictor of mortality in patients with nonmetastatic HCC. Methods: We reviewed a cohort of patients diagnosed with nonmetastatic HCC at our institution between 2001 and 2011. We evaluated potential predictors of overall survival, including baseline MELD-Na and the change in MELD-Na over 90 days. We explored survival times of cohorts grouped by baseline MELD-Na and the change in MELD-Na. Results: 182 patients met eligibility criteria. With a median follow-up of 21 months for surviving patients, 110 deaths were observed (60%). Median MELD-Na at the time of diagnosis was 9.7 (IQR 7.5 to 13.9). The median changes in percentage of MELD-Na over 90 days were an increase of 9% (IQR -4% to 55%). Multivariable Cox proportional hazards modeling demonstrated that both baseline MELD-Na (HR=1.07 per unit increase, 95% CI 1.03 to 1.11, p<0.001) and changes in MELD-Na exceeding 40% (HR=3.69, 95% CI 2.39 to 5.69, p<0.001) were independently associated with increased mortality risk. Median survival among patients whose changes in MELD-Na were greater than 40% was 4.5 months, and median survival among the 131 other patients was 25.8 months (p<0.001). Conclusions: We identified a subset of HCC patients who have extremely poor prognosis by incorporating the rate of short-term change in MELD-Na to baseline MELD-Na score.

Survival analysis of Hispanics in a cohort of patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) appears to have worse prognosis among Hispanics and other ethnic minorities in the United States. We investigated the overall survival (OS) of Hispanics with HCC and compared it with non-Hispanic (NH) whites and NH blacks. METHODS: Patients diagnosed and treated for HCC at an urban medical center between 2000 and 2011 were identified from the institutional cancer registry. A Cox proportional-hazard model was used to assess survival differences between Hispanics, NH whites, and NH blacks after adjusting for clinically and statistically significant variables. RESULTS: A total of 681 patients were identified, 24 of whom were excluded due to inability to confirm the diagnosis of HCC based on radiologic criteria and 24 due to unavailable ethnicity data. The remaining 633 patients were used for analysis. Of this final cohort, 49% (n = 309) were Hispanic, 23% (n = 144) were NH white, and 28% (n = 180) were NH black. The median OS among Hispanics was 16.3 months and was similar to that of NH whites (14.0 months) and NH blacks (17.3 months) (P = 0.76). Multivariate analysis revealed a hazard ratio for death for Hispanics of 0.78 (95% confidence interval 0.58-1.07, P = .12) when compared with NH whites and a hazard ratio for death of 0.89 (95% confidence interval 0.68-1.19, P = 0.46) when compared with NH blacks. CONCLUSIONS: In contrast to previous reports, Hispanics with HCC from this cohort experienced similar OS when compared with NH whites and NH blacks.

Prevalence and natural history of alcoholic liver disease.

Alcoholic liver disease is a major cause of morbidity and mortality among people who drink excessive amounts of alcohol. There is a spectrum of liver injury that ranges from steatosis to varying stages of hepatic fibrosis and cirrhosis, with subsequent risk for hepatocellular carcinoma. Steatohepatitis can occur at any stage of disease.

Hepatic and cardiac iron overload among patients with end-stage liver disease referred for liver transplantation.

