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The cavernous sinus is one of the dural venous sinuses which plays an important role in venous outflow from the brain and eye sockets and in the regulation of intracranial circulation. We report a case of septic cavernous sinus thrombosis in a female patient with COVID-19. The disease often results in alterations of blood rheology, thrombosis in different organs, and septic complications. This article aims to raise awareness of healthcare professionals about the characteristics of COVID-19 that might cause septic cavernous sinus thrombosis in patients with severe comorbidities. Laboratory testing revealed severe comorbidities, including diabetes mellitus and liver cirrhosis caused by hepatitis C. They manifested with an impaired protein production in the liver and coagulation disorders. Systemic effects of SARS-CoV-2 on the vascular endothelium aggravated preexisting coagulation disorders and led to hemorrhage into retrobulbar tissue and clinical signs of septic cavernous sinus thrombosis, including swelling of the eyelids, bilateral exophthalmos, and ophthalmoplegia, followed by necrosis of the facial skin.Copyright © 2022, Dynasty Publishing House. All rights reserved.
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Introduction/Objective Post-COVID-19 cholangiopathy is a novel entity first noted in patients recovering from critical COVID-19 infection. Since its initial description in May 2021, all cases reported to date have been in patients with a history of critical COVID-19, defined as requiring ICU admission, the development of respiratory or circulatory failure requiring intubation or ECMO, or vasopressor support. Here we report three cases of post-COVID-19 cholangiopathy arising in patients who recovered from non-severe COVID-19. Methods/Case Report Six cases of COVID-19-related cholangiopathy were identified by retrospective review, three of which involved patients who verifiably did not develop critical COVID-19. Histology slides for each case were reviewed and all showed features of secondary sclerosing cholangitis. Patient 1 is a 41yo female who developed COVID-19 after liver transplant (LT). Despite administration of monoclonal antibodies, she required re-transplantation 6 weeks later. Explant histology showed bile infarcts, severe hepatocytic and canalicular cholestasis, ductular reaction, organizing portal vein thrombi, and necrotic bile ducts accompanied by bile lakes. Patient 2 is a 47yo male with alcoholic cirrhosis who was diagnosed with COVID-19 at the time of LT workup, and underwent LT 90 days later. In addition to alcohol-related cirrhosis, explant histology showed dilated bile ducts with periductal fibrosis, as well as severe ductular reaction with proliferating ductules containing thick, inspissated bile. Patient 3 is a 54yo male with history of LT for PSC who developed mild COVID-19 five years after LT. Allograft function subsequently worsened and biopsy 6 months later showed bile duct damage and loss of ~35% of bile ducts;repeat biopsy 14 months after his COVID diagnosis showed periportal fibrosis with edema, ductular reaction, marked hepatocellular and canalicular cholestasis, and ductopenia with loss of 60% bile ducts. Average time between COVID-19 diagnosis and onset of COVID-related cholangiopathy was 3 months (range: 6 weeks-6 months). These patients were also all immunocompromised with two due to prior LT and one being cirrhotic. Results (if a Case Study enter NA) NA. Conclusion Although previously reported only in patients with severe COVID-19, the cases described represent the first evidence that cholangiopathy, manifested by sclerosing cholangitis, can arise even in patients who were not critically ill, although this may require an immunocompromised state to develop.
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Non-invasive ventilation (NIV) might be successful if carefully selected in adult patients with cardiac dysfunction presenting with community-acquired pneumonia. The main objective of this study was to identify the early predictors of NIV failure. Adult patients with left ventricle ejection fraction (LV EF) <50% admitted to the intensive care unit (ICU) with community-acquired pneumonia and acute respiratory failure were enrolled in this multicenter prospective study after obtaining informed consents (study registrationID: ISRCTN14641518). Non-invasive ventilation failure was defined as the requirement of intubation after initiation of NIV. All patients were assessed using the Acute Physiology and Chronic Health Evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores at admission, while their Heart rate Acidosis Consciousness Oxygenation and Respiratory rate (HACOR) and lung ultrasound (LUS) scores in addition to blood lactate were assessed at NIV initiation and 12 and 24 hours later. A total of 177 patients were prospectively enrolled from February 2019 to July 2020. Of them, 53 (29.9%) had failed NIV. The mean age of the study cohort was 64.1+or- 12.6 years, with a male predominance (73.4%) and a mean LV EF of 36.4 +or- 7.8%. Almost 55.9% of the studied patients had diabetes mellitus, 45.8% had chronic systemic hypertension, 73.4% had ischemic heart disease, 20.3% had chronic kidney disease, and 9.6% had liver cirrhosis. No significant differences were observed between the NIV success and NIV failure groups regarding underlying morbidities or inflammatory markers. Patients who failed NIV were significantly older and had higher mean SOFA and APACHE II scores than those with successful NIV. We also found that NIV failure was associated with longer ICU stay (p < 0.001), higher SOFA scores at 48 hours (p < 0.001) and higher mortality (p < 0.001) compared with the NIV success group. In addition, SOFA (Odds Ratio (OR): 4.52, 95% Confidence Interval (CI): 2.59-7.88, p < 0.001), HACOR (OR: 2.01, 95% CI: 0.97-4.18, p = 0.036) and LUS (OR: 1.33, 95% CI: 1.014-1.106, p = 0.027) scores and blood lactate levels (OR: 9.35, 95% CI: 5.32-43.26, p < 0.001) were independent factors for NIV failure. High initial HACOR and SOFA scores, persistent hyperlactatemia and non-decrementing LUS score were associated with early NIV failure in patients with cardiac dysfunction presenting with community-acquired pneumonia, and could be used as clinical and paraclinical variables for early decision making regarding invasive ventilation.
