TEN-YEAR OUTCOMES OF TIPS FOR BUDD-CHIARI SYNDROME: SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: Budd-Chiari syndrome (BCS) results from the obstruction of the hepatic venous flow, usually at the level of the hepatic vein or inferior vena cava. When left untreated, it can progress with several complications, including liver cirrhosis. Transjugular intrahepatic portosystemic shunt (TIPS) appears to be effective in a subgroup of BCS patients. OBJECTIVE: To perform a systematic review and meta-analysis of TIPS effectiveness in BCS treatment, considering the survival rate, reduction in portosystemic pressure, need for liver transplantation, technical failure, and shunt dysfunction for up to 10 years of follow-up. METHODS: We evaluated 17 studies published in PubMed, Science Direct, Web of Science, and SCOPUS databases, which used TIPS as a treatment for BCS, comprising 618 subjects between 18 and 78 years old. We assessed the bias risk by the NOS, NHI, and JBI scales for cohort stu-dies, before-after studies, and case series, respectively. We conducted the meta-analyses by extracting the number of events and the total patients evaluated to perform the proportion meta-analyses using the R software ("meta" package - version 4.9-6). RESULTS: The pooled results (95%CI) showed a 19% (25.9-12.5%) rate of portosystemic pressure reduction, 6% (1-12%) rate for the need for liver transplants despite the use of TIPS, 2% (1-6%) technical failure rate, 30% (18-46%) shunt dysfunction rate, and 88% (81-93%) for the mean frequency of patients alive between 1 and 10 years after the procedure. We stratified survival rate and found an 86% (74-93%) prevalence of living subjects during less than five years, 92% (83-97%) at five years, and a 77% frequency (68-83%) of patients alive ten years after the TIPS placement. CONCLUSION: TIPS is an effective treatment for BCS, providing a high 10-year frequency of living patients and a significant decrease in portosystemic pressure. The need for liver transplants after TIPS and the technical failure rate is low.

Hepatobiliary disease after bone marrow transplant: A cross-sectional study of 377 patients.

BACKGROUND: Bone marrow transplantation (BMT) is a standard treatment for several haematologic conditions. Following BMT, patients may develop hepatobiliary complications that impact morbidity and mortality. The differential diagnosis may include drug-induced liver injury (DILI), sepsis-associated liver injury (SALI), sinusoidal obstruction syndrome (SOS), graft-versus-host disease (GVHD), viral hepatitis, ischaemic hepatitis, and fulminant hepatitis. AIMS: To evaluate the frequency, clinical characteristics, and outcomes of patients with hepatobiliary alterations associated with BMT in a tertiary referral centre. METHODS: This was a cross-sectional study with data collected from the medical records of patients undergoing BMT between January 2017 and June 2022. We diagnosed hepatobiliary complications based on established criteria. RESULTS: We included 377 patients; 55.7% had hepatobiliary complications. Female gender, pre-BMT hepatobiliary alteration, and haploidentical allogeneic transplantation were associated with increased risk with odds ratios (OR) of 1.8 (p = 0.005), 1.72 (p = 0.013) and 3.25 (p = 0.003), respectively. Patients with hepatobiliary complications spent longer in the hospital than those without (27.7 × 19.3 days, respectively; p < 0.001). Among 210 patients with hepatobiliary complications, 28 died compared to 5 of 167 without complications (OR 4.98; p = 0.001). CONCLUSIONS: Hepatobiliary complications are frequent in patients undergoing BMT. There is a greater risk of their occurrence in women, people with pre-BMT liver alterations, and in haploidentical transplants. The occurrence of these complications increases the length of stay and is associated with a higher risk of death.

