Hepatopatías autoinmunes. Hallazgos clínicos y de laboratorio en pacientes de un hospital de referencia nacional / Autoimmune liver diseases. Clinical and laboratory findings in patients in a national reference hospital

Introducción. Las enfermedades autoinmunes del hígado son un grupo de patologías caracterizadas por una respuesta autoinmune contra los hepatocitos y/o el epitelio biliar. Sus manifestaciones clínicas son variadas, con alteraciones en las pruebas de función hepática y presencia de autoanticuerpos. Metodología. Estudio observacional descriptivo con 101 pacientes atendidos en el Hospital Universitario de La Samaritana de Bogotá D.C., entre enero a diciembre de 2019, con los diagnósticos de hepatitis autoinmune, colangitis biliar primaria, colangitis esclerosante primaria y síndrome de sobreposición. Se evaluaron los parámetros clínicos y de laboratorio, con el fin de caracterizar su frecuencia en estas patologías, debido a la importancia de un diagnóstico precoz. Resultados. Se encontraron 54 casos de hepatitis autoinmune, 19 casos de colangitis biliar primaria, 4 casos de colangitis esclerosante primaria y 24 casos de síndrome de sobreposición. El 81% fueron mujeres y la edad promedio fue de 55 años. El 39% de los pacientes tenían cirrosis. En general, los resultados se ajustaron a lo descrito internacionalmente, como es el predominio en mujeres y la comorbilidad autoinmune. Conclusión. Los hallazgos indican que cualquier alteración del perfil bioquímico hepático debe ser considerado, y se debe descartar la presencia de hepatopatías autoinmunes para diagnosticarlas de manera precoz, evitando que lleguen a cirrosis y sus complicaciones, con la necesidad de un trasplante hepático como única alternativa terapéutica.

Introduction. Autoimmune liver diseases are a group of pathologies characterized by an autoimmune response against hepatocytes and/or the biliary epithelium. Their clinical manifestations are varied, with alterations in liver function tests and the presence of autoantibodies. Methodology. Descriptive study with 101 patients who attended at the Hospital Universitario de La Samaritana in Bogota D.C., between January and December 2019, with the diagnoses of autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis and overlap syndrome. Clinical and laboratory parameters were evaluated in order to characterize their frequency in these pathologies, due to the importance of an early diagnosis. Results. There were 54 cases of autoimmune hepatitis, 19 cases of primary biliary cholangitis, 4 cases of primary sclerosing cholangitis, and 24 cases of overlap syndrome. Of all patients, 81% were women, the average age was 55 years, and 39% had cirrhosis. In general, the findings were consistent with what has been described worldwide, such as a higher prevalence in women and autoimmune comorbidity. Conclusion. The findings indicate that any alteration in the liver biochemical profile should be considered to rule out an autoimmune liver disease for an early diagnosis, avoiding the possibility of cirrhosis and its complications, with the need for a liver transplant as the only therapeutic alternative.

Recent Advances in the Concept and Pathogenesis of IgG4-Related Disease in the Hepato-Bilio-Pancreatic System

Recent studies have proposed nomenclatures of type 1 autoimmune pancreatitis (AIP) (IgG4-related pancreatitis), IgG4-related sclerosing cholangitis (IgG4-SC), IgG4-related cholecystitis, and IgG4-related hepatopathy as IgG4-related disease (IgG4-RD) in the hepato-bilio-pancreatic system. In IgG4-related hepatopathy, a novel concept of IgG4-related autoimmune hepatitis (AIH) with the same histopathological features as AIH has been proposed. Among organs involved in IgG4-RD, associations with pancreatic and biliary lesions are most frequently observed, supporting the novel concept of "biliary diseases with pancreatic counterparts." Targets of type 1 AIP and IgG4-SC may be periductal glands around the bile and pancreatic ducts. Based on genetic backgrounds, innate and acquired immunity, Th2-dominant immune status, regulatory T (Treg) or B cells, and complement activation via a classical pathway may be involved in the development of IgG4-RD. Although the role of IgG4 remains unclear in IgG4-RD, IgG4-production is upregulated by interleukin 10 from Treg cells and by B cell activating factor from monocytes/basophils with stimulation of toll-like receptors/nucleotide-binding oligomerization domain-like receptors. Based on these findings, we have proposed a hypothesis for the development of IgG4-RD in the hepato-bilio-pancreatic system. Further studies are necessary to clarify the pathogenic mechanism of IgG4-RD.