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Background: Lymphoproliferation is the persistent proliferation of lymphoid cells and it's incidence in inborn errors of immunity varies from 0.7 to 18%. Material(s) and Method(s): This is a retrospective analysis of patients referred to the department of Immunology, B. J. Wadia Hospital for Children, Mumbai between March 2017 to December 2022. Inclusion criteria consisted of 3 months duration of significant lymphadenopathy and/or splenomegaly or history of lymphoma. The clinical characteristics, laboratory and molecular findings of the included patients were analyzed. Result(s): A total of 66 patients were included. There was a male preponderance with male:female ratio of 25:8. Median age of onset of lymphoproliferation was 4.75 years(Range 1 year to 60 years). Splenomegaly was seen in 75%. Infections included recurrent pneumonia (14/66), recurrent ear infections(5/66), COVID(4/66), one episode of pneumonia(6/66), herpes zoster(3/66), recurrent subcutaneous abscess (3/66), abdominal koch(3/66), chronic sinusitis(2/66), dermatophytosis(2/66), esophageal candidiasis(2/66), recurrent malaria(1/66), recurrent varicella(1/66), cryptococcal meningitis(1/66), gram negative sepsis(1/66), BCG adenitis(1/66), pseudomonas osteomyelitis(1/66), impetigo (1/66), pseudomonas urinary tract infection (1/66), chicken pox(1/66), herpes keratitis(1/66), dengue(1/66), Other manifestations included Evans plus phenotype(10/66), Evans phenotype(8/66), Autoimmune hemolytic anemia(5/66), bronchiectasis(5/66), Type 1 diabetes(3/66), hyper reactive airway disease(2/66), inflammatory bowel disease(4/66), autoimmune thrombocytopenia(2/66), stroke(3/66), hemophagocytic lymphohistiocytosis(2/66), hypertriglyceridemia(2/66), hypothyroidism(2/66), celiac disease(1/66), Type 2 diabetes(1/66), autoimmune encephalitis(1/66), autoimmune hepatitis(2/66), anti-parietal cell antibody(1/66), arthritis(1/66), autoimmune enteropathy(1/66), systemic lupus erythromatosus(1/66), primary biliary cirrhosis requiring liver transplant(1/66), nephrotic syndrome(1/66), lymphoedema(1/66), hypersplenism(1/66), recurrent oral ulcers(1/66), gout(1/66), dermatitis(1/66), ovarian teratoma(1/66), alopecia areata(1/66). Hodgkin's lymphoma(HL) was the most common malignancy(9/66), followed by non Hodgkin lymphoma(NHL)(6/66), transformation from NHL to HL(1/66), Burkitt to T-cell lymphoma(1/66), HL to DLBCL(1/66), HL to anaplastic T-cell lymphoma(1/66). EBV driven lymphoproliferation was seen in biopsy of21/66. Genetic testing showed mutations in LRBA(11/66), PIK3CD(5/66), CTLA4(3/66), TET2(2/66), IL2RA (1/66), IL12RB1(1/66), BACH2(1/66), PRKCD(1/66), TNFSFR13B(1/66), TNFAIP3(1/66), FAS(2/66), FASL(1/66), Caspase8(1/66), CARD11(1/66), RTEL1(1/66), AICD(1/66), PIK3R1(1/66), IKBKB(1/66). Treatment included IVIG, chemotherapy, rituximab, sirolimus, abatacept, HSCT. Conclusion(s): All children with persistent lymphoproliferation, with or without autoimmunity and/or infections should be worked up for an underlying monogenic disorder of immune dysregulation. Lymphomas presenting at abnormal site and/or age, relapse and EBV driven lymphomas require further evaluation. Presence of monogenic cause helps in providing targeted therapy.Copyright © 2023 Elsevier Inc.
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BackgroundHepatitis C virus (HCV) infection is a major cause of chronic liver disease that can progress to cirrhosis and hepatocellular carcinoma. The WHO has identified HCV infection as a public health threat and set a global target for HCV elimination by 2030. Simple pangenotypic direct-acting antiviral regimens allow most patients to be cured with minimal pretreatment and on-treatment monitoring. To achieve the WHO goal, patients including previously diagnosed HCV-positive patients who have been lost to follow-up, need to be linked to care. Studies report that up to 60% of patients who test positive for HCV antibodies are lost to follow-up and not treated. This loss has been further exacerbated by the COVID-19 pandemic, and many patients put off receiving care. Here, we explore the effectiveness of care re-engagement programs for patients with HCV.MethodsWe assessed ReLink programs (sponsored by Gilead Sciences, Inc.), designed to identify and re-engage HCV-positive patients with medical care and start/restart HCV treatment. We evaluated these programs by analyzing the number of patients, steps in the care cascade where patients were lost to follow-up, and the efficacy of the engagement program (determined by the number relinked and treated).ResultsSix programs assessed 44,964 patient records, identifying 11,163 patients lost to follow-up and eligible for contact. The main reason for the loss of follow-up was the inability to contact patients. Overall, 3726 patients were relinked with care, and 701 were treated. Several key points were identified for improving patient engagement with care, including the use of electronic databases to identify patients lost to follow-up, securing reliable contact information for patients, and partnership with medical societies.ConclusionsActive case finding, patient navigation, and care coordination in these programs led to increased engagement and treatment rates. Engaging HCV-positive patients with care is urgent, as many may already have developed more advanced liver disease. Adopting and adapting effective strategies from these programs may be a feasible way to improve patient outcomes and increase treatment numbers, thus contributing to meeting the WHO goal of HCV elimination.
