Impact of chronic liver disease on SARS-CoV-2 infection outcomes: Roles of stage, etiology and vaccination.

Since the first identification in December of 2019 and the fast spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, it has represented a dramatic global public health concern. Though affecting mainly the respiratory system, SARS-CoV-2 disease, defined as coronavirus disease 2019 (COVID-19), may have a systemic involvement leading to multiple organ dysfunction. Experimental evidence about the SARS-CoV-2 tropism for the liver and the increasing of hepatic cytolysis enzymes during infection support the presence of a pathophysiological relationship between liver and SARS-CoV-2. On the other side, patients with chronic liver disease have been demonstrated to have a poor prognosis with COVID-19. In particular, patients with liver cirrhosis appear extremely vulnerable to infection. Moreover, the etiology of liver disease and the vaccination status could affect the COVID-19 outcomes. This review analyzes the impact of the disease stage and the related causes on morbidity and mortality, clinical outcomes during SARS-CoV-2 infection, as well as the efficacy of vaccination in patients with chronic liver disease.

Plasma cell myeloma initially diagnosed as light-chain deposition disease on liver biopsy: A case report and literature review.

RATIONALE: Light-chain deposition disease (LCDD) is a rare condition characterized by the abnormal deposition of monoclonal light chains (LCs) in multiple organs, leading to progressive organ dysfunction. Herein, we report a case of plasma cell myeloma initially diagnosed as LCDD on liver biopsy performed for prominent cholestatic hepatitis. PATIENT CONCERNS: A 55-year-old Korean man complained of dyspepsia as the main symptom. On abdominal computed tomography performed at another hospital, the liver showed mildly decreased and heterogeneous attenuation with mild periportal edema. Preliminary liver function tests revealed abnormal results. The patient was treated for an unspecified liver disease; however, his jaundice gradually worsened, prompting him to visit our outpatient hepatology clinic for further evaluation. Magnetic resonance cholangiography revealed liver cirrhosis with severe hepatomegaly of unknown cause. A liver biopsy was performed for the diagnosis. Hematoxylin and eosin staining revealed diffuse extracellular amorphous deposits in perisinusoidal spaces with compressed hepatocytes. The deposits, which morphologically resembled amyloids, were not stained by Congo red but stained strongly positive for kappa LCs and weakly positive for lambda LCs. DIAGNOSES: Therefore, the patient was diagnosed with LCDD. Further systemic examination revealed a plasma cell myeloma. INTERVENTIONS: Fluorescence in situ hybridization, cytogenetics, and next-generation sequencing tested in bone marrow showed no abnormalities. The patient initially received bortezomib/lenalidomide/dexamethasone as the treatment regimen for plasma cell myeloma. OUTCOMES: However, he died shortly thereafter because of coronavirus disease 2019 complications. LESSONS: This case demonstrates that LCDD may present with sudden cholestatic hepatitis and hepatomegaly, and may be fatal if patients do not receive appropriate and timely treatment because of delayed diagnosis. Liver biopsy is useful for the diagnosis of patients with liver disease of unknown etiology.

Risk of New-Onset Liver Injuries Due to COVID-19 in Preexisting Hepatic Conditions-Review of the Literature.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted the world and caused the 2019 coronavirus disease (COVID-19) pandemic. The clinical manifestations of the virus can vary from patient to patient, depending on their respective immune system and comorbidities. SARS-CoV-2 can affect patients through two mechanisms: directly by targeting specific receptors or by systemic mechanisms. We reviewed data in the latest literature in order to discuss and determine the risk of new-onset liver injuries due to COVID-19 in preexisting hepatic conditions. The particular expression of angiotensin-converting enzyme 2 (ACE2) receptors is an additional risk factor for patients with liver disease. COVID-19 causes more severe forms in patients with non-alcoholic fatty liver disease (NAFLD), increases the risk of cirrhosis decompensation, and doubles the mortality for these patients. The coinfection SARS-CoV-2-viral hepatitis B or C might have different outcomes depending on the stage of the liver disease. Furthermore, the immunosuppressant treatment administered for COVID-19 might reactivate the hepatic virus. The high affinity of SARS-CoV-2 spike proteins for cholangiocytes results in a particular type of secondary sclerosing cholangitis. The impact of COVID-19 infection on chronic liver disease patients is significant, especially in cirrhosis, influencing the prognosis and outcome of these patients.

