Thermal ablation alone vs thermal ablation combined with transarterial chemoembolization for patients with small (<3 cm) hepatocellular carcinoma.

PURPOSE: Thermal ablation (TA) and transarterial chemoembolization (TACE) may be used alone or in combination (TACE+TA) for the treatment of hepatocellular carcinoma (HCC). The aim of our study was to compare the time to tumor progression (TTP) and overall survival (OS) for patients who received TA alone or TACE+TA for HCC tumors under 3 cm. MATERIALS AND METHODS: This HIPAA-compliant IRB-approved retrospective analysis included 85 therapy-naïve patients from 2010 to 2018 (63 males, 22 females, mean age 62.4 ± 8.5 years) who underwent either TA alone (n = 64) or TA in combination with drug-eluting beads (DEB)-TACE (n = 18) or Lipiodol-TACE (n = 3) for locoregional therapy of early stage HCC with maximum tumor diameter under 3 cm. Kaplan-Meier analysis was performed using the log-rank test to assess TTP and OS. RESULTS: All TA and TACE+TA treatments included were technically successful. TTP was 23.0 months in the TA group and 22.0 months in the TACE+TA group. There was no statistically significant difference in TTP (p = 0.64). Median OS was 69.7 months in the TA group and 64.6 months in the TACE+TA group. There was no statistically significant difference in OS (p = 0.14). The treatment cohorts had differences in AFP levels (p = 0.03) and BCLC stage (p = 0.047). Complication rates between patient groups were similar (p = 0.61). CONCLUSION: For patients with HCC under 3 cm, TA alone and TACE+TA have similar outcomes in terms of TTP and OS, suggesting that TACE+TA may not be needed for these tumors unless warranted by tumor location or other technical consideration.

Pathological characteristics of liver sinusoidal thrombosis in COVID-19 patients: A series of 43 cases.

AIM: Coronavirus disease (COVID-19) is characterized by pneumonia with secondary damage to multiple organs including the liver. Liver injury (elevated alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) often correlates with disease severity in COVID-19 patients. The aim of this study is to identify pathological microthrombi in COVID-19 patient livers by correlating their morphology with liver injury, and examine hyperfibrinogenemia and von Willebrand factor (vWF) as mechanisms of their formation. METHODS: Forty-three post-mortem liver biopsy samples from COVID-19 patients were obtained from Papa Giovanni XXIII Hospital in Bergamo, Italy. Three morphological features of microthrombosis (sinusoidal erythrocyte aggregation [SEA], platelet microthrombi [PMT], and fibrous thrombi) were evaluated. RESULTS: We found liver sinusoidal microthrombosis in 23 COVID-19 patients (53%) was associated with a higher serum ALT and AST level compared to those without (ALT: 10-fold, p = 0.04; AST: 11-fold, p = 0.08). Of 43 livers, PMT and SEA were observed in 14 (33%) and 19 (44%) cases, respectively. Fibrous thrombi were not observed. Platelet microthrombi were associated with increased ALT (p < 0.01), whereas SEA was not (p = 0.73). In COVID-19 livers, strong vWF staining in liver sinusoidal endothelial cells was associated with significantly increased platelet adhesion (1.7-fold, p = 0.0016), compared to those with weak sinusoidal vWF (2-fold, p < 0.0001). Sinusoidal erythrocyte aggregation in 19 (83%) liver samples was mainly seen in zone 2. Livers with SEA had significantly higher fibrinogen (1.6-fold, p = 0.031) compared to those without SEA in COVID-19 patients. CONCLUSIONS: Liver PMT is a pathologically important thrombosis associated with liver injury in COVID-19, while SEA is a unique morphological feature of COVID-19 patient livers. Sinusoidal vWF and hyperfibrinogenemia could contribute to PMT and SEA formation.

Liver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy.

BACKGROUND AND AIMS: COVID-19 is associated with liver injury and elevated interleukin-6 (IL-6). We hypothesized that IL-6 trans-signaling in liver sinusoidal endothelial cells (LSECs) leads to endotheliopathy (a proinflammatory and procoagulant state) and liver injury in COVID-19. METHODS: Coagulopathy, endotheliopathy, and alanine aminotransferase (ALT) were retrospectively analyzed in a subset (n = 68), followed by a larger cohort (n = 3,780) of patients with COVID-19. Liver histology from 43 patients with COVID-19 was analyzed for endotheliopathy and its relationship to liver injury. Primary human LSECs were used to establish the IL-6 trans-signaling mechanism. RESULTS: Factor VIII, fibrinogen, D-dimer, von Willebrand factor (vWF) activity/antigen (biomarkers of coagulopathy/endotheliopathy) were significantly elevated in patients with COVID-19 and liver injury (elevated ALT). IL-6 positively correlated with vWF antigen (p = 0.02), factor VIII activity (p = 0.02), and D-dimer (p <0.0001). On liver histology, patients with COVID-19 and elevated ALT had significantly increased vWF and platelet staining, supporting a link between liver injury, coagulopathy, and endotheliopathy. Intralobular neutrophils positively correlated with platelet (p <0.0001) and vWF (p <0.01) staining, and IL-6 levels positively correlated with vWF staining (p <0.01). IL-6 trans-signaling leads to increased expression of procoagulant (factor VIII, vWF) and proinflammatory factors, increased cell surface vWF (p <0.01), and increased platelet attachment in LSECs. These effects were blocked by soluble glycoprotein 130 (IL-6 trans-signaling inhibitor), the JAK inhibitor ruxolitinib, and STAT1/3 small-interfering RNA knockdown. Hepatocyte fibrinogen expression was increased by the supernatant of LSECs subjected to IL-6 trans-signaling. CONCLUSION: IL-6 trans-signaling drives the coagulopathy and hepatic endotheliopathy associated with COVID-19 and could be a possible mechanism behind liver injury in these patients. LAY SUMMARY: Patients with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection often have liver injury, but why this occurs remains unknown. High levels of interleukin-6 (IL-6) and its circulating receptor, which form a complex to induce inflammatory signals, have been observed in patients with COVID-19. This paper demonstrates that the IL-6 signaling complex causes harmful changes to liver sinusoidal endothelial cells and may promote blood clotting and contribute to liver injury.

Value-based medicine, a compass to guide healthcare decisions in the COVID-19 aftermath.

The ongoing COVID-19 pandemics has claimed hundreds of thousands of lives among the elderly, the patients with chronic conditions and among underserved communities and people in social distress. In addition, the measures that succeeded in containing the epidemic created a profound economic crisis, which real dimension is still unclear. It is clear, however, that most healthcare systems were unprepared. Years of cost containments had eroded the ability of the healthcare sector to cope with the surge in cases. This editorial contends that rebuilding the healthcare systems will require forward thinking, a data-driven approach and avoidance of reactive decision making. The editorial proposes the Value Based Medicine approach as a way to avoid the errors of the past and to align decision making in healthcare with patient health and quality of life (Value). This is an approach that is gaining traction in several systems. It needs a built-in capability to collect and analyse outcome and costing data. Today the necessary informatic and computational capabilities are widely available.