Immunoglobulin G4 -related gastrointestinal disease associated with type 1 autoimmune pancreatitis: A case report.

Immunoglobulin G4 (IgG4)-related diseaseis a systemic inflammatory condition of unknown etiology characterized by increases in serum IgG4 and in the number of IgG4-positive cells in affected tissues. One of the commonly involved locations is the pancreas; this condition is known as type 1 autoimmune pancreatitis (AIP). Type 1 AIP, which shows a biliary stricture in the intrapancreatic bile duct, can be misdiagnosed as a malignancy due to similar cholangiography findings and clinical presentation. In rare cases complicated by post-bulbar duodenal ulcers, differentiating between type 1 AIP and malignancies is even more difficult. An 81-year-old male was referred to our hospital for the treatment of a pancreatic head mass and obstructive jaundice. Serological and radiological findings were consistent with both type 1 AIP and a malignancy. Gastroduodenoscopy revealed a post-bulbar duodenal ulcer with endoscopic features that evoked malignant duodenal invasion. Although biopsies were negative for malignant cells, subsequent bleeding from the lesion suggested the progression of malignancy, which led to surgical resection. Pancreatoduodenectomy and pathological examination indicated that type 1 AIP was present. Simultaneously, the involvement of IgG4-related disease in the ulcerative lesion was suggested. To our knowledge, this is the first reported case of type 1 AIP complicated by post-bulbar duodenal ulcers, which was misdiagnosed as malignancy and considered an IgG4-related gastrointestinal disease associated with type 1 AIP.

Successful Maintenance Therapy with Intravenous Immunoglobulin to Reduce Relapse Attacks and Steroid Dose in a Patient with Refractory Myelin Oligodendrocyte Glycoprotein Antibody-positive Optic Neuritis.

A 25-year-old Japanese man developed visual disturbance with eye pain and was diagnosed with optic neuritis associated with anti-myelin oligodendrocyte glycoprotein antibodies. His symptoms improved temporarily after steroid therapy but chronically relapsed many times after tapering the steroid dose. He became highly steroid-dependent and was referred to our department for reconsideration of the treatment strategy. Maintenance intravenous immunoglobulin (IVIg) therapy successfully decreased the annual recurrence rate from 1.15 to 0.27 times/year and the maintenance dose of oral prednisolone from 35 to 5 mg/day. Maintenance IVIg therapy is a promising option for preventing disease relapse in such cases.

Association between Killer Immunoglobulin-like receptor genes and susceptibility to inflammatory bowel disease: An updated meta-analysis.

Background: Several studies have associated members of the KIR genes as susceptibility factors to inflammatory bowel diseases (IBD): ulcerative colitis (UC) and Crohn's disease (CD). Objectives: To assess the association between the presence and absence KIR genes and IBD susceptibility through a meta-analysis. Method: A systematic search was performed through the PubMed, Scopus, and Web of Science databases to obtain relevant articles published before March 2024. Associations between genes and susceptibility to IBDs were estimated by OR with 95 % CI. Results: We found positive associations of the KIR2DS1 and KIR2DS3 genes with susceptibility to UC, while the KIR2DL3 and KIR2DS4 full genes showed a negative association. In addition, the KIR2DS1, KIR2DS3, KIR2DS4, KIR2DS5, and KIR3DS1 genes showed a positive association with susceptibility to CD, whereas the KIR2DL1 gene showed a negative association. Conclusions: Our meta-analysis indicates that individuals carrying the KIR2DS1 and KIR2DS3 genes exhibit increased susceptibility to UC, whereas carriers of the KIR2DS1, KIR2DS3, KIR2DS4, KIR2DS5, and KIR3DS1 genes are more prone to CD. However, further studies are required to clarify the role of the KIR genes and their corresponding ligands in the pathology of IBD.

LGI1 encephalitis: potentially complement-activating anti-LGI1-IgG subclasses 1/2/3 are associated with the development of hippocampal sclerosis.

