Hepatitis B Delta: assessment of the knowledge and practices of hepato-gastroenterologists practicing in non-academic settings in France.

BACKGROUND: Data on the management of Hepatitis B-Delta (HB-D) by hepatogastroenterologists (HGs) practicing in nonacademic hospitals or private practices are unknown in France. OBJECTIVE: We aimed to evaluate the knowledge and practices of HGs practicing in nonacademic settings regarding HB-D. METHODS: A Google form document was sent to those HGs from May to September 2021. RESULTS: A total of 130 HGs (mean age, 45 years) have participated in this survey. Among HBsAg-positive patients, Delta infection was sought in only 89% of cases. Liver fibrosis was assessed using FibroScan in 77% of the cases and by liver biopsy in 81% of the cases. A treatment was proposed for patients with >F2 liver fibrosis in 49% of the cases regardless of transaminase levels and for all the patients by 39% of HGs. Responding HGs proposed a treatment using pegylated interferon in 50% of cases, bulevirtide in 45% of cases and a combination of pegylated interferon and bulevirtide in 40.5% of cases. Among the criteria to evaluate the treatment efficacy, a decrease or a normalization of transaminases was retained by 89% of responding HGs, a reduction of liver fibrosis score for 70% of them, an undetectable delta RNA and HBsAg for 55% of them and a 2 log 10 decline in delta viremia for 62% of the cases. CONCLUSION: Hepatitis Delta screening was not systematically performed in HBsAg-positive patients despite the probable awareness and knowledge of the few responders who were able to prescribe treatments of hepatitis delta.

Early detection of liver injuries by the Serum enhanced binding test sensitive to albumin post-transcriptional modifications.

Early and sensitive biomarkers of liver dysfunction and drug-induced liver injury (DILI) are still needed, both for patient care and drug development. We developed the Serum Enhanced Binding (SEB) test to reveal post-transcriptional modifications (PTMs) of human serum albumin resulting from hepatocyte dysfunctions and further evaluated its performance in an animal model. The SEB test consists in spiking serum ex-vivo with ligands having specific binding sites related to the most relevant albumin PTMs and measuring their unbound fraction. To explore the hypothesis that albumin PTMs occur early during liver injury and can also be detected by the SEB test, we induced hepatotoxicity in male albino Wistar rats by administering high daily doses of ethanol and CCl4 over several days. Blood was collected for characterization and quantification of albumin isoforms by high-resolution mass spectrometry, for classical biochemical analyses as well as to apply the SEB test. In the exposed rats, the appearance of albumin isoforms paralleled the positivity of the SEB test ligands and histological injuries. These were observed as early as D3 in the Ethanol and CCl4 groups, whereas the classical liver tests (ALT, AST, PAL) significantly increased only at D7. The behavior of several ligands was supported by structural and molecular simulation analysis. The SEB test and albumin isoforms revealed hepatocyte damage early, before the current biochemical biomarkers. The SEB test should be easier to implement in the clinics than albumin isoform profiling.

Prevalence and clinical significance of the muscle retracting sign during endoscopic submucosal dissection of large macronodular colorectal lesions (with videos).

BACKGROUND AND AIMS: The muscle retracting sign (MRS) can be present during endoscopic submucosal dissection (ESD) of macronodular colorectal lesions. The prevalence of MRS and its pathologic and clinical implications is unclear. This study evaluated the effect of MRS on the technical and clinical outcomes of ESD. METHODS: All patients referred for ESD of protruding lesions or granular mixed lesions with >10 mm macronodule granular mixed laterally spreading tumors (LST-GMs) in 2 academic centers from January 2017 to October 2022 were prospectively included. Size of the macronodule was analyzed retrospectively. The primary outcome was the curative resection rate according to MRS status. Secondary outcomes were R0 resection, perforation, secondary surgery rate, and risk factors for MRS. RESULTS: Of 694 lesions, 84 (12%) had MRS (MRS+). The curative resection rate was decreased by MRS (MRS+ 41.6% vs lesions without MRS [MRS-] 81.3%), whereas the perforation (MRS+ 22.6% vs MRS- 9.2%), submucosal cancer (MRS+ 34.9% vs MRS- 9.2%), and surgery (MRS+ 45.2% vs MRS- 6%) rates were increased. The R0 resection rate of MRS+ colonic lesions was lower than that of rectal lesions (53% vs 74.3%). In multivariate analysis, protruding lesions (odds ratio, 2.47; 95% confidence interval, 1.27-4.80) and macronodules >4 cm (odds ratio, 4.24; 95% confidence interval, 2.23-8.05) were risk factors for MRS. CONCLUSIONS: MRS reduces oncologic outcomes and increases the perforation rate. Consequently, procedures in the colon should be stopped if MRS is detected, and those in the rectum should be continued due to the morbidity of alternative therapy.

