Liver fibrosis post SVR

Hepatitis C (HCV) recurrence after liver transplantation (LT) is universal if HCV-RNA persists at time of LT and progression to fibrosis can occur rapidly. Nowadays, sustained virological response (SVR) is obtained in 97% of HCV-infected patients treated with direct acting antivirals (DAA) after LT. Fibrosis diminishes in HCV patients after SVR but there is paucity of data on fibrosis regression occurring after SVR following LT. In addition, most studies evaluate fibrosis with non-invasive techniques while these are not validated after LT because of LT-specific complications. There are no data evaluating long-term evolution of fibrosis after SVR since the introduction of DAA treatments (> 5 - 10 years). The aim of this study is to histologically evaluate liver fibrosis evolution in short and long term follow-up biopsies after HCV-elimination in LT-patients

The clinical relevance of prior bariatric surgery in alcohol-related liver disease in a nationwide belgian liver transplant population

Background and aims: Patients with a history of bariatric surgery (BS) are susceptible to developing alcohol use disorder, which can lead to alcohol-related liver disease (ALD). Notably, we have previously shown that mortality can be higher compared to non-BS patients. Our aim was to describe the demographics, disease phenotype and mortality of patients transplanted for alcoholrelated liver disease, in relation to BS. Method: In this European Liver Transplant Registry (ELTR)-endorsed study, we included adult patients who underwent a liver transplantation (LT) in Belgium between 1/1/2013 and 31/12/2022 for ALD. We captured all patients with a history of BS prior to developing ALD, and included non-BS control patients from the same cohort. Data were retrieved retrospectively at each centre and collected via REDCap. Results: We identified 37 patients who underwent BS (83.8% Rouxen-Y gastric bypass) before developing ALD, who received a LT between 2013 and 2022, and included 328 non-BS patients with an LT for ALD as controls. The median time between BS and diagnosis of severe liver disease was 7.2 years. Confirming our previous findings, more BS patients were female, compared to non-BS patients (45.9% vs. 18.9%, p < 0.001), and BS patients were 8 years younger at the time of transplantation (p < 0.001). MELD score at listing was higher (median 20 vs. 15, p = 0.003), and complications including ascites, encephalopathy and bacterial infections were more prevalent in the BS group. These differences disappeared after excluding patients with hepatocellular carcinoma (HCC), which was more prevalent in the non-BS group (8.1% vs. 49.1%, p < 0.001). Despite the younger age, survival after a median follow-up time of 5.5 years following LT was similar, and patients with BS trended to have a lower survival after LT in Cox regression analysis (HR 1.86, p = 0.077). This risk became statistically significant after exclusion of patients transplanted for HCC (p = 0.043). Interestingly, causes of death also differed, with liver disease being listed in 70.0% vs. 14.3% of patients as the main cause of death. Twice as many BS patients experienced a relapse of alcohol use post-transplant (27.0 vs. 14.1%, p = 0.038), whereas the occurrence/recurrence of MASLD was similar between both groups. Conclusion: Following BS, excessive alcohol use can progress to endstage ALD and need for LT. These patients present at a younger age, with more signs of hepatic decompensation, and can be at a higher risk for post-LT mortality, especially liver-related death. Pre-surgery screening for risk of excessive alcohol use and continued postoperative follow-up of these patients are warranted

Intramyocellular lipids are associated with insulin resistance in metabolic dysfunction-associated steatotic liver disease

Background and Aims: Insulin resistance is considered an indicator of the severity of MASLD. In this context, the role of skeletal muscle fat and its intra- or extra-myocellular localisation on insulin sensitivity remains debated. The aim of this study is to assess muscle lipid content and cellular localisation using proton-magnetic resonance spectroscopy (1H-MRS) and its relationship with insulin resistance in a cohort of MASLD subjects. Method: MASLD patients were prospectively recruited based on the co-existence of liver steatosis measured by a controlled attenuation-parameter (CAP) above 251 dB/m and at least one cardiometabolic risk factor. Type 2 diabetes was defined by the intake of hypoglycemic drugs. Insulin resistance was estimated in non-diabetic patients using the homeostatic model assessment of insulin resistance (HOMA-IR). Intra (IMCL) and extramyocellular lipids (EMCL) were measured in vivo using 1H-MRS. Single voxel 1H-MRS was performed on a 3-Tesla Signa Premier scanner (GE healthcare) on tibialis anterior (TA) and soleus using a PRESS-sequence (voxel size 10 X 10 X 15 mm3, TE=27ms, TR=1500ms, 8 averages). JMRUI software, including the AMARES algorithm was used to quantify IMCL and EMCL on non-water suppressed spectra. Results: 54 MASLD patients were included. 32 patients were male (59%), with a mean age of 54 years (range: 19-75). 27 patients were diabetic (50%). Mean BMI was 35 (range: 24-60). Mean waist circumference was 118 cm (range: 89-160). Mean CAP and liver elasticity were 342 dB/m (range: 242-400) and 14.8 kPa (range: 3.6-35). In the entire cohort, mean TA lipid content was 0.6% for IMCL (range: 0.1-1.5) and 1.8% (0.3-6.8) for EMCL (p 0.05) or for IMCL for TA between diabetic and non-diabetic patients (0.55% versus 0.7%; p > 0.05). Conclusion: The majority of skeletal muscle lipids are extramyocellular. However, IMCL but not EMCL content assessed by 1H-MRS positively correlates with insulin resistance assessed by the HOMA-IR index in non-diabetic MASLD patients. This observation is reinforced by the IMCL content in diabetic patients being significantly higher compared to non-diabetic patients. This observation highlights a link between IMCL, systemic insulin resistance and type 2 diabetes in MASLD