The Association of Two Rare Diseases is Not Rare: Primary Immunodeficiencies and Autoimmune Liver Diseases

Abstract Purpose: PIDs associates with autoimmune diseases include autoimmune liver diseases (AILD); however, the frequency of PIDs among patients with AILD is unknown. This study aimed to evaluate the strength of the association between AILD and PIDs. Methods: We conducted this single-center, cross-sectional, and descriptive study in a tertiary hospital. We evaluated eighty-two patients with AILD (39 autoimmune hepatitis (AIH), 32 with primary biliary cholangitis (PBC), seven with variant syndromes (VS), and four with primary sclerosing cholangitis (PSC) for the presence of PIDs. We obtained a detailed history of infections, comorbidities, family history, and laboratory data from the files. All patients were evaluated in the immunology department for further examination, and PID diagnoses were made according to ESID (The European Society for Immunodeficiencies) criteria. Results: Out of 82 patients with AILD, PIDs were diagnosed in 18% (15 patients); there were four patients with common variable immunodeficiency (CVID), four with partial IgA deficiency (PIgAD), four with selective IgM deficiency (SIgMD), and three with combined immunodeficiency (CID). PIDs were present in 29% of patients with VS, 25 % of patients with PSC, 23% of patients with AIH, and 9% of patients with PBC. Conclusion: Although PIDs are rare diseases in the general population, they have a strong association with AILD and were detected in one-fifth of the patients. Further research with larger patient groups is needed to evaluate the diagnostic and prognostic impacts of PIDs on AILD.

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Current Trends and Characteristics of Hepatocellular Carcinoma in Patients with Autoimmune Liver Diseases

Cancers ◽

10.3390/cancers13051023 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1023

Author(s):

Eirini I. Rigopoulou ◽

George N. Dalekos

Keyword(s):

Risk Factors ◽

Hepatocellular Carcinoma ◽

Liver Diseases ◽

Treatment Modalities ◽

Primary Biliary Cholangitis ◽

Autoimmune Liver Diseases ◽

Increased Risk ◽

Liver Cancers ◽

Medium Risk ◽

Causes Of Mortality

Hepatocellular carcinoma (HCC), the commonest among liver cancers, is one of the leading causes of mortality among malignancies worldwide. Several reports demonstrate autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) to confer increased risk of hepatobiliary malignancies, albeit at lower frequencies compared to other liver diseases. Several parameters have been recognized as risk factors for HCC development in AIH and PBC, including demographics such as older age and male sex, clinical features, the most decisive being cirrhosis and other co-existing factors, such as alcohol consumption. Moreover, biochemical activity and treatment response have been increasingly recognized as prognostic factors for HCC development in AIH and PBC. As available treatment modalities are effective only when HCC diagnosis is established early, surveillance has been proven essential for HCC prognosis. Considering that the risk for HCC is not uniform between and within disease groups, refinement of screening strategies according to prevailing demographic, clinical, and molecular risk factors is mandated in AILDs patients, as personalized HCC risk prediction will offer significant advantage in patients at high and/or medium risk. Furthermore, future investigations should draw attention to whether modification of immunosuppression could benefit AIH patients after HCC diagnosis.

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Assessment of biochemistry request forms

Journal of Chitwan Medical College ◽

10.3126/jcmc.v5i3.16521 ◽

2017 ◽

Vol 5 (3) ◽

pp. 18-24 ◽

Cited By ~ 1

Author(s):

S Singh ◽

S Khatiwada

Keyword(s):