Risk of delayed bleeding after colorectal endoscopic submucosal dissection: the Limoges Bleeding Score.

BACKGROUND: Clinically significant delayed bleeding (CSDB) is a frequent, and sometimes severe, adverse event after colorectal endoscopic submucosal dissection (ESD). We evaluated risk factors of CSDB after colorectal ESD. METHODS: We analyzed a prospective registry of 940 colorectal ESDs performed from 2013 to 2022. The incidence of bleeding was evaluated up to 30 days. Risk factors for delayed bleeding were evaluated by multivariate logistic regression. A Korean scoring model was tested, and a new risk-scoring model was developed and internally validated. RESULTS: CSDB occurred in 75 patients (8.0%). The Korean score performed poorly in our cohort, with a receiver operating characteristic (ROC) curve of 0.567. In the multivariate analysis, risk factors were age ≥75 years (odds ratio [OR] 1.63; 95%CI 0.97-2.73; 1 point), use of antithrombotics (OR 1.72; 95%CI 1.01-2.94; 1 point), rectal location (OR 1.51; 95%CI 0.92-2.48; 1 point), size >50 mm (OR 3.67; 95%CI 2.02-7.14; 3 points), and American Society of Anesthesiologists (ASA) score of III or IV (OR 2.26; 95%CI 1.32-3.92; 2 points). The model showed fair calibration and good discrimination, with an area under the ROC curve of 0.751 (95%CI 0.690-0.812). The score was used to define two groups of patients, those with low-medium risk (0 to 4 points) and high risk (5 to 8 points) for CSDB (respective bleeding rates 4.1% and 17.5%). CONCLUSION: A score based on five simple and meaningful variables was predictive of CSDB.

Liver disease in germline mutations of telomere-related genes: Prevalence, clinical, radiological, pathological features, outcome, and risk factors.

BACKGROUND AND AIM: Germline mutations of telomere-related genes (TRG) induce multiorgan dysfunction, and liver-specific manifestations have not been clearly outlined. We aimed to describe TRG mutations-associated liver diseases. APPROACH AND RESULTS: Retrospective multicenter analysis of liver disease (transaminases > 30 IU/L and/or abnormal liver imaging) in patients with TRG mutations. Main measurements were characteristics, outcomes, and risk factors of liver disease in a TRG mutations cohort. The prevalence of liver disease was compared to a community-based control group (n = 1190) stratified for age and matched 1:3 for known risk factors of liver disease. Among 132 patients with TRG mutations, 95 (72%) had liver disease, with associated lung, blood, skin, rheumatological, and ophthalmological TRG diseases in 82%, 77%, 55%, 39%, and 30% of cases, respectively. Liver biopsy was performed in 52/95 patients, identifying porto-sinusoidal vascular disease in 48% and advanced fibrosis/cirrhosis in 15%. After a follow-up of 21 months (12-54), ascites, hepato-pulmonary syndrome, variceal bleeding, and HCC occurred in 14%, 13%, 13%, and 2% of cases, respectively. Five-year liver transplantation-free survival was 69%. A FIB-4 score ≥ 3·25 and ≥1 risk factor for cirrhosis were associated with poor liver transplantation-free survival. Liver disease was more frequent in patients with TRG mutations than in the paired control group [80/396, (20%)], OR 12.9 (CI 95%: 7.8-21.3, p < 0.001). CONCLUSIONS: TRG mutations significantly increase the risk of developing liver disease. Although symptoms may be mild, they may be associated with severe disease. Porto-sinusoidal vascular disease and cirrhosis were the most frequent lesions, suggesting that the mechanism of action is multifactorial.

Towards hepatitis C elimination in France: Scanvir, an effective model to test and treat drug users on dedicated days.