Two-thirds of published patients with anti-leucine rich, glioma inactivated 1 (LGI1) encephalitis develop hippocampal sclerosis (HS). It is likely that this contributes to residual cognitive long-term deficits and the risk of epilepsy. Almost all patients harbor anti-LGI1-immunoglobulin G-(IgG-) subclass 4, which is considered a "benign", non-destructive subclass. In contrast, neuropathological case studies have suggested that the classical complement cascade may contribute to mediotemporal cell death in patients with LGI1 antibodies. IgG subclasses 1, 2, or 3 are required to initiate this cascade. We hypothesized that patients with these anti-LGI1-IgG1/2/3 in addition to IgG4 have a higher risk of developing HS than patients with anti-LGI1-IgG4 alone. We retrospectively assessed all anti-LGI1 encephalitis patients from this center with anti-LGI1-IgG-subclass information and follow-up MRI available. Nine out of 20 patients had developed HS (45%). Volumetric FreeSurfer analysis confirmed the visual HS diagnoses. HS and a lower hippocampal volume were associated with anti-LGI1-IgG1/2/3. All six patients with this IgG subclass status developed HS. There was no association with older or younger age at onset, female sex, longer latency from disease onset to start of immunotherapy, less intense immunotherapy, higher serum titers of LGI1 antibodies, LGI1 antibodies in CSF or higher LGI1-specific antibody indices. There was no association between anti-LGI1-IgG1/2/3 status and neuropsychological performance, epilepsy, or general neurological performance. This confirms our hypothesis that anti-LGI1-IgG1/2/3 in serum puts patients at risk of developing HS. If these findings can be confirmed and clinically corroborated, patients with anti-LGI1-IgG1/2/3 might become candidates for anti-complement-directed immunological treatments.

Worse fibro-inflammatory activity on diagnostic liver biopsy adversely impacts biochemical remission in autoimmune hepatitis.

BACKGROUND: Autoimmune hepatitis (AIH) patients can present with advanced fibrosis at diagnosis or may progress to the same if biochemical remission on treatment is not achieved. METHODS: We conducted a single-center retrospective analysis of 34 pediatrics and 39 adult AIH patients. Three pathologists, blinded to clinical information, reviewed the diagnostic liver biopsy (DLB) slides of AIH patients. We evaluated the impact of clinical, laboratory, and histopathologic parameters on outcomes including biochemical remission (BR). RESULTS: Incidence of advanced (Ludwig stage 3 or 4) fibrosis on DLB was 45.2 %. AIH patients with advanced fibrosis had higher median Ishak score (p < 0.001) and higher IgG level (p = 0.01) at diagnosis. The incidence of BR at 6-month (31.2% vs. 88.6 %, p = 0.001) and 1-year (68.8% vs. 88.6 %, p = 0.04) post-diagnosis was significantly lower in AIH patients with advanced fibrosis. Although not statistically significant, a higher proportion of AIH patients with advanced fibrosis were on high dose of steroids (58% vs. 37.9 %, p = 0.1) at 1 year post diagnosis. Higher serum IgG level at diagnosis was associated with lower odds of achieving BR at 6-month (p = 0.004) and 1-year (p = 0.03) post-diagnosis in multivariate analysis. Pediatric age at diagnosis (p = 0.02) was associated with higher steroid dose at 1-year post-diagnosis in univariate analysis. CONCLUSIONS: Findings of advanced fibrosis on DLB of AIH patients was accompanied by more pronounced necro-inflammatory activity and higher serum IgG level, which translated to lower rates of BR and higher exposure to steroids during the first year after diagnosis.

Multiple cerebral infarctions after intravenous immunoglobulin for Guillain-Barré syndrome: two case reports and review of the literature.

Background: Guillain-Barré syndrome (GBS) is a polyradiculoneuropathy mediated by the immune system and is the primary reason for acute flaccid paralysis. Intravenous immunoglobulin (IVIg) is a recognized immunotherapeutic drug that can accelerate recovery from GBS. Limited literature exists concerning cerebral infarction complications with IVIg following its use in the treatment of GBS. Case presentation: A patient was diagnosed with the acute inflammatory demyelinating polyradiculoneuropathy subtype of GBS, while another patient was diagnosed with the acute bulbar palsy variant of GBS 2 years prior and experienced a relapse of GBS. Both patients received immunoglobulin therapy, during which multiple acute cerebral infarctions were detected using magnetic resonance imaging. Both patients had a history of coronary artery atherosclerotic heart disease and vertebral artery stenosis, and D-dimer and fibrinogen degradation products were significantly elevated after immunoglobulin therapy. Conclusions: The risk of cerebral infarction associated with IVIg is generally low in patients with different GBS variants. Nevertheless, the occurrence of cerebral infarction associated with IVIg might not be insignificant in older patients with vascular risk factors and should be carefully monitored.

Case report: Successful treatment of intestinal leiomyositis in a dog using adjunctive intravenous immunoglobulin.

