Impact of COVID-19 on the management of hepatocellular carcinoma in a high-prevalence area: What's new 12 months later?

INTRODUCTION AND OBJECTIVES: The lockdown policy introduced in 2020 to minimize the spread of the COVID-19 pandemic, significantly affected the management and care of patients affected by hepatocellular carcinoma (HCC). The aim of this follow-up study was to determine the 12 months impact of the COVID-19 pandemic on the cohort of patients affected by HCC during the lockdown, within six French academic referral centers in the metropolitan area of Paris. MATERIALS AND METHODS: We performed a 12 months follow-up of the cross-sectional study cohort included in 2020 on the management of patients affected by HCC during the first six weeks of the COVID-19 pandemic (exposed), compared to the same period in 2019 (unexposed). Overall survival were compared between the groups. Predictors of mortality were analysed with Cox regression. RESULTS: From the initial cohort, 575 patients were included (n = 263 Exposed_COVID, n = 312 Unexposed_COVID). Overall and disease free survival at 12 months were 59.9 ± 3.2% vs 74.3 ± 2.5% (p<0.001) and 40.2 ± 3.5% vs 63.5 ± 3.1% (p<0.001) according to the period of exposure (Exposed_COVID vs Unexposed_COVID, respectively). Adjusted Cox regression revealed that the period of exposure (Exposed_COVID HR: 1.79, 95%CI (1.36, 2.35) p<0.001) and BCLC stage B, C and D (BCLC B HR: 1.82, 95%CI (1.07, 3.08) p = 0.027 - BCLC C HR: 1.96, 95%CI (1.14, 3.38) p = 0.015 - BCLC D HR: 3.21, 95%CI (1.76, 5.85) p<0.001) were predictors of death. CONCLUSIONS: Disruption of routine healthcare services because of the pandemic translated to reduced 1 year overall and disease-free survival among patients affected by HCC, in the metropolitan area of Paris, France.

Assessment of Factors Associated with Morbidity and Textbook Outcomes of Laparoscopic Liver Resection in Obese Patients: A French Nationwide Study.

BACKGROUND: Liver surgeons need to know the expected outcomes of laparoscopic liver resection (LLR) in obese patients. OBJECTIVE: The purpose of the present study is to assess morbidity, mortality and textbook outcomes (TO) after LLR in obese patients. METHODS: This is a French multicenter study of patients undergoing LLR between 1996 and 2018. Obesity was defined by a BMI at or above 30 kg/m 2 . Short-term outcomes and TO were compared between obese (ob) and nonobese (non-ob) patients. Factors associated with severe morbidity and TO were investigated. RESULTS: Of 3,154 patients included, 616 (19.5%) were obese. Ob-group patients had significantly higher American Society of Anesthesiologists (ASA) score and higher incidence of metabolic syndrome and chronic liver disease and were less likely to undergo major hepatectomy. Mortality rates were similar between ob and non-ob groups (0.8 vs 1.1%; p = 0.66). Overall morbidity and hospital stay were significantly increased in the ob group compared with the non-ob group (39.4 vs 34.7%, p = 0.03; and 9.5 vs 8.6 days, p = 0.02), whereas severe 90-day morbidity (at or above Clavien-Dindo grade III) was similar between groups (8% in both groups; p = 0.90). TO rate was significantly lower for the ob group than the non-ob group (58.3 vs 63.7%; p = 0.01). In multivariate analysis, obesity did not emerge as a risk factor for severe 90-day morbidity but was associated with a lower TO rate after LLR (odds ratio = 0.8, 95% CI 0.7-1.0; p = 0.03). CONCLUSIONS: LLR in obese patients is safe and effective with acceptable mortality and morbidity. Obesity had no impact on severe morbidity but was a factor for failing to achieve TO after LLR.

Impact of COVID-19 on the management of hepatocellular carcinoma in a high-prevalence area.