Naltrexone for alcohol use disorder: Hepatic safety in patients with and without liver disease.

Naltrexone is an approved drug for management of alcohol use disorder (AUD), but data in patients with liver disease (LD) are limited. We aimed to evaluate the safety of naltrexone in those with LD. This is a retrospective cohort of adults with and without LD who were prescribed naltrexone for AUD from 2015 to 2019 in a safety-net setting. Naltrexone hepatic safety was determined by liver enzyme changes during and after compared to before naltrexone prescription as well as rates of subsequent hospitalization and death by Kaplan-Meier methods. Factors associated with hospitalization were examined by Cox regression. Of 160 patients prescribed naltrexone for AUD, 100 (63%) had LD and 47 (47%) of those with LD had cirrhosis (47% decompensated). The total cohort, LD, and cirrhosis groups had lower adjusted mean aspartate aminotransferase and alanine aminotransferase levels after versus before naltrexone prescription (p < 0.001). Two-year survival was 97.7% (95% confidence interval [CI], 84.6-99.7), 95.4% (95% CI, 82.8-98.8), 90.8% (95% CI, 73.5-97.0), and 81.3% (95% CI, 41.2-93.8) in those without LD, LD without cirrhosis, cirrhosis, and decompensated cirrhosis groups (p = 0.46), respectively. Alcohol-related 2-year hospitalization rates were 8.2% (95% CI, 2.7-24), 27.7% (95% CI, 16.6-44.0), 40.5% (95% CI, 24.8-61.6), and 41.7% (95% CI, 23.3-66.6) for the groups without LD, LD without cirrhosis, cirrhosis, and decompensated cirrhosis (p = 0.007), respectively. Independent predictors of subsequent hospitalization were LD, (hazard ratio [HR], 3.70; 95% CI, 1.19-11.51; p = 0.02), cirrhosis (HR, 5.16; 95% CI, 1.69-15.75), and shorter duration (≤30 days) of naltrexone prescription (HR, 2.50; 95% CI, 1.l2-5.20; p = 0.01). Conclusion: Naltrexone is safe to use in patients with underlying LD, including those with compensated cirrhosis. Although encouraging, more safety data are needed for those with decompensated cirrhosis.

COVID-19 and hepatorenal syndrome.

Coronavirus disease 2019 (COVID-19) is a highly infectious disease which emerged into a global pandemic. Although it primarily causes respiratory symptoms for affected patients, COVID-19 was shown to have multi-organ manifestations. Elevated liver enzymes appear to be commonly observed during the course of COVID-19, and there have been numerous reports of liver injury secondary to COVID-19 infection. It has been established that patients with pre-existing chronic liver disease (CLD) are more likely to have poorer outcomes following COVID-19 infection compared to those without CLD. Co-morbidities such as diabetes, hypertension, obesity, cardiovascular and chronic kidney disease frequently co-exist in individuals living with CLD, and a substantial population may also live with some degree of frailty. The mechanisms of how COVID-19 induces liver injury have been postulated. Hepatorenal syndrome (HRS) is the occurrence of kidney dysfunction in patients with severe CLD/fulminant liver failure in the absence of another identifiable cause, and is usually a marker of severe decompensated liver disease. Select reports of HRS following acute COVID-19 infection have been presented, although the risk factors and pathophysiological mechanisms leading to HRS in COVID-19 infection or following COVID-19 treatment remain largely unestablished due to the relative lack and novelty of published data. Evidence discussing the management of HRS in high-dependency care and intensive care contexts is only emerging. In this article, we provide an overview on the speculative pathophysiological mechanisms of COVID-19 induced HRS and propose strategies for clinical diagnosis and management to optimize outcomes in this scenario.

COVID-19 Severity and Mortality Among Chronic Liver Disease Patients: A Systematic Review and Meta-Analysis.