Laboratory Data ◽

Tertiary Hospital ◽

Cross Sectional Study ◽

Successful Outcome ◽

Ethical Review ◽

Sample Type ◽

Cross Sectional ◽

Laboratory Errors ◽

Specimen Collection ◽

Drug History

Oversight of information on biochemistry requisition forms may lead to laboratory errors. The aim of this study was to evaluate the level of completion of these forms. The observational cross-sectional study was conducted between December 2014 and March 2015 in the biochemistry department of a tertiary hospital in Kathmandu after approval by the Institutional Ethical Review Committee. Two thousand and thirty nine request forms were randomly assessed for the completeness of information provided by the requesting physician. Microsoft excels software and SPSS-17 was used for analysis. Patient confidentiality was maintained. Out of 2039 request forms examined, the only 100% documented parameter was the patient’s name. Date of specimen collection was recorded in 79.74% of forms and age in 98.53%. The working diagnosis was recorded in 28.44% but no information regarding patient preparation. While the consultants name were stated in 13.29% of cases, drug history in 0.24%. Parameters like gender were recorded in 98.82%, sample type in 0.29%. Whether the patient was present in the ward or in the outpatient department was documented in 15.11% whereas patient number in 38.35%. Doctors were more likely to sign the forms rather than providing their name/designation. This study demonstrates that the custom of completion of request forms was poor. As laboratory data plays a significant role in medical diagnosis and research, incomplete data provided to the laboratory could significantly impact on the comments and successful outcome of treatment. Closer interaction between clinicians and laboratory personnel by means of request forms can improve the quality of services to patients.

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Variety of lung involvement in autoimmune liver diseases

Terapevticheskii arkhiv ◽

10.26442/terarkh2018908107-112 ◽

2018 ◽

Vol 90 (8) ◽

pp. 107-112

Author(s):

L A Akulkina ◽

M Yu Brovko ◽

V I Sholomova ◽

T P Rozina ◽

A S Yanakayeva ◽

...

Keyword(s):

Liver Diseases ◽

Primary Biliary Cholangitis ◽

Extrahepatic Manifestations ◽

Specific Procedure ◽

High Resolution Computed Tomography ◽

Lung Lesions ◽

Autoimmune Liver Diseases ◽

Pulmonary Parenchyma ◽

Lung Vessels

The primary autoimmune liver diseases conventionally include primary biliary cholangitis, primary sclerosing cholangitis and autoimmune hepatitis. Despite of primary autoimmune affection of different parts of the hepatobiliary system, in the recent decades, a lot of data has emerged indicating the presence of extrahepatic manifestations of these diseases, in particular, lung lesions, such as nodular and interstitial changes with possible progression and development of fibrosis and respiratory failure. In case of lungs disease, both pulmonary parenchyma and lung vessels, pleura, and intrathoracic lymph nodes can be involved. The most sensitive and specific procedure to assess the extent of the lung lesions and their evolution is high-resolution computed tomography. Due to the possibility of long-term asymptomatic course of the pulmonary disease with development of irreversible changes in patients with autoimmune liver diseases, it seems reasonable to conduct screening studies aimed at early detection and treatment of lung lesions in this population.

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Human Immunodeficiency Virus and Tuberculosis Coinfection in a Tertiary Hospital in Southern Brazil: Clinical Profile and Outcomes

Microbiology Insights ◽

10.1177/1178636118813367 ◽

2018 ◽

Vol 11 ◽

pp. 117863611881336 ◽

Cited By ~ 1

Author(s):

Francine Teixeira ◽

Sonia M Raboni ◽

Clea EL Ribeiro ◽

João CB França ◽

Anne C Broska ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Extrapulmonary Tuberculosis ◽

Laboratory Data ◽

Case Fatality ◽

Tertiary Hospital ◽

Cross Sectional Study ◽

People Living With Hiv ◽

High Morbidity ◽

Cross Sectional ◽

Immunodeficiency Virus

Worldwide, the convergence of tuberculosis (TB) and human immunodeficiency virus type 1 (HIV-1) infection epidemics is a public health challenge. In Brazil, TB is the leading cause of death by infectious disease in people living with HIV (PLWH). This study aimed to report the clinical, demographic, epidemiological, and laboratory data for TB in PLWH. This cross-sectional study involved a retrospective analysis of data for patients with TB/HIV coinfection who attended from 2006 to 2015 through a review of medical records. A total of 182 patients were identified, of whom 12 were excluded. Patients were divided according to whether they had pulmonary tuberculosis (PTB; n = 48; 28%) or extrapulmonary tuberculosis (EPTB; n = 122; 72%). The diagnosis was laboratory confirmed in 75% of PTB patients and 78.7% of EPTB patients. The overall 1-year mortality rate was 37.6%, being 22.9% in PTB patients and 69% in EPTB patients; 84% of these deaths were TB-related. The CD4+ count and disseminated TB were independent risk factors for death. The frequency of resistance among Mycobacterium tuberculosis (MTB) isolates was 14%. TB in PLWH is associated with high morbidity and mortality, and severe immunosuppression is a risk factor for death. Appropriate measures for early TB detection should reduce the case fatality rate in high-burden settings.