BACKGROUND & AIMS: Patients affected by hepatocellular carcinoma (HCC) represent a vulnerable population during the COVID-19 pandemic and may suffer from altered allocation of healthcare resources. The aim of this study was to determine the impact of the COVID-19 pandemic on the management of patients with HCC within 6 referral centres in the metropolitan area of Paris, France. METHODS: We performed a multicentre, retrospective, cross-sectional study on the management of patients with HCC during the first 6 weeks of the COVID-19 pandemic (exposed group), compared with the same period in 2019 (unexposed group). We included all patients discussed in multidisciplinary tumour board (MTB) meetings and/or patients undergoing a radiological or surgical programmed procedure during the study period, with curative or palliative intent. Endpoints were the number of patients with a modification in the treatment strategy, or a delay in decision-to-treat. RESULTS: After screening, n = 670 patients were included (n = 293 exposed to COVID, n = 377 unexposed to COVID). Fewer patients with HCC presented to the MTB in 2020 (p = 0.034) and fewer had a first diagnosis of HCC (n = 104 exposed to COVID, n = 143 unexposed to COVID, p = 0.083). Treatment strategy was modified in 13.1% of patients, with no differences between the 2 periods. Nevertheless, 21.5% vs. 9.5% of patients experienced a treatment delay longer than 1 month in 2020 compared with 2019 (p <0.001). In 2020, 7.1% (21/293) of patients had a diagnosis of an active COVID-19 infection: 11 (52.4%) patients were hospitalised and 4 (19.1%) patients died. CONCLUSIONS: In a metropolitan area highly impacted by the COVID-19 pandemic, we observed fewer patients with HCC, and similar rates of treatment modification, but with a significantly longer treatment delay in 2020 vs. 2019. LAY SUMMARY: During the coronavirus disease 2019 (COVID-19) pandemic era, fewer patients with hepatocellular carcinoma (HCC) presented to the multidisciplinary tumour board, especially with a first diagnosis of HCC. Patients with HCC had a treatment delay that was longer in the COVID-19 period than in 2019.

Definition and Prospective Assessment of Functional Recovery After Liver Transplantation: A New Objective Consensus-Based Metric for Safe Discharge.

Standardized discharge criteria are critical to reduce premature discharge and avoid unnecessary hospital stays. No such criteria exist for patients undergoing liver transplantation (LT). To achieve a consensus-based checklist of criteria for safe patient discharge after LT, this mixed-method study included the following: a systematic literature review and expert discussion to draft a first checklist of post-LT discharge criteria, defining patient recovery and indications for hospital discharge (functional recovery); an exploratory online electronic Delphi (e-Delphi) study; a single-center pilot study to test checklist feasibility; and a final e-Delphi study with an extended interdisciplinary expert panel to validate the final checklist. The first round provided a 10-point discharge checklist with 5 patient-centered items derived from discharge criteria after liver surgery and 5 graft-centered items derived from expert discussion. The restricted panel (9 experts) e-Delphi provided 100% consensus after the second round, with slight modifications to the criteria. During the pilot study, 19 of 45 (42.2%) patients included fulfilled the complete checklist (100% of 10 items) after median (IQR) 16 (8-21) days (functional recovery) and a length of stay of 20 (9-24) days. The item with the lowest completion rate was minimum serum tacrolimus level in the target on 2 consecutive blood samples (n = 21; 47%), achieved at 13 (9-15) days. The extended panel (66 experts) e-Delphi provided 95%-98% consensus after the third round, with slight modifications of the criteria. This study provided substantial consensus on discharge criteria after LT. We anticipate that these criteria will be useful in clinical practice to guide patient discharge and increase the comparability of results between future studies.

Use of Artificial Intelligence as an Innovative Method for Liver Graft Macrosteatosis Assessment.

The worldwide implementation of a liver graft pool using marginal livers (ie, grafts with a high risk of technical complications and impaired function or with a risk of transmitting infection or malignancy to the recipient) has led to a growing interest in developing methods for accurate evaluation of graft quality. Liver steatosis is associated with a higher risk of primary nonfunction, early graft dysfunction, and poor graft survival rate. The present study aimed to analyze the value of artificial intelligence (AI) in the assessment of liver steatosis during procurement compared with liver biopsy evaluation. A total of 117 consecutive liver grafts from brain-dead donors were included and classified into 2 cohorts: ≥30 versus <30% hepatic steatosis. AI analysis required the presence of an intraoperative smartphone liver picture as well as a graft biopsy and donor data. First, a new algorithm arising from current visual recognition methods was developed, trained, and validated to obtain automatic liver graft segmentation from smartphone images. Second, a fully automated texture analysis and classification of the liver graft was performed by machine-learning algorithms. Automatic liver graft segmentation from smartphone images achieved an accuracy (Acc) of 98%, whereas the analysis of the liver graft features (cropped picture and donor data) showed an Acc of 89% in graft classification (≥30 versus <30%). This study demonstrates that AI has the potential to assess steatosis in a handy and noninvasive way to reliably identify potential nontransplantable liver grafts and to avoid improper graft utilization.