A 10-year-old spayed female Dachshund presented with abdominal pain and generalized severe ileus. An exploratory laparotomy was performed, confirming a severe ileus of undetermined origin. Multiple intestinal biopsy results confirmed acute intestinal leiomyositis. Immunohistochemistry (IHC) stains confirmed a T-cell predominant inflammatory infiltrate. Intravenous immunoglobulin (hIVIG) was administered prior to immunosuppressive therapy. Within 10 days of hIVIG treatment, functional peristaltic activity returned, and symptoms resolved. Long-term management, including the use of mycophenolate, resulted in sustained functional peristaltic recovery. Further studies are needed to explore the potential benefits of hIVIG treatment in the stabilization phase of this commonly fatal, treatment-refractory disease.

Immune thrombocytopenia and pregnancy: challenges and opportunities in diagnosis and management.

INTRODUCTION: Immune thrombocytopenia (ITP) affecting pregnancy is a diagnostic and often a therapeutic challenge. AREAS COVERED: We review the current diagnostic criteria for ITP in pregnancy and the potential utility of laboratory tests. We discuss the impact of ITP on pregnancy outcomes and the effects of pregnancy on patients living with chronic ITP.  We describe the criteria for intervention, the evidence supporting first-line treatment approaches and the therapeutic decisions and challenges in cases refractory to steroids and IVIG. We review the evidence supporting the potential use of thrombopoietin receptor agonists for refractory thrombocytopenia. Finally, we describe the diagnostic, prognostic, and treatment approaches to neonatal ITP and considerations regarding breastfeeding. We searched the terms 'immune thrombocytopenia' and 'pregnancy' on PubMed to identify the relevant literature published before 31 December 2023, including within cited references. EXPERT OPINION: Decreased platelet production may play a role in pregnancy-related ITP exacerbation. Putative mechanisms include placental hormones, such as inhibin. Although IVIG and prednisone usually suffice to achieve hemostasis for delivery, second-line agents are sometimes required to allow for neuraxial anesthesia. There is growing evidence supporting the use of romiplostim during pregnancy; however, its risk of venous thromboembolism warrants further evaluation.

[Immunosuppression, tonsillectomy and remissions in high-risk IgA-nephropathy].

AIM: To evaluate the efficacy of immunosuppressive therapy (IST) and tonsillectomy (TE) in patients with high-risk IgA nephropathy (IgAN). Materials and мethods. The retrospective study cohort included cases with primary IgAN (n=213, age 34±11 years, male 52%) at high risk of progression with clinical and morphological data collected. The follow-up was 26 (10; 61) months. The association of IST without TE (IST; n=141) or with TE (IST+TE; n=72) with the development of complete (PR), partial (PR) and overall (PR or PR, OR) remissions was investigated. RESULTS: The incidence of achieving early PR or OR in the IST and IST+TE groups was 65.2% and 86.1%, respectively (p=0.002). The probability of early PR or OR was significantly increased in the IST+TE group compared to IST [HR 1.714 (1.214-2.420) and HR 3.410 (1.309-8.880), respectively]. IST+TE was associated with a 3- to 4-fold increase in the likelihood of PR or OR at the end of follow-up [HR 2.575 (1.679-3.950) and HR 4.768 (2.434-9.337), respectively]. Analyses using pseudorandomisation methods yielded similar results. CONCLUSION: TE may be effective for remission induction in high-risk IgAN.

Subcutaneous G-CSF administration improves IVF outcomes in patients with recurrent implantation failure presenting a KIR/HLA-C mismatch.

