Loss of muscle mass and function is a common occurrence in both patients with decompensated cirrhosis and those undergoing liver transplantation. Sarcopenia is associated with morbidity and mortality ...before and after liver transplantation. The ability of skeletal muscle mass to recover after transplant isquestionable, and long term adverse events associated with persistent sarcopenia have not been well studied. Limited data is available examining mechanisms by which decreased muscle mass might develop. It is not clear which interventions might reduce the prevalence of sarcopenia and associated health burdens. However, measures to either decrease portal hypertension or improve nutrition appear to have benefit. Research on sarcopenia in the liver transplant setting is hampered by differing methodology to quantify muscle mass and varied thresholds determining the presence of sarcopenia. One area highlighted in this review is the heterogeneity used when defining sarcopenia. The health consequences, clinical course and potential pathophysiologic mechanisms of sarcopenia in the setting of cirrhosis and liver transplantation are further discussed.
Loss of muscle mass and function, or sarcopenia, is a common feature of cirrhosis and contributes significantly to morbidity and mortality in this population. Sarcopenia is a main indicator of ...adverse outcomes in this population, including poor quality of life, hepatic decompensation, mortality in patients with cirrhosis evaluated for liver transplantation (LT), longer hospital and intensive care unit stay, higher incidence of infection following LT, and higher overall health care cost. Although it is clear that muscle mass is an important predictor of LT outcomes, many questions remain, including the best modality for assessing muscle mass, the optimal cut‐off values for sarcopenia, the ideal timing and frequency of muscle mass assessment, and how to best incorporate the concept of sarcopenia into clinical decision making. For these reasons, we assembled a group of experts to form the North American Working Group on Sarcopenia in Liver Transplantation to use evidence from the medical literature to address these outstanding questions regarding sarcopenia in LT. We believe sarcopenia assessment should be considered in all patients with cirrhosis evaluated for liver transplantation. Skeletal muscle index (SMI) assessed by computed tomography constitutes the best‐studied technique for assessing sarcopenia in patients with cirrhosis. Cut‐off values for sarcopenia, defined as SMI < 50 cm2/m2 in male and < 39 cm2/m2 in female patients, constitute the validated definition for sarcopenia in patients with cirrhosis. Conclusion: The management of sarcopenia requires a multipronged approach including nutrition, exercise, and additional pharmacological therapy as deemed necessary. Future studies should evaluate whether recovery of sarcopenia with nutritional management in combination with an exercise program is sustainable as well as how improvement in muscle mass might be associated with improvement in clinical outcomes.
The metabolic syndrome is common after liver transplant being present in approximately half of recipients. It has been associated with adverse outcomes such as progression of hepatitis C and major ...vascular events. As the United States population ages and the rate of obesity increases, prevention of the metabolic syndrome in the post-transplant population deserves special consideration. Currently, the metabolic syndrome after transplant appears at least two times more common than observed rates in the general population. Specific guidelines for patients after transplant does not exist, therefore prevention rests upon knowledge of risk factors and the presence of modifiable elements. The current article will focus on risk factors for the development of the metabolic syndrome after transplant, will highlight potentially modifiable factors and propose potential areas for intervention. As in the non-transplant population, behavioral choices might have a major role. Opportunities exist in this regard for health prevention studies incorporating lifestyle changes. Other factors such as the need for immunosuppression, and the changing characteristics of wait listed patients are not modifiable, but are important to know in order to identify persons at higher risk. Although immunosuppression after transplant is unavoidable, the contribution of different agents to the development of components of the metabolic syndrome is also discussed. Ultimately, an increased risk of the metabolic syndrome after transplant is likely unavoidable, however, there are many opportunities to reduce the prevalence.
Nonalcoholic fatty liver disease （NAFLD） is highly prevalent and can result in nonalcoholic steatohepatitis （NASH） and progressive liver disease including cirrhosis and hepatocellular carcinoma. A ...growing body of literature implicates the peroxisome proliferators- activated receptors （PPARs） in the pathogenesis and treatment of NAFLD. These nuclear hormone receptors impact on hepatic triglyceride accumulation and insulin resistance. The aim of this review is to describe the data linking PPARα and PPART to NAFLD/NASH and to discuss the use of PPAR ligands for the treatment of NASH.
Nonalcoholic fatty liver disease (NAFLD) disproportionally affects Hispanic/Latino populations. However, the magnitude varies among Hispanic/Latino ethnic groups. We investigated the mechanisms of ...these disparities.
We examined associations of NAFLD-associated genetic variants and continental ancestry with suspected NAFLD, levels of alanine aminotransferase (ALT), and liver fibrosis using data from the Hispanic Community Health Study/Study of Latinos-a population-based study of Hispanic/Latino adults in the United States. We evaluated data from 16,415 Hispanic/Latino adults in 4 cities from 2008 through 2011. Subjects suspected of having NAFLD or liver fibrosis were identified based on unexplained increases in levels of aminotransferases and FIB-4 score, respectively.
