Antibody response after a booster dose of SARS-CoV-2 vaccine in liver transplant recipients and those with chronic liver diseases.

INTRODUCTION AND OBJECTIVES: Lower antibody (Ab) responses after SARS-CoV-2 vaccination have been reported in liver transplant (LT) recipients and those with chronic liver diseases (CLD). The role of a booster dose in those with poor responses to initial vaccination is not well defined. METHODS: In this prospective study, we determined antibody (Ab) response to spike protein after a booster dose in LT recipients and those with chronic liver diseases (CLD) with and without cirrhosis after they had a poor response to an initial standard regimen. RESULTS: Of the 80 patients enrolled, 45 had LT, and 35 had CLD (18 with cirrhosis). A booster dose was given at a median of 138.5 days after the completion of the standard regimen. After the booster dose, 58 (73%, 31 LT, 27 CLD) had good response (≥250 U/mL), and 22 (28%, 14 LT, and 8 CLD) had poor response (7 undetectable and 15 with low Ab levels). No patient had any serious adverse events. The antibody responses were lower in those who had undetectable Ab (80 U/mL) than those who had low levels of Ab (0.80-249 U/mL) after the standard vaccination regimen (42% vs. 87%, p=0.0001). The antibody responses after homologous and heterologous booster doses were similar. CONCLUSIONS: We have shown that a booster dose will enhance Ab responses in LT recipients and those with CLD who had poor responses after an initial vaccine regimen.

Vaccination in Chronic Liver Disease: An Update.

Patients with chronic liver disease (CLD) with or without cirrhosis remain at risk of developing hepatic decompensation when infected with viral or bacterial pathogens. The Advisory Committee on Immunization Practices (ACIP) currently recommends vaccination in CLD against hepatitis A virus (HAV), hepatitis B virus (HBV), influenza, pneumococcus, herpes zoster, tetanus, diphtheria, pertussis, and SARS-CoV-2. Inactivated vaccines are preferred over live attenuated ones, especially in transplant recipients where live vaccines are contraindicated. As the severity of the liver disease progresses, vaccine efficacy declines, and therefore, vaccines should be ideally administered early in the disease course for optimal immune response. Despite the strong recommendations, overall vaccination coverage in CLD remains poor; however, it is encouraging to note that in recent years coverage against influenza and pneumococcus has shown some improvement. Inadequate access to healthcare, lack of information on vaccine safety, poor financial reimbursement for healthcare providers, and vaccine misinformation are often responsible for low immunization rates. This review summarizes the impact of vaccine-preventable illness in those with CLD, updated vaccine guidelines, seroconversion rates in the vaccinated, and barriers faced by healthcare professionals in immunizing those with liver disease.

Analysis of antibody responses after COVID-19 vaccination in liver transplant recipients and those with chronic liver diseases.

