The coronavirus disease 2019 (COVID-19) pandemic has caused changes in the global health system, causing significant setbacks in healthcare systems worldwide. This pandemic has also shown resilience, flexibility, and creativity in reacting to the tragedy. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection targets most of the respiratory tract, resulting in a severe sickness called acute respiratory distress syndrome that may be fatal in some individuals. Although the lung is the primary organ targeted by COVID-19 viruses, the clinical aspect of the disease is varied and ranges from asymptomatic to respiratory failure. However, due to an unorganized immune response and several affected mechanisms, the liver may also experience liver cell injury, ischemic liver dysfunction, and drug-induced liver injury, which can result in respiratory failure because of the immune system\'s disordered response and other compromised processes that can end in multisystem organ failure. Patients with liver cirrhosis or those who have impaired immune systems may be more likely than other groups to experience worse results from the SARS-CoV-2 infection. We thus intend to examine the pathogenesis, current therapy, and consequences of liver damage concerning COVID-19.

OBJECTIVE: Vitamins and homocysteine (Hcy) are involved in liver metabolism and related to the pathogenesis of autoimmune liver disease (AILD), but consensus is lacking. This study aims to systematically summarize relevant evidence to clarify the association of serum vitamins and Hcy levels with AILD.
METHODS: The English and Chinese literature was searched until August 29, 2023. Studies were included if they were observational studies of investigating serum vitamins and Hcy levels in patients with AILD and their healthy comparisons. Quality assessment was performed by using the Newcastle-Ottawa Scale, and a meta-analysis was conducted using ReviewManager 5.3. The protocol was registered in the international prospective register of systematic reviews (PROSPERO), with registration number CRD42023455367.
RESULTS: A total of 25 case-control studies comprising 3487 patients (1673 patients and 1814 healthy controls) were included for analysis. There were 548 autoimmune hepatitis (AIH) cases, 1106 primary biliary cholangitis (PBC) cases, and 19 primary sclerosing cholangitis (PSC) cases. We found that serum A and E were decreased in both AIH and PBC/PSC; but vitamin C was reduced only in patients with PBC, not AIH. In addition, decreased content of 25(OH)D3 was found in both AIH and PBC. However, levels of 25(OH)D did not differ between the patients and controls, and were independent of disease types and the country. Only one study that met the inclusion criteria reported vitamin B6, B9, B12, and Hcy changes, and found that vitamin B6 and B9 were significantly decreased in patients with PBC, while serum vitamin B12 and Hcy levels were significantly elevated in them. One eligible study each confirmed a reduction in plasma vitamin K1 and 1,25(OH)2D3 in patients with PBC.
CONCLUSIONS: Most vitamins are deficient in AILD, so appropriate vitamin supplementation should be necessary. Further studies with larger sample sizes are needed to validate these findings.

BACKGROUND: Noninvasive methods have been developed to detect fibrosis in many liver diseases due to the limits of liver biopsy. However, previous studies have focused primarily on chronic viral hepatitis and nonalcoholic fatty liver disease. The diagnostic value of transient elastography for autoimmune liver diseases (AILDs) is worth studying.
OBJECTIVE: To compare the diagnostic accuracy of imaging techniques with serum biomarkers of fibrosis in AILD.
METHODS: The PubMed, Cochrane Library and EMBASE databases were searched. Studies evaluating the efficacy of noninvasive methods in the diagnosis of AILDs [autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC)] were included. The summary area under the receiver operating characteristic curve (AUROC), diagnostic odds ratio, sensitivity and specificity were used to assess the accuracy of these noninvasive methods for staging fibrosis.
RESULTS: A total of 60 articles were included in this study, and the number of patients with AIH, PBC and PSC was 1594, 3126 and 501, respectively. The summary AUROC of transient elastography in the diagnosis of significant fibrosis, advanced fibrosis and cirrhosis in patients with AIH were 0.84, 0.88 and 0.90, respectively, while those in patients with PBC were 0.93, 0.93 and 0.91, respectively. The AUROC of cirrhosis for patients with PSC was 0.95. However, other noninvasive indices (aspartate aminotransferase to platelet ratio index, aspartate aminotransferase/alanine aminotransferase ratio, fibrosis-4 index) had corresponding AUROCs less than 0.80.
CONCLUSIONS: Transient elastography exerts better diagnostic accuracy in AILD patients, especially in PBC patients. The appropriate cutoff values for staging advanced fibrosis and cirrhosis ranged from 9.6 to 10.7 and 14.4 to 16.9 KPa for PBC patients.

