Nail ridging in rheumatoid arthritis patients and relation to disease activity: An integrated rheumatology-dermatology multi-centre study

Aim of the work: To evaluate the frequency of nail ridging (NR) in patients with rheumatoid arthritis (RA) and to study its relation to disease activity. Patients and methods: 230 RA patients and 97 matched controls from Helwan, Ain Shams and Mansoura university hospitals were studied. Disease activity score (DAS28) was assessed. NR has been searched for in all patients. The number of affected fingers was recorded. NR was determined by a magnifying lens, seen by naked eye or seen and felt. Dermoscopic photography of the NR using Dermalite DL4 3Gen dermatoscope has been recorded. Results: The median age of patients was 49 years (42–58 years);they were 221 females and 19 males (F:M 11.1:1) with a disease duration 9 years (5–11 years). Their DAS28 was 3.6 (2.9–4.6). NR was significantly increased in RA cases vs. control;73% vs 20%;p < 0.001. In patients, NR was detected by a magnifying lens in 32.6%, seen in 27% and seen and felt in 13.5%. Joint deformities were significantly higher in those with NR. DAS28 was a significant independent predictor of NR;for every one-point increase in DAS28, there was a 153 times higher odds to exhibit NR at a sensitivity of 93.5%, specificity 80.3% and at a diagnostic accuracy of 90%. Conclusion: NR is a frequent finding in RA. An integrated rheumatological- dermatological clinical evaluation may be helpful and further studies are required to prove the importance of this sign for follow up of RA patients.

Safety and immunogenicity of booster dose in patients with chronic liver disease

Background/Aims: Several studies showed that patients with liver cirrhosis have an immune dysregulation leading to poor immunological response to vaccination. However, in literature there are few data about the response to SARS-CoV-2 vaccination in patients with chronic liver disease (CLD). Aims of the study are (is) the evaluation of safety and immunogenicity of booster dose in patients with CLD. Methods: From September 2021 to April 2022, all consecutive outpatients with CLD who completed the primary vaccination course and the booster dose for anti-SARS-CoV-2 vaccination were enrolled. Blood samples were collected 12-16 weeks after second dose and after booster dose. Collected samples were analyzed for detecting anti-Spike protein IgG using LIAISON TrimericS IgG chemiluminescent assay (Diasorin, Italy). Results: We enrolled 340 patients (187 Males, mean age:64.32±17.34years). Stratified by the presence of cirrhosis, 249 had CLD and 91 were cirrhotic whose 57 (62.24%) had portal hypertension. At the end of the primary vaccination course, 60 patients (17.65%) did not develop a protective antibody titer, with no statistically significant differences between the two groups (19.7% in cirrhotic vs 16.8% in non-cirrhotic;p=0.076). The majority of them (53/60 patients;88.3%) developed a protective titer after booster dose, without differences between cirrhotics and non-cirrhotics (p=0.089). At multivariate analysis, factors associated with a higher humoral response after booster dose were young age (p=0.0098);porto-sinusoidal vascular disorder (p=0.005), none or a single comorbidity rather than two or more (p=0.05) and Spikevax booster dose compared with Comirnaty (p=0.001). Moreover, the antibody titer is inversely related to age (p=0.000). Conclusions: In a large cohort of patients with CLD booster dose of anti-Sars-CoV-2 vaccine has an excellent immunogenicity and leads to an adequate antibody response even in those who had not produced a protective titer after the primary vaccination course. Cirrhosis is not associated with a reduced humoral response.

