IL-22 and IL-22 binding protein (IL-22BP) regulate fibrosis and cirrhosis in hepatitis C virus and schistosome infections.

UNLABELLED: Interleukin (IL)-22 acts on epithelia, hepatocytes, and pancreatic cells and stimulates innate immunity, tissue protection, and repair. IL-22 may also cause inflammation and abnormal cell proliferation. The binding of IL-22 to its receptor is competed by IL-22 binding protein (IL-22BP), which may limit the deleterious effects of IL-22. The role of IL-22 and IL-22BP in chronic liver diseases is unknown. We addressed this question in individuals chronically infected with schistosomes or hepatitis C virus (HCV). We first demonstrate that schistosome eggs stimulate production of IL-22 transcripts and inhibit accumulation of IL22-BP transcripts in schistosome-infected mice, and that schistosome eggs selectively stimulate production of IL-22 in cultures of blood leukocytes from individuals chronically infected with Schistosoma japonicum. High IL-22 levels in cultures correlated with protection against hepatic fibrosis and portal hypertension. To test further the implication of IL-22/IL-22BP in hepatic disease, we analyzed common genetic variants of IL22RA2, which encodes IL-22BP, and found that the genotypes, AA, GG of rs6570136 (P = 0.003; odds ratio [OR] = 2), and CC, TT of rs2064501 (P = 0.01; OR = 2), were associated with severe fibrosis in Chinese infected with S. japonicum. We confirmed this result in Sudanese (rs6570136 GG [P = 0.0007; OR = 8.2], rs2064501 TT [P = 0.02; OR = 3.1]), and Brazilians (rs6570136 GG [P = 0.003; OR = 26], rs2064501 TC, TT (P = 0.03; OR = 11]) infected with S. mansoni. The aggravating genotypes were associated with high IL22RA2 transcripts levels. Furthermore, these same variants were also associated with HCV-induced fibrosis and cirrhosis (rs6570136 GG, GA [P = 0.007; OR = 1.7], rs2064501 TT, TC (P = 0.004; OR = 2.4]). CONCLUSIONS: These results provide strong evidence that IL-22 protects against and IL-22BP aggravates liver fibrosis and cirrhosis in humans with chronic liver infections. Thus, pharmacological modulation of IL-22 BP may be an effective strategy to limit cirrhosis.

Transplante de fígado em hospital universitário do Recife: resultados iniciais / Liver transplantation in an university hospital in Recife: Initial results

OBJETIVO: Apresentar a experiência e enfatizar o aprendizado obtido em um programa incipiente de transplante hepático desenvolvido em Hospital Universitário de Recife-PE. MÉTODO: Foram estudados os primeiros 20 pacientes submetidos a transplante ortotópico de fígado, de maneira simplificada, no período de agosto de 1999 a março de 2002. Foram analisadas as indicações, a reserva funcional hepática pré-operatória, o volume de sangue transfundido, o tempo de isquemia, o tempo de permanência em UTI, a morbidade e a mortalidade. A cirrose por vírus C foi a indicação de transplante em 9 pacientes (45 por cento), seguida de cirrose alcoólica em 7 (35 por cento). Quarenta e cinco por cento dos pacientes foram classificados como CHILD-PUGH A, 35 por cento como B, e apenas 20 por cento como C. RESULTADOS: O tempo de isquemia médio foi de 9h 09' (+ 2h 33'). Foram utilizadas em média 2,88 (+ 2,11) unidades de hemácias. A técnica empregada foi a convencional sem bypass em 90 por cento dos casos e piggyback nos restantes. No pós-operatório, houve um caso de trombose de artéria hepática e outro de veia porta. Oito pacientes apresentaram complicações biliares, todas resolvidas por via endoscópica ou percutânea. A sobrevida global é de 100 por cento, no período de seguimento de 2 a 32 meses. CONCLUSÃO: Conclui-se que é possível realizar transplantes de fígado, com bons resultados, em hospital universitário do Nordeste do Brasil, desde que se reúnam as mínimas condições de estrutura física e recursos humanos.

BACKGROUND: This paper describes the experience and emphasizes the learning process with a program in liver transplantation developed at a University Hospital in Recife-PE. METHODS: Twenty patients were submitted to conventional orthotopic liver transplantation in a simplified way during the period from August 1999 to March 2002. Indications, liver function, blood transfusion, allograft ischemia time, intensive care period and morbidity and mortality rates were analyzed. VHC cirrhosis was the transplant indication in 9 (45 percent) patients, followed by alcoholic cirrhosis in 4 (20 percent) patients. Fifty per cent of the transplanted patients were classified in CHILD-PUGH as B, 40 percent as A, and 10 percent as C. RESULTS: The mean allograft ischemia time was 9 hours and 9 minutes (+ 2h 33'). The average of blood transfusion was 2,8 (+ 2,11) units. The operative technique was conventional without bypass in 18(90 percent) cases. There was one case of hepatic artery thrombosis and one of portal vein thrombosis. Eight patients (40 percent) presented biliary complications wich were resolved using endoscopic or percutaneus methods. A 100 percent of overall survival rate was achieved during a follow up of 2 to 32 months. CONCLUSION: The results of this initial study show that it is possible to perform liver transplantation with good results at a university hospital in the northeast region when a minimum of physical structure and human resources is assembled.

Transplante de figado em Hospital Publico de Pernambuco / Liver transplantation in a public Hospital, recife-Pernambuco -Brasil

Os autores apresentam os oito primeiros casos de transplante ortotopico de figado em adultos, com doador cadaver, realizados em Hospital Universitario do Recife, capital de uma regi'ao pobre e populosa do Brasil. As intervencoes foram realizadas em condicoes estruturais adequadas, mas ainda sub-otimas. Mesmo assim todos os pacientes obtiveram alta hospitalar e passaram a viver normalmente. Os autores concluem que o transplante hepatico deve ser estimulado no Nordeste, onde existe uma demanda estimada de 900 transplate por ano