Autoimmune hepatitis (AIH) is a chronic liver disease characterized by immune-mediated destruction of hepatocytes, leading to inflammation and fibrosis. In recent years, significant advances have been made in understanding the pathogenesis, epidemiology, diagnosis, and treatment of AIH. This comprehensive narrative review aims to provide an up-to-date overview of these advances. The review begins by outlining the historical background of AIH, dating back to its initial recognition in the 1940s, and highlights the evolution of diagnostic criteria and classification based on autoantibody profiles. The epidemiology of AIH is explored, discussing its varying prevalence across different regions and the role of genetic predisposition, viral infections, and drug exposure as risk factors. Furthermore, the review delves into the pathogenesis of AIH, focusing on the dysregulated immune response, involvement of T cells, and potential contribution of the gut microbiome. Clinical presentation, diagnostic criteria, and liver biopsy as crucial tools for diagnosis are also discussed. Regarding management, the review provides an in-depth analysis of the standard first-line treatments involving glucocorticoids and azathioprine, as well as alternative therapies for non-responsive cases. Additionally, emerging second and third-line treatment options are examined. In conclusion, this narrative review highlights the complexity of AIH and underscores the importance of early diagnosis and individualized treatment approaches to improve patient outcomes. Further research and clinical trials are needed to optimize AIH management and ensure a better long-term prognosis for affected individuals.

UNASSIGNED: Primary squamous cell carcinoma of the thyroid (PSCCT) is a rare malignant tumor. The incidence rate of PSCCT is less than 1%. However, the diagnosis and treatment of PSCCT are limited. Surgical resection is considered to be one of the few effective intervention methods. In this article, we reported a case of taking tyrosine kinase inhibitors (TKIs) combined with immune checkpoint inhibitors (ICIs) for PSCCT.
UNASSIGNED: An 80-year-old male was admitted to our hospital with dyspnea, cough, wheezing, and hoarseness for a giant thyroid mass. He underwent bronchoscopy and tracheal stent implantation to alleviate the respiratory obstruction. Then he accepted right partial thyroid and right lymph node biopsy. Postoperative pathology revealed squamous cell carcinoma. Subsequently, he underwent an endoscopy to exclude upper gastrointestinal squamous cell carcinoma. Finally, he was diagnosed with PSCCT. The patient was tentatively treated with a combination of Anlotinib and Sintilimab. After two courses, the tumor volume significantly reduced in MRI images and shrank further after five courses of combined treatment. Unfortunately, the patient died of fulminant liver failure and autoimmune liver disease after 5-month-treatment.
UNASSIGNED: TKIs combined with ICIs may be an effective and novel way for PSCCT treatment, but immune-related complications, especially liver damage, should be cared.

OBJECTIVE: Liver involvement in celiac disease (CeD) is known but its various etiologies and the effect of gluten free diet (GFD) on it is understudied.
METHODS: We searched PubMed, Medline and Embase databases from date of inception to March 7, 2022, to look for studies reporting on CeD and liver abnormalities. Pooled proportion of CeD patients with deranged transaminases, etiologies of various other liver diseases with CeD and the response to GFD were estimated. Subgroup analyses based on the age group, geographic distribution and duration of GFD were also carried out.
RESULTS: Total 42 studies (8976 patients) reported hyper-transaminasemia in patients with celiac disease. The pooled proportion of patients with elevated transaminases was 21.42% (95% CI: 17.02-26.59, I2  = 94%) overall, with similar prevalence among adults (21.20%) and children (21.51%). The commonest etiology was celiac hepatitis at 49.23% (95% CI: 30.09-68.59, I2  = 87%). Compliance with GFD was noted in 90.27%. The proportion of CeD patients with liver abnormalities who showed response to GFD was 86.39% (95% CI: 80.04-90.95, I2  = 74%) overall.
CONCLUSIONS: Liver involvement was noted in 21.42% of CeD patients. Celiac hepatitis was reported in nearly half of them. Good compliance and response were noted with GFD.

Acute hepatitis presenting with blood eosinophilia are scarcely reported. Different clinical courses of autoimmune hepatitis (AIH) have been associated with acute hepatitis with eosinophilia, however it is still unclear if the latter is a common manifestation of different autoimmune diseases, part of a similar spectrum of eosinophil-associated liver injury or even a trigger to AIH. We report a case of a 32 years old woman who presented with subacute hepatitis, peripheral eosinophilia, hypergammaglobulinemia and liver biopsy suggestive of AIH. The role of eosinophils in autoimmune liver diseases deserves further studies in order to clarify its physiopathology aspects.