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The risk of liver cancer in autoimmune liver diseases

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835919861914 ◽

2019 ◽

Vol 11 ◽

pp. 175883591986191 ◽

Cited By ~ 5

Author(s):

Ana Lleo ◽

Ynto S. de Boer ◽

Rodrigo Liberal ◽

Massimo Colombo

Keyword(s):

Early Diagnosis ◽

Liver Diseases ◽

Close Association ◽

Fatal Outcome ◽

Primary Biliary Cholangitis ◽

Primary Malignancy ◽

Abdominal Ultrasonography ◽

Systematic Analysis ◽

Acid Therapy ◽

Autoimmune Liver Diseases

Hepatocellular carcinoma (HCC), the dominant primary malignancy of the liver, has almost invariably a fatal outcome that can be averted only by early diagnosis and treatment. While the close association of HCC with chronic viral hepatitis and alcohol abuse has impacted favourably on screening and treatment of this deadly tumour, at the same time it has long obscured the etiologic role of autoimmune liver diseases. Recently, a systematic analysis of 25 published cohorts disclosed a 3.1 × 1000 patients/year incidence of HCC in autoimmune hepatitis patients that tripled in those with cirrhosis. HCC is also a sequela of primary biliary cholangitis, where the incidence is more relevant in males, those with advanced liver disease and nonresponders to ursodeoxycholic acid therapy. Cholangiocarcinoma (CCA), the second ranking primary cancer of the liver, is also on the rise with its intrahepatic pattern, in part reflecting an association with chronic liver diseases of diverse aetiology. In the USA and northern Europe, perihilar CCA is a frequent complication of primary sclerosing cholangitis, a cholestatic disorder thought to be immune mediated. International Guidelines clearly recommend HCC screening with abdominal ultrasonography every 6 months in autoimmune cirrhotic patients. While surveillance of patients with autoimmune liver disorders who are at risk of HCC affects both early diagnosis and radical therapy of this tumour, this is not the case for CCA, where early diagnosis is challenged by the lack of sensitive and accurate tests for screening.

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Serum Cytokine Levels and Their Relation to Clinical Features in Patients with Autoimmune Liver Diseases

Journal of Immunology Research ◽

10.1155/2017/9829436 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 9

Author(s):

Dilyara Akberova ◽

Andrei P. Kiassov ◽

Diana Abdulganieva

Keyword(s):

Liver Diseases ◽

Serum Levels ◽

Cross Sectional Study ◽

Overlap Syndrome ◽

Sectional Study ◽

Serum Cytokine ◽

Cross Sectional ◽

Autoimmune Liver Diseases ◽

Cytokine Levels ◽

Adjusted Logistic Regression

Serum cytokine levels were explored in a combined group of patients with autoimmune liver diseases (AILDs) and separately in patients with autoimmune hepatitis (AIH) and overlap syndrome. Overall, 60 patients with AILD, among them 32 patients with AIH and 28 patients with overlap syndrome, were included in the cross-sectional study. Serum cytokine levels were measured at baseline and compared to those of 21 healthy controls. Patients with AILD had significantly higher levels of IL-6 (0.70 (range 0.17–99.86) in patients with AILD compared to 0.40 (range 0.14–2.65) in controls,p<0.01), IL-8 (1.66 (0.45–34.58) versus 0.53 (0.35–2.38), resp.,p<0.01), and TNF-α(2.61 (0.23–120.88) versus 1.65 (0.21–7.54), resp.,p<0.01). Adjusted logistic regression analysis revealed a pronounced relation of IL-8 and AILD, 48.36 (3.63–643.60), as well as AIH, 18.54 (1.08–318.54), and overlap syndrome, 23.85 (2.37–240.23), while the associations between the level of other cytokines and AILD were assessed as nonsignificant. In the language of absolute numbers, the increase of IL-8 serum level by 1 pg/mL had increased the chance for a patient to find himself in a group of AILD by 48.36 times. Also, high IL-8 serum levels were strongly related to clinical parameters.