According to the French recommendations, the elimination of the hepatitis C virus by 2025 could be a realistic public health goal. Screening policies are being intensified, and access to treatment is promoted for patients who escape the usual care pathway. The 'Scanvir' program is an original strategy based on dedicated screening days, as part of the 'test, treat and cure HCV' event in addiction care centers in a French region, during which innovative screening technologies (RDTs, FibroScan® and point-of-care HCV RNA testing) are brought on site and access to a multidisciplinary team is offered. A total of 392 patients attended the 67 regional Scanvir sessions: 31.6% were HCV Ab-positive and 66% of them were HCV RNA-positive. Treatment was initiated in 79.3% of the patients. RDTs were accepted by 62% of the PWIDs (including those who already knew their status) and FibroScan® by 99.5% of the patients. 80% of the viremic patients started their treatment on site and are now cured or still under treatment. Advanced fibrosis evaluated by FibroScan® (LSM > 8 KPa) was suspected in 13.4% and 14.1% of the global and the HCV population, respectively. Scanvir is an efficient strategy for HCV elimination based on dedicated days aimed at increasing cost-effectiveness and offering a multidisciplinary service while saving human care resources. It is an exportable strategy that also offers comprehensive screening of associated chronic liver diseases via the elastometry device and interviews.

Iohexol plasma and urinary concentrations in cirrhotic patients: A pilot study.

BACKGROUND: Renal failure is an independent prognostic factor for survival in patients with cirrhosis. Equations to calculate serum creatinine significantly overestimate the glomerular filtration rate (GFR). Plasma clearance of direct biomarkers has been used to improve the accuracy of evaluations of GFR in this population, but no study has simultaneously measured plasma and urinary clearance, which is the gold standard. AIM: To study calculated plasma and urinary concentrations of iohexol, based on the kinetics of samples collected over 24 h from cirrhotic patients with three different grades of ascites. METHODS: One dose of iohexol (5 mL) was injected intravenously and plasma concentrations were measured 11 times over 24 h in nine cirrhotic patients. The urinary concentration of iohexol was also measured, in urine collected at 4, 8, 12 and 24 h. RESULTS: The plasma and urinary curves of iohexol were similar; however, incomplete urinary excretion was detected at 24 h. Within the estimated GFR limits of our population (> 30 and < 120 mL/min/1.73 m²), the median measured GFR (mGFR) was 63.7 mL/min/1.73 m² (range: 41.3-111.3 mL/min/1.73 m²), which was an accurate reflection of the actual GFR. Creatinine-based formulas for estimating GFR showed significant bias and imprecision, while the Brochner-Mortensen (BM) equation accurately estimated the mGFR (r = 0.93). CONCLUSION: Plasma clearance of iohexol seems useful for determining GFR regardless of the ascites grade. We will secondly devise a pharmacokinetics model requiring fewer samples andvalidate the BM equation.

A Hybrid Model Associating Population Pharmacokinetics with Machine Learning: A Case Study with Iohexol Clearance Estimation.

BACKGROUND: Maximum a posteriori Bayesian estimation (MAP-BE) based on a limited sampling strategy and a population pharmacokinetic model is frequently used to estimate pharmacokinetic parameters in individuals, however with some uncertainty (bias). Recent works have shown that the performance in individual estimation or pharmacokinetic parameters can be improved by combining population pharmacokinetic and machine learning algorithms. OBJECTIVE: The objective of this work was to investigate the use of a hybrid machine learning/population pharmacokinetic approach to improve individual iohexol clearance estimation. METHODS: The reference iohexol clearance values were derived from 500 simulated profiles (samples collected between 0.1 and 24.7 h) using a population pharmacokinetic model we recently developed in Monolix and obtained using all the concentration timepoints available. Xgboost and glmnet algorithms able to predict the error of MAP-BE clearance estimates based on a limited sampling strategy (0.1 h, 1 h, and 9 h) versus reference values were developed in a training subset (75%) and were evaluated in a testing subset (25%) and in 36 real patients. RESULTS: The MAP-BE limited sampling strategy estimated clearance was corrected by the machine learning predicted error leading to a decrease in root mean squared error by 29% and 24%, and in the percentage of profiles with the mean prediction error out of the ± 20% bias by 60% and 40% in the external validation dataset for the glmnet and Xgboost machine learning algorithms, respectively. These results were attributable to a decrease in the eta-shrinkage (shrinkage for a MAP-BE limited sampling strategy = 32.4%, glmnet = 18.2%, and Xgboost = 19.4% in the external dataset). CONCLUSIONS: In conclusion, this hybrid algorithm represents a significant improvement in comparison to MAP-BE estimation alone.

A single Bayesian estimator for iohexol clearance estimation in ICU, liver failure and renal transplant patients.