Efficacy of Vaccine Protection Against COVID-19 Virus Infection in Patients with Chronic Liver Diseases

The outbreak of coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. Vaccination against coronavirus disease 2019 is a use-ful weapon to combat the virus. Patients with chronic liver diseases (CLDs), including compensated or decompensated liver cirrhosis and noncirrhotic diseases, have a decreased immunologic response to coronavirus disease 2019 vaccines. At the same time, they have increased mortality if infected. Current data show a reduction in mortality when patients with chronic liver diseases are vaccinated. A suboptimal vac-cine response has been observed in liver transplant recipi-ents, especially those receiving immunosuppressive therapy, so an early booster dose is recommended to achieve a better protective effect. Currently, there are no clinical data com-paring the protective efficacy of different vaccines in patients with chronic liver diseases. Patient preference, availability of the vaccine in the country or area, and adverse effect profiles are factors to consider when choosing a vaccine. There have been reports of immune-mediated hepatitis after coronavi-rus disease 2019 vaccination, and clinicians should be aware of that potential side effect. Most patients who developed hepatitis after vaccination responded well to treatment with prednisolone, but an alternative type of vaccine should be considered for subsequent booster doses. Further prospec-tive studies are required to investigate the duration of immu-nity and protection against different viral variants in patients with chronic liver diseases or liver transplant recipients, as well as the effect of heterologous vaccination.

Predictors of in-hospital mortality in HIV-infected patients with COVID-19.

BACKGROUND: Underlying immunodeficiency is associated with severe COVID-19, but the prognosis of persons with HIV (PWH) with COVID-19 is under debate. METHODS: Nationwide, retrospective, observational analysis of all hospitalizations with COVID-19 during year 2020 in Spain. Stratification was made according to HIV status. The National Registry of Hospital Discharges was used with the ICD-10 coding list. RESULTS: A total of 117,694 adults were hospitalized with COVID-19 during 2020. Only 234 (0.2%) were HIV-positives. More than 95% were on antiretroviral therapy. Compared to HIV-negatives, PWH were younger (mean age 53.2 vs 66.5 years-old; p < 0.001) and more frequently male (74.8% vs 56.6%; p < 0.001). Most co-morbidities predisposing to severe COVID-19 (diabetes, hypertension, dementia, cardiovascular disease) were more frequent in HIV-negatives. In contrast, the rate of baseline liver disease was over 6-fold higher in PWH (27.4% vs 4.4%; p < 0.001). In-hospital mortality was lower in PWH (9.4% vs 16%; p = 0.004). In multivariate analysis, older age, dementia and especially advanced liver disease (RR: 7.6) were the major determinants of death in PWH hospitalized with COVID-19. CONCLUSION: HIV-infected patients hospitalized in Spain with COVID-19 during 2020 had better survival than HIV-negatives, most likely explained by younger age and lower rate of co-morbidities. However, advanced liver disease was a major predictor of death in PWH hospitalized with COVID-19.

Immunogenicity of COVID-19 vaccines in chronic liver disease patients and liver transplant recipients: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Chronic liver disease (CLD) patients and liver transplant (LT) recipients have an increased risk of morbidity and mortality from coronavirus disease 2019 (COVID-19). The immunogenicity of COVID-19 vaccines in CLD patients and LT recipients is poorly understood. The present study aimed to evaluate the immunogenicity of COVID-19 vaccines in CLD patients and LT recipients. METHODS: We searched electronic databases for eligible studies. Two reviewers independently conducted the literature search, extracted the data and assessed the risk of bias of included studies. The rates of detectable immune response were pooled from single-arm studies. For comparative studies, we compared the rates of detectable immune response between patients and healthy controls. The meta-analysis was conducted using the Stata software with a random-effects model. RESULTS: In total, 19 observational studies involving 4191 participants met the inclusion criteria. The pooled rates of detectable humoral immune response after two doses of COVID-19 vaccination in CLD patients and LT recipients were 95% (95% confidence interval [CI] = 88%-99%) and 66% (95% CI = 57%-74%) respectively. After two doses of vaccination, the humoral immune response rate was similar in CLD patients and healthy controls (risk ratio [RR] = 0.96; 95% CI = 0.90-1.02; p = .14). In contrast, LT recipients had a lower humoral immune response rate after two doses of vaccination than healthy controls (RR = 0.68; 95% CI = 0.59-0.77; p < .01). CONCLUSIONS: Our meta-analysis demonstrated that COVID-19 vaccination induced strong humoral immune responses in CLD patients but poor humoral immune responses in LT recipients.