Eficácia do TIPS em 10 anos na síndrome de Budd-Chiari: revisão sistemática e metanálise / Ten-year outcomes of tips for budd-chiari syndrome: systematic review and meta-analysis

ABSTRACT Background: Budd-Chiari syndrome (BCS) results from the obstruction of the hepatic venous flow, usually at the level of the hepatic vein or inferior vena cava. When left untreated, it can progress with several complications, including liver cirrhosis. Transjugular intrahepatic portosystemic shunt (TIPS) appears to be effective in a subgroup of BCS patients. Objective: To perform a systematic review and meta-analysis of TIPS effectiveness in BCS treatment, considering the survival rate, reduction in portosystemic pressure, need for liver transplantation, technical failure, and shunt dysfunction for up to 10 years of follow-up. Methods: We evaluated 17 studies published in PubMed, Science Direct, Web of Science, and SCOPUS databases, which used TIPS as a treatment for BCS, comprising 618 subjects between 18 and 78 years old. We assessed the bias risk by the NOS, NHI, and JBI scales for cohort stu­dies, before-after studies, and case series, respectively. We conducted the meta-analyses by extracting the number of events and the total patients evaluated to perform the proportion meta-analyses using the R software ("meta" package - version 4.9-6). Results: The pooled results (95%CI) showed a 19% (25.9-12.5%) rate of portosystemic pressure reduction, 6% (1-12%) rate for the need for liver transplants despite the use of TIPS, 2% (1-6%) technical failure rate, 30% (18-46%) shunt dysfunction rate, and 88% (81-93%) for the mean frequency of patients alive between 1 and 10 years after the procedure. We stratified survival rate and found an 86% (74-93%) prevalence of living subjects during less than five years, 92% (83-97%) at five years, and a 77% frequency (68-83%) of patients alive ten years after the TIPS placement. Conclusion: TIPS is an effective treatment for BCS, providing a high 10-year frequency of living patients and a significant decrease in portosystemic pressure. The need for liver transplants after TIPS and the technical failure rate is low.

RESUMO Contexto: A síndrome de Budd-Chiari (SBC) é resultante da obstrução do fluxo venoso hepático, usualmente no nível da veia hepática ou da veia cava inferior. Quando não tratada, pode evoluir com complicações, incluindo a cirrose hepática. O tratamento com TIPS parece ser eficaz em um subgrupo de pacientes. Objetivo: Realizar uma revisão sistemática e meta-análise da eficácia do TIPS no tratamento da síndrome de Budd-Chiari, considerando sobrevida, redução de pressão portossistêmica, necessidade de transplante hepático, falha técnica e disfunção no shunt em 10 anos de seguimento. Métodos: Foram avaliados 17 estudos publicados nas bases de dados PubMed, Science direct, Web of Science e SCOPUS, que utilizaram TIPS como tratamento da SBC, correspondendo a um total de 618 pacientes, entre 18 e 78 anos. O risco de viés foi avaliado pelas escalas de NOS, NHI e JBI, para estudos de coorte, antes e depois e séries de casos, respectivamente. As meta-análises foram conduzidas, extraindo o número de eventos e o total de pacientes avaliados para realizar as meta-análises de proporções usando o software R, com o pacote "meta" (versão 4.9-6). Resultados: Os resultados agrupados (IC de 95%) foram de 19% (25,9-12,5%) para a taxa de redução da pressão portossistêmica, 6% (1-12%) para a taxa de necessidade de transplantes hepáticos a despeito do uso do TIPS, 2% (1-6%) para a taxa de falha técnica, 30% (18-46%) para a taxa de disfunção do shunt e 88% (81-93%) para a sobrevida entre 1 e 10 anos depois do procedimento. Estratificando essa sobrevida, foi detectada 86% (74-93%) no período menor do que 5 anos, 92% (83-97%) com 5 anos, e 77% (68-83%) de frequência de pacientes vivos 10 anos após a realização do TIPS. Conclusão: O TIPS é um tratamento eficaz para a SBC, proporcionando elevada sobrevida em 10 anos e uma diminuição significativa da pressão portossistêmica. A necessidade de transplantes de fígado após TIPS e a taxa de falha técnica são baixas.

Hepatobiliary disease after bone marrow transplant.