Manifestaciones cutáneas de las enfermedades sistémicas / Cutaneous manifestations of systemic diseases

La piel posee un doble origen embriológico ectomesodérmico, por lo que se relaciona con todos los órganos y sistemas del organismo. Es por esto que la piel puede reflejar alteraciones sistémicas de todo tipo, existiendo algunos marcadores dermatológicos bien reconocidos que pueden preceder, acompañar o seguir al diagnóstico de una enfermedad sistémica. La fácil accesibilidad de la piel para toma de muestra (cultivos, biopsias) facilita el estudio a cabalidad. El integrar los hallazgos clínicos con las lesiones de la piel, es una tarea difícil, que tanto dermatólogos como otros especialistas deben poner especial atención. Al estudiar el organismo humano desde el punto de vista de los diferentes sistemas se puede observar cómo en cada casoexisten lesiones cutáneas que están íntimamente ligadas a estaspatologías. En algunos casos estas lesiones son parte de la enfermedad o en otros casos son producto de la enfermedad.

The skin has a double embryological origin therefore relates to all organs and body systems. For this reason, the skin may reflect systemic changes of all kinds, with some well-recognized dermatological markers that may precede, accompany or follow the diagnosis of systemic disease. The easy accessibility of skin samples (for cultures, biopsies) facilitates research. Integrating clinical findings and skin lesions is a difficult task, for both dermatologists and other specialists, close attention is necessary. In studying the human organism from the view point of the different systems you can see how in each case there are skin lesions that are closely related to these pathologies. In some cases these lesions are part of the disease or in other cases are caused by the disease.

The presence of Helicobacter pylori in the liver depends on the Th1, Th17 and Treg cytokine profile of the patient

The hypothesis that Helicobactermight be a risk factor for human liver diseases has arisen after the detection of Helicobacter DNA in hepatic tissue of patients with hepatobiliary diseases. Nevertheless, no explanation that justifies the presence of the bacterium in the human liver has been proposed. We evaluated the presence of Helicobacterin the liver of patients with hepatic diseases of different aetiologies. We prospectively evaluated 147 patients (106 with primary hepatic diseases and 41 with hepatic metastatic tumours) and 20 liver donors as controls. Helicobacter species were investigated in the liver by culture and specific 16S rDNA nested-polymerase chain reaction followed by sequencing. Serum and hepatic levels of representative cytokines of T regulatory cell, T helper (Th)1 and Th17 cell lineages were determined using enzyme linked immunosorbent assay. The data were evaluated using logistic models. Detection of Helicobacter pylori DNA in the liver was independently associated with hepatitis B virus/hepatitis C virus, pancreatic carcinoma and a cytokine pattern characterised by high interleukin (IL)-10, low/absent interferon-γ and decreased IL-17A concentrations (p < 10-3). The bacterial DNA was never detected in the liver of patients with alcoholic cirrhosis and autoimmune hepatitis that are associated with Th1/Th17 polarisation. H. pylori may be observed in the liver of patients with certain hepatic and pancreatic diseases, but this might depend on the patient cytokine profile.

Frequency of hepatitis D virus infection in hepatitis B surface antigen-positive liver diseases

To determine the frequency of HDV among hepatitis B surface antigen [HBsAg]-positive liver disorders. An observational cross-sectional study. Medical Unit I, Chandka Medical College Hospital, Larkana, from July 2003 to June 2008. Adult patients with HBs liver related disorders were evaluated for the presence of delta antibodies using commercially available ELISA kits. Descriptive statistcs were used for describing data. Proportions of anti D antibodies between gender and age were compared using chi-square test with significance at p < 0.05. Of the 774 cases, 438 were males [60.4%] and 336 were females [39.6%]. The mean age was 36.5 +/- 14.39 for males and 34.03 +/- 13.16 years for females ranging from 15 to 60 years. Anti-HDV was positive in 183 patients [23.6%].The frequency of HDV was not significantly different between the gender groups [p=0.718]. HDV infection was markedly higher in chronic than acute liver disorders. The HBV/HDV co-infection is frequent in the studied area. Therefore, practitioners and health care managers should be made aware of the risk of dual infection with HBV and HDV

Serum lipoproteins in liver diseases.