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The hepatic consequences of SARS-CoV-2 infection are now recognized as an important component of CoronaVIrus Disease 2019 (COVID-19). This aspect is most clinically relevant in patients with pre-existing chronic liver disease (CKD), who are at extremely high risk of severe COVID-19 and death. Risk factors for severe CKD, especially in people with liver cirrhosis and non-alcoholic fatty liver disease, are the direct and indirect cytotoxic effects of coronavirus against the background of systemic inflammation, blood clotting disorders and immune dysfunction. The severe negative impact of the pandemic in the presence of CKD and the difficulties of patient relationships contribute to the progressive increase in the global burden of liver disease on the health system.
Subject(s)
COVID-19 , Non-alcoholic Fatty Liver Disease , Renal Insufficiency, Chronic , Humans , Pandemics , SARS-CoV-2 , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/therapyABSTRACT
Background: The immune response and safety of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with chronic hepatitis B (CHB), especially those with cirrhosis, are not clear. Therefore, this study was conducted to evaluate the efficacy and safety of inactivated SARS-CoV-2 vaccines among CHB patients with and without cirrhosis. Patients and methods: A total of 643 CHB patients who received two doses of inactivated SARS-CoV-2 vaccines (BBIBP-CorV and CoronaVac) were enrolled. Serum samples were collected and tested for SARS-CoV-2 S-receptor-binding domain (S-RBD) immunoglobulin G (IgG) at enrollment. Data on adverse events (AEs) within 7 days after the second dose were obtained using a questionnaire. Results: A total of 416 non-cirrhotic and 227 cirrhotic patients were included in the analysis. Cirrhotic patients had lower antibody titers than non-cirrhotic patients after adjusting for age, sex, and time interval (2.45 vs. 2.60 ng/ml, p = 0.034). Furthermore, the study revealed that cirrhotic patients demonstrated a slower rate of seropositivity increase, with the highest rate being recorded at week 4 and reaching 94.7%. On the other hand, among non-cirrhotic patients, the seropositivity rate peak was observed at week 2 and reached 96.0%. In addition, cirrhotic patients displayed a more rapid decline in the seropositivity rate, dropping to 54.5% after ≥16 weeks, while non-cirrhotic patients exhibited a decrease to 67.2% after the same time period. The overall incidence of AEs was low (18.4%), and all AEs were mild and self-limiting. In addition, 16.0% of participants had mild liver function abnormalities, and half of them returned to normality within the next 6 months without additional therapy. The participants who experienced liver function abnormalities showed a higher seropositivity rate and antibody titer than those who did not (91.6% vs. 79.5%, p = 0.005; 2.73 vs. 2.41 ng/ml, p < 0.001). Conclusion: Cirrhotic CHB patients had lower antibody titers to inactivated SARS-CoV-2 vaccines than non-cirrhotic patients. The vaccines were generally well tolerated in both non-cirrhotic and cirrhotic CHB patient groups. Patients with abnormal liver function may have a better antibody response than those without.
Subject(s)
COVID-19 , Hepatitis B, Chronic , Humans , Antibody Formation , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Hepatitis B, Chronic/complications , Liver Cirrhosis , SARS-CoV-2 , Male , FemaleABSTRACT
Introduction: Lactulose is a non-absorbable disaccharide which acts in the large bowel, and is commonly used in the treatment of hepatic encephalopathy. We present an interesting case of altered mental status due to hepatic encephalopathy successfully managed with lactulose in a patient with history of total colectomy. Case Description/Methods: A 67-year-old male with non-alcoholic cirrhosis and inflammatory bowel disease (IBD) post total proctocolectomy with a continent ileostomy known as a Kock-pouch (K-pouch) presented to the hospital with flu like symptoms and altered mental status. He was subsequently found to be positive for COVID-19. At the time of initial evaluation, the patient was obtunded with an elevated ammonia level of 91 umol/L. Colorectal surgery was consulted as the patient was not able to empty his K-pouch. Recently, he complained of inability to catheterize and with bleeding from the stoma. Initial catheterization with a Water's tube yielded 400 cc of effluent. Nasogastric tube was placed through which he was receiving lactulose 30 mg q8 hours. The patient's mental status improved within 24 hours. The patient ultimately underwent flexible pouchoscopy with endoscopic dilation and placement of a 22 French mushroom catheter for decompression of the K-pouch. Discussion(s): Lactulose is a non-absorbable disaccharide composed of galactose and fructose. The small intestine does not have the enzymes required to breakdown lactulose so it reaches the large bowel in its original form. In the large bowel, it is metabolized by colonic bacteria into monosaccharides and then to volatile fatty acids, hydrogen and methane. Lactulose decreases both the production and absorption of ammonia mainly through the presence of gut bacteria. The question arises as to how lactulose decreased ammonia levels in this patient without a large bowel. One proposed mechanism is the translocation of bacteria normally found in the large bowel to the small intestine. Small Intestinal Bacterial Overgrowth (SIBO), is a condition causing an increased number of bacteria in the small intestine. Patients with IBD and structural abnormalities are at increased risk of developing SIBO. Lactulose is commonly used in the diagnosis through the administration of lactulose and subsequent measurements of hydrogen and methane gas in expired air. This condition, in our patient with history of ulcerative colitis and colectomy, is a proposed mechanism of the efficacy of lactulose in the treatment of hepatic encephalopathy.
