Benefit and harm of waiting time in liver transplantation for HCC.

Liver transplantation is the most successful treatment for limited-stage HCC. The waiting time for liver transplantation (LT) can be a critical factor affecting the oncological prognosis and outcome of patients with HCC. Efficient strategies to optimize waiting time are essential to maximize the benefits of LT and to reduce the harm of delay in transplantation. The ever-increasing demand for donor livers emphasizes the need to improve the organization of the waiting list for transplantation and to optimize organ availability for patients with and without HCC. Current progress in innovations to expand the donor pool includes the implementation of living donor LT and the use of grafts from extended donors. By expanding selection criteria, an increased number of patients are eligible for transplantation, which necessitates criteria to prevent futile transplantations. Thus, the selection criteria for LT have evolved to include not only tumor characteristics but biomarkers as well. Enhancing our understanding of HCC tumor biology through the analysis of subtypes and molecular genetics holds significant promise in advancing the personalized approach for patients. In this review, the effect of waiting time duration on outcome in patients with HCC enlisted for LT is discussed.

Effect of sarcopenia on survival in patients with cirrhosis: A meta-analysis.

BACKGROUND & AIMS: The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, stratified by sex, underlying liver disease etiology, and severity of hepatic dysfunction. METHODS: PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with an additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included. RESULTS: Twenty-two studies involving 6,965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), and was higher in male patients, those with alcohol-associated liver disease, those with Child-Pugh grade C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index). Sarcopenia was associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in a sensitivity analysis of patients with cirrhosis without hepatocellular carcinoma (aHR 2.35, 95% CI 1.95-2.83) and in subgroups stratified by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the association between sarcopenia and poor prognosis (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in any of our analyses. CONCLUSIONS: Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis. LAY SUMMARY: The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% of patients with alcohol-related liver disease or Child-Pugh class C cirrhosis. Sarcopenia was independently associated with an ∼2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer durations of sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.

Growth of hepatocellular adenoma during pregnancy: A prospective study.

BACKGROUND & AIMS: The presence of hepatocellular adenoma (HCA) in pregnant women requires special consideration, as it has been reported to carry the risk of growth and clinically significant haemorrhage. In this prospective study we assessed aspects of growth of HCA <5 cm during pregnancy. METHODS: This was a multicentre prospective cohort study in pregnant women with suspected HCA <5 cm on imaging. Definitive HCA diagnosis was established by MRI with hepatobiliary contrast agents (LCE-MRI), preferably before pregnancy. If at study inclusion a definitive diagnosis was lacking, LCE-MRI was performed after giving birth. Growth of the adenoma (defined as an increase of >20%) was closely monitored with ultrasound examinations throughout pregnancy. RESULTS: Of the 66 women included, 18 were excluded from analysis because postpartum LCE-MRI did not confirm the diagnosis of HCA and showed the lesion to be focal nodular hyperplasia. The remaining 48 women, with an HCA confirmed by LCE-MRI, were followed during 51 pregnancies. Median age was 30 years (IQR 27-33) and median body mass index 31.9 kg/m2 (IQR 26.3-36.6). Growth of HCA was seen in 13 of the pregnancies (25.5%); the median increase was 14 mm (IQR 8-19). One woman whose HCA grew to >70 mm successfully underwent transarterial embolization at week 26 of pregnancy to prevent further growth. The other 50 pregnancies proceeded without complications. CONCLUSION: This study suggests that an HCA <5 cm confers minimal risk to a pregnant woman and none to her child. HCA increased in size during a quarter of pregnancies, so we recommend close monitoring with ultrasound examinations, enabling intervention if needed. In light of the large proportion of misdiagnosed HCA, LCE-MRI should be performed to prevent unnecessary anxiety in women with a benign liver lesion. LAY SUMMARY: The presence of hepatocellular adenoma in pregnant women requires special consideration, as it carries the risk of growth and haemorrhage. In this study we followed 48 patients with hepatocellular adenoma <5 cm during 51 pregnancies and found that a hepatocellular adenoma during pregnancy confers minimal risk to the pregnant woman and none to her child.

Development and Validation of a Model to Predict Regression of Large Size Hepatocellular Adenoma.