AIMS: Iohexol clearance has been proposed to estimate the glomerular filtration rate (GFR). A population pharmacokinetics (popPK) model was developed from heterogeneous patients. A Bayesian estimator (MAP-BE) based on a limited sampling strategy (LSS) was derived and evaluated in external patients. METHODS: Full pharmacokinetic data (7-12 samples) from 172 patients receiving iohexol for measurement of their GFR (unstable and stable ICU patients, liver failure patients and kidney transplant patients) were split into development (n = 136) and validation (n = 36) datasets. A PopPK model was developed in Monolix and was used to develop MAP-BE based on LSS. Its performance for GFR estimation was evaluated in the validation set. RESULTS: A two-compartment model with first-order elimination best described the data. The final model included the type of patients on volume of distribution (Vd), clearance and intercompartmental constants, serum creatinine on clearance and body weight on Vd. The best LSS included samples at 0.1-1-9 h exhibiting a relative mean prediction error (MPE) (RMSE) = -3.7% (14.3%) and better performance than the Bröchner-Mortensen formula (-3.0%/17%). Split by type of patients, the highest interindividual variability and imprecision was observed in unstable ICU patients (MPE (RMSE) = 3.7% (18.8%)) while the best performances were obtained for renal transplant patients (MPE (RMSE) = 1.0% (5.8%)). All LSS that included samples before 9 hours for the third sample were associated with an increased imprecision. CONCLUSION: A single MAP-BE of iohexol based on a three-sample LSS for four heterogeneous populations was developed and allowed accurate estimation of GFR in kidney transplant patients, slightly biased in stable ICU patients and slightly imprecise in unstable ICU patients.

Alpha-fetoprotein and focal nodular hyperplasia: An unconventional couple.

We report the case of a 36-year-old patient who was initially managed for gynecomastia. The first biological analyses showed a moderately elevated alpha-fetoprotein (AFP) level. After an endocrine etiology was excluded, an abdominal computed tomography scan showed typical focal nodular hyperplasia (FNH) proven by biopsy and showing expression of AFP in FNH cells. After follow-up for 24 months, the serum AFP and liver radiology remained unchanged. The association between an elevated AFP and FNH is rarely described in the medical literature.

Double-clip traction could be superior to the pocket-creation method with cylindrical cap for colonic ESD: a randomized study in an ex vivo model.

INTRODUCTION: In Western countries, debates between ESD vs piece-meal EMR as the best treatment for large colorectal adenomas persist regarding the difficulty of ESD the colon, and the safety and relatively good results of piece-meal endoscopic mucosal resection (EMR). Pocket-creation method (PCM) and double-clip countertraction (DCT) are two strategies recently published to facilitate ESD in this challenging situation. METHOD: This is a randomized animal study to compare PCM and DCT strategies for colonic ESD on ex vivo models (bovine colon) performed by 3 operators novice in ESD. Hybridknife type T was used to inject normal saline tinted with a small amount of blue dye in all procedures. Randomization was stratified according to the use of gravity assist. Primary endpoint was the difference in resection speed between PCM and DCT strategies. RESULTS: Resection speed was significantly higher in the DCT group than in the PCM group (56.3 vs. 31.6 mm2/min, p = 0.01). Technical success rate, defined as en bloc resection in under 60 min, was significantly better in the DCT group than in the PCM group (100% vs. 84.4%, p = 0.024), perforation rate was lower (0% vs. 18.8%, p = 0.012), and difficulty score was better (2.4 vs. 6.2, p < 0.0001) as was procedure duration (24.2 vs. 40.2 min, p < 0.0001). CONCLUSION: DCT was superior to PCM for ESD in our validated bovine colon model. This strategy is inexpensive, easy to use and adaptive. It might facilitate the widespread use of colonic ESD in Western countries and change Western ideas regarding the use of colonic ESD compared with piece-meal EMR for large benign lesions.

Rooibos, a fake friend.

Rooibos is consumed worldwide and its use considered safe. It contains scavengers of free radicals and is so is deemed to be a liver protector. Nevertheless, hepatic toxicity exists even if rare. It is probably underdiagnosed and clinicians should think about it in case of acute hepatitis. We report a case of liver injury attributed to Rooibos.

Effect of implementing a regional referral network on surgical referral rate of benign polyps found during a colorectal cancer screening program: A population-based study.