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Genetic Risk and the Development of Autoimmune Liver Disease

Digestive Diseases ◽

10.1159/000440706 ◽

2015 ◽

Vol 33 (Suppl. 2) ◽

pp. 13-24 ◽

Cited By ~ 19

Author(s):

Tom H. Karlsen ◽

Brian K. Chung

Keyword(s):

Genetic Risk ◽

Liver Diseases ◽

Disease Risk ◽

Association Studies ◽

Strong Association ◽

Human Leukocyte ◽

Biliary Cirrhosis ◽

Genome Wide Association Studies ◽

Autoimmune Liver Diseases ◽

Study Designs

Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) have collectively been recognized as autoimmune liver diseases. They have all been subjected to genome-wide association studies (GWAS) and several dozens susceptibility loci have been determined. The predominant feature of the genetic findings is that of a strong association with the human leukocyte antigen (HLA) and numerous weak associations scattered throughout the remainder of the genome. The non-HLA associations show some degree of overlap, not only between PBC, PSC and AIH, but also with other autoimmune and immune-mediated diseases. Mathematical modelling shows that the main fraction of autoimmune disease risk (including that of autoimmune liver diseases) is not explained by GWAS, proposing a major role of environmental factors. The HLA associations and autoantibodies observed in these conditions may hold clues as to the nature of such factors, which are exceedingly difficult to map by means of epidemiological study designs. The present review article explores the potential relationship between genetic risk as determined by GWAS and environmental risk in autoimmune liver diseases, and proposes a model for relevant thinking on the susceptibility genes in PBC, PSC and AIH.

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The Microbiome in Autoimmune Liver Diseases: Metagenomic and Metabolomic Changes

Frontiers in Physiology ◽

10.3389/fphys.2021.715852 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yanping Zheng ◽

Ying Ran ◽

Hongxia Zhang ◽

Bangmao Wang ◽

Lu Zhou

Keyword(s):

Gut Microbiome ◽

Metabolic Pathways ◽

Liver Diseases ◽

Critical Role ◽

Short Chain Fatty Acids ◽

Primary Biliary Cholangitis ◽

Mechanistic Studies ◽

Autoimmune Liver Diseases ◽

Acid Metabolites

Recent studies have identified the critical role of microbiota in the pathophysiology of autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Metagenomic studies reveal significant decrease of gut bacterial diversity in AILDs. Although profiles of metagenomic vary widely, Veillonella is commonly enriched in AIH, PBC, and PSC. Apart from gut microbiome, the oral and bile microbiome seem to be associated with these diseases as well. The functional analysis of metagenomics suggests that metabolic pathways changed in the gut microbiome of the patients. Microbial metabolites, including short-chain fatty acids (SCFAs) and microbial bile acid metabolites, have been shown to modulate innate immunity, adaptive immunity, and inflammation. Taken together, the evidence of host–microbiome interactions and in-depth mechanistic studies needs further accumulation, which will offer more possibilities to clarify the mechanisms of AILDs and provide potential molecular targets for the prevention and treatment in the future.

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Low yield but high levels of multidrug resistance in urinary tract infections in a tertiary hospital, Nepal

Public Health Action ◽

10.5588/pha.21.0044 ◽

2021 ◽

Vol 11 (1) ◽

pp. 70-76

Author(s):

R. Baral ◽

L. B. Shrestha ◽

N. Ortuño-Gutiérrez ◽

P. Pyakure ◽

B. Rai ◽

...