BACKGROUND & AIMS: Liver transplant (LT) recipients or other immunocompromised patients were not included in the registration trials studying the efficacy of vaccines against SARS-CoV-2. Although the clinical efficacy of COVID-19 vaccines in immunocompromised patients is unknown, many societies have recommended vaccination of this highly vulnerable patient population. METHODS: In this prospective study, we determined antibody responses to spike protein, 4 weeks after the 2nd dose of mRNA vaccines or after the single dose of Johnson & Johnson vaccine, in LT recipients and those with chronic liver disease (CLD) with and without cirrhosis. RESULTS: Of the 233 patients enrolled so far, 62 were LT recipients, 79 had cirrhosis (10 decompensated) and 92 had CLD without cirrhosis. Antibody titers were defined as undetectable (<0.40 U/ml), suboptimal (0.40-250 U/ml) and adequate (>250 U/ml). Of the 62 patients who had LT, antibody levels were undetectable in 11 patients and suboptimal (median titer 17.6, range 0.47-212 U/ml) in 27 patients. Among 79 patients with cirrhosis, 3 had undetectable antibody levels and 15 had suboptimal (median titer 41.3, range 0.49-221 U/L) antibody responses. Of the 92 patients without cirrhosis, 4 had undetectable antibody levels and 19 had suboptimal (median titer 95.5, range 4.9-234 U/L) antibody responses. Liver transplantation, use of 2 or more immunosuppression medications and vaccination with a single dose of the Johnson & Johnson vaccine were associated with poor immune response on multivariable analysis. No patient had any serious adverse events. CONCLUSIONS: Poor antibody responses after SARS-CoV-2 vaccination were seen in 61% of LT recipients and 24% of those with CLD. LAY SUMMARY: The clinical efficacy of COVID-19 vaccines in immunocompromised patients is unknown. We performed a prospective study to evaluate immune responses to COVID-19 vaccines (Moderna, Pfizer or Johnson & Johnson) in 62 liver transplant recipients, 79 patients with cirrhosis and 92 with chronic liver diseases without cirrhosis. We found that 17.8% of liver transplant recipients, 3.8% of those with cirrhosis and 4.3% of those with chronic liver diseases without cirrhosis had undetectable antibody levels. In total, 61.3% of liver transplant recipients and 24% of those with chronic liver diseases (with or without cirrhosis) had poor antibody responses (undetectable or suboptimal). Liver transplantation, use of immunosuppressive medications and vaccination with a single dose of Johnson & Johnson vaccine were associated with poor antibody responses when adjusted for other factors.

Liver injury in COVID-19: The hepatic aspect of the respiratory syndrome - what we know so far.

The 2019 novel coronavirus disease (COVID-19) pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to global public health. Although primarily, the infection causes lung injury, liver enzyme abnormalities have also been reported to occur during the course of the disease. We conducted an extensive literature review using the PubMed database on articles covering a broad range of issues related to COVID-19 and hepatic injury. The present review summarizes available information on the spectrum of liver involvement, the possible mechanisms and risk factors of liver injury due to SARS-CoV-2 infection, and the prognostic significance of the presence of liver injury. Hopefully, this review will enable clinicians, especially the hepatologists, to understand and manage the liver derangements they may encounter in these patients better and provide guidance for further studies on the liver injury of COVID-19.

What GI Physicians Need to Know During COVID-19 Pandemic.

The worldwide pandemic of COVID-19, caused by the virus SARS-CoV-2, continues to cause significant morbidity and mortality in both low- and high-income countries. Although COVID-19 is predominantly a respiratory illness, other systems including gastrointestinal (GI) system and liver may be involved because of the ubiquitous nature of ACE-2 receptors in various cell lines that SARS-CoV-2 utilizes to enter host cells. It appears that GI symptoms and liver enzyme abnormalities are common in COVID-19. The involvement of the GI tract and liver correlates with the severity of disease. A minority (10-20%) of patients with COVID-19 may also present initially with only GI complaints. The most common GI symptoms are anorexia, loss of smell, nausea, vomiting, and diarrhea. Viral RNA can be detected in stool in up to 50% of patients, sometimes even after pharyngeal clearance, but it is unclear whether fecal-oral transmission occurs. Liver enzymes are elevated, usually mild (2-3 times), in a substantial proportion of patients. There are many confounding factors that could cause liver enzyme abnormalities including medications, sepsis, and hypoxia. Although infection rates in those with preexisting liver disease are similar to that of general population, once infected, patients with liver disease are more likely to have a more severe disease and a higher mortality. There is a paucity of objective data on the optimal preventive or management strategies, but few recommendations for GI physicians based on circumstantial evidence are discussed.

Prevalence of chronic liver disease in patients with COVID-19 and their clinical outcomes: a systematic review and meta-analysis.

