Features and distribution of CD8 T cells with human leukocyte antigen class I-specific receptor expression in chronic hepatitis C.: NKRs+ CD8 T cells in chronic Hepatitis C.

CD8(+) T cells represent a sizable component of the liver inflammatory infiltrate in chronic hepatitis C and are thought to contribute to immune-mediated tissue injury. Because chronic stimulation may promote the expression by CD8(+) T cells of distinct human leukocyte antigen class I-specific natural killer cell receptors (NKRs) susceptible to both inhibiting effector functions and promoting cell survival, we examined the distribution and characteristics of CD8(+) T cells with such receptors in chronic hepatitis C patients. NKR CD8(+) T cells were detectable in liver and peripheral blood from hepatitis C virus (HCV)-infected patients but were not major subsets. However, the frequency of NKG2A(+) CD8(+) in the liver and in a lesser extent in the peripheral blood was positively correlated to histological activity in HCV-infected patients. No such correlation was found with KIR(+) T cells in liver in HCV-infected patients and with the both NKR CD8(+) T cells in hepatitis B virus (HBV) infected patients. Circulating CD8(+) T cells expressing KIRs exhibited phenotypic features of memory T cells with exacerbated expression of the senescence marker CD57 in patients. NKG2A(+)CD8(+) T cells were committed T cells that appeared less differentiated than KIR(+)CD8(+) T cells. In HCV-infected patients, their content in perforin was low and similar to that observed in NKG2A(-)CD8(+) T cells; this scenario was not observed in healthy subjects and HBV-infected patients. Both NKG2A and KIRs could inhibit the response of HCV-specific CD8(+) T cells ex vivo. CONCLUSION: These results support the concept that an accumulation in the liver parenchyma of NKR(+)CD8(+) T cells that have functional alterations could be responsible for liver lesions. They provide novel insights into the complexity of liver-infiltrating CD8(+) T cells in chronic hepatitis C and reveal that distinct subsets of antigen-experienced CD8(+) T cells are differentially sensitive to the pervasive influence of HCV

Semiquantitative analysis of intrahepatic CC-chemokine mRNas in chronic hepatitis C.

BACKGROUND: The mechanisms leading to hepatic injury in chronic hepatitis C virus (HCV) infection are only incompletely understood. Recent data propose a correlation of the intrahepatic expression of the CC chemokine RANTES and the degree of periportal and portal inflammatory liver damage. AIM: Here, we have studied the intrahepatic mRNA levels of CC chemokines RANTES together with that of other members of this chemokine family (MIP-1beta, MCP-1, and MCP-2) in chronic hepatitis C as compared with healthy controls. METHODS: Liver samples from 22 HCV-infected patients, nine individuals with primary biliary cirrhosis and from 12 normal controls were included into this study. Intrahepatic mRNA levels of CC chemokines RANTES, MIP-1beta, MCP-1, and MCP-2 were analyzed by a semi-quantitative reverse transcription/real-time polymerase chain reaction assay. RESULTS: In chronic HCV infection, intrahepatic RANTES mRNA levels were significantly higher than in non-infected controls (7.2-fold, p < 0.001) or in the disease control group (2.8-fold, p < 0.001) and higher levels of RANTES mRNA levels were observed in livers with an advanced stage of liver cell injury (histologic activity index > or = 6), although this difference was not statistically significant (p = 0.08). In contrast, mRNA levels of MIP-1beta (p = 0.021) and MCP-1 (p = 0.021) were significantly lower in HCV liver samples while MCP-2 expression was similar in all groups analyzed. CONCLUSION: The data support the concept of chemokines as mediators of liver cell injury in chronic hepatitis C

Inmunopatogénesis de la hepatitis C.

El conocimiento de la patogénesis de la infección crónica por el virus de la hepatitis C (VHC) es crucial tanto para la determinación de una terapia antiviral exitosa como para encontrar una vacuna. En este trabajo se explica como inmediatamente después de la infección por el VHC, este se replica eficientemente, induciendo la producción de interferones tipo I, sin embargo, el rápido incremento en la replicación viral no es reconocido en forma adecuada por la respuesta inmune adaptativa y después de un intervalo corto, la carga viral se incrementa y persiste en la mayoría de los individuos infectados. Se considera que este fenómeno tiene una naturaleza inmunológica, que involucra tanto a linfocitos T citotóxicos, como a un mecanismo indirecto que implica la síntesis de citocinas que son inducidas por el VHC. Se considera que si ocurre una respuesta insuficiente o inadecuada de células T (CD4+ y CD8+) específicas del virus, el ARN-VHC persiste en células T hepáticas, situación que se observa aún en aquellos individuos que alcanzan una respuesta terapéutica con una inhibición viral considerada como sostenida. El VHC ha desarrollado varias estrategias para escapar a la erradicación mediada por las células T, que incluye interferir con la vía de presentación de las moléculas del Complejo Mayor de Histocompatibilidad (MHC) Clase I del huésped o teniendo un “escondite” en células a las que les falta la expresión de las MHC clase I. Finalmente, se describe y reconoce la importancia que tienen varias citocinas en la respuesta inmune por el huésped posterior a la exposición al VHC

