Serum levels of immunoglobulin free light chains in patients with chronic hepatitis C presenting cryoglobulinemia

Hepatitis C virus (HCV) infects B-lymphocytes, provokes cellular dysfunction and causes lymphoproliferative diseases such as cryoglobulinemia and non-Hodgkin's B-cell lymphoma. In the present study, we investigated the serum levels of kappa and lambda free light chains (FLC) of immunoglobulins and the kappa/lambda FLC ratio in Brazilian patients with chronic HCV infection and cryoglobulinemia. We also analyzed the immunochemical composition of the cryoglobulins in these patients. Twenty-eight cryoglobulinemic HCV patients composed the target group, while 37 HCV patients without cryoglobulinemia were included as controls. The median levels of kappa and lambda FLC were higher in patients with cryoglobulinemia compared to controls (p = 0.001 and p = 0.003, respectively), but the kappa/lambda FLC ratio was similar in patients with and without cryoglobulinemia (p > 0.05). The median FLC ratio was higher in HCV patients presenting with advanced fibrosis of the liver compared to HCV patients without fibrosis (p = 0.004). Kappa and lambda FLC levels were strongly correlated with the IgA, IgG and IgM levels in the patients with cryoglobulinemia. In patients without cryoglobulinemia, the kappa FLC level was only correlated with the IgG level, whereas the lambda FLC were weakly correlated with the IgA, IgG and IgM levels. An immunochemical pattern of mixed cryoglobulins (MC), predominantly IgM, IgG, IgA and kappa light chain, was verified in these immune complexes. We concluded that HCV-infected patients presenting cryoglobulinemia have vigorous polyclonal B-lymphocyte activation due to chronic HCV infection and persistent immune stimulation.

Clinical relevance of cryoglobulinaemia and extrahepatic neurocutaneous manifestations of chronic hepatitis C

To examine the prevalence of cryoglobulinaemia in patients with chronic hepatitis C infection and its relation to extrahepatic neuro-cutaneous manifestations. Forty patients [26 males and 14 females], with clinical, laboratory and histologically established chronic hepatitis C infection, with a mean age of 37.5 years, were submitted to clinical examination, dermatological and neurological evaluation. Neuroimaging as well as neurophysiological evaluation, laboratory assessment including liver function tests, serum cryoprecipitate immunoelectrophoresis, and revision of histopathlogical findings were performed. A high prevalence of cryglobulenemia: 62.5% in patients with chronic hepatitis C infection, the presenting symptoms were fatigue [67.5%], arthralgia [32.5%], paresthesia [30%] and pruritus [25%]; however, there were no statistically significant difference between cryo + ve versus cryo - ve patients except for pruritis, and face pigmentation. Skin manifestations including face pigmentation [42.5%], leukocytoclastic vasculitis [22.5%], porphyria cutanea tarda [20%], lichen planus [17.5%], acral necrolytic erythema [15%] and vitiligo [15%]. Neurological manifestations; symptomatic neuropathy in 10%, neuropathic changes in 30% and electroencephalographic changes in 22.5%. These cutaneous and neurological manifestations were significantly associated with the presence of cryoglobulinaemia. Our findings support an association between cryoglobuliaemia and extrahepatic neurocutaneous manifestations of hepatitis C infection. The presence of all these manifestations in the appropriate clinical setting should suggest the presence of hepatitis C infection

Hepatitis C virus infection, cryoglobulinemia, and peripheral neuropathy: a case report

Hepatitis C virus (HCV) is essentially hepatotropic but its manifestations can extend beyond the liver. It can be associated with autoimmune diseases, such as mixed cryoglobulinemia, membranoproliferative glomerulonephritis, autoimmune thyroiditis, and lymphoproliferative disorders. The mechanisms that trigger these manifestations are not completely understood. We describe a 48-year-old man with chronic HCV infection (circulating HCV RNA and moderate hepatitis as indicated by liver biopsy), cryoglobulinemia, and sensory and motor peripheral neuropathy. The diagnosis of multineuropathy was confirmed by clinical examination and electromyographic tests. A nerve biopsy revealed an inflammatory infiltrate in the perineurial space and signs of demyelination and axonal degeneration. The patient had no improvement of neurological symptoms with the use of analgesics and neuro-modulators. He was then treated with interferon-alpha (3 million units subcutaneously, 3 times per week) and ribavirin (500 mg orally, twice a day) for 48 weeks. Six months after the end of therapy, the patient had sustained viral response (negative HCV RNA) and remission of neurological symptoms, but cryoglobulins remained positive. A review of the literature on the pathogenesis and treatment of neurological manifestations associated with HCV infection is presented. This report underscores the need for a thorough evaluation of HCV-infected patients because of the possibility of extrahepatic manifestations. Antiviral treatment with interferon and ribavirin can be effective and should be considered in patients with neurological complications associated with HCV infection.