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Background: The virulence and severity of SARS-CoV-2 infections have decreased over time in the general population due to vaccinations and improved antiviral treatments. Whether a similar trend has occurred in patients with cirrhosis is unclear. We used the National COVID Cohort Collaborative (N3C) to describe the outcomes over time in this patient population. Method(s): We utilized the N3C data set with uncensored dates of service to identify all chronic liver disease (CLD) patients with and without cirrhosis who had SARS-CoV-2 infection as of 9/10/2022. We described the observed 30-day case fatality rate by month of infection. We used adjusted Cox survival analyses to calculate relative hazard of death by month of infection compared to infection in March 2020 at the onset of the COVID-19 pandemic. Result(s): We identified 110,477 total CLD patients infected with SARS-CoV-2 between 3/2020-7/2022: 25,067 (23%) with cirrhosis and 85,410 (77%) without cirrhosis. Of the 110,477 total CLD patients, 39,595 (36%) were vaccinated and 70,882 (64%) unvaccinated. The overall observed 30-day case fatality rate during the entire study period was 1.4% (1,198) for CLD patients without cirrhosis and 7.7% (1,930) for those with cirrhosis. The observed 30-day case fatality rate by month of infection is displayed in Fig. 1. Compared to infection in March 2020, the adjusted hazard of death at 30 days for infection in July 2022 was HR 0.083 (95% CI 0.026-0.27) for CLD patients without cirrhosis and HR 0.32 (95% CI 0.17-0.61) for those with cirrhosis. Conclusion(s): In this N3C study, we found that the observed 30-day case fatality rate decreased progressively for both CLD patients with and without cirrhosis. Yet, the decrease in all-cause mortality was four times greater for patients without cirrhosis compared to those with cirrhosis. Despite improvements in SARS-CoV-2 treatments, patients with cirrhosis remain at risk of adverse outcomes. (Figure Presented).
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Introduction: Bupivacaine is a local anesthetic which has been increasingly used in the post-operative state for pain control. Hepatotoxicity is a rare complication, and few cases are reported in patients with chronic liver disease. We present a case of acute liver injury from bupivacaine use in a healthy patient without prior history of liver disease. Case Description/Methods: A 68-year-old female with a past medical history of primary hypertension and recent nontraumatic complete tear of the right rotator cuff, presents to the hospital with fatigue, loss of appetite, and nausea. She recently underwent an arthroscopy of the right shoulder with repair of the rotator cuff two weeks prior. Her surgery was uncomplicated, and patient was started on bupivacaine ONQ pump infusion at 5 ml/hr for three days for post-operative pain. Further history reveals patient is non-alcoholic without prior liver disease, including cirrhosis. Review of systems is concerning for associated generalized abdominal discomfort. Physical exam demonstrated jaundice with scleral icterus with mild periumbilical tenderness to palpation without hepatosplenomegaly or ascites. Labs demonstrated elevated total bilirubin of 10.2 mg/dL with Alkaline phosphatase, ALT, and AST being 924 U/L, 429 U/L, and 279 U/L, respectively. Imaging studies including CT abdomen and pelvis with contrast, abdominal ultrasound, MRCP, and portal vein doppler were negative. Additional work up for underlying liver disease including acetaminophen and ethanol levels, SARS-CoV2, Hepatitis panel, EBV antigen, and urine toxicology were negative. It was determined patient had bupivacaine induced hepatotoxicity. Patient's health improved with conservative management and she was discharged with instructions for close monitoring of her LFTs. Discussion(s): Bupivacaine is an amino-amide anesthetic which binds to the intracellular portion of voltage-gated sodium channels and prevents depolarization of pain signals. It is metabolized by the liver and thus reports of hepatotoxicity, although rare, occur in patients with underlying liver pathology. Our patient became symptomatic with acute rise in LFTs. An extensive workup for other etiologies of acute liver toxicity was negative. Rapid vascular uptake of the drug is the most common reason for bupivacaine toxicity;and this remains a possibility for the mechanism of toxicity in our patient. A prior case report of bupivacaine hepatotoxicity demonstrated a cholestatic pattern, which is consistent with our findings.