Pure laparoscopic versus open hemihepatectomy: a critical assessment and realistic expectations - a propensity score-based analysis of right and left hemihepatectomies from nine European tertiary referral centers.

INTRODUCTION: A stronger evidence level is needed to confirm the benefits and limits of laparoscopic hemihepatectomies. METHODS: Laparoscopic and open hemihepatectomies from nine European referral centers were compared after propensity score matching (right and left hemihepatectomies separately, and benign and malignant diseases sub-analyses). RESULTS: Five hundred and forty-five laparoscopic hemihepatectomies were compared with 545 open. Laparoscopy was associated with reduced blood loss (P < 0.001), postoperative stay (P < 0.001) and minor morbidity (P = 0.002), supported by a lower Comprehensive Complication Index (CCI) (P = 0.035). Laparoscopic right hemihepatectomies were associated with lower ascites (P = 0.016), bile leak (P = 0.001) and wound infections (P = 0.009). Laparoscopic left hemihepatectomies exhibited a lower incidence of bile leak and cardiovascular complications (P = 0.024; P = 0.041), lower minor and major morbidity (P = 0.003; P = 0.044) and reduced CCI (P = 0.002). Laparoscopic major hepatectomies (LMH) for benign disease were associated with lower blood loss (P = 0.001) and bile leaks (P = 0.037) and shorter total stay (P < 0.001). LMH for malignancy were associated with lower blood loss (P < 0.001) and minor morbidity (P = 0.027) supported by a lower CCI (P = 0.021) and shorter stay (P < 0.001). CONCLUSION: This multicenter study confirms some associated advantages of laparoscopic left and right hemihepatectomies in malignant and benign conditions highlighting the need for realistic expectations of the minimally invasive approach based on the resected hemiliver and the patients treated.

Interest of preoperative immunonutrition in liver resection for cancer: study protocol of the PROPILS trial, a multicenter randomized controlled phase IV trial.

BACKGROUND: Malnutrition is an independent risk factor of postoperative morbidity and mortality and it's observed in 20 to 50% of surgical patients. Preoperative interventions to optimize the nutritional status, reduce postoperative complications and enteral nutrition has proven to be superior to the parenteral one. Moreover, regardless of the nutritional status of the patient, surgery impairs the immunological response, thus increasing the risk of postoperative sepsis. Immunonutrition has been developed to improve the immunometabolic host response in perioperative period and it has been proven to reduce significantly postoperative infectious complications and length of hospital stay in patients undergoing elective gastrointestinal surgery for tumors. We hypothesize that a preoperative oral immunonutrition (ORAL IMPACT®) can reduce postoperative morbidity in liver resection for cancer. METHODS/DESIGN: Prospective multicenter randomized placebo-controlled double-blind phase IV trial with two parallel treatment groups receiving either study product (ORAL IMPACT®) or control supplement (isocaloric isonitrogenous supplement--IMPACT CONTROL®) for 7 days before liver resection for cancer. A total of 400 patients will be enrolled. Patients will be stratified according to the type of hepatectomy, the presence of chronic liver disease and the investigator center. The main end-point is to evaluate in intention-to-treat analysis the overall 30-day morbidity. Secondary end-points are to assess the 30-day infectious and non-infectious morbidity, length of antibiotic treatment and hospital stay, modifications on total food intake, compliance to treatment, side-effects of immunonutrition, impact on liver regeneration and sarcopenia, and to perform a medico-economic analysis. DISCUSSION: The overall morbidity rate after liver resection is 22% to 42%. Infectious post-operative complications (12% to 23%) increase the length of hospital stay and costs and are responsible for a quarter of 30-day mortality. Various methods have been advocated to decrease the rate of postoperative complications but there is no evidence to support or refute the use of any treatment and further trials are required. The effects of preoperative oral immunonutrition in non-cirrhotic patients undergoing liver resection for cancer are unknown. The present trial is designed to evaluate whether the administration of a short-term preoperative oral immunonutrition can reduce postoperative morbidity in non-cirrhotic patients undergoing liver resection for cancer. TRIAL REGISTRATION: Clinicaltrial.gov: NCT02041871.

Is computed tomography volumetric assessment of the liver reliable in patients with cirrhosis?