Abnormal liver enzymes are seen in 20% of hospitalized patients with COVID-19. The etiology of elevated liver enzymes is thought to be multifactorial including medications and underlying liver disease. The true prevalence and clinical significance of underlying chronic liver diseases (CLD) in COVID-19 remains poorly defined. In this systematic review and meta-analysis, we included 74 clinical studies that were identified after a thorough literature search across three databases. The prevalence of CLD patients (73 studies, 24,299 patients) was 3% among all COVID-19 patients. The prevalence of CLD patients was similar in COVID-19 positive and negative population (pooled OR 0.79 [95% CI 0.60, 1.05], p = 0.10). The presence of CLD was significantly associated with more severe COVID-19 infection (pooled OR 1.48 [95% CI 1.17, 1.87], p = 0.001) and overall mortality (pooled OR 1.78 [95% CI 1.09, 2.93], p = 0.02). Additionally, there was a non-significant trend noted for increased ICU admissions and need for invasive mechanical ventilation among COVID-19 patients with CLD. To date, the clinical importance of chronic liver diseases among COVID-19 infection has remained undefined. In this novel systematic review and meta-analysis, the presence of underlying chronic liver disease was significantly associated with more severe COVID-19 infections and mortality.

Elevated Liver Biochemistries in Hospitalized Chinese Patients With Severe COVID-19: Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Several recent studies have reported an abnormal liver chemistry profile among patients with coronavirus disease 2019 (COVID-19), although its clinical significance remains unknown. APPROACH AND RESULTS: This systematic review and meta-analysis identified six studies of 586 patients delineating liver chemistries among patients with severe/critical illness versus mild cases of COVID-19 infection. Patients with severe/critical illness with COVID-19 infection have increased prevalence of coronary artery disease, cerebrovascular disease, and chronic obstructive pulmonary disease as compared with mild cases. A significant association between severe/critical COVID-19 infections with elevations in aspartate aminotransferase (pooled mean difference [MD], 11.70 U/L; 95% confidence interval [CI], 2.97, 20.43; P = 0.009), elevated total bilirubin (pooled MD, 0.14 mg/dL; 95% CI, 0.06, 0.22; P = 0.0005), and decreased albumin (pooled MD, -0.68 g/L; 95% CI, -0.81, -0.55; P < 0.00001) was noted. There was also a trend toward elevated alanine aminotransferase levels among these severe cases (pooled MD, 8.84 U/L; 95% CI, -2.28, 19.97; P = 0.12); however, this did not reach statistical significance. More severe/critically ill cases were associated with leukocytosis, neutrophilia, lymphopenia, elevated creatinine kinase, elevated lactate dehydrogenase (LDH), and elevated prothrombin time (PT). CONCLUSIONS: Comorbidities, including coronary artery disease, cerebrovascular disease and chronic obstructive pulmonary disease, are more prevalent in hospitalized Chinese patients with severe/critical illness from COVID-19, and these patients are more likely to manifest with abnormal liver chemistries. Further prospective studies are crucial to understand the pathophysiologic mechanisms underlying the hepatic manifestations of the novel COVID-19 infection and its clinical significance.

Gastrointestinal and Liver Manifestations of COVID-19.

The worldwide pandemic of COVID-19, caused by the virus SARS-CoV,-2 has continued to progress, and increasing information is becoming available about the incidence of digestive symptoms as well as abnormal liver-associated enzymes in patients who are infected. These are postulated to be related to the virus's use of ACE-2 receptors located on certain intestinal cells, cholangiocytes, and hepatocytes. This brief review summarizes the available limited data on digestive manifestations of COVID-19. A significant proportion of COVID-19 patients can present initially with only digestive complaints. The most common digestive symptoms are anorexia, nausea, vomiting, and diarrhea. Liver-related transaminases are elevated in a substantial proportion of patients, although generally only mildly elevated. Currently there is no firm evidence to suggest that severity of digestive symptoms corresponds to severity of COVID-19 clinical course, however, more severe alterations in liver enzymes may correlate with worse clinical course. Given use of antiviral and antibacterial agents in sicker patients, drug-induced liver injury cannot be ruled out either in these cases. Although viral RNA can be detected in stool, it is unclear whether fecal-oral transmission can be achieved by the virus. As further data becomes available, our understanding of the digestive manifestations of COVID-19 will continue to evolve.