Agarose gel electrophoresis is a rapid technique yielding dependable results than any other conventional older ones, more cases in shorter time can be conveniently studied using this technique. In cirrhosis and hepatitis patients the alpha lipoprotein and the pre beta lipoprotein are found to be lower than that of normal healthy subjects.

Immunoglobulins in liver diseases.

Immunoglobulin are not produced in normal liver, but in chronic hepatic disease, they have been identified in the lymphoid and plasma cells infiltrating portal areas and parenchyma. It is reported that IgG appears to be the predominant Ig synthesized by mesenchymal cell in active chronic hepatitis and the IgM is the predominant Ig synthesized by lymphoid aggregates around the damaged bile ductules in primary bilary cirrhosis. In present study significant rise in the levels of IgA and IgM are observed in viral hepatitis patients.

Markers of autoimmune liver diseases in postmenopausal women with osteoporosis

INTRODUCTION: Osteoporosis is a common complication of chronic liver diseases. However, there is limited information about autoimmune liver diseases as a factor of secondary osteoporosis. Therefore, we aimed to investigate the autoantibodies of autoimmune liver diseases in patients with osteoporosis. METHODS: One hundred fifty female patients with postmenopausal osteoporosis were included. Bone mineral density was measured by dual energy X-ray absorptiometry. We analysized autoantibodies including antinuclear antibodies, liver membrane antibodies, anti-liver/kidney microsomal autoantibodies1, liver-specific protein, antismooth muscle antibodies, and anti-mitochondrial antibodies by indirect immunofluorescence. Serum was assayed for the levels of aminotransferases. RESULTS: The mean age of the patients was 63,13±8,6 years. The mean values of L1-L4 T-scores and femur total T-scores were -3,08±0,58 and -1,53±0,81, respectively. Among the 150 patients with osteoporosis, 14 (9.3 percent) were antinuclear antibodies, four (2.7 percent) were liver membrane antibodies, three (2.0 percent) were anti-liver/kidney microsomal autoantibodies1, and two (1.3 percent) were liver-specific protein positive. None of the patients had anti-mitochondrial antibodies or smooth muscle antibodies positivity. The mean values of levels of aminotransferases were within normal range. CONCLUSIONS: The presence of liver membrane antibodies, liver-specific protein, and anti-liver/kidney microsomal autoantibodies1 has permitted us to see that there may be some suspicious clues of autoimmune liver diseases in patients with osteoporosis as a secondary risk factor. On the other hand, there is a need for comprehensive studies with a larger sample size and studies designed to compare the results with a normal population to understand the clinical importance of our findings.

Non-viral chronic active liver disease in Yemeni patients and the possible implication of Qat chewing

Twenty eight Yemeni patients with nonviral chronic active liver disease were retrospectively studied for underlying causes and possible predisposing risk factors. They were 17 males and 11 females with age range between 17 and 42 years [median 29.5 years]. The diagnosis was based on their clinical, biochemical and imaging criteria, and was consistent with severe chronic liver disease that was persistent for more than six months. Seroimmunological markers for autoimmune liver disease were found in 8 patients [4 males and 4 females]. Slit-lamp examination for Kaiser-Fleicher ring, which is characteristic for Wilson's disease, was negative in all patients and serum iron and serum ferritin were normal in two patients over 40 years. Habitual qat chewing was found in 27 patients, of which 20 were daily qat chewers. Meanwhile, good response to immune suppressive treatment was documented in 22 patients. These results indicate that most Yemeni patients with nonviral chronic active liver disease are young, heavy qat chewers and have good response to immune suppressive treatment. These findings may suggest an underlying immunologic pathogenic mechanism for the chronic active liver disease in these patients. Further studies are needed to investigate the nonviral causes of chronic liver disease and the possible implication of qat chewing habit in liver diseases as well as in other diseases in Yemeni population

impact of immune response to schistosoma hematobium infection on the outcome of HCV in patients with concomitant HCV and Schistosoma hematobium infection in El-Minya governorate in Egypt

