Impact of the COVID-19 pandemic on liver transplant waitlist outcome in France.

The objective of this study was to investigate the impact of the COVID-19 pandemic on the outcome of patients on the liver transplantation (LT) waitlist in 2020 in France, in particular, the incidence of deaths and delisting for worsening condition, depending on the allocation score component. The 2020 cohort of patients on the waiting list was compared with the 2018/2019 cohorts. 2020 saw fewer LTs than in either 2019 or 2018 (1128, 1356, and 1325, respectively), together with fewer actual brain dead donors (1355, 1729, and 1743). In 2020, deaths or delisting for worsening condition increased significantly versus 2018/2019 (subdistribution hazard ratio 1.4, 95% confidence interval [CI] 1.2-1.7), after adjustment for age, place of care, diabetes, blood type, and score component, although COVID-19-related mortality was low. This increased risk mainly concerned patients with hepatocellular carcinoma (1.52, 95% CI 1.22-1.90), with 650 MELD exception points (2.19, 95% CI 1.08-4.43), and especially those without HCC and MELD scores from 25 to 30 (3.36 [95% CI 1.82-6.18]). In conclusion, by significantly decreasing LT activity in 2020, the COVID-19 pandemic increased the number of waitlist deaths and delisting for worsening condition, and significantly more for particular components of the score, including intermediate severity cirrhosis.

Targeted Therapies for Hepatocellular Carcinoma Treatment: A New Era Ahead-A Systematic Review.

Hepatocellular carcinoma (HCC) remains one of the most common malignancies and the third cause of cancer-related death worldwide, with surgery being the best prognostic tool. Among the well-known causative factors of HCC are chronic liver virus infections, chronic virus hepatitis B (HBV) and chronic hepatitis virus C (HCV), aflatoxins, tobacco consumption, and non-alcoholic liver disease (NAFLD). There is a need for the development of efficient molecular markers and alternative therapeutic targets of great significance. In this review, we describe the general characteristics of HCC and present a variety of targeted therapies that resulted in progress in HCC therapy.

Viral hepatitis in persons living with HIV in the post-COVID era.

Coinfection with hepatitis viruses A to E is frequent in persons living with HIV (PLWH) and causes significant morbidity and mortality. Oro-fecal transmissible hepatitis A and E mostly produce acute self-limited episodes in poor income regions and in non-vaccinated travelers. In high-income countries, outbreaks of hepatitis A occur in men having sex with men (MSM) and chronic hepatitis E is occasionally reported among PLWH with severe immunodeficiency. Chronic hepatitis B, C, and D are frequent in PLWH in highly endemic regions and globally in persons who inject drugs (PWID) and MSM. Progression to liver cirrhosis and development of hepatocellular carcinoma (HCC) is major clinical complications in coinfected patients. Current estimates for PLWH are of 38 million worldwide. Roughly 12% have chronic viral hepatitis (5 million). Coinfection figures are of 5-10% for HBV (2-4 million), 4% for HCV (1.5 million), and 15% of HBsAg+ for HDV (0.5 million). Oral direct-acting antivirals (DAA) cure almost all treated patients with hepatitis C. However, given that there is no protective HCV immunity, PLWH with high-risk behaviors may experience HCV reinfection episodes. Tenofovir is the drug of choice in PLWH with chronic hepatitis B, given its dual effect on HIV and HBV. Lifelong oral tenofovir suppresses HBV replication and ameliorate liver damage. However, the risk of HCC persists even in the absence of cirrhosis. Finally, HDV causes the worst of viral hepatitis with faster progression to cirrhosis and HCC. An entry inhibitor, bulevirtide, has recently been approved and another drug, lonafarnib, is completing Phase 3 trials. Combination antiviral therapy for hepatitis D could improve dramatically the poor prognosis of HIV-HDV coinfected patients. The resumption of good medical practices in PLWH after the big disruption caused by COVID-19 will reduce the burden of viral hepatitis coinfections. Renewed efforts on HAV and HBV vaccination of susceptible individuals and earlier and wider prescription of antiviral therapy for HBV, HCV, and/or HDV coinfection should be prioritized in PLWH. The benefits of innovative strategies for viral hepatitis, including pre-exposure prophylaxis or use of long-acting antivirals, warrant further consideration in PLWH.

COVID-19: Has the Liver Been Spared?

The liver is a secondary and often collateral target of COVID-19 disease but can lead to important consequences. COVID-19 might directly cause a high number of complications in patients with pre-existing chronic liver disease, increasing their risk of hepatic decompensation. Moreover, it also determines indirect consequences in the management of patients with liver disease, especially in those suffering from decompensated cirrhosis and HCC, as well as in the execution of their follow-up and the availability of all therapeutic possibilities. Liver imaging in COVID-19 patients proved to be highly nonspecific, but it can still be useful for identifying the complications that derive from the infection. Moreover, the recent implementation of telemedicine constitutes a possible solution to both the physical distancing and the re-organizational difficulties arising from the pandemic. The present review aims to encompass the currently hypothesized pathophysiological mechanisms of liver injury in patients with COVID-19 mediated by both the direct invasion of the virus and its indirect effects and analyze the consequence of the pandemic in patients with chronic liver disease and liver tumors, with particular regard to the management strategies that have been implemented to face this worldwide emergency and that can be further improved.

Management of liver diseases: Current perspectives.

