RESUMO A doença metabólica e doença hepática gordurosa metabólica estão aumentando a prevalência mundial e, portanto, espera-se um número maior de carcinoma hepatocelular (CHC) relacionado à doença hepática gordurosa não alcóolica (DHGNA) nos próximos anos. Esta revisão descreve os fatores de risco associados ao CHC em pacientes com DHGNA. A presença de cirrose hepática é a preponderante. Sexo masculino, variantes do gene PNPLA3, diabetes e obesidade também parecem predispor ao desenvolvimento de CHC, mesmo em indivíduos não cirróticos. Até agora, modificações significativas no estilo de vida, incluindo controle glicêmico e tratamento da obesidade, são terapias eficazes para DHGNA/ Esteatohepatite não-alcoolica e, portanto, provavelmente, também para CHC. Alguns medicamentos que propunham-se diminuir a atividade inflamatória e fibrose, bem como a obesidade, foram estudados. Outros dados sugeriram a possibilidade de quimioprevenção do CHC. Até o momento, no entanto, não há evidências definitivas para o uso rotineiro desses medicamentos. Esperamos, no futuro, poder traçar o perfil de pacientes com maior risco de DHGNA-CHC e traçar estratégias para diagnóstico precoce e prevenção. portanto esperase espera se (CHC DHGNA (DHGNA anos preponderante masculino PNPLA3 PNPLA cirróticos agora vida nãoalcoolica alcoolica provavelmente propunhamse propunham fibrose estudados momento entanto Esperamos futuro DHGNACHC prevenção

ABSTRACT Non-alcoholic fatty liver disease is growing in worldwide prevalence and thus, is expected to have a higher number of NAFLD-related hepatocellular carcinoma (HCC) in the following years. This review describes the risk factors associated with HCC in NAFLD-patients. The presence of liver cirrhosis is the preponderant one. Male gender, PNPLA3 variants, diabetes, and obesity also appear to predispose to the development of HCC, even in non-cirrhotic subjects. Thus far, intensive lifestyle modifications, including glycemic control, and obesity treatment, are effective therapies for NAFLD/ non-alcoholic steatohepatitis and, therefore, probably, also for HCC. Some drugs that aimed at decreasing inflammatory activity and fibrosis, as well as obesity, were studied. Other data have suggested the possibility of HCC chemoprevention. So far, however, there is no definitive evidence for the routine utilization of these drugs. We hope, in the future, to be able to profile patients at higher risk of NAFLD-HCC and outline strategies for early diagnosis and prevention. Nonalcoholic Non alcoholic thus NAFLDrelated NAFLD related (HCC years NAFLDpatients. NAFLDpatients patients. NAFLD-patients one gender PNPLA variants diabetes noncirrhotic non cirrhotic subjects far modifications control treatment nonalcoholic therefore probably fibrosis studied chemoprevention however hope future NAFLDHCC prevention

RESUMO Contexto O transplante de fígado com doador falecido é a primeira escolha, mas o transplante de doador vivo é uma alternativa a ser considerada em situações especiais, como falta de órgãos doados e emergências. Até o momento, não há consenso sobre qual método de transplante proporciona melhor sobrevida e menos complicações, sendo, ainda, um ponto em aberto para discussão. Métodos Esta meta-análise comparou as taxas de sobrevida de pacientes e enxertos de 1, 3 e 5 anos de transplante de doador vivo e transplante de fígado com doador falecido. Incluímos estudos publicados de abril de 2009 a junho de 2021 e adotamos o modelo genérico do inverso da variância para o efeito aleatório das razões de risco. A adequação dos estudos foi determinada por meio da Escala de Newcastle-Ottawa — NOS (WELLS). Resultados Para análise de sobrevida do paciente, incluímos um total de 32.258 indivíduos. Encontramos uma melhor sobrevida estatisticamente significativa para o grupo de transplante de fígado de doador vivo em 1, 3 e 5 anos, respectivamente: 1,35 HR (IC95% 1,10—1,66, P=0,005), 1,26 HR (IC95% 1,09—1,46, P=0,002) e 1,27 HR (IC95% 1,09—1,48, P=0,002). Nossa meta-análise avaliou um total de 21.276 enxertos. Na análise geral, a sobrevida em 1 ano foi melhorada em favor do grupo de transplante de doador vivo (1,36 HR, IC95% 1,16—1,60, P<0,0001), enquanto a sobrevida em 3 anos (1,13 HR, IC95% 0,96—1,33, P<0,13) e 5 (0,99 HR, IC95% 0,74—1,33, P<0,96), não diferiram significativamente. Conclusão Esta meta-análise detectou uma sobrevida estatisticamente significativa maior do paciente em 1, 3 e 5 anos favorecendo o transplante de doador vivo em comparação com o transplante de fígado com doador falecido, bem como uma diferença estatisticamente significativa melhor na sobrevida do enxerto em 1 ano favorecendo o grupo de transplante de doador vivo.