INTRODUCTION: Pre-existing comorbid conditions in COVID-19 patients are risk factors for developing severe disease and death. We aimed to determine the association of chronic liver disease (CLD), a comorbid condition, with severity of disease and death among COVID-19 patients. METHODS: We searched for studies reporting COVID-19 outcomes among CLD and non-CLD patients in databases including Medline, EMBASE, ScienceDirect, Google Scholar, and Cochrane Library from inception of the pandemic until February 2022. Risk of bias assessment was conducted by using the Newcastle-Ottawa Scale for assessing the quality of nonrandomized studies in meta-analyses. We conducted a meta-analysis with a random-effects model and reported pooled odds ratios (ORs) with 95% CIs. RESULTS: We included 40 studies with 908,032 participants. Most studies were conducted in China and the US. COVID-19 patients with CLD had significantly higher odds of having a severe form of COVID-19 (pooled OR = 2.44; 95% CI, 1.89-3.16) and death (pooled OR = 2.35; 95% CI, 1.85-3.00) when compared with COVID-19 patients without CLD. CONCLUSION: The presence of CLD is significantly related to adverse clinical outcomes among COVID-19 patients in terms of severity and mortality. Clinicians should develop a comprehensive intervention plan to manage these high-risk patients and reduce COVID-19-related deaths.

Spontaneous large liver haematoma with extensive intraperitoneal bleeding in a patient with COVID-19 infection.

Thrombotic complications during COVID-19 infections occur frequently, and anticoagulants to prevent and treat deep vein thrombosis appear to have a good safety profile in these patients. In addition, haemorrhagic complications during COVID-19 infections have also been reported. Hepatic inflammation can occur in COVID-19 infections as a direct consequence of cellular infection and cytopathy. Spontaneous subcapsular hepatic haematoma is extremely rare and can be life-threatening.A woman in her 40s presented to the hospital with fever and shortness of breath and was diagnosed with COVID-19 infection with respiratory failure requiring intubation. On day 49 of hospitalisation, she developed melena and acute anaemia; her haemoglobin dropped from 97g/L (9.7g/dL) to 56g/L (5.6g/dL). Abdominal and pelvic CT scans showed a large subcapsular liver haematoma with retroperitoneal extension. The patient received blood transfusions and remained haemodynamically stable. She was eventually extubated and discharged home.

COVID-19 and liver disease.

Knowledge on SARS-CoV-2 infection and its resultant COVID-19 in liver diseases has rapidly increased during the pandemic. Hereby, we review COVID-19 liver manifestations and pathophysiological aspects related to SARS-CoV-2 infection in patients without liver disease as well as the impact of COVID-19 in patients with chronic liver disease (CLD), particularly cirrhosis and liver transplantation (LT). SARS-CoV-2 infection has been associated with overt proinflammatory cytokine profile, which probably contributes substantially to the observed early and late liver abnormalities. CLD, particularly decompensated cirrhosis, should be regarded as a risk factor for severe COVID-19 and death. LT was impacted during the pandemic, mainly due to concerns regarding donation and infection in recipients. However, LT did not represent a risk factor per se of worse outcome. Even though scarce, data regarding COVID-19 specific therapy in special populations such as LT recipients seem promising. COVID-19 vaccine-induced immunity seems impaired in CLD and LT recipients, advocating for a revised schedule of vaccine administration in this population.

Covid19 vaccination-associated portal vein thrombosis-An interdisciplinary clinical challenge.

Despite one of the largest vaccination campaigns in human history, the COVID-19 pandemic has not been yet defeated. More than 10 billion doses of COVID-19 vaccine have been administered worldwide. AstraZeneca's Vaxzevria (ChAdOx1 nCoV-19 / AZD1222) was approved as the first viral vector-based vaccine in the EU on 29 January 2021. Thromboembolic events are a rare complication of vaccination with ChAdOx1 nCoV-19 in the context of, now known as vaccine-induced immune thrombotic thrombocytopenia (VITT), with an incidence of 1.5-3 in 100,000 vaccinations. VITT is clinically as well as pathophysiologically comparable to heparin-induced thrombocytopenia. Illustrated by a fulminant patient case, a multidisciplinary step-by-step guideline was developed for the recognition, diagnosis, and management of patients with severe acute portosplanchic venous thrombosis with mesenteric ischemia due to vaccine-induced immunogenic thrombotic thrombocytopenia.

Antibody Responses after SARS-CoV-2 Vaccination in Patients with Liver Diseases.