RESEARCH QUESTION: Despite advances in assisted reproductive technologies, many blastocysts are lost unexpectedly during implantation. Alterations in maternal immune tolerance towards fetal antigens may contribute to adverse IVF outcomes. The purpose of this study is to evaluate whether administering Granulocyte Colony-Stimulating Factor (G-CSF) to couples with a Human Leukocyte Antigen/Killer-Cell Immunoglobulin-Like Receptor (HLA/KIR) mismatch could positively modulate the implantation process in patients with recurrent implantation failure (RIF). A KIR/HLA-C mismatch occurs when the interaction between KIRs and HLA-C causes an inhibition of NK cells, which may result in reduced G-CSF secretion leading to impaired placentation and increased risk of miscarriage, pre-eclampsia and fetal growth restriction. DESIGN: A retrospective monocentric cohort study conducted at the IVI Clinic in Rome, including women with a history of at least two failed blastocyst transfers. Couples underwent KIR and HLA-C testing. Couples with a KIR/HLA-C mismatch received G-CSF subcutaneously up to week nine of gestation. The mismatch included cases with inhibitory KIR genotypes and HLA-C2C2 females with HLA-C1C1, or C1C2 males or HLA-C1C2 females with male HLA-C2C2. The reproductive outcomes were assessed, and the logistic regression models controlled for potential confounders affecting IVF outcomes. RESULTS: 79 patients with RIF and a KIR/HLA-C mismatch were included in the study. 30 patients were administered G-CSF, and 49 received no treatment. In the univariate analysis, no statistically significant differences were reported in the reproductive outcomes after IVF between the women treated with G-CSF and the control group. However, the logistic regression analysis that controlled for confounding factors showed that patients treated with subcutaneous G-CSF had statistically significant higher ongoing-pregnancy (aOR=3.808) and live-birth (aOR=4.998) rates, and a lower miscarriage rate (aOR=0.057). No statistically significant differences were found in other reproductive outcomes. CONCLUSION: The use of subcutaneous G-CSF in patients with a KIR/HLA-C mismatch undergoing IVF may reduce miscarriage and improve live-birth rates. G-CSF may modulate NK-mediated immune mechanisms and improve trophoblast invasion and development. Randomized trials are warranted to validate these findings and enhance the chances of successful pregnancies in couples with an immunological mismatch.

Towards an optimized model of food allergy in zebrafish.

BACKGROUND: The prevalence of food allergies is on the rise, posing a significant challenge to public health. Rodents serve as the predominant animal model in food allergy research; yet, the application of rodent models proves to be a laborious and time-consuming endeavor. It is imperative to develop novel in vivo models. METHODS: Ovalbumin (OVA) was administered as the allergen, following the recommended dosage used in other species. During the sensitization phase, a dosage of 0.25 mg per 10 tails per 1 L was administered twice daily, and during the challenge phase, the dosage was increased to 3 times the initial level. The study explored two dimensions of sensitization: the mode of exposure, which can be either continuous or intermittent, and the duration of exposure, which includes 3 days, 5 days, and 7 days. We examined midgut pathological changes, immunoglobulins contents, and mRNA expressions associated to T helper cells (Th) 2 cytokines following exposure. RESULTS: A significant 109.3 % increase in the number of eosinophils was observed in the midgut histopathology following intermittent 5-day OVA exposure, which emerged as the most effective model. OVA exposure increased concentrations of immunoglobulin M (IgM) (105.2 %), IgZ (312.1 %), and IgD (304.3 %) in this model. The mRNA expressions of Th2-related interleukin (IL)-4 and IL-13 were also elevated by 132.8 % and 421.0 %, respectively. CONCLUSION: The intermittent 5-day OVA exposure was suggested to be the best constructed zebrafish food allergy model, which may be a potential tool for research into food allergies.

A Rare Presentation of Multiple Myeloma With Spontaneous Haematoma.

Multiple myeloma (MM) typically presents with characteristic symptoms such as bone pain, hypercalcaemia, renal dysfunction, and anaemia. However, atypical presentations of MM, though rare, have been reported. These atypical presentations pose a diagnostic challenge due to their varied clinical manifestations, leading to potential delays in diagnosis and treatment initiation. We present the case of a 75-year-old woman who presented to the emergency department with a spontaneous haematoma on the dorsal aspect of her left hand and wrist. Despite lacking classical symptoms of MM, such as bone pain or renal dysfunction, laboratory investigations revealed abnormal findings, including high serum protein levels, low albumin, and abnormal immunoglobulin levels. Serum protein electrophoresis and immunotyping confirmed a diagnosis of MM, specifically the immunoglobulin-G lambda type. Additionally, urine protein electrophoresis further supported the diagnosis. Imaging studies did not show radiological evidence of myeloma. The absence of classical symptoms in our patient underscores the importance of considering MM in the differential diagnosis of atypical cutaneous presentations. Laboratory investigations, particularly serum protein electrophoresis and immunotyping, played a crucial role in establishing the diagnosis. The patient was treated with pulsed dexamethasone and plasmapheresis, followed by initiation of VCD chemotherapy protocol. Atypical presentations of MM present diagnostic challenges for clinicians. Our case highlights the importance of maintaining a high index of suspicion for MM, even in the absence of classical symptoms. Early recognition and diagnosis are essential for prompt management and improved patient outcomes. Clinicians should remain vigilant for atypical presentations of MM to ensure timely intervention and treatment initiation.