BACKGROUND: Iron overload is associated with fatal cardiovascular events following liver transplantation. Myocardial iron deposits were observed post-mortem in patients who died of cardiac events after transplantation at our institution. This observation prompted testing to exclude cardiac iron in subsequent transplant candidates. AIMS: To assess the results of testing for iron overload in liver transplant candidates at our institution. METHODS: Ferritin, TIBC, and serum iron were measured in cirrhotics referred for transplantation. Patients with transferrin saturation ≥50% and ferritin ≥250 ng/mL underwent liver biopsy graded for iron. Patients with 3-4+ hepatic iron deposits underwent HFE mutation analysis and endomyocardial biopsy with iron staining. RESULTS: Eight hundred and fifty-six patients were evaluated for liver transplantation between January 1997 and March 2005. Two hundred and eighty-seven patients (34%) had transferrin saturation ≥50% and ferritin ≥250 ng/mL. Patients with markers of iron overload had more advanced liver disease than those with normal iron indices. One hundred and fifty-three patients underwent liver biopsy. Twenty-six patients (17%) had 3-4+ hepatic iron staining. One patient was a C282Y heterozygote. Endomyocardial biopsy was performed in 14 patients of whom nine had cardiac iron deposition. CONCLUSIONS: Non-HFE-related cardiac iron overload can occur in advanced liver disease We therefore recommend screening for cardiac iron prior to liver transplantation.

Uveitis in patients with autoimmune hepatitis.

PURPOSE: To report seven cases of uveitis occurring in patients with autoimmune hepatitis (AIH), raising the possibility that uveitis may be an extrahepatic feature of AIH. DESIGN: Multicenter, retrospective, observational case series of patients with AIH and uveitis. METHODS: One index case was identified at Oregon Health & Science University. Further cases were identified by a web-based survey of members of the American Uveitis Society, the International Uveitis Study Group, the Proctor Foundation mailing list server, and the First SUN International Workshop. Respondents were asked to provide clinical information about uveitis phenotype, AIH features, and treatment. RESULTS: Clinical information was obtained for seven individuals (four females and three males; age range, seven to 67 years) who suffered from AIH and uveitis. Average duration of follow-up was 5.5 years. All patients had chronic, persistent bilateral uveitis that was anterior (n = 3), intermediate (n = 1), or pan (n = 3) in location. Every patient had complications arising from his or her uveitis, including cataract (n = 5), glaucoma (n = 3), cystoid macular edema (n = 3), and posterior synechiae (n = 3). Final visual acuities ranged from 20/16 to hand movements. To treat the uveitis and/or AIH, the majority of patients required oral prednisone and all seven patients were treated with systemic immunosuppression. CONCLUSION: Despite the small size of this study, our findings suggest an association between AIH and uveitis. The uveitis is chronic, bilateral, and associated with sight-threatening complications, necessitating systemic immunosuppression in some individuals.

Liver transplantation for hepatocellular carcinoma: a survey of practices.

GOAL: To survey physician practices regarding liver transplantation for patients with hepatocellular carcinoma (HCC). BACKGROUND: Many issues surrounding liver transplantation for HCC are controversial and physician practices have not been well characterized. METHODS: Transplant physicians and surgeons were electronically surveyed regarding surveillance, diagnosis, selection criteria for deceased and living donor transplantation, and use of adjunctive therapy for HCC. RESULTS: Eighty-nine of 174 (51%) physicians completed the survey (39 hepatologists, 41 transplant surgeons, and 9 others). Most respondents were from large US transplant centers. All reported screening for HCC during transplant evaluation, and 98% surveyed patients awaiting transplant. Sixty percent of respondents would biopsy lesions under selective conditions, whereas 32% never biopsy lesions, and 8% biopsy all lesions. Eighty two percent of respondents claimed to adhere to the Milan criteria (single lesion

Hepatitis C infection increases the risk of new-onset diabetes after transplantation in liver allograft recipients.

BACKGROUND: Recent evidence suggests that new-onset diabetes after transplant (NODAT) adversely affects orthotopic liver transplant (OLTX) patient and graft survival. The objective of this study is to evaluate the effect of hepatitis C infection on the natural history of NODAT. METHODS: A retrospective review of 492 OLTX recipients at a single center was conducted from January 1993 to January 2003. Patients were followed for a minimum of 12 months (range 12 months-10 years). The study population consisted of 444 OLTX recipients who were either HCV positive (n = 206) or HCV negative (n = 238). NODAT was defined by the need for antidiabetic medication for at least 7 days starting anytime after OLTX. Statistical analysis was performed by using the Student t test, Kaplan-Meier survival, and chi-square tests. RESULTS: The overall incidence of NODAT was 33% (146/444). There was a significant difference in the development of NODAT between the HCV-positive group (82/206, 40%) and the HCV-negative group (64/238, 27%) (P < .001). Other independent risk factors for development of NODAT were male gender and age >50 years. CONCLUSION: Hepatitis C infection contributes to the development of diabetes mellitus in OLTX recipients. The mechanisms behind HCV infection and associated NODAT in HCV-positive OLTX recipients warrant further investigation.