OBJECTIVES: The estimation of liver volume (LV) has been widely studied in normal liver, the density of which is considered to be equivalent to 1 kg/l. In cirrhosis, volumetric evaluation and its correlation to liver mass remain unclear. The aim of this study was to evaluate the accuracy of computed tomography (CT) scanning to assess LV in patients with cirrhosis. METHODS: Liver volume was evaluated by CT (CTLV) and correlated to the explanted liver weight (LW) in 49 patients. Liver density (LD) and its association with clinical features were analysed. Commonly used formulae for estimating LV were also evaluated. The real density of cirrhotic liver was prospectively measured in explant specimens. RESULTS: Wide variations between CTLV (in ml) and LW (in g) were found (range: 3-748). Cirrhotic livers in patients with hepatitis B virus infection presented significantly increased LD (P = 0.001) with lower CTLV (P = 0.005). Liver volume as measured by CT was also decreased in patients with Model for End-stage Liver Disease scores of >15 (P = 0.023). Formulae estimating LV correlated poorly with CTLV and LW. The density of cirrhotic liver measured prospectively in 15 patients was 1.1 kg/l. CONCLUSIONS: In cirrhotic liver, LV assessed by CT did not correspond to real LW. Liver density changed according to the aetiology and severity of liver disease. Commonly used formulae did not accurately assess LV.

Prospective assessment of renal histopathological lesions in patients with end-stage liver disease: effects on long-term renal function after liver transplantation.

BACKGROUND & AIMS: The incidence of organic renal lesions in patients with end-stage liver disease is unknown. The goal of this study was to make a prospective evaluation of renal histological lesions in a group of unselected patients awaiting liver transplantation. METHODS: Sixty cirrhotic patients underwent a renal biopsy via the transjugular route. The potential effect of renal lesions on renal function was evaluated five years after transplantation. RESULTS: The yield of biopsies enabling satisfactory analysis was 77%, and no major complications occurred. Proteinuria>0.5 g/day was observed in only 8.7% of these patients, microscopic haematuria in 4.3%, creatinine levels>133 mmol/L (1.5mg/dl) in 10.9%, and Modification of the Diet in Renal Disease (MDRD) clearance<60 ml/min in 13.0%. Twenty-five patients (55.3%) had a morphological diagnosis of renal disease, 15 displayed IgA nephropathy and immunofluorescence testing showed that 12 had specific diabetic linear staining for IgG and albumin, of whom seven had associated histological lesions of diabetic nephropathy. Five years after liver transplantation, renal function had significantly deteriorated more in patients with initial diabetic lesions than in those with normal histology or IgA nephropathy alone. CONCLUSIONS: In patients with end-stage liver disease, IgA nephropathy and diabetic lesions were frequently found despite the absence of renal impairment and/or urinalysis anomalies. Our results strongly suggest that severe renal failure develops preferentially in liver transplant recipients with diabetes or carbohydrate intolerance, and that pre-existing arterial lesions may favour the nephrotoxicity of calcineurin inhibitors. Diabetes prior to transplantation needs to be strictly managed and requires a renal sparing immunosuppressive regimen after transplantation.

Might physicians be restricting access to liver transplantation for patients with alcoholic liver disease?

BACKGROUND/AIMS: In France, the most common cause of cirrhosis is excessive alcohol consumption. Post-transplant survival rates in patients with alcoholic liver disease (ALD) are at least as good as those seen with other indications. However, fewer of these patients are found on the waiting list. To understand the reasons for this discrepancy, it was decided to examine physicians' attitudes concerning the allocation of deceased donor liver allografts. METHODS: Using a standardized postal questionnaire, 1739 physicians were asked to allocate 100 liver transplants to two competing groups of patients who were equivalent except for the cause of their cirrhosis (i.e. alcohol-related or primary biliary cirrhosis). A composite score was then used to assess their attitude regarding the behavior of alcoholics and their responsibility for their illness. RESULTS: Among the 475 respondents (response rate: 27.3%), 55.2% allocated fewer than 50 transplants to ALD patients. This lower rate was independently associated with factors such as being a general practitioner (odds ratio [OR]=3.2, 95% confidence interval [95%CI]=1.8-5.9), a misinterpretation of ALD patients being equivalent to others (OR=1.8, 95%CI=1.1-3.0) or unfavorable attitudes regarding alcoholics (OR=4.0, 95%CI=1.7-9.5, to OR=126.8, 95%CI=34.0-472.1). CONCLUSIONS: Greater information and education of physicians may improve access to liver transplantation for ALD patients.