There is increasing incidence and prevalence of acute and chronic liver diseases (CLDs) all over the world which influence the quality of life and can give rise to life threatening complications. The burden of advanced liver disease due to hepatitis B has been controlled by antivirals but its eradication is difficult soon. Highly effective directly acting antiviral therapy has reduced the burden of hepatitis C but is partially offset by increasing IV drug abuse. Non-alcoholic fatty liver disease pandemic is on and there is recent alarming increase in alcohol related liver disease, both of which have no drug cure apart from control of the risk factors. Genetic factors have been identified in progression of all forms of CLD. Due to better management of complications of CLD, the life span of patients have increased spiking the number of hepatocellular carcinoma (HCC) and patients needing liver transplantation (LT). The present severe acute respiratory syndrome coronavirus pandemic has affected the outcome CLD including LT in addition to causing acute hepatitis. Better diagnostics and therapeutics are available for liver fibrosis, portal hypertension, HCC and post LT management and many drugs are under trial. The present review summarises the current scenario of the epidemiology and the advances in diagnosis and treatment of liver diseases including their complications like portal hypertension, HCC and LT.

15-Year progression to liver cancer in the lack of treatment for lysosomal acid lipase deficiency: A case report.

RATIONALE: Lysosomal acid lipase deficiency (LAL-D) is a poorly diagnosed genetic disorder characterized by the accumulation of cholesteryl esters and triglycerides in many tissues, leading to dyslipidemia and cardiovascular complications. In the liver, deposits are found within hepatocytes and Kupffer cells, generating microvesicular steatosis, progressive fibrosis, and cirrhosis. Sebelipase alfa is the target therapy which can improve laboratory changes and reduce the progression of liver damage, but this is not yet widely available. PATIENT CONCERNS: We are reporting a 15-year follow-up of a Brazilian man who was diagnosed with cirrhosis at age 43 and with LAL-D at age 53, but he has never been treated with sebelipase alfa for economic reasons. During the coronavirus disease 2019 (COVID-19) pandemic, he lost follow-up and missed three 6-month ultrasound exams for liver cancer screening. DIAGNOSIS: At age 58, a remarkable deterioration in liver function was observed and he was diagnosed with hepatocellular carcinoma (HCC) outside the Milan Criteria (two nodules measuring 48mm and 25mm). Three other individuals with LAL-D and progression to liver cancer have been reported so far and none of them underwent enzyme replacement therapy: an 11-year-old girl with HCC, a 51-year-old male with cholangiocarcinoma, and a 21-year-old male with hepatocellular-cholangiocarcinoma. The latter had the same mutation in the gene LIPA as our patient, but a relationship between this variant and malignancies has not yet been established. LESSONS: We emphasize how important is to treat LAL-D patients after diagnosis in order to avoid worsening liver function and progression to neoplasms. Untreated individuals should be considered at a higher risk but the most appropriate liver cancer screening program for this subgroup is still unknown.

Hepatocellular carcinoma.

Liver cancer remains a global health challenge, with an estimated incidence of >1 million cases by 2025. Hepatocellular carcinoma (HCC) is the most common form of liver cancer and accounts for ~90% of cases. Infection by hepatitis B virus and hepatitis C virus are the main risk factors for HCC development, although non-alcoholic steatohepatitis associated with metabolic syndrome or diabetes mellitus is becoming a more frequent risk factor in the West. Moreover, non-alcoholic steatohepatitis-associated HCC has a unique molecular pathogenesis. Approximately 25% of all HCCs present with potentially actionable mutations, which are yet to be translated into the clinical practice. Diagnosis based upon non-invasive criteria is currently challenged by the need for molecular information that requires tissue or liquid biopsies. The current major advancements have impacted the management of patients with advanced HCC. Six systemic therapies have been approved based on phase III trials (atezolizumab plus bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab) and three additional therapies have obtained accelerated FDA approval owing to evidence of efficacy. New trials are exploring combination therapies, including checkpoint inhibitors and tyrosine kinase inhibitors or anti-VEGF therapies, or even combinations of two immunotherapy regimens. The outcomes of these trials are expected to change the landscape of HCC management at all evolutionary stages.

The COVID-19 pandemic will have a long-lasting impact on the quality of cirrhosis care.

The coronavirus disease 2019 (COVID-19) pandemic has shattered the meticulously developed processes by which we delivered quality care for patients with cirrhosis. Care has been transformed by the crisis, but enduring lessons have been learned. In this article, we review how COVID-19 will impact cirrhosis care. We describe how this impact unfolds over 3 waves; i) an intense period with prioritized high-acuity care with delayed elective procedures and routine care during physical distancing, ii) a challenging 'return to normal' following the end of physical distancing, with increased emergent decompensations, morbidity, and systems of care overwhelmed by the backlog of deferred care, and iii) a protracted period of suboptimal outcomes characterized by missed diagnoses, progressive disease and loss to follow-up. We outline the concrete steps required to preserve the quality of care provided to patients with cirrhosis. This includes an intensification of the preventative care provided to patients with compensated cirrhosis, proactive chronic disease management, robust telehealth programs, and a reorganization of care delivery to provide a full service of care with flexible clinical staffing. Managing the pandemic of a serious chronic disease in the midst of a global infectious pandemic is challenging. It is incumbent upon the entire healthcare establishment to be strong enough to weather the storm. Change is needed.