Paroxysmal nocturnal hemoglobinuria: a case report in a pandemic environment

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal, rare, complement-mediated hemolytic anemia. PNH can be associated with marrow failure and thrombophilia. We present a clinical report of splenic vein thrombosis in a patient with classic PNH. A 41-year-old male with classic PNH, naïve to complement inhibitor therapy, developed splenic vein thrombosis as a major adverse effect after vaccination protocol to prevent meningococcal disease. We also report anticoagulant and eculizumab treatment outcomes. In PNH patients, vaccination should be monitored to prevent major outcome events, like vaccine-induced thrombosis. Eculizumab proves effective for treating intravascular hemolysis and preventing more thrombotic events. The potential protective role of eculizumab on controlling complement activity and consequent inflammation may help the patient to not experience breakthrough hemolysis when infected with SARS-CoV-2. Extravascular hemolysis remains present, but new molecules are being studied to inhibit proximal complement and there is a good health prospective for PNH patients.info:eu-repo/semantics/publishedVersio

A quantificação de CD4+ e CD8+ portal em hepatite C crônica está relacionada com a intensidade da hepatite de interface

BACKGROUND: The pathogenesis of chronic hepatitis C is still a matter of debate. CD4+ and CD8+ T lymphocytes (TL) are typically observed within the portal and periportal spaces of affected livers, but their functional role in hepatitis C progression has not been fully elucidated. METHODS: CD4+ and CD8+ TL were quantified by immunohistochemistry in portal and periportal spaces of 39 liver biopsies from patients with chronic hepatitis C. They were associated to demographic data, histological parameters, laboratory findings of patients and hepatitis C genotypes. RESULTS: There was high numbers of CD4+ and CD8+ TL from which the density of CD4+ T was higher than CD8+ TL in portal and periportal spaces. CD4+ and CD8+ TL were directly correlated to intensity of interface hepatitis. CD8+ TL correlated to serum enzyme levels. CONCLUSION: The high numbers of CD4+ and CD8+ TL in portal and periportal spaces and their correlation to interface hepatitis suggest that hepatitis C evolution depends on the action of intrahepatic T lymphocytes, lending support to the notion of an immune-mediated mechanism in the pathogenesis of chronic hepatitis C.INTRODUÇÃO: A patogênese da hepatite C crônica ainda está em discussão. Sabe-se que linfócitos T (LT) CD4+ e CD8+ são tipicamente observados no espaço portal e peri-portal de pacientes com hepatite C crônica, mas o conhecimento exato de suas ações no fígado, bem como sua influência na progressão da doença hepática ainda estão em discussão. MÉTODOS: Os LT CD4+ e T CD8+ foram quantificados por imunohistoquímica nos espaços porta e peri-portais em 39 biópsias hepáticas de pacientes cronicamente infectados pelo vírus da hepatite C. Esses dados foram associados com os dados demográficos, as alterações histológicas, os achados laboratoriais dos pacientes com hepatite C e com os genótipos do vírus da hepatite C. RESULTADOS: Houve grande quantidade tanto de LT CD4+ como de CD8+, sendo que houve maior densidade de LTCD4+ do que CD8+ nos espaços portal e peri-portal. Tanto o número de linfócitos T CD4+ como de CD8+ foram diretamente relacionados com a intensidade da hepatite de interface. Os linfócitos T CD8+ foram estatisticamente relacionados às enzimas hepáticas. CONCLUSÃO: O encontro de numerosos linfócitos T CD4+ e linfócitos T CD8+ no espaço-portal e peri-portal e sua correlação com a hepatite de interface sugerem que a evolução da hepatite C dependa da ação dos linfócitos T intra-hepáticos, ou seja, há um mecanismo imuno-mediado na patogênese da hepatite C crônica

Clinical Implications of Chemokines in Acute and Chronic Hepatitis C Virus Infection

Hepatitis C virus (HCV), a non-cytopathic positive-stranded RNA virus, is one of the most common causes of chronic liver diseases such as chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Upon HCV infection, the majority of patients fail to clear the virus and progress to chronic hepatitis C. Chemokines are small chemotactic cytokines that direct the recruitment of immune cells and coordinate immune responses upon viral infection. Chemokine production during acute HCV infection contributes to the recruitment of immune cells with antiviral effector functions and subsequent viral clearance. In chronic HCV infection, however, continuous production of chemokines due to persistent viral replication might result in incessant recruitment of inflammatory cells to the liver, giving rise to persistence of chronic inflammation and liver injury. In this review, we will summarize the roles of chemokines in acute and chronic settings of HCV infection and the clinical relevance of chemokines in the treatment of hepatitis C

