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Liver transplantation in a patient with sitosterolemia and cirrhosis.

ABSTRACT: Sitosterolemia (MIM 210250) is a rare genetic disorder caused by disruption of the normal mechanisms that regulate dietary cholesterol absorption and prevent the accumulation of noncholesterol sterols. As a result of this defect, affected individuals accumulate high concentrations of plant sterols in plasma and tissues. They present clinically with tendon or tuberoeruptive xanthomas, premature coronary artery disease, and/or hemolytic anemia. Two genes, ABCG5 and ABCG8, compose the STSL locus, and complete mutation in either, but not both, results in disease. The expression of these genes is confined to the intestine and liver. They are thought to function as sterol efflux pumps. It is not clear which organ, liver or intestine, is of greater importance in maintaining sterol balance with respect to noncholesterol sterols. We report here a case of a patient who presented with "chronic active liver disease" and was found to have sitosterolemia by chance and subsequently underwent orthotopic liver transplantation. Following transplantation, the grossly elevated pretransplantation serum plant sterol levels decreased to values only slightly higher than those of the patient's heterozygous father. This case highlights 2 important features: (1) The liver functions as the predominant organ for maintaining noncholesterol sterol balance (because the intestinal defect was not altered), and (2) a new clinical feature of undiagnosed sitosterolemia may be "idiopathic" liver disease. Because the diagnosis of sitosterolemia is based on specialized plasma analyses, we would propose that some consideration to this diagnosis should be given in appropriate cases.

SUBMITTER: Miettinen TA

PROVIDER: S-EPMC1391914 | biostudies-literature | 2006 Feb

REPOSITORIES: biostudies-literature

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Liver transplantation in a patient with sitosterolemia and cirrhosis.

Miettinen Tatu A TA Klett Eric L EL Gylling Helena H Isoniemi Helena H Patel Shailendra B SB

Gastroenterology 20060201 2

Sitosterolemia (MIM 210250) is a rare genetic disorder caused by disruption of the normal mechanisms that regulate dietary cholesterol absorption and prevent the accumulation of noncholesterol sterols. As a result of this defect, affected individuals accumulate high concentrations of plant sterols in plasma and tissues. They present clinically with tendon or tuberoeruptive xanthomas, premature coronary artery disease, and/or hemolytic anemia. Two genes, ABCG5 and ABCG8, compose the STSL locus, a ...[more]

PMID: 16472606

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Project description:Background & aimsLiver transplantation (LT) is the only available treatment for end-stage non-alcoholic fatty liver disease (NAFLD) (related decompensated cirrhosis and/or hepatocellular carcinoma). The aim of our study was to evaluate the risk of disease recurrence after LT and the factors influencing it.MethodThis retrospective multicenter study included adults transplanted for NAFLD cirrhosis between 2000 and 2019 in 20 participating French-speaking centers. Disease recurrence (steatosis, steatohepatitis and fibrosis) was diagnosed from liver graft biopsies.ResultsWe analyzed 150 patients with at least one graft liver biopsy available ≥6 months after transplantation, among 361 patients transplanted for NAFLD. The median (IQR) age at LT was 61.3 (54.4-64.6) years. The median follow-up after LT was 4.7 (2.8-8.1) years. The cumulative recurrence rates of steatosis and steatohepatitis at 5 years were 80.0% and 60.3%, respectively. Significant risk factors for steatohepatitis recurrence in multivariate analysis were recipient age at LT <65 years (odds ratio [OR] 4.214; p = 0.044), high-density lipoprotein-cholesterol <1.15 mmol/L after LT (OR 3.463; p = 0.013) and grade ≥2 steatosis on the graft at 1 year after LT (OR 10.196; p = 0.001). The cumulative incidence of advanced fibrosis (F3-F4) was 20.0% at 5 years after LT and significant risk factors from multivariate analysis were metabolic syndrome before LT (OR 8.550; p = 0.038), long-term use of cyclosporine (OR 11.388; p = 0.031) and grade ≥2 steatosis at 1 year after LT (OR 10.720; p = 0.049). No re-LT was performed for NAFLD cirrhosis recurrence.ConclusionOur results strongly suggest that recurrence of initial disease after LT for NAFLD is inevitable and progressive in a large proportion of patients; the means to prevent it remain to be further evaluated.Impact and implicationsNon-alcoholic fatty liver disease (NAFLD) is a growing indication for liver transplantation, but the analysis of disease recurrence, based on graft liver biopsies, has been poorly studied. Cumulative incidences of steatosis, steatohepatitis and NAFLD-related significant fibrosis recurrence at 5 years were 85.0%, 60.3% and 48.0%, respectively. Grade ≥2 steatosis on graft biopsy at 1 year (present in 25% of patients) is highly predictive of recurrence of steatohepatitis and advanced fibrosis: bariatric surgery should be discussed in these patients specifically.

Project description:UnlabelledCirrhosis is characterized by sarcopenia and malnutrition, leading to progressive functional decline. We aimed to objectively measure functional decline in patients with cirrhosis awaiting liver transplantation and its association with waiting list mortality. Consecutive adults listed for liver transplantation with laboratory Model for End-Stage Liver Disease (MELD) ≥12 at a single center underwent functional status assessments at every outpatient visit using the Short Physical Performance Battery (0 = impaired to 12 = robust), consisting of gait, chair stands, and balance tests. Joint linear time-to-event analyses modeled the simultaneous impact of the longitudinal trajectory of physical function on waiting list mortality (=death or delisted for being too sick for liver transplantation). Included were 309 liver transplantation candidates. Median laboratory MELD was 15, serum albumin was 3.0 g/dL, 28% had ascites, 18% had hepatic encephalopathy, and 83% were Child class B or C. At a median follow-up of 14 months, 15% died or were delisted and 28% underwent liver transplantation. Average physical function worsened per 3 months on the waiting list: -0.38 kg in grip strength, -0.05 meters/second in gait, 0.03 seconds in chair stands, and -0.16 Short Physical Performance Battery points. In joint models of longitudinal trajectories of physical function and waiting list mortality adjusted for MELD-Na, albumin, hepatocellular carcinoma, and baseline physical function, the longitudinal trajectories of each physical function measure were significantly associated with waiting list mortality: grip (hazard ratio = 0.89, 95% confidence interval 0.83-0.95), gait (hazard ratio = 0.72, 95% confidence interval 0.62-0.84), chair stands (hazard ratio = 1.17, 95% confidence interval 1.09-1.25), and Short Physical Performance Battery <10 (hazard ratio = 1.45, 95% confidence interval 1.15-2.20).ConclusionLiver transplantation candidates experience significant functional decline on the waiting list, despite modest wait time and low baseline MELD; decline in physical function is associated with an increased risk of death or delisting, independent of liver disease severity.

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Liver transplantation in a patient with sitosterolemia and cirrhosis.

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Liver transplantation in a patient with sitosterolemia and cirrhosis.

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