INTRODUCTION: Bone marrow transplantation (BMT) is the standard treatment for several hematologic pathologies. Post-BMT patients may develop hepatobiliary complications that impact morbidity and mortality. The differential diagnosis may include drug-induced liver injury (DILI), sepsis-associated liver injury (SALI), sinusoidal obstruction syndrome (SOS), graft-versus-host disease (GVHD), viral hepatitis, ischemic and fulminant hepatitis, among others. AREA COVERED: Defining the etiology of hepatobiliary injury is challenging due to the overlapping symptoms. Thus, it is necessary to be aware of and understand the clinical characteristics of these hepatobiliary complications and provide adequate management with possible better outcomes. We reviewed the scientific literature focused on early hepatobiliary complications associated with BMT. We searched the PubMed database using the following descriptors: hepatic complications, drug-induced liver disease, graft-versus-host disease, cholestasis, sepsis, sinusoidal obstruction syndrome, cytomegalovirus, viral hepatitis, bone marrow transplantation, and hematopoietic stem cell transplantation. EXPERT OPINION: Post-BMT hepatobiliary complications comprise several differential diagnoses and are challenges for the hepatologist's clinical practice. When evaluating these patients, it is necessary to consider the temporality between the use of certain medications, the increase in liver enzymes, and the presence of infection, in addition to applying diagnostic criteria and complementary tests for a specific diagnosis.

RISK FACTORS FOR HEPATOCELLULAR CARCINOMA IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE.

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.

Fatores de risco para carcinoma hepatocelular em pacientes com doença gordurosa não alcóolica do fígado / Risk factors for hepatocellular carcinoma in patients with non-alcoholic fatty liver disease

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.

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.

African genetic ancestry is associated with lower frequency of PNPLA3 G allele in non-alcoholic fatty liver in an admixed population.

INTRODUCTION AND OBJECTIVES: PNPLA3 (rs738409) and TM6SF2 (rs58542926) variants, interindividual and ethnic differences may be risk factors for non-alcoholic fatty liver disease (NAFLD). The PNPLA3 G allele is associated with worse NAFLD evolution in Hispanics and Caucasians. TM6SF2 is associated with hypertriglyceridemia, NAFLD, and cardiovascular disease. We aimed to evaluate the association between genetic ancestry by Ancestry Informative Markers (AIM), PNPLA3 and TM6SF2 polymorphisms in patients with biopsy-proven NAFLD in an admixed population. METHODS: We included adults with biopsy-proven NAFLD and excluded patients with the presence of other chronic liver disease, alcohol intake >100g/week, HIV, drug-induced fatty liver disease, or liver transplantation. We classified NAFLD using the Non-Alcoholic Steatohepatitis Clinical Research Network (NASH-CRN) histological scoring system. The PNPLA3 (rs738409 c.444C>G) and TM6SF2 (rs58542926 c.449C>T) genotyping were performed by RT-PCR. Genetic ancestry was determined using 46 insertion-deletion AIM; α<0.05 was considered significant. RESULTS: A total of 248 patients with NAFLD were enrolled [34 with simple steatosis (NAFL); 214 with NASH]. Overall, we detected a greater European ancestry contribution (0.645), followed by African (0.173), Amerindian (0.095), and East Asian (0.087) ancestry contribution, without differences between NAFL and NASH patients. However, we found a higher African genetic ancestry contribution among patients with NAFL who had the PNPLA3 C/C genotype than those with the G allele (0.216 ± 0.205 versus 0.105 ± 0.101, respectively; p=0.047). Ancestry contributions did not differ among TM6SF2 genotypes. CONCLUSION: Among NAFL patients, greater African genetic ancestry was associated to a lower frequency of the PNPLA3 G allele, demonstrating a possible NASH ancestry-related protective factor.

BETTER LIVING DONOR LIVER TRANSPLANTATION PATIENT SURVIVAL COMPARED TO DECEASED DONOR - A SYSTEMATIC REVIEW AND META-ANALYSIS.

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.

Sobrevida de pacientes submetidos ao transplante hepático com enxerto de doador vivo é melhor em comparação com doador falecido — uma revisão sistemática e meta-análise / Better living donor liver transplantation patient survival compared to deceased donor — a systematic review and meta-analysis

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.

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.

Sweet syndrome as a paraneoplastic manifestation of cholangiocarcinoma: A case report.