Patients with schistosoma haematobium display immune response may alter the outcome of HCV in-patients with concomitant HCV and schistosoma haematobium. This study was aimed at evaluation of the effect of immune response to schistosoma haematobium on the outcome of HCV in-patients with concomitant infection [HCV and schistosoma haematobium]. This study was conducted on 70 subjects 59 of them were infected with HCV and/or schistosomiasis selected form the outpatient clinic of El-Minya University Hospital while the remaining eleven subjects were healthy control volunteers with no history and negative serology to both HCV and schistosomiasis. The patients were grouped into three groups. Group [I] it included 24 patients with concomitant HCV and schistosomal infections. Group [II] it included 19 patients with schistosoma haematobium infection. Group [III] it included 16 patients with HCV infection alone and control group. It included 11 healthy subjects. All groups were subjected to history taking, clinical examination, abdominal ultrasonography and rectal snip were done for all groups and liver biopsy was done for HCV +ve patients. Routine laboratory investigations and ELISA assessed hepatitis markers [A, B, C] antibodies and Special investigations, CD3, CD4, CD8, and estimation of CD[4]/CD[8] ratio and detection of ant-bilharzial antibody titer. Absolute CD4 was highly significant higher in group 3 when compared to control group [p- value < 0.001] and was highly significant lower in group 1 when compared to control group [p- value < 0.001]. As regard to absolute CD4 between different groups of patient it was high in group 3 then less in group 2 and much lower in group 1 and these differences were highly significant [p- value <0.001]. Absolute CD8 was highly significant higher in group 3 when compared to control group [p- value < 0.001] and was highly significant lower in group 1 when compared to control group [p- value < 0.001]. As regard to absolute CD8 between different groups of patient it was high in group 3 then less in group 2 and much lower in group 1 and these differences were highly significant [p- value <0.001]. Absolute CD4 / CD8 ratio was highly significant lower in group 1, 2 and 3 when compared to control group [p-value < 0.001] and was highly significant lower in group 1 when compared to group 3 [p- value < 0.001]. As regard to absolute CD3, CD4, CD8 and CD4/ CD8 ratio absolute CD4 and CD4/CD8 ratio were higher in-patients treated with praziquantel versus those not receiving this medication. While CD8 was higher in-patients not received this medications versus those received the medications. This study has documented that schistosoma haematobium display a suppressive effect on the immune system so that a concomitant infection with HCV will present with a more protracted disease with severe sequel and adverse complications. Also this study has documented that CD4, CD8, and CD4/CD8 ratio may be good indicators of the disease activity. It is recommended that strict control and treatment of schistosomiasis may ameliorate the problem of HCV induced chronic liver disease in Egypt

Afecciones hepatobiliares autoinmunes / Auto-immune hepatobiliary diseases

Las afecciones hepato-biliares autoinmunes son relativamente infrecuentes en la práctica clínica y es posible que una cierta proporción de ellas pasen inadvertida o se incluyan en el grupo de las hepatopatías criptogénicas. Histológicamente se caracterizan por una inflamación crónica, persistente y progresiva de las células y conductos intrahepáticos que es característica sólo en las etapas iniciales ya que en las avanzadas son ocultadas por la fibrosis propia de la cirrosis. Clínicamente se destacan las formas colestásicas con prurito, ictericia, compromiso del estado general. En las formas avanzadas aparecen las manifestaciones de insuficiencia hepática; la hipertensión portal y las neoplasias (hepatocarcinoma y colangiocarcinomas) que son menos frecuentes en estas hepatologías autoinmunes que en las por virus C. El tratamiento médico se basa en el empleo de corticoides y/o azatioprina en el caso de las hepatitis autoinmunes y de colestiramina o ácido ursodeoxicólico en la cirrosis biliar primaria y en la colangitis esclerosante.

Vaccination for hepatitis A virus is not required for patients with chronic liver disease in India.

BACKGROUND: Hepatitis A virus (HAV) vaccination is recommended worldwide for patients with chronic liver disease to prevent decompensation due to superinfection with HAV. India being endemic for HAV, the prevalence of pre-existing antibodies against HAV due to subclinical exposure to the virus in childhood among patients with chronic liver disease may be high and, therefore, vaccination may not be needed. However, data are lacking on the prevalence of HAV antibody among patients with chronic liver disease in India. METHODS: Two hundred fifty-four patients attending the Liver Clinic at the All India Institute of Medical Sciences, New Delhi during the past 5 years and diagnosed to have either chronic hepatitis due to the hepatitis B virus (n = 76), hepatitis C virus (n = 84) or cirrhosis of the liver due to the hepatitis B (n = 47) or C (n = 47) virus were tested for the presence of IgG anti-HAV antibody in their sera (using a commercial ELISA kit). RESULTS: Two hundred forty-eight (97.6%) patients tested positive for IgG anti-HAV. The prevalence of anti-HAV positivity was similar among patients with chronic hepatitis B (74, 97.4%), chronic hepatitis C (82, 97.6%), cirrhosis of the liver due to the hepatitis B (46, 97.8%) and hepatitis C (46, 97.8%) virus. CONCLUSION: Vaccination against HAV is not required among patients with chronic liver disease in India as there is a very high prevalence of pre-existing antibodies in these patients.