Survey of the Impact of COVID-19 on Chronic Liver Disease Patient Care Experiences and Outcomes.

Background: The COVID-19 pandemic has a secondary impact on the health of patients with chronic liver disease (CLD). Our objective was to study this impact on care provision, telemedicine, and health behaviours in CLD patients. Methods: CLD patients of an urban gastroenterology clinic who attended a telemedicine appointment between March 17, 2020 and September 17, 2020, completed an online survey on care delays, health behaviours, and experience with telemedicine. Chart review was conducted in 400 randomly selected patients: 200 charts from during the pandemic were compared to 200 charts the previous year. Data were extracted for clinicodemographic variables, laboratory investigations, and clinical outcomes. Results: Of 399 patients invited to participate, 135 (34%) completed the online survey. Fifty (39%) patients reported 83 care delays due to the COVID-19 pandemic, with the majority (71%) of delays persisting beyond 2 months. Ninety-five (75%) patients were satisfied with telemedicine appointments. There was a longer delay between lab work and appointments in patients seen during the pandemic compared to 2019 (P = 0.01). Compared to the year prior, during the COVID pandemic, there was a similar number of cases of cirrhosis decompensation (n = 26, 13% versus n = 22, 11%) and hospitalization (n = 12, 6% versus n = 5, 3%). Conclusion: The COVID-19 pandemic has led to care delays for CLD outpatients, with most delays on the scale of months. These patient-reported experiences and clinical observations can direct optimization of CLD care as effects from the pandemic evolve.

Infection prevention and control programme and COVID-19 measures: Effects on hospital-acquired infections in patients with cirrhosis.

Background & Aims: Bacterial infections affect survival of patients with cirrhosis. Hospital-acquired bacterial infections present a growing healthcare problem because of the increasing prevalence of multidrug-resistant organisms. This study aimed to investigate the impact of an infection prevention and control programme and coronavirus disease 2019 (COVID-19) measures on the incidence of hospital-acquired infections and a set of secondary outcomes, including the prevalence of multidrug-resistant organisms, empiric antibiotic treatment failure, and development of septic states in patients with cirrhosis. Methods: The infection prevention and control programme was a complex strategy based on antimicrobial stewardship and the reduction of patient's exposure to risk factors. The COVID-19 measures presented further behavioural and hygiene restrictions imposed by the Hospital and Health Italian Sanitary System recommendations. We performed a combined retrospective and prospective study in which we compared the impact of extra measures against the hospital standard. Results: We analysed data from 941 patients. The infection prevention and control programme was associated with a reduction in the incidence of hospital-acquired infections (17 vs. 8.9%, p <0.01). No further reduction was present after the COVID-19 measures had been imposed. The impact of the infection prevention and control programme remained significant even after controlling for the effects of confounding variables (odds ratio 0.44, 95% CI 0.26-0.73, p = 0.002). Furthermore, the adoption of the programme reduced the prevalence of multidrug-resistant organisms and decreased rates of empiric antibiotic treatment failure and the development of septic states. Conclusions: The infection prevention and control programme decreased the incidence of hospital-acquired infections by nearly 50%. Furthermore, the programme also reduced the prevalence of most of the secondary outcomes. Based on the results of this study, we encourage other liver centres to adopt infection prevention and control programmes. Impact and implications: Infections are a life-threatening problem for patients with liver cirrhosis. Moreover, hospital-acquired infections are even more alarming owing to the high prevalence of multidrug-resistant bacteria. This study analysed a large cohort of hospitalised patients with cirrhosis from three different periods. Unlike in the first period, an infection prevention programme was applied in the second period, reducing the number of hospital-acquired infections and containing multidrug-resistant bacteria. In the third period, we imposed even more stringent measures to minimise the impact of the COVID-19 outbreak. However, these measures did not result in a further reduction in hospital-acquired infections.