INTRODUCTION: Surgical management is too often performed as the first-line treatment for large, benign colorectal polyps. We report the management of benign lesions detected by organised colorectal cancer (CRC) screening. METHODS: Population-based study in 2012, 2016, and 2017, analyzing the evolution of surgical management of benign polyps of≥2cm diameter discovered in the context of organised CRC screening after the implementation of a regional referral network for the management of superficial colorectal lesions. RESULTS: A total of 1571 patients underwent colonoscopy following a positive test during the study period, among which 981 colonoscopies yielded at least one lesion. The adenoma detection rate was lower in 2012 (Guaiac test) than in 2016 and 2017 (fecal immunochemical test) (40% vs. 60% vs. 57%, P<0.0001). The surgery rate for benign lesions decreased from 14.6% in 2012 to 7.7% in 2016 and 5% in 2017 (P=0.017). The risk factors for surgery for benign lesions were year 2012 (odds ratio [OR]=3.35, P=0.022), high-grade dysplasia (OR=2.49, P=0.04), in situ carcinoma (OR=5, P=0.003), size≥20mm (OR=17.39, P<0.0001), and private sector (OR=6.6, P=0.0002). The morbidity rate of surgery for benign polyp≥2cm was 20.4% at 1month and its cost was sixfold higher than that of endoscopy. CONCLUSION: The establishment of a regional referral network for the management of large colorectal polyps reduces the rate of surgical management of such lesions.

BDNF levels and liver stiffness in subjects with alcohol use disorder: Evaluation after alcohol withdrawal.

Background: Brain-derived neurotrophic factor (BDNF) plays a key role in the processes of withdrawal and addiction in alcohol use disorder (AUD), and is also involved in liver homeostasis. The role of BDNF in liver damage and its link with liver stiffness are not known. We hypothesize that serum BDNF levels are linked to changes in hepatic elasticity, both of which depend on variations in alcohol consumption.Objectives: We aimed to study the evolution of BDNF levels and changes in the liver stiffness (LS) of AUD subjects, within two months following withdrawal.Methods: We measured LS by FibroScan® (as an indicator of the degree of liver fibrosis), gamma glutamyl transferase (GGT) levels (as a nonspecific but sensitive marker of liver status) and serum BDNF levels of 62 alcohol-dependent subjects without previously identified liver complications. Measures were obtained at the time of withdrawal (M0) and two months later (M2). Results: BDNF levels increased after alcohol withdrawal and small variations of LS were observed. BDNF values increased significantly according to fibrosis stages measured by LS (p = .028 at M0), and were predicted by GGT levels in a regression model (p = .007 at M0 and p = .003 at M2).Conclusion: In AUD, BDNF levels were associated with measured LS when divided into fibrosis risk categories. Changes in LS and BDNF levels after alcohol withdrawal may be related to changes in homeostatic mechanisms, in addition to those of liver status.

Evaluation of Longitudinal Exposure to Tacrolimus as a Risk Factor of Chronic Kidney Disease Occurrence Within the First-year Post-Liver Transplantation.

BACKGROUND: Renal failure is predictive of mortality in the early postliver-transplantation period and calcineurin inhibitors toxicity is a main challenge. Our aim is to assess the impact of longitudinal tacrolimus exposure (TLE) and other variables on chronic kidney disease (CKD)-free 1-year-survival. METHODS: Retrospective data of consecutive patients transplanted between 2011 and 2016 and treated with tacrolimus were collected. TLE and all relevant pre- and post-liver transplantation (LT) predictive factors of CKD were tested and included in a time-to-event model. CKD was defined by repeated estimated glomerular filtration rate (eGFR) values below 60 mL/min/1.73m2 at least for the last 3 months before M12 post-LT. RESULTS: Data from 180 patients were analyzed. CKD-free survival was 74.5% and was not associated with TLE. Pre-LT acute kidney injury (AKI) and eGFR at 1-month post-LT (eGFRM1) <60 mL/min/1.73m2 were significant predictors of CKD. By distinguishing 2 situations within AKI (ie, with or without hepatorenal syndrome [HRS]), only HRS-AKI remained associated to CKD. HRS-AKI and eGFRM1 <60 mL/min/1.73m2 increased the risk of CKD (hazard ratio, 2.5; 95% confidence interval, 1.2-4.9; hazard ratio, 4.8; 95% confidence interval, 2.6-8.8, respectively). CONCLUSIONS: In our study, TLE, unlike HRS-AKI and eGFRM1, was not predictive of CKD-free survival at 1-year post-LT. Our results once again question the reversibility of HRS-AKI.

Liver elastometry and alcohol withdrawal: Median-term follow-up in a psychiatric unit.