The novel mRNA-based vaccines against SARS-CoV-2 display encouraging safety and efficacy profiles. However, there is a paucity of data regarding their immunogenicity and safety in patients with liver diseases (PWLD), especially in those with cirrhosis. We prospectively assessed anti-SARS-CoV-2 S-spike IgG antibodies and neutralizing activity in fully vaccinated PWLD (n = 87) and controls (n = 40). Seroconversion rates were 97.4% (37/38) in cirrhotic PWLD, 87.8% (43/49) in non-cirrhotic PWLD and 100% (40/40) in controls. Adequate neutralizing activity was detected in 92.1% (35/38), 87.8% (43/49) and 100% (40/40) of cirrhotics, non-cirrhotics and controls, respectively. On multivariable analysis, immunosuppressive treatment was negatively correlated with anti-SARS-CoV-2 antibody titers (coefficient (SE): -2.716 (0.634), p < 0.001) and neutralizing activity (coefficient (SE): -24.379 (4.582), p < 0.001), while age was negatively correlated only with neutralizing activity (coefficient (SE): -0.31(0.14), p = 0.028). A total of 52 responder PWLD were reassessed approximately 3 months post-vaccination and no differences were detected in humoral responses between cirrhotic and non-cirrhotic PWLD. No significant side effects were noted post vaccination, while no symptomatic breakthrough infections were reported during a 6-month follow up. Overall, our study shows that m-RNA-based SARS-CoV-2 vaccines are safe and efficacious in PWLD. However, PWLD under immunosuppressive treatment and those of advanced age should probably be more closely monitored after vaccination.

SARS-CoV-2 infection in people with pre-existing liver disease: Further research is warranted.

Patients with severe liver disease who have been infected with severe acute respiratory syndrome coronavirus-2 (coronavirus disease 2019) frequently develop acute respiratory distress syndrome and multiple organ failure, with a high mortality rate, as a result of the hyper-proinflammatory state known as the cytokine storm. Clinicians must recognize cytokine storms earlier to avoid intensive care admission and multi-organ damage, a critical life-threatening condition with prognostic and therapeutic implications.

The histologic and molecular correlates of liver disease in fatal COVID-19 including with alcohol use disorder.

Hepatic disease is common in severe COVID-19. This study compared the histologic/molecular findings in the liver in fatal COVID-19 (n = 9) and age-matched normal controls (n = 9); three of the fatal COVID-19 livers had pre-existing alcohol use disorder (AUD). Controls showed a high resident population of sinusoidal macrophages that had variable ACE2 expression. Histologic findings in the cases included periportal/lobular inflammation. SARS-CoV2 RNA and nucleocapsid protein were detected in situ in 2/9 COVID-19 livers in low amounts. In 9/9 cases, there was ample in situ SARS-CoV-2 spike protein that co-localized with viral matrix and envelope proteins. The number of cells positive for spike/100× field was significantly greater in the AUD/COVID-19 cases (mean 5.9) versus the non-AUD/COVID-19 cases (mean 0.4, p < 0.001) which was corroborated by Western blots. ACE2+ cells were 10× greater in AUD/COVID-19 livers versus the other COVID-19/control liver samples (p < 0.001). Co-expression experiments showed that the spike protein localized to the ACE2 positive macrophages and, in the AUD cases, hepatic stellate cells that were activated as evidenced by IL6 and TNFα expression. Injection of the S1, but not S2, subunit of spike in mice induced hepatic lobular inflammation in activated macrophages. It is concluded that endocytosed viral spike protein can induce hepatitis in fatal COVID-19. This spike induced hepatitis is more robust in the livers with pre-existing AUD which may relate to why patients with alcohol abuse are at higher risk of severe liver disease with SARS-CoV2 infection.

Liver Injury in COVID-19: A Direct Hit or Collateral Damage?