BACKGROUND: Sweet's syndrome, also known as acute febrile neutrophilic dermatosis, is a rare skin disorder that may be associated with cancer. CASE SUMMARY: A 58-year-old female presented with a cholestatic syndrome and significant weight loss three months before admission. Five months earlier, she had abruptly developed skin lesions with erythematous papules that evolved to erythematous blisters. Clinical evaluation and laboratory tests confirmed hepatic cholangiocarcinoma. Skin lesions histopathological findings showed neutrophilic dermatosis, massive edema, fibrin, necrosis, and elastosis. These results, in association with the macroscopic aspects of the findings, led to the diagnosis of paraneoplastic Sweet's syndrome due to cholangiocarcinoma. As staging was consistent with an advanced tumor without a cure perspective, we opted to perform percutaneous biliary drainage, and subsequently, palliative care. Eventually, after a few weeks, the patient died. CONCLUSION: In conclusion, the diagnosis of the underlying disease-causing Sweet's syndrome must be accurate, and patients need to be followed-up, as neoplasia such as cholangiocarcinoma may be a later manifestation.

Epidemiological profile of alcoholic liver disease hospital admissions in a Latin American country over a 10-year period.

BACKGROUND: Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide. AIM: To describe the epidemiological profile and mortality rates of patients with ALD admitted to public hospitals in different regions of Brazil from 2006 to 2015. METHODS: This is a descriptive study that evaluated aggregate data from the five Brazilian geographic regions. RESULTS: A total of 160093 public hospitalizations for ALD were registered. There was a 34.07% increase in the total number of admissions over 10 years, from 12879 in 2006 to 17267 in 2015. The region with the highest proportion (49.01%) of ALD hospitalizations was Southeast (n = 78463). The North region had the lowest absolute number of patients throughout the study period, corresponding to 3.9% of the total (n = 6242). There was a 24.72% increase in the total number of ALD deaths between 2006 and 2015. We found that the age group between 50 and 59 years had the highest proportion of both hospitalizations and deaths: 28.94% (n = 46329) of total hospital admissions and 29.43% (n = 28864) of all deaths. Men were more frequently hospitalized than women and had the highest proportions of deaths in all regions. Mortality coefficient rates increased over the years, and simple linear regression analysis indicated a statistically significant upward trend in this mortality (R² = 0.744). CONCLUSION: Our study provides a landscape of the epidemiological profile of public hospital admissions due to ALD in Brazil. We detected an increase in the total number of admissions and deaths due to ALD over 10 years.

Predictive factors associated with hepatitis C antiviral therapy response.

Hepatitis C virus (HCV) infection may lead to significant liver injury, and viral, environmental, host, immunologic and genetic factors may contribute to the differences in the disease expression and treatment response. In the early 2000s, dual therapy using a combination of pegylated interferon plus ribavirin (PR) became the standard of care for HCV treatment. In this PR era, predictive factors of therapy response related to virus and host have been identified. In 2010/2011, therapeutic regimens for HCV genotype 1 patients were modified, and the addition of NS3/4a protease inhibitors (boceprevir or telaprevir) to dual therapy increased the effectiveness and chances of sustained virologic response (SVR). Nevertheless, the first-generation triple therapy is associated with many adverse events, some of which are serious and associated with death, particularly in cirrhotic patients. This led to the need to identify viral and host predictive factors that might influence the SVR rate to triple therapy and avoid unnecessary exposure to these drugs. Over the past four years, hepatitis C treatment has been rapidly changing with the development of new therapies and other developments. Currently, with the more recent generations of pangenotipic antiviral therapies, there have been higher sustained virologic rates, and prognostic factors may not have the same importance and strength as before. Nonetheless, some variables may still be consistent with the low rates of non-response with regimens that include sofosbuvir, daclatasvir and ledipasvir. In this manuscript, we review the predictive factors of therapy response across the different treatment regimens over the last decade including the new antiviral drugs.

Genetic ancestry analysis in non-alcoholic fatty liver disease patients from Brazil and Portugal.