El virus C de la hepatitis y las enfermedades que produce / Hepatitis C virus and the diseases that it produces

In 1989, the main agent causing non A non B hepatitis was identified as a RNA virus of the flavivirus family, with several serotypes, and was denominated virus C. At the present moment, the knowledge about the infection features and diseases that it causes has expanded thanks to the availability of reliable laboratory techniques to detect the antibody and the virus. The prevalence of infection and the frequency of serotypes varies in different regions of the world. Chile is a country with a low prevalence. The detection of infected blood in blood banks has reduced the spreading of the disease. Other means of infection such as the use of intravenous drugs, hemodialysis and transplantation have acquired greater importance. Sexual, maternal and familial transmission is exceptional. Infected people develop an acute hepatitis, generally asymptomatic. Eighty percent remain with a chronic hepatic disease, that can be mild or progressive, evolving to cirrhosis or hepatic carcinoma. Chronic hepatitis, closely resembling an autoimmune disease, can be caused by the virus. Alcohol intake increases viral activity causing severe hepatic diseases, refractory to treatments. Several non hepatic diseases are associated to hepatitis C virus infection such as essential mixed cryoglobulinemia, mesangiocapillary glomerulonephritis, porphyria cutanea tarda, dysglobulinemias and probably type 2 diabetes mellitus. The only available treatment is interferon, that is successful in a minority of patients, frequently causing a transient improvement. The use of ribaravine associated to interferon improve the effectiveness of therapy. Liver transplantation is the only therapy for severe hepatic disease. The use of new antiviral drugs should improve the prognosis of the disease

Crioglobulinemia

Objetivo: Realizar una revisión de la literatura sobre el tema de las crioglobulinemias, su comportamiento biológico, su presentación clínica y sus nuevas perspectivas terapéuticas. En nuestro medio es una patología autoinmune olvidada a pesar de sus implicaiones clínicas y es necesario tenerla en cuenta en el diagnóstico diferencial o complementario de muchas entidades. Fuente de datos. Se realizó una revisión bibliografica de la base de datos Medline (1990 a 1998) y se incluyeron los artículos fundamentales descriptivos entre 1973 y 1983, realizados por el grupo de inmunología del Hospital Saint-Louis de París. Se lección y extracción de datos. Se estudiaron 858 referncias bibliográficas, de las cuales se seleccionaron 50, entre ellas revisiones, actualizaciones y reportes de casos clínicos con información concreta sobre el tema. Síntesis de los datos. El diagnóstico de la crioglobulinemia depende de la calidad de la toma y del procesamiento de las muestras. Las crioglobulinas son inmunoglobulinas séricas que precipitan a temperaturas frías y se disuelven con el calentamiento. Es necesario tener en cuenta ciertas precauciones durante la tima de la muestra de sangre que debe hacerse a 37 grados centigrados durante 8 días y una vez se obtiene el crioprecipitado, se purifica mediante centrifugación repetida y lavando a 4 grados centigrados. Si la toma de la muestra so se realiza a 37 grados centrigrados, se altern los resultados del cuadro hemático, la velocidad de sedimentación globular, la electroforesis de proteínas y algunas fracciones del complemento debido a la precipitación de proteínas. La identificación de las crioglobulinas se realiza por medio de la electroforesis y la inmunoelectroforesis en presencia de antisueros monoespecíficos dirigidos contra las cadenas pesadas µ,y,Ó y ligeras k y ï. La determinación de las cadenas ligeras permite definir la naturaleza monoclonal o policlonal de los constituyentes de la crioglobulinemia. Con frecuencia se asocia con otras patologías y su tratamiento depende de la presentación clínica y de la patología subyacente. Conclusión. El diagnóstico preciso de crioglobulinemia es indispensable ya que el algoritmo terapéutico disponible ofrece posibilidades de tratamiento dicotómicas, de acuerdo con los subtipos de clasificación y las enfermedades asociadas.

Relación entre algunos agentes microbianos y ciertas dermatosis, incluidas algunas colagenopatías / The relation between some microbial agents and some dermatoses, including collagen diseases

Basándonos en una amplia revisión bibliográfica, consideramos que la mayoría, sino todas las enfermedades del tejido conectivo tienen agentes etiológicos disparadores de fenómenos inmunes. La identificación de éstos permitirá ajustar las medidas terapéuticas y profilácticas e impedir, cuando sea posible, el contagio y/o las consecuencias alejadas de estas infecciones

Manifestaçoes extra-hepáticas das hepatites virais / Extrahepatic manifestations of viral hepatitis

Manifestaçoes extra-hepáticas das hepatites virais, sao raras e causadas por vírus A,B,C,D,ou E. As mais comumentes observadas sao vasculites sistêmicas, crioglobulinemias essenciais, polimialgias reumáticas, anemia aplástica, glomerulonefrites membranosas e membranoproliferativas, síndrome de Sjogren, encefalite aguda e urticária. Algumas destas sao graves, inclusive com índices elevados de mortalidade. A maioria porém, assume curso clínico leve. Serao comentadas neste artigo