Treatment of Hepatocellular Carcinoma.

The incidence of hepatocellular carcinoma (HCC) is increasing in the United States. Several modalities are available for the treatment of HCC, and decisions regarding the optimal choice of therapy are based on tumor burden and severity of liver disease. Classification systems are helpful for prognostic purposes and to guide in the choice of therapy. Surgical resection is a mainstay of therapy for patients with solitary small tumors and preserved liver function (noncirrhotic or Child-Pugh class A cirrhotic patients without portal hypertension). Unfortunately, a minority of patients is eligible for resection, and postoperative recurrence or de novo HCC is common. Liver transplantation offers the best chance of curing HCC in cirrhotic patients. Patients with a solitary tumor less than 5 cm or no more than three tumors each 3 cm or less have a survival rate of 70% with less than 20% recurrence at 5 years. Access to liver transplantation is limited by organ availability, and tumor progression during the waiting period can lead to ineligibility. Ethanol injection and radiofrequency ablation are effective modalities to ablate small tumors (generally <5 cm) in patients who are not candidates for resection or liver transplantation. These modalities can also be used to treat HCC prior to liver transplantation. Transarterial chemoembolization is used to treat patients with multifocal or large HCC who are ineligible for other therapies. Chemotherapeutic agents are infused into the tumor via the hepatic artery along with embolic material in order to induce tumor necrosis. This technique should be used in selective patients with relatively preserved liver function, absence of portal vein thrombosis, or encephalopathy. Limited data exist to support the use of this modality as a primary treatment option for small HCC. Chemotherapeutic or hormonal therapies have a limited role in the management of patients with HCC. Despite mixed outcomes, we routinely use the somatostatin analog octreotide in advanced, multifocal HCC. Emerging therapies should focus on treatment of small tumors and targeted pharmacologic therapy for advanced disease.

High prevalence of potentially hepatotoxic herbal supplement use in patients with fulminant hepatic failure.

HYPOTHESIS: The use of potentially hepatotoxic herbal and dietary supplements is highly prevalent in the fulminant hepatic failure (FHF) patient population at our institution, and this subgroup of patients has a worse prognosis. DESIGN: Retrospective case series. Settings An adult tertiary care university hospital and a Veterans Affairs hospital in Oregon. PATIENTS: All patients referred to the liver transplantation service for FHF from January 2001 through October 2002 (N = 20). We defined FHF as onset of encephalopathy within 8 weeks of onset of jaundice in the absence of preexisting liver disease. All patients underwent investigation for potential causes of liver injury. Potentially hepatotoxic supplements were defined as those with previously published reports of hepatic injury related to their use. RESULTS: Ten patients (50%) were recent or active users of potentially hepatotoxic supplements or herbs; 10 had no history of supplement use. In the supplement group, 7 patients (35%) had no other identified cause for hepatic failure. Six patients in the supplement group and 2 patients in the nonsupplement group underwent orthotopic liver transplantation. Five patients in each group died. There were no significant differences in transplantation rate (P =.07) or survival (P>.99) between groups. Supplement use alone accounted for the most cases of FHF during this period, exceeding acetaminophen toxicity and viral hepatitis. CONCLUSIONS: Herbal and dietary supplements were potential hepatotoxins in a high proportion of patients with FHF at our institution. Enhanced public awareness of the potential hepatotoxicity of these commonly used agents and increased regulatory oversight of their use is strongly urged.