Epidemiology and Disease Burden of Alcohol Associated Liver Disease.

Consumption of alcohol in excess leads to substantial medical, economic, and societal burdens. Approximately 5.3% of all global deaths may be attributed to alcohol consumption. Moreover, the burden of alcohol associated liver disease (ALD) accounts for 5.1% of all disease and injury worldwide. Alcohol use disorder (AUD) affects men more than women globally with significant years of life loss to disability in low, middle and well-developed countries. Precise data on global estimates of alcohol related steatosis, alcohol related hepatitis, and alcohol related cirrhosis have been challenging to obtain. In the United States (US), alcohol related steatosis has been estimated at 4.3% based on NHANES data which has remained stable over 14 years. However, alcohol-related fibrotic liver disease has increased over the same period. In those with AUD, the prevalence of alcohol related hepatitis has been estimated at 10-35%. Globally, the prevalence of alcohol-associated cirrhosis has been estimated at 23.6 million individuals for compensated cirrhosis and 2.46 million for those with decompensated cirrhosis. The contribution of ALD to global mortality and disease burden of liver related deaths is substantial. In 2016 liver disease related to AUD contributed to 50% of the estimated liver disease deaths for age groups 15 years and above. Data from the US report high cost burdens associated with those admitted with alcohol-related liver complications. Finally, the recent COVID-19 pandemic has been associated with marked increase in alcohol consumption worldwide and will likely increase the burden of ALD.

Prevention, diagnostic evaluation, management and prognostic implications of liver disease in critically ill patients with COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, broke out in December 2019 in Wuhan city of China and spread rapidly worldwide. Therefore, by March 2020, the World Health Organization declared the disease a global pandemic. Apart from the respiratory system, various other organs of the human body are also seriously affected by the virus. Liver injury in patients with a severe form of COVID-19 is estimated to be 14.8%-53.0%. Elevated levels of total bilirubin, aspartate aminotransferase and alanine aminotransferase and low levels of serum albumin and prealbumin are the main laboratory findings. Patients with pre-existing chronic liver disease and cirrhosis are much more prone to develop severe liver injury. This literature review presented the recent scientific findings regarding the pathophysiological mechanisms responsible for liver injury in critically ill patients with COVID-19, the various interactions between drugs used to treat the disease and the function of the liver and the specific tests providing the possibility of early diagnosis of severe liver injury in these patients. Moreover, it highlighted the burden that COVID-19 put on health systems worldwide and its effect on transplant programs and the care provided to critically ill patients in general and particularly to those with chronic liver disease.

Cirrhosis is associated with lower serological responses to COVID-19 vaccines in patients with chronic liver disease.