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Background and Aims: The treatment of chronic hepatitis C (CHC) has evolved from genotype-specific to pan-genotypic direct acting antivirals (DAAs) with high efficacy and safety. However, drug-drug interactions (DDIs) must be avoided when used in combination with other medications, especially with the possible concomitant use of COVID-19 infection antivirals during the COVID-19 pandemic. This study aimed to access the potential DDIs of concomitant drugs with pan-genotypic DAAs and COVID-19 infection antivirals, and actual incidence of DDIs in real-world experience. Method(s): From January 2022 to October 2022, consecutive 116 HCV patients receiving pan-genotypic DAAs were retrospectively enrolled in Taipei Veterans General Hospital. The number of comedications and their potential DDIs with three pan-genotypic DAA regimens and three COVID-19 infection antivirals were analyzed. The actual incidence of DDIs during DAAs treatment were also investigated. Result(s): The mean age was 60.9 years old, with male predominant (55.2%). Of them, 12 (10.3%) patients had cirrhosis, and 24 (20.7%) patients had diabetes mellitus. Most patients were within Child-Pugh class A (109/116, 94.0%). The distribution of HCV genotypes was 8.6% in GT 1a, 36.2% in GT 1b, 39.7% in GT 2, 6.9% in GT 6, and 8.6% in indeterminate genotype, respectively. Of them, 43 (37.1%) patients received GLE/PIB, 69 (59.5%) received SOF/VEL 7plusmn;RBV, and 4 (3.4%) received SOF/VEL/VOX as DAAs regimen. Noteworthy, four patients had COVID-19 infection during DAAs treatment course. The rates of ETVR and SVR12 were 97.6% and 95.3%. The mean number of concomitant medications was 2.01. The distribution of concomitant drugs was 64.7% with no concomitant drug, 11.2% with 1-3 drugs, 11.2% with 4-6 drugs, 9.5% with 7-9 drugs, and 3.4% had more than 9 drugs, respectively. In potential contraindicated (red) DDI class, GLE/PIB was the most prevalent (7.3%), followed by SOF/VEL/VOX (6.4%), and SOF/VEL (1.8%) for non-cirrhosis and compensated cirrhosis patients;and no red DDI occurred in decompensated cirrhosis patients. In addition, the percentage of patients without potential DDIs was higher with SOF/VEL (79.8%) than with the other regimens. The potential red DDIs were predominantly with lipid-lowering agents for DAAs. For potential red DDI class with COVID-19 infection antivirals, Nirmatrelvir/Ritonavir was the most prevalent (6%), followed by Remdesivir (0.9%), and no potential DDIs with Molnupiravir. For COVID-19 antivirals, the potential red DDIs was mainly with central nervous system drugs. Finally, the actual incidence of DDIs during DAAs treatment showed no red DDI occurred for all patients, and GLE/PIB was the most prevalent (93%) of no potential DDIs. Conclusion(s): The potential DDIs between these comedications differed, with the most potential DDIs occurring with GLE/PIB and Nirmatrelvir/Ritonavir. After careful assessment of comedications and their potential DDIs, the actual incidence of DDIs could be reduced, and optimize safety in real-world practice.
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Globally, hepatitis C (26%), alcohol (24%), and hepatitis B (23%) contribute almost equally to the global burden of cirrhosis. The contribution from nonalcoholic fatty liver disease (8%) is small but increasing. Patients with acutely decompensated cirrhosis have a dismal prognosis and frequently progress to acuteon-chronic liver failure, which is characterised by hepatic and extrahepatic organ failure, Cardiovascular alterations including portal hypertension trigger the formation of portocaval shunts and varices. Systemic under filling and arterial hypotension is compensated by vasoconstriction but might decline into a state of aggravated portal hypertension and cirrhotic cardiomyopathy, leading to a hyperdynamic state, microvascular dysfunction and reduced organ perfusion culminating in decompensation. The immune system is dysfunctional showing a contrary co-existence of immune paralysis and immune overstimulation leading to secondary infections and inflammatory response syndrome aggravating cardiovascular alterations but also initiating tissue injury and metabolic alteration. This transition from compensated to decompensated cirrhosis is characterised by the occurrence of ascites, variceal bleeding and/or hepatic encephalopathy or organ failures (in the case of ACLF. Precipitating events for ACLF vary between Western countries (bacterial infection, alcohol intake) and Eastern countries (flare of HBV, superimposed HAV or HEV). In the majority of patients, systemic inflammation is a major driver of progression from compensated to decompensated cirrhosis. Once the first episode of AD develops, systemic inflammation follows a chronic course, with transient periods of aggravation due to proinflammatory precipitants or bursts of bacterial translocation resulting in repeated episodes of AD. The multistate model describing the clinical outcomes of decompensated cirrhosis has been well validated. State 3 is defined by the occurrence of variceal bleeding alone, state 4 by any single non-bleeding event, state 5 by any 2 or more events and the late decompensate state by any event with organ failures either with or without ACLF. 5-year mortality across states from 3 to 5 is in the order of, respectively: 20%, 30%, 88%. With late decompensation mortality ranges between 60 and 80% at 1 year. Cirrhosis is increasingly common and morbid. Optimal utilisation of therapeutic strategies to prevent and control the complications of cirrhosis are central to improving clinical and patient-reported outcomes. Aetiology-focused therapies that can prevent cirrhosis and its complications. These include anti-viral therapies, psychopharmacological therapy for alcohol-use disorder, management of hepatic encephalopathy (HE), ascites, hepatorenal syndrome, non-pain symptoms of cirrhosis including pruritis, muscle cramps, sexual dysfunction and fatigue, and reduce the risk of hepatocellular carcinoma. New disease-modifying agents are expected to be identified in the next few years by systematic drug repurposing and the development of novel molecules currently undergoing pre-clinical or early clinical testing. COVID-19 continues to pose a significant healthcare challenge throughout the world. Comorbidities including diabetes and hypertension are associated with a significantly higher mortality risk. Cirrhosis is associated with an increased risk of all-cause mortality in COVID-19 infection compared to non-cirrhotic patients. Patients with cirrhosis should be considered for targeted public health interventions to prevent COVID-19 infection, such as shielding and prioritisation of vaccination.