AIM: To study the association between genetic ancestry, non-alcoholic fatty liver disease (NAFLD) metabolic characteristics in two cohorts of patients, from Brazil and Portugal. METHODS: We included 131 subjects from Brazil [(n = 45 with simple steatosis (S. Steatosis) and n = 86 with nonalcoholic steatohepatitis (NASH)] and 90 patients from Portugal (n = 66, S. Steatosis; n = 24, NASH). All patients had biopsy-proven NAFLD. In histologic evaluation NAFLD activity score was used to assess histology and more than 5 points defined NASH in this study. Patients were divided into two groups according to histology diagnosis: simple steatosis or non-alcoholic statohepatitis. Genetic ancestry was assessed using real-time polymerase chain reaction. Seven ancestry informative markers (AT3-I/D, LPL, Sb19.3, APO, FY-Null, PV92, and CKMM) with the greatest ethnic-geographical differential frequencies (≥ 48%) were used to define genetic ancestry. Data were analyzed using R PROJECTS software. Ancestry allele frequencies between groups were analyzed by GENEPOP online and the estimation of genetic ancestry contribution was evaluated by ADMIX-95 software. The 5% alpha-error was considered as significant (P < 0.05). RESULTS: In the Brazilian sample, NASH was significantly more frequent among the elderly patients with diabetes (NASH 56 ± 1.1 years old vs S. Steatosis 51 ± 1.5 years old, P = 3.7 x 10(-9)), dyslipidemia (NASH 63% vs S. Steatosis 37%, P = 0.009), higher fasting glucose levels (NASH 124 ± 5.2 vs S. Steatosis 106 ± 5.3, P = 0.001) and Homeostatic Model of Assessment index > 2.5 [NASH 5.3 (70.8%) vs S. Steatosis 4.6 (29.2%) P = 0.04]. In the Portuguese study population, dyslipidemia was present in all patients with NASH (P = 0.03) and hypertension was present in a larger percentage of subjects in the S. Steatosis group (P = 0.003, respectively). The genetic ancestry contribution among Brazilian and Portuguese individuals with NASH was similar to those with S. Steatosis from each cohort (Brazilian cohort: P = 0.75; Portuguese cohort: P = 0.97). Nonetheless, the genetic ancestry contribution of the Brazilian and Portuguese population were different, and a greater European and Amerindian ancestry contribution was detected in the Portuguese population while a higher African genetic ancestry contribution was observed in Brazilian population of both NASH and S. Steatosis groups. CONCLUSION: There was no difference between the genetic ancestry contribution among Brazilian and Portuguese individuals with NASH and S. Steatosis from each cohort.

Myxovirus resistance, osteopontin and suppressor of cytokine signaling 3 polymorphisms predict hepatitis C virus therapy response in an admixed patient population: comparison with IL28B.

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.

Myxovirus resistance, osteopontin and suppressor of cytokine signaling 3 polymorphisms predict hepatitis C virus therapy response in an admixed patient population: comparison with IL28B

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 ...

Natural killer cell receptor and HLA-C gene polymorphisms among patients with hepatitis C: a comparison between sustained virological responders and non-responders.

BACKGROUND/AIMS: Killer cell immunoglobulin-like receptors (KIR) are involved in the activation/inhibition of NK cells through an interaction with HLA class I molecules on target cells. Our study aimed to evaluate the association between KIR gene polymorphisms and the response of patients with CHC to antiviral therapy. METHODS: We compared the frequency of KIR genes, as well as that of compound KIR/HLA-C genotypes, between groups of patients with CHC who presented a sustained virological response (n=66) and who were non-responders to a combination of pegylated or standard interferon and ribavirin (n=101). KIR and HLA-C genotyping were performed using commercial kits. RESULTS: We detected a greater frequency of the KIR2DL5 gene among non-responders to antiviral therapy compared with sustained virological responders (68.3 vs. 40.9%) (P<0.001). We used multiple logistic regression analysis to determine the association between therapy response and the presence of KIR2DL5, after a control for potentially confounding variables (genotype, alcohol, fibrosis, gender, age, ethnic background and route of HCV infection). The results confirmed the strong association between the presence of KIR2DL5 and the non-response to antiviral treatment (P=0.001). CONCLUSIONS: Host genetic factors may be associated with a non-response to antiviral therapy. KIR2DL5 is a candidate gene involved in immunomodulation associated with non-response to antiviral therapy.

Hepatite crônica B / Chronic hepatitis B

A infecção pelo vírus da hepatite B (VHB) é um importante problema de saúde pública, associado a significante morbidade e mortalidade por doença crônica do fígado. Em pacientes com infecção crônica pelo VHB as lesões hepáticas são imunomediadas, através de citocinas, expressando a tentativa do sistema imune de destruir o agente viral. O ccDNA, entretanto, persiste na célula infectada, caracterizando não haver a cura da infecção viral mesmo quando há evidência sorológica de "clearence viral" e a viremia está indetectável.