Background & Aims: The response of patients with chronic liver disease (CLD) to COVID-19 vaccines remains unclear. Our aim was to assess the humoral immune response and efficacy of two-dose COVID-19 vaccines among CLD patients of different etiologies and disease stages. Methods: 357 patients were recruited in clinical centers from 6 European countries. 132 healthy volunteers served as controls. Serum IgG, IgM (nM) and neutralizing antibodies (NAb; %) against the Wuhan-Hu-1, B.1.617 and B.1.1.529 SARS-CoV-2 spike proteins were determined prior to vaccination (T0), 14 days (T2) and 6 months (T3) after second dose vaccination. Patients fulfilling inclusion criteria at T2 (n=212) were stratified into "low" or "high" responders according to IgG levels. Infection rates and severity were collected throughout the study. Results: Wuhan-Hu-1 IgG, IgM and neutralization levels significantly increased from T0 to T2 in patients vaccinated with either BNT162b2 (70.3%), mRNA-1273 (18.9%) or ChAdOx1 (10.8%). In multivariate analysis, age, cirrhosis and type of vaccine (ChAdOx1 > BNT162b2 > mRNA-1273) predicted "low" humoral response, while viral hepatitis and antiviral therapy predicted "high" humoral response. Comparing with Wuhan-Hu-1, B.1.617 and, further, B.1.1.529 IgG levels were significantly lower at both T2 and T3. Compared with healthy individuals, CLD patients presented with lower B.1.1.529 IgGs at T2 with no additional key differences. No major clinical or immune IgG parameters associated with SARS-COV-2 infection rates or vaccine efficacy. Conclusions: Patients with CLD and cirrhosis exhibit lower immune responses to COVID-19 vaccination, irrespective of disease etiology. The type of vaccine leads to different antibody responses, that appear not to associate with distinct efficacy, although this needs validation in larger cohorts with a more balanced representation of all vaccines. Lay summary: In patients with CLD vaccinated with two-dose vaccines, age, cirrhosis and type of vaccine (Vaxzevria > Pfizer BioNTech > Moderna) predict a "lower" humoral response, while viral hepatitis etiology and prior antiviral therapy predict a "higher" humoral response. This differential response appears not to associate with SARS-COV-2 infection incidence or vaccine efficacy. Still, compared with Wuhan-Hu-1, humoral immunity was lower for the Delta and Omicron variants, and all decreased after 6 months. As such, patients with CLD, particularly those older and with cirrhosis, should be prioritized for receiving booster doses and/or recently approved adapted vaccines.

Updated Review about Liver Cirrhosis in the COVID-19 Era

Background: The clinical manifestations in patients with COVID-19 may be nonspecific, but most have fever, cough, followed by dyspnea, fatigue, or sputum production. approximately 14% to 53% of patients experience various degrees of liver damage, although most of these injuries are mild and transient, with a satisfactory prognosis in patients without prior liver disease. In contrast, COVID-19 in patients with pre-existing liver disease has been reported to result in higher hospitalization and mortality rates. Among these pre-existing liver diseases, cirrhosis is a chronic liver disease that involves the collapse of the structure of the liver and distortion of the vascular architecture. Cirrhosis is associated with inherent immune dysfunction and an altered gut-liver axis;patients with cirrhosis are particularly at elevated risk of infections and the associated complications. It remains uncertain whether immunocompromised patients with COVID-19 have a higher risk of adverse outcomes. Patients with cancer or solid organ transplant recipients may have an elevated risk of more severe COVID-19;whereas patients taking biologic therapies may not have a greater risk of developing severe COVID-19. No additional risk of death was observed in cancer patients receiving active treatment except in those undergoing chemotherapy. Whether patients with human immunodeficiency virus infection are at higher risk of mortality due to COVID-19 is unclear.Limited evidence has shown that the clinical manifestations in cirrhotic patients with COVID-19 are similar to those in the general population with COVID-19, with fever and cough remaining the most common symptoms, followed by shortness of breath and sputum production. Interestingly, whereas similar proportions of cirrhotic and noncirrhotic patients developed respiratory and cardiovascular symptoms, cirrhotic patients were less likely to develop gastrointestinal symptoms (e.g., diarrhea, nausea, vomiting). Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Sarcopenia in Children with Liver Disease: A Pilot Study