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COVID-19 pandemic has been affecting the whole world for more than 3 years since late 2019. It is often to encounter COVID-19 patients with abnormal liver function, either in the form of hepatitis, cholestasis or both. The clinical implication of such liver derangement may be variable in different clinical scenarios. With the growing evidence of the clinical significance of such liver derangement, it would be clinically helpful to provide practice recommendations to various common clinical scenarios of liver derangement during COVID-19 pandemic. The Asia-Pacific Working Group for Liver Derangement during the COVID-19 Pandemic was formed to systematically review the literature on specified domains of interest, with special focus on clinical management of patients who have been or are at risk of developing liver derangement during COVID-19 pandemic. This Asia-Pacific position statement reports an in-depth review and a position statement on liver derangement during COVID- 19 pandemic. Ten clinical scenarios covering the use of pharmacological treatment for COVID-19 in case of liver derangement, assessment and management of patients with chronic hepatitis B or C, nonalcoholic fatty liver disease (NAFLD), liver cirrhosis, liver transplantation are discussed. Specifically, some treatments target the patient's dysregulated inflammatory response during COVID-19 infection and may cause hepatitis B reactivation (HBVr) in patients with current or past hepatitis B virus (HBV) infection. Current evidence suggests that current or past HBV infection is not associated with an increased risk of liver injury and severe disease in COVID-19 patients. Among patients who received high-dose corticosteroids, various immunosuppressive monoclonal antibodies and inhibitors of Janus kinase, the risk of HBVr exists, especially among those without antiviral prophylaxis.
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Purpose: The efficacy and safety of SARS-CoV-2 vaccination have been confirmed in several clinical trials. However, patients with autoimmune liver disease were not subject to clinical trials, and data on the efficacy and safety of vaccines have been not available in these population. Therefore, we retrospectively investigated the safety and effectiveness of SARS-CoV-2 vaccination by questionnaire survey targeting Japanese patients with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). Method(s): This is a multi-center, retrospective, cross-sectional, questionnaires-based study. Patients with AIH and PBC who are outpatients at participating facilities, 18 years of age or older, and have given consent to participate in this study are included. We distributed questionnaires asking about sex, date of birth, number and type of vaccinations, the presence and degree of adverse effects (AEs), and the presence or absence of SARS-CoV-2 infection before and after vaccination, and asked them to fill in the questionnaire. In addition, we collected the result of liver tests before and after vaccinations of participating patients from each facility. Result(s): The survey was conducted from September 2021 to May 2022. A total of 471 questionnaires were collected from 220 AIH patients (male/female = 33/187, average age 63.5 +/- 13.1 years old) and 251 PBC patients (38/213, 65.8 +/- 10.1). The number of vaccinations was 0/1/2/unknown = 4/0/210/6 for AIH and 4/2/244/1 for PBC. The median time from the second dose to the completion of the questionnaire was 156 days for AIH and 148 days for PBC. By vaccine type, 193 Pfizer, 11 Moderna, and 16 unknown in AIH, and 223/12/16 in PBC. As for AEs, pain and swelling at the injection site were the most common in both AIH and PBC (75% in the first and 64% in the second in AIH, 64%/61% in PBC), followed by general malaise (19%/21% in AIH, 19%/31% in PBC), and myalgia (16%/ 19% in AIH, 19%/14% in PBC). Fever above 38.5 degreeC was observed in 11%/11% of AIH and 11%/24% of PBC, indicating that more patients with PBC experiencing fever that AIH. Only 1 case of PBC had an anaphylactic reaction. By comparing liver tests before and after vaccinations, 4 (1.8%) and 16 (6.4%) patients with AIH and PBC, respectively, demonstrated elevation to 1.5 times the pre-vaccination value and exceeding the upper normal limit. No patients experienced severe deterioration of liver function. SARS-CoV-2 infection was reported in 4 cases (1.8%) in AIH and 3 cases (1.3%) in PBC. Conclusion(s): The safety and effectiveness of SARS-CoV-2 vaccination is comparable to those in the general population.
ABSTRACT
COVID-19 is characterized by predominant respiratory and gastrointestinal symptoms. Liver enzymes derangement is seen in 15-55% of the patients. Cirrhosis is characterized by immune dysregulation, leading to concerns that these patients may be at increased risk of complications following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients with metabolic dysfunction-associated fatty liver (MAFLD) had shown a 4-sixfold increase in severity of COVID-19, and its severity and mortality increased in patients with higher fibrosis scores. Patients with chronic liver disease had shown that cirrhosis is an independent predictor of severity of COVID-19 with increased hospitalization and mortality. An international European registry study included 756 patients with chronic liver disease from 29 countries reports high mortality in patients with cirrhosis (32%). Data of 228 patients collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19 (APCOLIS study) showed that SARSCoV- 2 infection produces acute liver injury in 43% of CLD patients without cirrhosis. Additionally, 20% of compensated cirrhosis patients develop either ACLF or acute decompensation. In decompensated cirrhotics, the liver injury was progressive in 57% of patients, with 43% mortality. Patients with CLD and associated diabetes and obesity had a worse outcome. Liver related complications were seen in nearly half of the decompensated cirrhotics, which were of greater severity and with higher mortality. Increase in Child Turcotte Pugh (CTP) score and model for end-stage liver disease (MELD) score increases the mortality in these patients. In a subsequent study of 532 patients from 17 Asian countries was obtained with 121 cases of cirrhosis. An APCOLIS risk score was developed, which included presence of comorbidity, low platelet count, AKI, HE and respiratory failure predicts poor outcome and an APCOLIS score of 34 gave a sensitivity and specificity of 79.3%, PPV of 54.8% and NPV of 92.4% and predicted higher mortality (54.8% vs 7.6%, OR = 14.3 [95 CI 5.3-41.2], p<0.001) in cirrhosis patients with Covid-19. The APCOLIS score is helpful in triaging and prognostication of cirrhotics with Coivd-19. The impact of COVID-19 on patients with cirrhosis due to non-alcoholic fatty liver disease (NASH-CLD) was separately studied in 177 NASH-CLD patients. Obese patients with diabetes and hypertension had a higher prevalence of symptomatic COVID. Presence of diabetes [HR 2.27], fraility [HR 2.68], leucocyte counts [HR 1.69] and COVID-19 were independent predictors of worsening liver functions in patients with NASH-CLD. Severity of Covid in Cirrhosis could also be assessed by measuring ICAM1 the Intercellular Adhesion Molecule, an indicator of Endothelial Injury Marker. in Cirrhosis with Covid 19 Immunosuppression should be reduced prophylactically in patients with autoimmune liver disease and post-transplantation with no COVID-19. Hydroxychloroquine and remdesivir are found to be safe in limited studies in a patient with cirrhosis and COVID-19. And is safe in cirrhosis patients. However, flare of AIH has been reported in AIH patients. For hepatologists, cirrhosis with COVID-19 is a pertinent issue as the present pandemic cause severe disease in patients with chronic liver disease leading to more hospitalization and decompensation.