Case Report: C3 deficiency in two siblings.

The complement system, a vital component of innate immunity, consists of various proteins and pathways crucial for the recognition and elimination of pathogens. In addition, it plays a major role in the initiation of adaptive response through the opsonization of antigens, contributing to B-cell activation and memory maintenance. Deficiencies in complement proteins, particularly C3, can lead to severe and recurrent infections as well as immune complex disorders. Here, we present a case report of two siblings with total C3 deficiency resulting from compound heterozygous mutations in C3 (NM_000064.4): c.305dup; [p.Asn103GlnfsTer66] and c.1269 + 5G>T, previously unreported in C3-related diseases. Both, the index case and her sister, presented a history of recurrent infections since early childhood and one of them developed hemolytic uremic syndrome (HUS). Immunological evaluation revealed absent plasma C3 levels, decreased memory B cells, hypogammaglobulinemia, and impaired response to polysaccharide antigens. The siblings showed partial responses to antimicrobial prophylaxis and vaccination, requiring intravenous immunoglobulin replacement therapy, resulting in clinical improvement. Genetic analysis identified additional risk polymorphisms associated with atypical HUS. This case highlights the importance of comprehensive genetic and immunological evaluations in complement deficiencies, along with the potential role of immunoglobulin replacement therapy in managing associated antibody defects.

Idiopathic Thrombocytopenic Purpura (ITP) Complicated by a Hemorrhagic Ovarian Cyst and Hemoperitoneum: A Case Report.

Idiopathic thrombocytopenic purpura (ITP) is characterized by a persistently low platelet count, which can lead to serious bleeding such as gastritis and hemorrhagic stroke. The formation of auto-antibodies in ITP leads to increased destruction of platelets and then hampers hematopoiesis. Corticosteroids and intravenous immunoglobulin are among the common treatments used for ITP, but they have significant side effects. This is a case report of a 27-year-old woman with ITP who was found to be anemic, thrombocytopenic, and had a ruptured ovarian cyst after the initial romiplostim therapy. The patient benefited from fluid resuscitation, blood transfusion, and corticosteroid therapy; then, the patient's condition improved. This case highlights the complications associated with managing ITP, emphasizing the importance of personalizing therapy regimens through regular monitoring to improve the balance of benefits and risk, resulting in a comprehensive treatment for chronic patients suffering from ITP.

Early Diagnosis of Hemophagocytic Lymphohistiocytosis in an Adult Presenting With Sickle Cell Disease: A Case Report.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially life-threatening syndrome characterized by excessive immune activation and tissue inflammation. This case report describes the early diagnosis of HLH in an adult patient who initially presented with a febrile syndrome associated with low back pain. The patient, a 33-year-old male, exhibited bicytopenia, hepatosplenomegaly, and hyperferritinemia without a previous diagnosis of sickle cell disease (SCD). Diagnostic challenges arose due to the overlapping clinical manifestations of SCD and HLH and their uncommon association. However, timely recognition and intervention were achieved through comprehensive diagnostic evaluations, including a bone marrow biopsy. The patient was promptly started on an appropriate therapeutic regimen, which led to significant clinical improvement. This case underscores the importance of considering HLH in the differential diagnosis of adults presenting with hematologic abnormalities and systemic inflammation. Early diagnosis and treatment are critical to improving outcomes for patients with this complex and severe disorder.

Papillary Thyroid Cancer in a Patient With Graves' Disease and Hyperfunctioning (Hot) Thyroid Nodules: An Unexpected Presentation.

Hyperfunctioning (hot) nodules are considered benign while cold nodules are associated with a higher risk of thyroid cancer. In this case report, we present a patient diagnosed with Graves' disease and later found to have papillary thyroid carcinoma (Bethesda VI), confirmed by fine needle aspiration (FNA) biopsy, with regional metastasis to the neck and possible metastasis to the lungs. This paper demonstrates that hot nodules are not always benign, and could be associated with malignancy.

Efgartigimod as a promising add-on therapy for myasthenic crisis: a prospective case series.