Among the 9342 participants with available genetic and aminotransferase data, the PNPLA3 G allele (odds ratio OR, 1.53; 95% CI, 1.41-1.66), TM6SF2 T allele (OR, 1.41; 95% CI, 1.20-1.67), and PPP1R3B G allele (OR, 1.16; 95% CI, 1.06-1.28) were associated with suspected NAFLD. PNPLA3 G was also associated with increased levels of ALT, except in participants with Dominican and South American backgrounds, and with liver fibrosis. The frequency of PNPLA3 G was high (41%) and TM6SF2 T (5%) was low in Hispanic/Latinos. PNPLA3 G frequency differed among Hispanic background groups with the highest proportion in Mexicans (52%) and the lowest proportion in Dominicans (23%). After adjustment for demographic, clinical, and behavioral factors, as well as PNPLA3 G, TM6SF2 T, and PPP1R3B G, American ancestry had a positive association with level of ALT (r = 6.61%; P < .001), whereas African (r = -3.84%; P < .001) and European (r = -4.31%; P < .001) ancestry were inversely associated with level of ALT.
American ancestry and PNPLA3 G are independent predictors of ALT levels in US Hispanic/Latinos and may in part explain NAFLD disparities in US Hispanic/Latinos.
Nonalcoholic fatty liver disease (NAFLD) was shown to disproportionally affect Hispanic persons. We examined the prevalence of suspected NAFLD in Hispanic/Latino persons with diverse backgrounds.
We ...studied the prevalence of suspected NAFLD among 12,133 persons included in the Hispanic Community Health Study/Study of Latinos. We collected data on levels of aminotransferase, metabolic syndrome (defined by National Cholesterol Education Program-Adult Treatment Panel III guidelines), demographics, and health behaviors. Suspected NAFLD was defined on the basis of increased level of aminotransferase in the absence of serologic evidence for common causes of liver disease or excessive alcohol consumption. In multivariate analyses, data were adjusted for metabolic syndrome, age, acculturation, diet, physical activity, sleep, and levels of education and income.
In multivariate analysis, compared with persons of Mexican heritage, persons of Cuban (odds ratio OR, 0.69; 95% confidence interval CI, 0.57-0.85), Puerto Rican (OR, 0.67; 95% CI, 0.52-0.87), and Dominican backgrounds (OR, 0.71; 95% CI, 0.54-0.93) had lower rates of suspected NAFLD. Persons of Central American and South American heritage had a similar prevalence of suspected NAFLD compared with persons of Mexican heritage. NAFLD was less common in women than in men (OR, 0.49; 95% CI, 0.40-0.60). Suspected NAFLD associated with metabolic syndrome and all 5 of its components.
On the basis of an analysis of a large database of health in Latino populations, we found the prevalence of suspected NAFLD among Hispanic/Latino individuals to vary by region of heritage.
According to the American Association for the Study of Liver Disease, screening is recommended for HIV+ patients with anti-HDV, IVDU, those at risk for sexually transmitted infections, immigrants ...from endemic areas, and in those with low HBV DNA with an elevated ALT 16. Unlike other RNA viruses, HDV does not encode its own polymerarse but rather manipulates the hosts RNA polymerase II for replication 17. Currently, the only drug approved for HDV treatment by the Food and Drug Administration (FDA) is IFN, which has suboptimal response rates 5. Prevalence and burden of hepatitis D virus infection in the global population: a systematic review and meta-analysis.
This study aimed to assess the risk of maintenance immunosuppression on the post-transplant risk of malignancy across all solid organ transplant types.
This is a retrospective cohort study from a ...multicenter hospital system in the United States. The electronic health record was queried from 2000 to 2021 for cases of solid organ transplant, immunosuppressive medications, and post-transplant malignancy.
A total of 5,591 patients, 6,142 transplanted organs, and 517 post-transplant malignancies were identified. Skin cancer was the most common type of malignancy at 52.8%, whereas liver cancer was the first malignancy to present at a median time of 351 days post-transplant. Heart and lung transplant recipients had the highest rate of malignancy, but this finding was not significant upon adjusting for immunosuppressive medications (heart HR 0.96, 95% CI 0.72 - 1.3, p = 0.88; lung HR 1.01, 95% CI 0.77 - 1.33, p = 0.94). Random forest variable importance calculations and time-dependent multivariate cox proportional hazard analysis identified an increased risk of cancer in patients receiving immunosuppressive therapy with sirolimus (HR 1.41, 95% CI 1.05 - 1.9, p = 0.04), azathioprine (HR 2.1, 95% CI 1.58 - 2.79, p < 0.001), and cyclosporine (HR 1.59, 95% CI 1.17 - 2.17, p = 0.007), while tacrolimus (HR 0.59, 95% CI 0.44 - 0.81, p < 0.001) was associated with low rates of post-transplant neoplasia.
Our results show varying risks of immunosuppressive medications associated with the development of post-transplant malignancy, demonstrating the importance of cancer detection and surveillance strategies in solid organ transplant recipients.
Hepatitis C virus (HCV) is the leading indication for liver transplantation in the United States. It recurs universally after transplant but the rate of fibrosis and the development of graft failure ...is variable. Different donor and recipient features have been demonstrated to impact fibrosis. Plasma cell hepatitis, a histologic finding, is one feature associated with poor graft and patient outcomes. The pathogenic mechanism resulting in plasma cell hepatitis is poorly understood, with evidence suggesting a role for both the HCV and the immune system.A recent publication described plasma cell hepatitis in a larger context of immune medicated graft dysfunction in transplant recipients receiving interferon based therapy. This manuscript will highlight the topic of plasma cell hepatitis and provide commentary on the lack of recognition, the data regarding pathophysiologic mechanisms and the potential management options.
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