SARS-CoV-2 is a novel coronavirus that has been identified, in December 2019, in Wuhan, China, and since it has become a worldwide pandemic, it has imposed far-reaching impacts on global human health and socio-economic activity. Worldwide, over 4 million Covid-19 related deaths were reported until September 2021. Recently published case studies have reported that Covid-19 patients develop different degrees of liver dysfunction. Inevitably, in hospitalized Covid-19 patients who develop acute liver derangement, there are a plethora of potential pathogenic causes such as direct-viral, immune-driven, and drug-induced and/or ischaemic liver injury. Patients with advanced chronic liver diseases (e.g., cirrhosis) and/or autoimmune liver disease have a poor immune function and associated poorer outcomes compared to other critically ill cohorts. However, largely any immediate liver derangement tends to be relatively mild, and as such, any de novo liver injury may not be a significant feature of Covid-19. There is an immediate necessity, therefore, to better understand the liver-specific pathophysiology of COVID-19. This review focuses on the up-to-date information regarding Covid-19 and associated indices for liver dysfunction, possible mechanisms, and potential drug targeted therapies in Covid-19 patients with and without liver dysfunction. PubMed database was used to perform an extensive literature search using the keywords liver and SARS-CoV-2, liver and Covid-19, Covid 19 and treatment, etc.

The impact of the COVID-19 epidemic on hospital admissions for alcohol-related liver disease and pancreatitis in Japan.

During the coronavirus disease 2019 (COVID-19) pandemic, there have been health concerns related to alcohol use and misuse. We aimed to examine the population-level change in cases of alcohol-related liver disease and pancreatitis that required admission during the COVID-19 epidemic by interrupted time series (ITS) analysis using claims data. We defined the period from April 2020, when the Japanese government declared a state of emergency, as the beginning of the COVID-19 epidemic. This ITS analysis included 3,026,389 overall admissions and 10,242 admissions for alcohol-related liver disease or pancreatitis from 257 hospitals between July 2018 and June 2020. The rate of admissions per 1000 admissions during the COVID-19 epidemic period (April 2020-June 2020) was 1.2 times (rate ratio: 1.22, 95% confidence interval: 1.12-1.33) compared to the pre-epidemic period. Analyses stratified by sex revealed that the increases in admission rates of alcohol-related liver disease or pancreatitis for females were higher than for males during the COVID-19 epidemic period. The COVID-19 epidemic in Japan might associates an increase in hospital admissions for alcohol-related liver disease and pancreatitis. Our study could support the concern of alcohol consumption and health problems during the COVID-19 pandemic.

COVID-19 in gastroenterology: Where are we now? Current evidence on the impact of COVID-19 in gastroenterology.

BACKGROUND: The COVID-19 pandemic has created unprecedented challenges in all fields of society with social, economic, and health-related consequences worldwide. In this context, gastroenterology patients and healthcare systems and professionals have seen their routines changed and were forced to adapt, adopting measures to minimize the risk of infection while guaranteeing continuous medical care to chronic patients. OBJECTIVE: At this point, it is important to evaluate the impact of the pandemic on this field to further improve the quality of the services provided in this context. METHODS/RESULTS/CONCLUSION: We performed a literature review that summarizes the main aspects to consider in gastroenterology, during the pandemic crisis, and includes a deep discussion on the main changes affecting gastroenterology patients and healthcare systems, anticipating the pandemic recovery scenario with future practices and policies.

Association of alpha-1-antitrypsin deficiency with vitamin D status: who is most at risk of getting severe COVID-19?

INTRODUCTION: Coronavirus disease 2019 (COVID-19), a new disease that we do not know yet how to treat, is rapidly evolving and has forced us to stay indoors. Surprisingly, a broad range of symptoms has been reported since COVID-19 emergence. Individual variations in susceptibility to SARS-CoV-2 can be due to non-genetic and genetic factors. Alpha-1-antitrypsin deficiency (AATD) is an inherited condition that is associated with an increased risk of liver and lung diseases which may increase susceptibility to COVID-19 infection. At the same time, there could be a possibility of developing non-hereditary AATD. DISCUSSION: In addition to some evidence showing the role of vitamin D deficiency in COVID-19 pathology, it has been recognized that there is a biological link between AAT and vitamin D. Therefore, here we offer a new perspective that lower vitamin D levels in COVID-19 patients can cause acquired AATD that provide a condition with more disease severity and a higher risk of death. As a consequence, COVID-19 individuals with vitamin D deficiency may have a higher risk of morbidity and mortality. CONCLUSION: Therefore, early vitamin D and AAT assessments and optimal interventions could be helpful to prevent severe COVID-19 outcomes.