Introduction: Efgartigimod is effective and well-tolerated in patients with anti-acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (MG). However, the therapeutic potential and the safety profile of efgartigimod in myasthenic crisis (MC) remained largely unknown. Methods: This is an observational, prospective, multicenter, real-world study to follow 2 MC patients who initiated efgartigimod as a first-line rescue therapy and 8 cases who used it as an add-on therapy. Baseline demographic features and immunotherapies were collected, and the MG-activities of daily living (MG-ADL) scale was evaluated every week since efgartigimod treatment for 8 weeks. Additionally, serum IgG and anti-AChR antibody levels and the peripheral CD4+ T lymphocytes were measured before and after one cycle of treatment. Results: Ten patients with MC were enrolled in the study, including 9 anti-AChR antibody positive and 1 anti-muscle-specific kinase (MuSK) positive. All patients were successfully weaned from the ventilation after receiving efgartigimod treatment, with a length of 10.44 ± 4.30 days. After one cycle of infusions, the MG-ADL score reduced from 15.6 ± 4.4 at the baseline to 3.4 ± 2.2, while the corticosteroid dose was tapered from 55.0 ± 20.7 mg to 26.0 ± 14.1 mg. The proportions of regulatory T cells and naïve T cells (% in CD4+ T) significantly decreased post-efgartigimod treatment (5.48 ± 1.23 vs. 6.90 ± 1.80, P=0.0313, and 34.98 ± 6.47 vs. 43.68 ± 6.54, P=0.0313, respectively). Conclusion: These findings validated the rapid action of efgartigimod in facilitating the weaning process with a good safety profile in patients with MC.

Orchestrating the Impact of KIR/HLA Interactions on Kidney Transplant.

This study examines the interplay between human leukocyte antigen (HLA) compatibility and killer-cell immunoglobulin-like receptor (KIR) genotypes in influencing kidney transplantation outcomes. Understanding these interactions is crucial for improving graft survival and minimizing rejection risks. We evaluated 84 kidney transplant recipients, dividing them into two groups based on post-transplant outcomes: there were 68 with stable graft function (SGF) and 16 who experienced chronic rejection (CR). Patients were selected based on specific inclusion criteria. HLA mismatches (Class I: HLA-A, -B; Class II: HLA-DR) and KIR genotypes were determined using standard genotyping techniques. Statistical analyses, including logistic regression, were performed to correlate these factors with transplant outcomes. Significant age differences were observed, with younger patients more likely to experience graft rejection, while no significant gender-based differences were noted. A significant correlation was found between Class II mismatches and increased rejection rates, highlighting the importance of HLA-DR compatibility. Further analysis revealed that certain inhibitory KIRs, such as KIR3DL1, were associated with favorable outcomes, suggesting a protective role against graft rejection. These findings were corroborated by evaluating serum creatinine levels over multiple years, serving as a biomarker for renal function post transplant. This study underscores the critical need for meticulous HLA matching and the consideration of KIR genotypes in pre-transplant evaluations to enhance graft survival and minimize rejection risks. Integrating these genetic factors into routine clinical assessments could significantly improve personalized transplant medicine strategies, ultimately enhancing patient outcomes. Further research is needed to explore the underlying mechanisms and validate these findings in larger, diverse populations.

Immune Response and Risk of Decompensation following SARS-CoV-2 Infection in Outpatients with Advanced Chronic Liver Disease.

Advanced chronic liver disease (ACLD) is associated with a wide spectrum of immune dysfunction. The clinical impact of SARS-CoV-2 on the development of decompensation and immune response in unvaccinated outpatients has not as yet been clearly defined. This study aimed to evaluate the clinical and immunological impact of SARS-CoV-2 on outpatients with ACLD. This is an observational case-control study, in which ACLD outpatients were included prospectively and consecutively and classified into two groups: SARS-CoV-2 infected and non-infected. Patients' baseline characteristics and infection data were collected and analyzed. Immunoglobulin G (IgG) levels against Spike 1 were evaluated. The primary endpoint was risk of liver decompensation during follow-up, assessed after propensity score matching and adjusted by Cox regression. Between October 2020 and July 2021, ACLD outpatients (n = 580) were identified, and 174 patients with clinical follow-up were included. SARS-CoV-2 infection incidence was 7.6% (n = 44). Risk of liver decompensation was significantly higher after infection (HR = 2.43 [1.01-5.86], p = 0.048) vs. non-infection. The time of IgG evaluation was similar in all patients (n = 74); IgG concentrations were significantly higher in compensated vs. decompensated patients (1.02 ± 0.35 pg/mL vs. 0.34 ± 0.16 pg/mL, p < 0.0001) and correlated with hemoglobin levels. The dysregulation of the innate immune response in patients with decompensated liver disease increased the risk of further decompensation following SARS-CoV-2, mainly due to a worsening of ascites.