Background and Aims Sarcopenia can be defined as loss of muscle mass, strength and function and has been shown to be associated with increased morbidity and mortality in the adult population. Sarcopenia has been assessed by decreased psoas muscle surface area (PMSA) on Computer tomography (CT) and has been validated in paediatric studies. The impact of Sarcopenia in children with end stage liver disease and oncological conditions is now being recognised. There is scarce literature on the effect of sarcopenia on motor function. CT imaging exposes children to radiation and hence is done in a select group of children at the time of transplant assessment. The aim of this audit was to assess the prevalence of Sarcopenia in children undergoing liver transplant assessment and its relationship on laboratory variables, functional activity and clinical outcomes. Methods Retrospective single centre case review of patients with liver disease undergoing transplant assessment and CT imaging between 2018-2020. Psoas muscle was analysed at the level of L4/L5. The z-Scores were calculated using ageand gender-specific reference values. Sarcopenia was defined as tPMA z score less than -2. We assessed the relationship of Sarcopenia to the biochemical parameters, nutritional status, effect on motor delay/physical abilities (assessed by a range of age appropriate standardised developmental and physical assessments due to COVID pandemic isolation restrictions) and post-transplant complications. Results Thirty one children that met the inclusion criteria were included. Sarcopenia was prevalent in 17 children (6 males: 11 females), with a median age of 3.5 years (SD = 4.9). The common conditions were biliary atresia (n= 11, 35%), hepatoblastoma (n=6, 19%), Autoimmune hepatitis (n=3) etc. Twenty- four patients required additional nutritional support (77% nasogastric feeding, 13% PN and 6% oral supplementation). Mean tPMA z-score was -2.27. Data for the assessment of physical abilities/functional activity was available in 21 children. Impairment of motor skills/physical abilities was overall noted in 14/21 children (67%);9/13 (69%) in the sarcopenic group (6 significant impairment) vs 5/8 (63%) in non sarcopenic group (4 significant impairment). Sarcopenia was associated with increased complications (27 vs 7, p = 0.005) and hypoalbuminaemia (p=0.01), but was not statistically significant (p> 0.05) for the overall length of stay (total and intensive care). Discussion Sarcopenia was commonly identified in children with liver diseases undergoing transplant assessment. Reduction in physical abilities/functional activity was observed in both groups which may be a consequence of loss of muscle mass in children secondary to liver diseases or underlying oncological conditions leading to delay in gross motor skills. Although there was no statistical difference in the duration of stay or impairment of motor skills, complications were higher in the sarcopenic group. Conclusion In this pilot study, sarcopenia is prevalent in children being assessed for liver transplantation and was associated with increased complications. Better non-invasive methods (aside from CT scan) of assessing sarcopenia needs to be developed and validated for the paediatric age group, which would help to better characterise the true incidence and prevalence of sarcopenia in children with chronic liver disease. There is a need to offer nutritional support and assess physical function early in the pre transplant period in order to initiate appropriate physiotherapy interventions to halt and even reverse the progression of sarcopenia.

Hepatic manifestations of COVID-19 in the obstetric population

COVID-19 has and continues to affect healthcare across the world. Pregnant women have been identified as a moderate-risk group with regards to clinical susceptibility to COVID-19. Acute liver injury in pregnancy secondary to COVID-19 has been documented sparsely across the world. In this report, we describe the case of a pregnant women who presented with COVID-19 liver injury. A second women with a similar presentation and outcome also presented during the same COVID-19 wave but contact details were lost and consent not gained. Description The cases occurred in December 2020 during which time the predominant reported variant was the alpha strain of COVID-19. Patient A was a multiparous woman, who presented to the labour ward at 37 weeks, a few days after a positive COVID-19 test with vomiting. Investigations revealed significant derangement of liver function tests (LFTs) but with normal bilirubin and clotting. On a working diagnosis of acute fatty liver of pregnancy and with breech presentation, she underwent a caesarean section. Liver enzymes continued to deteriorate with a mild coagulopathy. A non-invasive liver screen and ultrasound did not reveal any significant abnormalities. She was discussed with the tertiary liver centre and started on a Nacetylcysteine infusion with some additional vitamin K. A few days later LFTs began to improve and she was discharged home with follow-up in the community. Her baby was treated with antibiotics for 5 days empirically due to the unknown nature of the transaminitis but remained well. Following further discussion with the tertiary centre, a diagnosis of acute liver injury secondary to COVID-19 was made. Discussion Extra-pulmonary features of COVID-19 have been reported in the literature. A number of theories have been postulated to describe the hepatic effects. This has mainly manifested itself as a transaminitis with varying outcomes. The prevalence in the obstetric population has been more sparsely reported but most isolated cases have been relatively self-limiting with positive outcomes [1]. This case also highlighted the diagnostic difficulties with other severe hepatic diseases of pregnancy. A handful of case reports have already described some of the crossover and difficulty in decisionmaking when these patients present acutely unwell to hospital [2]. The severity and rapid progression of some hepatic disorders in pregnancy not only warrants decisive decision-making but also involvement of the multidisciplinary team.