INTRODUCTION: Surgery is advocated in hepatocellular adenomas (HCA) >5 cm that do not regress to <5 cm after 6-12 months. The aim of this study was to develop a model for these patients, estimating the probability of HCA regression to <5 cm at 1 and 2 years follow-up. METHODS: Data were derived from a multicenter retrospective cohort of female patients diagnosed with HCA >5 cm at first follow-up. Potential predictors included age, body mass index, and HCA diameter at diagnosis (T0), HCA-subtype (hepatocyte nuclear factor 1α inactivated HCA, inflammatory-HCA, unclassified HCA) and "T0-T1 regression-over-time" (percentage of regression between T0 and first follow-up (T1) divided by weeks between T0 and T1). Cox proportional hazards regression was used to develop a multivariable model with time to regression of HCA < 5 cm as outcome. Probabilities at 1 and 2 years follow-up were calculated. RESULTS: In total, 180 female patients were included. Median HCA diameter at T0 was 82.0 mm and at T1 65.0 mm. Eighty-one patients (45%) reached the clinical endpoint of regression to <5 cm after a median of 34 months. No complications occurred during follow-up. In multivariable analysis, the strongest predictors for regression to <5 cm were HCA diameter at T0 (logtransformed, hazard ratio (HR) 0.05), T0-T1 regression-over-time (HR 2.15) and HCA subtype inflammatory-HCA (HR 2.93) and unclassified HCA (HR 2.40), compared to hepatocyte nuclear factor 1α inactivated HCA (reference). The model yielded an internally validated c-index of 0.79. DISCUSSION: In patients diagnosed with HCA > 5 cm that still exceed 5 cm at first follow-up, regression to <5 cm can be predicted at 1 and 2 years follow-up using this model. Although external validation in an independent population is required, this model may aid in decision-making and potentially avoid unnecessary surgery.

Evidence of good prognosis of hepatocellular adenoma in post-menopausal women.

BACKGROUND & AIMS: Hepatocellular adenoma (HCA) is a rare benign liver tumor, which typically develops in women in their reproductive phase and is associated with the use of oral contraceptives. The aim of this study was to evaluate whether follow-up of HCA can be safely terminated after the occurrence of menopause. Secondary, we studied the impact of the diagnosis HCA on health-related quality of life (HRQoL). METHODS: This was a cross-sectional cohort study, including 48 post-menopausal women with HCA. Patients underwent ultrasound examination and the size of HCA was compared to size at the last follow-up imaging (CT, MRI or ultrasound). HRQoL was evaluated by the Liver Disease Symptom Index 2.0 and Short Form 12. RESULTS: Median time since last follow-up was 60.5months. In 44 patients 43.5% of the lesions were undetectable, 32.6% were stable in size and 19.6% became smaller. Mean diameter of HCA was 17.2mm compared to 35.9mm at last follow-up (p<0.001). There was a positive correlation between difference in size and time since last follow-up (p<0.001). No significant effect of HCA subtype on difference in size was found. Regarding HRQoL, study patients scored significantly lower on the mental component summary score compared to the general female Dutch population. CONCLUSIONS: HCA diameter became significantly smaller after the occurrence of menopause and as time progresses, this regression increased. This suggests that routine follow-up of HCA <5cm in post-menopausal women after subsequent follow-up is not required. Notably we found that patient's mental HRQoL was inferior to that of the general population. LAY SUMMARY: In this study we investigated if hepatocellular adenoma, a benign tumor of the liver that is found mostly in women and is associated with female hormones, regresses in size after the occurrence of menopause in female patients over 50years of age. We made an ultrasound of the liver lesion and found that the average size of the adenomas becomes significantly smaller. This could mean that female patients with a small (<5cm) hepatocellular adenoma who are post-menopausal do not have to remain in follow-up. CLINICAL TRIAL NUMBER: MEC-2015-385.

Neutrophil Gelatinase-Associated Lipocalin, but Not Kidney Injury Marker 1, Correlates with Duration of Delayed Graft Function.

BACKGROUND: No specific early biomarker is available to measure kidney injury after kidney transplantation (KT). Both neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury marker 1 (KIM-1) increase after oxidative injury. Their potential as early biomarkers was evaluated in this one-arm pilot study. MATERIALS AND METHODS: Twenty consecutive KT patients receiving a kidney from a donation after circulatory death donor were included. Graft perfusate was collected, as well as serum samples before transplantation, at the end of surgery, and 1, 4, and 7 days after transplantation. NGAL and KIM-1 were measured using ELISA. Kidney function and delayed graft function (DGF) were monitored. RESULTS: In this cohort, 85% of the KT patients developed DGF. Perfusate NGAL correlated with donor age (r2 = 0.094, p = 0.01) and serum creatinine (r2 = 0.243, p = 0.05). A cardiac cause of death was associated with higher NGAL in the perfusate (p = 0.03). Serum NGAL at day 1 was significantly higher in patients with DGF (730 ng/ml, range 490-1,655, vs. 417 ng/ml, range 232-481; p = 0.01). Serum NGAL levels at day 1, 4, and 7 correlated with the duration of DGF. KIM-1 was not detectable in the perfusate or in the serum until postoperative day 4 in 80% of patients. CONCLUSIONS: NGAL in the perfusate correlates with known donor risk factors for DGF. For the first time, we describe that serum NGAL at day 1 can discriminate between DGF and immediate graft function. Also, serum NGAL levels at day 1, 4, and 7 correlate with the duration of DGF. No association with KIM-1 was found. These data suggest that NGAL may be used as an early biomarker to detect DGF and warrants further study.