Anonymous live organ donors or unspecified donors are individuals willing to be organ donors for any transplant recipient with whom they have no biological or antecedent emotional relationship. ...Despite excellent recipient outcomes and the potential to help address organ scarcity, controversy surrounds the unconditional act of gifting one's organs to an unrelated recipient. This qualitative systematic review provides insights into the first-hand experiences, motivations, and challenges that unspecified donors face.
A systematic search was conducted on Medline, Embase, CINAHL, PsycINFO, and Web of Science database for qualitative literature regarding unspecified living donors' motivations and experiences in liver and kidney transplantation. An inductive thematic analysis was conducted to generate themes and supportive subthemes.
12 studies were included. The four major themes were (i) motivations, (ii) perception of risks, (iii) donor support, and (iv) benefits of donation. Unspecified donors demonstrated a deep sense of social responsibility but tended to underestimate health risks in favour of benefits for recipients. Despite the lack of emotional support from family and friends, the decision to donate was a resolute personal decision for donors. Majority benefitted emotionally and did not express regret.
This qualitative review bridges the gap in literature on unspecified living donor psychology and provides a comprehensive understanding of the decision-making matrix and experiences of donors.
Summary
Background
Retrospective studies report that visualisation of the liver may be severely limited using ultrasound (US), potentially contributing to diminished sensitivity for detection of ...hepatocellular carcinoma (HCC) among patients with nonalcoholic fatty liver disease (NAFLD) and cirrhosis, but there are limited prospective data.
Aims
To compare liver visualisation scores prospectively for US and abbreviated hepatobiliary phase (HBP) magnetic resonance imaging (AMRI) in a cohort of participants with NAFLD cirrhosis and a clinical indication for HCC surveillance.
Methods
This prospective multicenter study included 54 consecutive participants (67% women) with NAFLD cirrhosis who underwent contemporaneous US as well as HBP‐AMRI with gadoxetic acid. Primary outcome was the proportion of imaging examinations with severe limitations in liver visualisation (visualisation score C) compared head‐to‐head between US and AMRI.
Results
The mean (± standard deviation) age was 63.3 years (±8.4) and body mass index was 32.0 kg/m2 (±6.0). Nineteen participants (35%) had severe visualisation limitations on US, compared with 10 (19%) with AMRI, p < 0.0001. Nine (17%) participants had <90% of the liver visualised on US, compared with only 1 (2%) participant with AMRI, p < 0.0001. Obesity was a strong and independent predictor for severe visualisation limitation on US (OR 5.1, CI 1.1–23.1, p = 0.03), after adjustment for age, sex and ethnicity.
Conclusion
More than one‐third of participants with NAFLD cirrhosis had severe visualisation limitations on US for HCC screening, compared with one‐sixth on AMRI. US adequacy should be reported in all clinical studies and when suboptimal then AMRI may be considered for HCC screening.
Retrospective studies suggest that abbreviated magnetic resonance imaging (AMRI) provides adequate liver visualization more frequently than ultrasound (US), but a prospective, head‐to‐head comparative study is lacking. We conducted a prospective, multicenter study of US versus AMRI performed head‐to‐head for hepatocellular carcinoma screening among well characterized patients with NAFLD cirrhosis. Our study demonstrates that more than a third of patients with NAFLD cirrhosis have severe visualization limitations on US but only one‐sixth have severe visualization limitations on AMRI.
Chronic liver disease is a major global health threat and is the 11th leading cause of death globally. A liver biopsy is frequently required in assessing the degree of steatosis and fibrosis, ...information that is important in diagnosis, management, and prognostication. However, liver biopsies have limitations and carry a considerable risk, leading to the development of various modalities of noninvasive testing tools. These tools have been developed in recent years and have improved markedly in diagnostic accuracy. Moving forward, they may change the practice of hepatology.
Nonalcoholic steatohepatitis (NASH) is the fastest growing indication of liver transplantation (LT) and is projected to be the leading cause of LT in the near future. The systemic pathogenesis of ...NASH increases risks of adverse clinical outcomes in patients with NASH receiving LT. Thus, this study aimed to conduct a time-dependent survival analysis between LT recipients with and without NASH using hazard ratios.
A search was conducted on Medline and Embase databases for articles relating to LT outcomes for NASH recipients. A survival analysis was conducted of hazard ratios using the DerSimonian and Laird random-effects model with meta-regression. To account for censoring, survival data were reconstructed from published Kaplan-Meier curves and pooled to derive more accurate hazard estimates and all-cause mortality in NASH patients after LT. Pairwise meta-analysis was conducted to analyze secondary outcomes.
Fifteen studies involving 119,327 LT recipients were included in our analysis with a prevalence of NASH of 20.2% (95% CI, 12.9-30.2). The pooled 1-year, 5-year, and 10-year all-cause mortality in NASH patients after LT were 12.5%, 24.4%, and 37.9%, respectively. Overall survival was comparable between LT recipients for NASH vs non-NASH (hazard ratio, 0.910; 95% CI, 0.760 to 1.10; P = .34). Meta-regression showed that a higher model for end-stage liver disease score was associated with significantly worse overall survival in NASH compared with non-NASH after LT (95% CI, -0.0856 to -0.0181; P = .0026).
This study shows that patients undergoing LT for NASH cirrhosis have comparable complication rates, overall survival, and graft survival compared with non-NASH patients, although close monitoring may be indicated for those with higher model for end-stage liver disease scores.
Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is closely associated with diabetes. The cumulative impact of both diseases synergistically increases risk of adverse events. However, ...present population analysis is predominantly conducted with reference to non-NAFLD individuals and has not yet examined the impact of prediabetes. Hence, we sought to conduct a retrospective analysis on the impact of diabetic status in NAFLD patients, referencing non-diabetic NAFLD individuals.Methods: Data from the National Health and Nutrition Examination Survey 1999–2018 was used. Hepatic steatosis was defined with United States Fatty Liver Index (US-FLI) and FLI at a cut-off of 30 and 60 respectively, in absence of substantial alcohol use. A multivariate generalized linear model was used for risk ratios of binary outcomes while survival analysis was conducted with Cox regression and Fine Gray model for competing risk.Results: Of 32,234 patients, 28.92% were identified to have NAFLD. 36.04%, 38.32% and 25.63% were non-diabetic, prediabetic and diabetic respectively. Diabetic NAFLD significantly increased risk of cardiovascular disease (CVD), stroke, chronic kidney disease, all-cause and CVD mortality compared to non-diabetic NAFLD. However, prediabetic NAFLD only significantly increased the risk of CVD and did not result in a higher risk of mortality.Conclusions: Given the increased risk of adverse outcomes, this study highlights the importance of regular diabetes screening in NAFLD and adoption of prompt lifestyle modifications to reduce disease progression. Facing high cardiovascular burden, prediabetic and diabetic NAFLD individuals can benefit from early cardiovascular referrals to reduce risk of CVD events and mortality.
HCC risk in chronic hepatitis B (CHB) is higher in the indeterminate phase compared with the inactive phase. However, it is unclear if antiviral therapy reduces HCC risk in this population. We aimed ...to evaluate the association between antiviral therapy and HCC risk in the indeterminate phase.
We analyzed 855 adult (59% male), treatment-naïve patients with CHB infection without advanced fibrosis in the indeterminate phase at 14 centers (USA, Europe, and Asia). Inverse probability of treatment weighting (IPTW) was used to balance the treated (n = 405) and untreated (n = 450) groups. The primary outcome was HCC development. The mean age was 46±13 years, the median alanine transaminase was 38 (interquartile range, 24-52) U/L, the mean HBV DNA was 4.5±2.1 log 10 IU/mL, and 20% were HBeAg positive. The 2 groups were similar after IPTW. After IPTW (n = 819), the 5-, 10-, and 15-year cumulative HCC incidence was 3%, 4%, and 9% among treated patients (n = 394) versus 3%, 15%, and 19%, among untreated patients (n = 425), respectively ( p = 0.02), with consistent findings in subgroup analyses for age >35 years, males, HBeAg positive, HBV DNA>1000 IU/mL, and alanine transaminase<upper limit of normal. In multivariable Cox proportional hazards analysis adjusted for age, sex, HBeAg, HBV DNA, alanine transaminase, diabetes, and platelets, antiviral therapy remained an independent predictor of reduced HCC risk (adjusted HR = 0.3, 95% CI: 0.1-0.6, p = 0.001).
Antiviral therapy reduces HCC risk by 70% among patients with indeterminate-phase CHB. These data have important implications for the potential expansion of CHB treatment criteria.
Unfortunately, available liver cancer treatments are associated with modest survival advantage. The biggest factor improving survival is early detection, but the current understanding of early ...transformation events is limited. Therefore, we set up a model to study these early events and investigated the relationship of premalignant, senescent hepatocytes, a regenerative environment, and the influence of secreted factors on liver tumorigenesis. Oncogene-induced senescence (OIS) was triggered in a subset of mouse hepatocytes, which under normal conditions, are eliminated by immunosurveillance. Inducing liver damage and regeneration was sufficient to trigger immunosurveillance escape of OIS hepatocytes, resulting in premalignant to malignant transformation and hepatocellular tumor development. Trefoil factor 3 (TFF3) was found to be overexpressed in OIS hepatocytes and in hepatocellular carcinoma. TFF3 deficiency strongly attenuated malignant transformation by increasing insulin-like growth factor binding protein 5 (IGFBP5) expression, which consequently dampened IGF receptor signaling. Furthermore, analysis of precancerous liver tissue validated TFF3 as an early liver cancer biomarker. Altogether, these findings provide mechanistic insights into early transformation and immunosurveillance escape in liver cancer, revealing TFF3 and IGFBP5 to be important players with opposite roles in tumorigenesis.
Liver damage induces a compensatory regenerative response that can drive premalignant to malignant transformation of senescent hepatocytes.
HDV is a defective virus that uses the HBV surface antigen to enter hepatocytes. It is associated with an accelerated course of liver fibrosis progression and an increased risk of hepatocellular ...carcinoma. Negative HDV RNA 24 weeks after the end of therapy has been proposed as an endpoint but late relapses make this endpoint suboptimal, hence HBsAg loss appears to be more appropriate. Current HBV antiviral agents have poor activity against HDV hence the search for improved therapy. Drugs only active against HDV, such as lonafarnib, have shown efficacy in combination with nucleoside analogues and peginterferon, but do not lead to HBsAg loss. HBsAg loss sustained 24 weeks after the end of therapy with negative HBV DNA is termed functional cure. Agents that are being investigated for functional cure include those that inhibit replication such as entry inhibitors, polymerase inhibitors and capsid assembly modulators but seldom lead to functional cure. Agents that reduce HBV antigen load such as RNA interference and inhibitors of HBsAg secretion are promising. Immunomodulators on their own seldom achieve functional cure, hence these agents in combination to assess the optimal combination are being investigated. Consequently, agents leading to functional cure of HBV are ideal for both HBV and HDV.