Immunopathology of liver diseases

Esta revisión resume los conocimientos actuales de la copatogénesis inmunopatológica de las principales enfermedades hepáticas, incluyendo la hepatitis viral, hepatitis autoinmune, rechazo de trasplante, reacción del huésped hacia el injerto y otras. El trabajo se refiere principalmente a las implicaciones de los datos para el diagnóstico de la práctica clínica y en menor grado a los datos de las más recientes investigaciones, por lo que está dirigido principalmente al hepatólogo y al patólogo en ejercicio. Los autores desean que la lectura de este trabajo sirva como referencia práctica para el diagnóstico diferencial de las enfermedades hepáticas cada vez más frecuentes

Comportamento dos mecanismos da defesa imunológica em pacientes com hepatopatia crônica descompensada / Evaluation of immunologic defense mechanisms in patients with chronic hepatopathy

Os autores avaliaram as concentraçöes séricas das proteínas de defesa em pacientes com hepatopatia crônica. Para tal, analisaram prospectivamente 85 pacientes, divididos em três grupos: 50 com cirrose e ascite, 17 com outras doenças que também cursam com ascite e 18 pacientes sem ascite e sem hepatopatia. Foram obtidas as seguintes determinaçöes: níveis de complemento em suas fraçöes C3, C4, complemento hemolítico total e imunoglobulinas G, A e M. No grupo de pacientes com cirrose, as concentraçöes de C3, C4 e do complemento hemolítico total foram significativamente inferiores e das imunoglobulinas A e M estatisticamente mais elevadas em comparaçäo com as do grupo com outras doenças. Os níveis da IgG näo diferiram significativamente entre os dois grupos. As concentraçöes das imunoglobulinas G, A e M foram estatisticamente superiores no grupo cirrótico em relaçäo aos pacientes sem ascite. Os níveis de C3 e C4 näo diferiram entre estes dois grupos

Immunological disorders in chronic hepatitis C Egyptian patients

This study aimed to estimate the prevalence of different autoimmune antibodies in cases of hepatitis C chronic liver disease and to assess whether such changes have any clinical significance or not. A total of thirty chronic hepatitis C patients [22 males and 8 females, with a mean age of 43.5 +/- 6.7 years] who were ELISA II positive and HbsAg negative with elevated ALT more than two folds of the normal in addition to 20 healthy controls of matched age and sex were tested for rheumatoid factor, cryoglobulin, antinuclear antibody, antismooth muscle antibody, antimitochondrial antibody and LKM1. It could be concluded that chronic hepatitis C patients showed prevalence of some autoimmune antibodies without any implication on the clinical presentation

Utilidad de la inmunocitoquímica en la identificación de cuerpos de Mallory: análisis teórico de su formación / Utility of immunocytochemistry in the identification of Mallory's bodies: theorical analysis of its formation

Mallory bodies are hepatocyte intracytoplasmic inclusions frequently observed in liver diseases. They contain altered intermediary filaments that have immunoreactivity with epidermic antikeratin antibodies (A-QEp). They also contain Ubiquitin (Ubq) a 76 residue polypeptide that has an important role in the proteolysis of rapid exchange and abnormal cytosol proteins. To standarize an immunohistochemical method for the detection of Mallory bodies in percutaneous liver biopsies. A-QEp and A-Ubq polyclonnal antibodies were used in the study of 131 percutaneous liver biopsies obtained from patients with different liver diseases. Mallory body immunoreactivity was confirmed with immunoelectron microscopy demonstrated that Mallory bodies are partially formed by altered intermediate filaments. In conclusion, antibodies againnst ubiquitin may be very useful for the detection of Mallory bodies in liver biopsies