ABSTRACT
Introduction: Hyperthyroidism is known to increase catabolism of vitamin-K-dependent clotting factors (II, VII, IX, X) and increase the response of vitamin K antagonists, usually warfarin. Primary biliary cirrhosis (PBC) has been associated with thyroid dysfunction (TD), especially with autoimmune thyroid disease. In the below case, a patient with known PBC on warfarin is found to have severely elevated INR related to new-onset hyperthyroidism with clinical consequences of hemorrhage including upper GI bleed. Case Description/Methods: A 64-year-old female with PBC and antiphospholipid antibody syndrome on warfarin was admitted for hemorrhagic epiglottitis requiring emergency intubation and supratherapeutic INR. Her PBC was diagnosed as stage II on biopsy 23 years ago and has remained clinically stable on ursodiol therapy. On presentation, the patient was tachycardic, tachypneic, and had O2 saturations <90% on HFNC prior to intubation. Physical exam significant for larger goiter with diffuse upper airway swelling. She was admitted and found to have COVID-19 infection, INR .16.0 and PT>200.0 (limit of lab), WBC of 22.8, and lactate of 2.5. LFTs WNL aside from albumin of 2.0. TSH was <0.0017 (limit of lab) and free T4 of 3.4, free T3 of 5.3. TSH receptor antibody (TRAB) and thyroid stimulating immunoglobulin (TSI) levels were normal. Her last TSH was normal a year ago. CTA chest found a 5.7cm heterogeneous, partially calcified superior mediastinal mass consistent with multinodular thyroid goiter. Patient was initially given prothrombin complex concentrate and vitamin K with correction of INR over the following few days. She was extubated and started on methimazole. During the hospital course, she was found to have coffee ground emesis for which an EGD was done with findings of non-bleeding gastric ulcer (Forrest Class IIc) and LA Grade D esophagitis with adherent clot and bleeding for which hemostatic spray was applied. Patient was discharged a few days later following resumption of warfarin and on pantoprazole and methimazole. Discussion(s): The above case demonstrates a rare case of PBC and new-onset hyperthyroidism due to multinodular thyroid goiter causing significantly elevated INR in the setting of warfarin use with hospital course complicated by GI bleed. PBC is associated with TD - hyperthyroidism, hypothyroidism, and thyroid cancer. Hyperthyroidism is less commonly associated with PBC compared to other TDs but should be considered especially with a finding of elevated INR.
ABSTRACT
Introduction: Hepatic inflammatory pseudotumor (HIP), albeit rare, is an important pathology to be included in differentials for hepatic masses. The benign nature and treatment of this disease process should be considered especially in comparison to malignant hepatic processes. Case Description/Methods: A 66-year-old male with pre-existing history of compensated Hepatitis C cirrhosis status post direct-acting antivirals with sustained virologic response presented in shock after a syncopal episode. Initial work up revealed leukocytosis, thrombocytopenia, acute renal injury, elevated liver enzymes, and COVID-19 positive test. Patient underwent initial liver ultrasound revealing intrahepatic and extrahepatic biliary ductal dilation. Subsequent MRCP demonstrated diffuse thickening of intra and extra hepatic bile ducts suggestive of cholangitis and several hepatic masses concerning for abscesses versus possible metastatic cholangiocarcinoma. Patient improved symptomatically with antibiotics and supportive care. A liver biopsy was performed with pathology showing lymphoplasmacytic inflammation and fibroblastic infiltration suggestive of hepatic inflammatory pseudotumor. A repeat MRCP one week later showed interval decrease in size of liver lesions and repeat liver function tests also showed improvement. Patient was discharged on a course of ciprofloxacin and metronidazole. Patient had repeat MRCP 3 months after discharge, with further significant improvement in size of liver lesions. After multi-disciplinary discussion the plan was for further surveillance with imaging and labs in 2 months. Discussion(s): Inflammatory pseudotumors are benign and non-neoplastic lesions that can occur in any organ. They can appear as a malignant lesion when they arise in the liver and an accurate identification can allow for conservative management and prevent unnecessary invasive procedures. Hepatic inflammatory pseudotumors are often seen with concomitant infection or inflammatory processes. Liver biopsies distinguish these tumors from other malignant processes as they demonstrate a characteristic dense inflammatory infiltrate interspersed in stroma of interlacing bundles of myofibroblasts. This case highlights the importance of maintaining HIP on the differential diagnosis. (Figure Presented).