Liver Enzyme Alterations in HCV-Monoinfected and HCV/HIV-Coinfected Patients

Hepatitis C virus (HCV) is the most common blood-borne infection in developed countries and co-infection with the Human Immunodeficiency Virus (HIV) is frequent in individuals with history of injecting drug use (IDU)

Distinct cellular responses differentiating alcohol- and hepatitis C virus-induced liver cirrhosis

BACKGROUND: Little is known at the molecular level concerning the differences and/or similarities between alcohol and hepatitis C virus induced liver disease. Global transcriptional profiling using oligonucleotide microarrays was therefore performed on liver biopsies from patients with cirrhosis caused by either chronic alcohol consumption or chronic hepatitis C virus (HCV). RESULTS: Global gene expression patterns varied significantly depending upon etiology of liver disease, with a greater number of differentially regulated genes seen in HCV-infected patients. Many of the gene expression changes specifically observed in HCV-infected cirrhotic livers were expectedly associated with activation of the innate antiviral immune response. We also compared severity (CTP class) of cirrhosis for each etiology and identified gene expression patterns that differentiated ethanol-induced cirrhosis by class. CTP class A ethanol-cirrhotic livers showed unique expression patterns for genes implicated in the inflammatory response, including those related to macrophage activation and migration, as well as lipid metabolism and oxidative stress genes. CONCLUSION: Stages of liver cirrhosis could be differentiated based on gene expression patterns in ethanol-induced, but not HCV-induced, disease. In addition to genes specifically regulating the innate antiviral immune response, mechanisms responsible for differentiating chronic liver damage due to HCV or ethanol may be closely related to regulation of lipid metabolism and to effects of macrophage activation on deposition of extracellular matrix components

Gambaran Status Gizi Pasien Penyakit Ginjal Kronik yang Menjalani Hemodialisis Rutin Minimal Tiga Bulan Berturut-turut di RSUP Dr. M. Djamil Padang

ABSTRAK GAMBARAN STATUS GIZI PASIEN PENYAKIT GINJAL KRONIK YANG MENJALANI HEMODIALISIS RUTIN MINIMAL TIGA BULAN BERTURUT-TURUT DI RSUP. DR. M. DJAMIL PADANG Oleh Yogi Andika Rahman Penderita penyakit ginjal kronik (PGK) dengan hemodialisis (HD) berisiko terjadi malnutrisi. Malnutrisi dan asupan energi protein yang tidak adekuat berhubungan erat dengan morbiditas dan mortalitas. Penilaian dan pemantauan status gizi pada penderita perlu dilakukan agar keadaan malnutrisi dapat dicegah. Penilaian tersebut dapat dilakukan dengan pengukuran antropometri seperti IMT (indeks massa tubuh), BBR (berat badan relatif) dan LOLA (lingkar otot lengan atas). Tujuan penelitian ini untuk mendeskripsikan status gizi penderita PGK yang menjalani hemodialisis rutin. Penelitian ini adalah deskriptif dengan desain potong lintang yang dilaksanakan di unit hemodialisis RSUP Dr. M. Djamil Padang tanggal 2 - 15 Januari 2019. Sampel penelitian berjumlah 32 orang diambil dengan teknik consecutive total sampling. Kriteria inklusi adalah penderita PGK yang telah menjalani hemodialisis rutin 2 kali seminggu minimal selama 3 bulan berturut-turut yang berusia 18-60 tahun. Data yang diperoleh meliputi karakteristik responden, status gizi yang diukur dengan menggunakan IMT, BBR dan LOLA. Responden terdiri 21 orang pria dan 11 orang wanita. Rerata umur responden 47,56 ± 10,80 (antara 18 ─ 60 tahun). Rerata lama HD 25,47 ± 24,83 (antara 3 – 98 bulan). Berdasarkan IMT responden yang tergolong gizi kurang 25%, status gizi normal 59,38% dan status gizi lebih 15,62%. Berdasarkan BBR responden yang tergolong status gizi kurang 31,25%, status gizi normal 62,5% dan status gizi lebih 6,25%. Berdasarkan LOLA responden yang tergolong gizi kurang 25%, gizi normal 43,75%, gizi lebih 31,25%. Kesimpulan penelitian ini adalah pengukuran IMT, BBR dan LOLA bermanfaat untuk memprediksi status gizi pasien PGK dengan HD. Kata kunci: Hemodialisis, status gizi, IMT, BBR, LOLA