Clinical characteristics and risk factors for mortality in patients with COVID-19: A retrospective nationwide study in Malaysia

Background: Age and multiple comorbidities have been reported to influence the case fatality rate of COVID-19 worldwide, so also in Malaysia;however, to date, no scientific study among the local population has been published to confirm this. This study aimed to determine the overall demographics and clinical characteristics of COVID-19 non-survivors in Malaysia, stratified by age (< 65 vs. >= 65 years old). The mortality was also compared between two half-year periods: March-August 2020 and September 2020-March 2021. Method(s): Daily reports containing demographics and medical history of COVID-19 non-survivors from March 2020 to March 2021 were obtained from the Malaysian Ministry of Health website. All information was extracted retrospectively and analysed using descriptive and inferential statistics with SPSS. Result(s): Of 1192 COVID-19 non-survivors, the overall mean (SD) age was 64.8 (15.7) years, with 64.7% male. Death was seen mostly among 50- to 64-year-olds (33.1%) and 65- to 74-year-olds (24.8%). The presence of underlying hypertension (61.8%) and diabetes mellitus (48.2%) were the most common comorbid diseases encountered in the COVID-19 non-survivors. Underlying hypertension, stroke, heart disease and dyslipidaemia were significantly higher among COVID-19 non-survivors who were >= 65 years old compared to those < 65 (p < 0.05). Mortality was a lot higher in September 2020-March 2021 compared to March 2020-August 2020 (91.3% vs. 8.3%). Conclusion(s): Older age, male gender and the presence of multimorbidity (hypertension, diabetes mellitus, stroke and heart disease) are risk factors that contribute to mortality due to COVID-19 in Malaysia, especially among those >= 65 years old. Copyright © The Author(s) 2022.

Chronic liver disease-related mortality in diabetes before and during the COVID-19 in the United States.

BACKGROUND: Global pandemic of COVID-19 represents an unprecedented challenge. COVID-19 has predominantly targeted vulnerable populations with pre-existing chronic medical diseases, such as diabetes and chronic liver disease. AIMS: We estimated chronic liver disease-related mortality trends among individuals with diabetes before and during the COVID-19 pandemic. METHODS: Utilizing the US national mortality database and Census, we determined the quarterly age-standardized chronic liver disease-related mortality and quarterly percentage change (QPC) among individuals with diabetes. RESULTS: The quarterly age-standardized mortality for chronic liver disease and/or cirrhosis among individuals with diabetes remained stable before the COVID-19 pandemic and sharply increased during the COIVD-19 pandemic at a QPC of 8.5%. The quarterly mortality from nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) increased markedly during the COVID-19 pandemic. Mortality for hepatitis C virus (HCV) infection declined with a quarterly rate of -3.3% before the COVID-19 pandemic and remained stable during the COVID-19 pandemic. While ALD- and HCV-related mortality was higher in men than in women, NAFLD-related mortality in women was higher than in men. CONCLUSIONS: The sharp increase in mortality for chronic liver disease and/or cirrhosis among individuals with diabetes during the COVID-19 pandemic was associated with increased mortality from NAFLD and ALD.

Impact of the COVID-19 pandemic on liver disease-related mortality rates in the United States.