ABSTRACT Background Deceased donor liver transplantation (DDLT) is the first choice, but living donor transplantation (LDLT) is an alternative to be considered in special situations, such as lack of donated organs and emergencies. So far, there is no consensus on which transplantation method provides better survival and fewer complications, which is still an open point for discussion. Methods This meta-analysis compared the 1, 3, and 5-year patient and graft survival rates of LDLT and DDLT. We included studies published from April-2009 to June-2021 and adopted the generic model of the inverse of variance for the random effect of hazard ratios. The adequacy of the studies was determined using the Newcastle-Ottawa Scale — NOS (WELLS). Results For patient survival analysis, we included a total of 32,258 subjects. We found a statistically significant better survival for the LDLT group at 1, 3 and 5 years, respectively: 1.35 HR (95%CI 1.10—1.66, P=0.005), 1.26 HR (95%CI 1.09—1.46, P=0.002) and 1.27 HR (95%CI 1.09—1.48, P=0.002). Our meta-analysis evaluated a total of 21,276 grafts. In the overall analysis, the 1-year survival was improved in favor of the LDLT group (1.36 HR, 95%CI 1.16—1.60, P<0.0001), while the 3-year survival (1.13 HR, 95%CI 0.96—1.33, P<0.13), and 5 (0.99 HR, 95%CI 0.74—1.33, P<0.96), did not differ significantly. Conclusion This metanalysis detected a statistically significant greater 1-, 3- and 5-years patient survival favoring LDLT compared to DDLT as well as a statistically significant difference better 1-year graft survival favoring the LDLT group.

OBJECTIVES: Suppressor of cytokine signaling 3, myxovirus resistance protein and osteopontin gene polymorphisms may influence the therapeutic response in patients with chronic hepatitis C, and an association with IL28 might increase the power to predict sustained virologic response. Our aims were to evaluate the association between myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 gene polymorphisms in combination with IL28B and to assess the therapy response in hepatitis C patients treated with pegylated-interferon plus ribavirin. METHOD: Myxovirus resistance protein, osteopontin, suppressor of cytokine signaling 3 and IL28B polymorphisms were analyzed by PCR-restriction fragment length polymorphism, direct sequencing and real-time PCR. Ancestry was determined using genetic markers. RESULTS: We analyzed 181 individuals, including 52 who were sustained virologic responders. The protective genotype frequencies among the sustained virologic response group were as follows: the G/G suppressor of cytokine signaling 3 (rs4969170) (62.2%); T/T osteopontin (rs2853744) (60%); T/T osteopontin (rs11730582) (64.3%); and the G/T myxovirus resistance protein (rs2071430) genotype (54%). The patients who had ≥3 of the protective genotypes from the myxovirus resistance protein, the suppressor of cytokine signaling 3 and osteopontin had a greater than 90% probability of achieving a sustained response (p<0.0001). The C/C IL28B genotype was present in 58.8% of the subjects in this group. The sustained virological response rates increased to 85.7% and 91.7% by analyzing C/C IL28B with the T/T osteopontin genotype at rs11730582 and the G/G suppressor of cytokine signaling 3 genotype, respectively. Genetic ancestry analysis revealed an admixed population. CONCLUSION: Hepatitis C genotype 1 patients who were responders to interferon-based therapy had a high frequency of multiple protective polymorphisms in the myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 genes. The combined analysis of the suppressor of cytokine signaling 3 and IL28B genotypes more effectively predicted sustained virologic response than IL28B analysis alone.