OBJECTIVE: To estimate psychiatric comorbidity in childhood onset immune-mediated inflammatory diseases (IMID).
METHODS: The PRISMA guidelines were followed, and the protocol was registered at Prospero (ID: CRD42021233890). Literature was searched in PubMed, PsycINFO and Embase. Original papers on prevalence rates of diagnosed psychiatric disorders and/or suicide in paediatric onset inflammatory bowel disease (pIBD), rheumatic diseases (RD) and autoimmune liver diseases were selected. Pooled prevalence rates of psychiatric disorders (grouped according to ICD-10 criteria) within the various IMID were calculated using random-effects meta-analysis. Risk of bias was evaluated by the Newcastle-Ottawa scale.
RESULTS: Twenty-three studies were included; 13 describing psychiatric disorders in pIBD and 10 in RD. Anxiety and mood disorders were mostly investigated with pooled prevalence rates in pIBD of 6% (95% confidence interval (CI): 4%-9%) and 4% (95%CI: 2%-8%), respectively, in register-based studies, and 33% (95%CI: 25%-41%) and 18% (95%CI: 12%-26%), respectively, in studies using psychiatric assessment. In RD, rates were 13% (95%CI: 12%-15%) for anxiety disorders and 20% (95%CI: 15%-26%) for mood disorders based on psychiatric assessment.
CONCLUSIONS: Anxiety and depression are commonly reported in childhood onset IMID. Physicians should be attentive to mental health problems in these patients as they seem overlooked.

BACKGROUND: Recent studies have identified an increased risk of hepatocellular carcinoma (HCC) in autoimmune hepatitis (AIH). Sex and regional disparities in incidence of HCC in AIH continue to be reported worldwide. Nevertheless, the magnitude of this gap remains unknown.
METHODS: We searched several databases including PubMed, Embase, Web of Science, Cochrane Library, Wanfang Data, CNKI and SinoMed. Incidence rates of HCC in AIH were combined and analyzed following the EBayes method. Incidence rate ratios were pooled to assess the sex differences. The impact of population difference, sex, age, cirrhotic condition was further analyzed with subgroup analysis and linear regression analysis.
RESULTS: 39 studies meeting our eligibility criteria were chosen for the analysis. The pooled incidence rate of HCC in AIH was 3.54 per 1000 person years (95% CI 2.76-4.55). Pooled IRR for the risk of HCC in male AIH patients compared to female was 2.16 (95% CI 1.25-3.75), with mild heterogeneity among studies. The pooled HCC incidence rate in AIH by continents was as follows: Europe 2.37 per 1000 person-years (95% CI 1.45-3.88), Asia 6.18 per 1000 person-years (95%CI 5.51-6.93), North America 2.97 per 1000 person-years (95%CI 2.40-3.68), Oceania 2.60 (95%CI 0.54-7.58). The pooled HCC incidence rate in AIH-related cirrhosis by continent was as follows: Europe 6.35 per 1000 person-years (95%CI 3.94-10.22), Asia 17.02 per 1000 person-years (95%CI 11.18-25.91), North America 10.89 per 1000 person-years (95%CI 6.69-17.74).
CONCLUSIONS: A higher HCC incidence in AIH was observed among male and in Asian populations. Cirrhosis status at AIH diagnosis is significantly associated with an increased incidence rate for HCC, and routine HCC surveillance is recommended for patients with AIH cirrhosis, especially for those in Asia.

Aminotransferases are commonly found to be elevated in patients with celiac disease in association with two different types of liver dysfunction: cryptogenic liver disorders and autoimmune disorders. The purpose of this review is to discuss the mechanisms by which aminotransferases become elevated in celiac disease, clinical manifestations, and response to gluten-free diet. Many studies have shown that celiac patients with cryptogenic liver disease have normalization in aminotransferases, intestinal histologic improvement and serologic resolution after 6-12 months of strict gluten-free diet. In patients with an underlying autoimmune liver disease, simultaneous treatment for both conditions resulted in normalized elevated aminotransferases. The literature suggests that intestinal permeability may be at least one of the mechanisms by which liver damage occurs. Patients with celiac disease should have liver enzymes routinely checked and treated with a strict gluten-free diet if found to be abnormal. Lack of improvement in patients who have strictly adhered to gluten-free diet should prompt further workup for other causes of liver disease.