BACKGROUND: The pandemic has resulted in an increase of deaths not directly related to COVID-19 infection. We aimed to use a national death dataset to determine the impact of the pandemic on people with liver disease in the U.S, focusing on alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). METHODS: Using data from the National Vital Statistic System from the CDC WONDER platform and ICD-10 codes, we identified deaths associated with liver disease. We evaluated observed versus predicted mortality for 2020-2021 based on trends from 2010-2019 with joinpoint and prediction modeling analysis. RESULTS: Among 626,090 chronic liver disease-related deaths between 2010 and 2021, Age-standardized mortality rates (ASMR) for ALD dramatically increased between 2010-2019 and 2020-2021 (annual percentage change [APC] 3.5% to 17.6%, P<0.01), leading to a higher observed ASMR (per 100,000 persons) than predicted for 2020 (15.67 vs.13.04) and 2021 (17.42 vs.13.41). ASMR for NAFLD also increased during the pandemic (APC:14.5%), while the rates for hepatitis B and C decreased. Notably, the ASMR rise for ALD was most pronounced in non-Hispanic Whites, Blacks, and Alaska Indians/Native Americans (APC: 11.7%, 10.8%, 18.0%, all P<0.05), with similar but less critical findings for NAFLD while rates were steady for non-Hispanic Asians throughout 2010-2021 (APC: 4.9%). The ASMR rise for ALD was particularly severe for the 25-44 age group (APC: 34.6%, versus 13.7% and 12.6% for 45-64 and ≥65, all P<0.01), which were also all higher than pre-COVID-19 rates (all P<0.01). CONCLUSIONS: ASMR for ALD and NAFLD increased at an alarming rate during the COVID-19 pandemic with the largest disparities among the young, non-Hispanic White, and Alaska Indian/Native American populations. LAY SUMMARY: The impact of the pandemic on people with liver disease in the U.S remains unclear. This study indicated that age-standardized mortality rates for alcohol associated liver disease and non-alcohol fatty liver disease greatly accelerated during the COVID-19 pandemic with the largest disparities among the young, non-Hispanic White, and Alaska Indian/Native American populations. Increasing awareness about the care importance of chronic liver disease in specific populations must be prioritized.

Molecular mechanisms implicated in SARS-CoV-2 liver tropism.

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hepatic involvement is common in SARS-CoV-2-infected individuals. It is currently accepted that the direct and indirect hepatic effects of SARS-CoV-2 infection play a significant role in COVID-19. In individuals with pre-existing infectious and non-infectious liver disease, who are at a remarkably higher risk of developing severe COVID-19 and death, this pathology is most medically relevant. This review emphasizes the current pathways regarded as contributing to the gastrointestinal and hepatic ailments linked to COVID-19-infected patients due to an imbalanced interaction among the liver, systemic inflammation, disrupted coagulation, and the lung.

Association between COVID-19 and chronic liver disease: Mechanism, diagnosis, damage, and treatment.

As the outbreak evolves, our understanding of the consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) on the liver has grown. In this review, we discussed the hepatotropic nature of SARS-CoV-2 and described the distribution of receptors for SARS-CoV-2 (e.g., angiotensin-converting enzyme 2) in the vascular endothelium and cholangiocytes of the liver. Also, we proposed mechanisms for possible viral entry that mediate liver injury, such as liver fibrosis. Due to SARS-CoV-2-induced liver damage, many COVID-19 patients develop liver dysfunction, mainly characterized by moderately elevated serum aminotransferase levels. Patients with chronic liver disease (CLD), such as cirrhosis, hepatocellular carcinoma, nonalcoholic fatty liver disease, and viral hepatitis, are also sensitive to SARS-CoV-2 infection. We discussed the longer disease duration and higher mortality following SARS-CoV-2 infection in CLD patients. Correspondingly, relevant risk factors and possible mechanisms were proposed, including cirrhosis-related immune dysfunction and liver deco-mpensation. Finally, we discussed the potential hepatotoxicity of COVID-19-related vaccines and drugs, which influence the treatment of CLD patients with SARS-CoV-2 infection. In addition, we suggested that COVID-19 vaccines in terms of immunogenicity, duration of protection, and long-term safety for CLD patients need to be further researched. The diagnosis and treatment for liver injury caused by COVID-19 were also analyzed in this review.