The measurement of liver stiffness (LS) shows promise as a follow-up tool after alcohol withdrawal, but it has mainly been studied in the early phase or in patients with severe liver disease. A 6-month ancillary study of a specific psychiatric cohort of alcoholic patients without known liver disease followed after withdrawal was conducted (Clinical Trial NCT01491347). Clinical and biological data and LS values were collected every 2 months. A total of 129 patients were included in the study; 93 had an LS assessment within the first 7 days, and 37 had all four LS measurements. Only seven (7.5%) patients had an initial LS > 12.1 kPa, the threshold used to define severe fibrosis. Abstinence was not associated with changes in LS at the various median-term follow-up periods. However, LS of abstinent subjects decreased significantly relative to that of non-abstinent subjects between M0 and M2. CAP™ values were not associated with abstinence. The systematic median-term follow-up of withdrawn patients does not appear to be contributory. However, LS could help to detect relapse in the first 2 months after withdrawal for subjects treated in a psychiatric hospital for dependence. It thus could serve as a motivation tool. Prospective studies with various and higher baseline LS values are warranted for simultaneous longitudinal assessment, including for very short- and long-term LS after withdrawal.

Subclinical proximal tubulopathy in hepatitis B: The roles of nucleot(s)ide analogue treatment and the hepatitis B virus.

BACKGROUND: The recommended monitoring tools for evaluating nucleot(s)ide analogue renal toxicity, such as estimated glomerular filtration rate (eGFR) and phosphatemia, are late markers of proximal tubulopathy. Multiple early markers are available, but no consensus exists on their use. AIM: To determine the 24 mo prevalence of subclinical proximal tubulopathy (SPT), as defined with early biomarkers, in treated vs untreated hepatitis B virus (HBV)-monoinfected patients. METHODS: A prospective, non-randomized, multicenter study of HBV-monoinfected patients with a low number of renal comorbidities was conducted. The patients were separated into three groups: Naïve, starting entecavir (ETV) treatment, or starting tenofovir disoproxil (TDF) treatment. Data on the early markers of SPT, the eGFR and phosphatemia, were collected quarterly. SPT was defined as a maximal tubular reabsorption of phosphate/eGFR below 0.8 mmoL/L and/or uric acid fractional excretion above 10%. The prevalence and cumulative incidence of SPT at month 24 (M24) were calculated. Quantitative data were analyzed using analyses of variance or Kruskal-Wallis tests, whereas chi-squared or Fisher's exact tests were used to analyze qualitative data. Multivariate analyses were used to adjust for any potential confounding factors. RESULTS: Of the 196 patients analyzed, 138 (84 naïve, 28 starting ETV, and 26 starting TDF) had no SPT at inclusion. At M24, the prevalence of SPT was not statistically different between naïve and either treated group (21.1% vs 30.7%, P < 0.42 and 50.0% vs 30.7%, P = 0.32 for ETV and TDF, respectively); no patient had an eGFR lower than 50 mL/min/1.73 m² or phosphatemia less than 0.48 mmoL/L. In the multivariate analysis, no explanatory variables were identified after adjustment. The cumulative incidence of SPT over 24 mo (25.5%, 13.3%, and 52.9% in the naïve, ETV, and TDF groups, respectively) tended to be higher in the TDF group vs the naïve group (hazard ratio: 2.283, P = 0.05). SPT-free survival at M24 was 57.6%, 68.8%, and 23.5% for the naïve, ETV, and TDF groups, respectively. The median survival time without SPT, evaluated only in the TDF group, was 5.9 mo. CONCLUSION: The prevalence and incidence of SPT was higher in TDF-treated patients compared to naïve patients. SPT in the naïve population suggests that HBV can induce renal tubular toxicity.

Cirrhotic patients and older people.

The global population is aging, and so the number of older cirrhotic patients is increasing. Older patients are characterised by a risk of frailty and comorbidities, and age is a risk factor for mortality in cirrhotic patients. The incidence of non-alcoholic fatty liver disease as an aetiology of cirrhosis is increasing, while that of chronic viral hepatitis is decreasing. Also, cirrhosis is frequently idiopathic. The management of portal hypertension in older cirrhotic patients is similar to that in younger patients, despite the greater risk of treatment-related adverse events of the former. The prevalence of hepatocellular carcinoma increases with age, but its treatment is unaffected. Liver transplantation is generally recommended for patients < 70 years of age. Despite the increasing prevalence of cirrhosis in older people, little data are available and few recommendations have been proposed. This review suggests that comorbidities have a considerable impact on older cirrhotic patients.