ABSTRACT
Introduction: Intensive care outcomes in patients with cirrhosis are relatively poor. The comparison between outcomes, especially related to infections, remains unclear in those with and without cirrhosis. With the emergence of resistant and fungal organisms, the changes in infection profiles over time are important to analyze. The aim of this study is to determine the impact of cirrhosis and infections on inpatient death over time in a qSOFA-matched cohort of patients with and without cirrhosis. Method(s): Inpatients admitted to ICUs throughout 2015-2021 were analyzed. Patients with cirrhosis were matched 1:1 by age, gender, and admission qSOFA to patients without;COVID-positive patients were excluded. Admission demographics, labs, the reasons for ICU transfer, infections, and inpatient death or hospice referral were obtained for each patient. Comparisons were made between patients with and without cirrhosis and those who died/referred to hospice versus not. Logistic regression for death/hospice was performed. In patients with cirrhosis, the culture results were compared over the years. Result(s): 1669 patients;833 cirrhosis and 836 non-cirrhosis patients were included. Patients with cirrhosis had higher rates of infection, positive culture, abdominal infection, and bacteremia. They also had higher gram-positive and fungal infections with a higher rate of VRE. They showed a greater organ failure load, death, and hospice referral compared to patients without cirrhosis. Logistic regression showed that cirrhosis (OR 4.0, p< 0.0001), admission qSOFA (1.60, p< 0.0001), WBC (1.02, p=0.003), reasons for ICU (altered mental status 1.69, hypotension 1.79, renal support 2.77, respiratory failure 1.79, CVA 1.96, all p< 0.0001) with Infection (1.77, p< 0.0001, >1 microbe isolated 1.86, p=0.05) were risk factors for death/hospice. The infection trend in the cirrhosis group showed a significant decrease in positive cultures and gram-negative infections and an increase in fungal and gram-positive infections over time. Conclusion(s): Despite matching for demographics and qSOFA, patients with cirrhosis had higher risks of death and organ failures. They were more likely to develop gram-positive and fungal infections with multiple organisms and VRE. Time trends in cirrhosis showed lower rates of positive cultures and gram-negative infections and an increase in fungal and gram-positive infections over time, which should encourage re-evaluation of diagnostic and prophylactic strategies in cirrhosis-related infections. (Figure Presented).
ABSTRACT
The cavernous sinus is one of the dural venous sinuses which plays an important role in venous outflow from the brain and eye sockets and in the regulation of intracranial circulation. We report a case of septic cavernous sinus thrombosis in a female patient with COVID-19. The disease often results in alterations of blood rheology, thrombosis in different organs, and septic complications. This article aims to raise awareness of healthcare professionals about the characteristics of COVID-19 that might cause septic cavernous sinus thrombosis in patients with severe comorbidities. Laboratory testing revealed severe comorbidities, including diabetes mellitus and liver cirrhosis caused by hepatitis C. They manifested with an impaired protein production in the liver and coagulation disorders. Systemic effects of SARS-CoV-2 on the vascular endothelium aggravated preexisting coagulation disorders and led to hemorrhage into retrobulbar tissue and clinical signs of septic cavernous sinus thrombosis, including swelling of the eyelids, bilateral exophthalmos, and ophthalmoplegia, followed by necrosis of the facial skin.Copyright © 2022, Dynasty Publishing House. All rights reserved.
ABSTRACT
Background: Severe outcomes of COVID-19 are associated with advancing age, and multiple medical comorbidities. The impact of COVID-19 on the clinical course of patients with cirrhosis has not been well studied. We determined the effect of SARS-CoV-2 infection on the hospitalization and survival rates of patients with cirrhosis. Method(s): Using ICD-10-CM codes, we identified all Veterans with a diagnosis of cirrhosis in the VA Corporate Data Warehouse and COVID-19 Shared Data Resource. Study cohort included Veterans who were tested for SARS-CoV-2 and had no history of organ transplantation or malignancies. Each SARS-CoV-2 positive case was propensity-score matched by demographics and comorbidities with up to two SARS-CoV-2 negative controls. The primary endpoints were acute care hospitalization, admission to intensive care, respiratory support, or death. Result(s): Of 1,115,037 individuals tested for SARS-CoV-2, 31,680 were noted to have cirrhosis and among them 5,047 (16%) were SARS-CoV-2 positive. After exclusions and propensity-score matching, 5,047 SARS-CoV-2 positive and 9,913 propensity score matched SARS-CoV-2 negative individuals were included in the analysis cohort. Median age was 67 years, 95% were men and 25% were of black race. Median BMI was 30 and history of hypertension, diabetes, cardiovascular and chronic pulmonary disease was noted among 81%, 54%, 56% and 32% respectively. Among all cirrhotic individuals, SARS-CoV-2 positive individuals less frequently progressed to hepatic decompensation (3.1% vs 4.8%, P< 0.0001) or hospitalization (35.7% vs 38.2%, P=0.002), but more frequently required ICU admission 15% vs 12.2%, P< 0.0001) or respiratory support (7.3% vs 8.4%, P=0.01). Among those admitted, length of hospital stay was longer among SARS-CoV-2 positive individuals (7 vs 4 days, P< 0.0001). In Cox regression analysis, SARS-CoV-2 positivity was associated with a higher risk of all-cause mortality (HR 1.37, 95% CI 1.19,1.56). Conclusion(s): Although patients with cirrhosis and COVID-19 were less often hospitalized, they had longer duration of hospitalization and were at higher risk of severe or critical illness and death. (Figure Presented).