Keyword(s):

Multidrug Resistance ◽

Seasonal Changes ◽

Laboratory Data ◽

Tertiary Hospital ◽

Cross Sectional ◽

E Coli ◽

Culture Positivity ◽

Low Culture ◽

Tract Infections ◽

Culture Positive

SETTING: There are concerns about the occurrence of multidrug resistance (MDR) in patients with urine tract infections (UTI) in Nepal.OBJECTIVE: To determine culture positivity, trends in MDR among Escherichia coli and Klebsiella pneumoniae infections and seasonal changes in culture-positive UTI specimens isolated from 2014 to 2018 at the B P Koirala Institute of Health Sciences, Dharan, Eastern Nepal.DESIGN: This was a cross-sectional study using secondary laboratory data.RESULTS: Among 116,417 urine samples tested, 19,671 (16.9%) were culture-positive, with an increasing trend in the number of samples tested and culture positivity. E. coli was the most common bacteria (54.3%), followed by K. pneumoniae (8.8%). Among E. coli and K. pneumoniae isolates, MDR was found in respectively 42.5% and 36.0%. MDR was higher in males and people aged >55 years, but showed a decreasing trend over the years. The numbers of isolates increased over the years, with a peak always observed from July to August.CONCLUSION: Low culture positivity is worrying and requires further work into improving diagnostic protocols. Decreasing trends in MDR are a welcome sign. Information on seasonal changes that peak in July–August can help laboratories better prepare for this time with adequate buffer stocks to ensure culture and antibiotic susceptibility testing.

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A Vein-Viewing Application Enabled Detecting Abdominal Wall Varices Related to the Presence of Non-Treated Gastroesophageal Varices: A Cross-Sectional Study

10.21203/rs.3.rs-411097/v1 ◽

2021 ◽

Author(s):

Yoshiki Hoshino ◽

Takaaki Sugihara ◽

Suguru Ikeda ◽

Yukako Matsuki ◽

Takakazu Nagahara ◽

...

Keyword(s):

Abdominal Wall ◽

Liver Diseases ◽

Cross Sectional Study ◽

Chronic Liver ◽

Primary Biliary Cholangitis ◽

Independent Factor ◽

Cross Sectional ◽

Gastroesophageal Varices ◽

Life Threatening ◽

The Relationship

Abstract Background Gastroesophageal varices (GOV) are a life-threatening complication in chronic liver disease. A method for non-invasively predicting GOV is crucial for management. This study aimed to determine whether a vein-viewing application can detect abdominal wall varices (AWV) and elucidate the relationship between AWV and GOV. Methods One-hundred patients with chronic liver diseases were prospectively enrolled. All the patients underwent esophagogastroduodenoscopy within three months of the enrollment. Unmanipulated images (UI) and Vein-weighted images (VWI) were taken for assessing AWV by a vein-viewing application on iPhone. Two doctors independently evaluated both image types. We defined the grading of both UI and AWV as grade 0 (non-detectable), grade 1 (slightly detectable), and grade 2 (distinct). Results The causes of liver diseases among the 71 men and 29 women (median age, 70.5 year) included Hepatitis B (n = 19), Hepatitis C (n = 21), alcoholism (n = 3), primary biliary cholangitis (n = 4), autoimmune hepatitis (n = 4) and others (n = 20). GOV were indicated in 60 patients, and half of them had not been treated previously (non-treated). VWI could significantly visualize AWV than UI (24% vs 72%, p = 0.0005). The presence of cirrhosis (chronic hepatitis vs cirrhosis = 64.6% vs 91.4%, p = 0.004) and GOV (52.3% vs 74.3%, p = 0.032) were significantly higher in the VWI-AWV grade 2 group. Multivariate analysis demonstrated that VWI-AWV grade 2 was an independent factor related to the presence of non-treated GOV [OR = 2.97 (1.17–7.53), p = 0.022]. Conclusions The vein-viewing application non-invasively detected AWV related to the presence of cirrhosis and GOV, and VWI-AWV grade 2 was an independent factor related to the presence of non-treated GOV.

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