ABSTRACT Background: Recent studies show an increase in nonalcoholic fatty liver disease (NAFLD) in populations with higher consumption of red meat, processed and cooked at high temperatures. On the other hand, the single nucleotide polymorphism rs738409 in the Patatin-like phospholipase domain containing 3 (PNPLA3) gene has been implicated in susceptibility to NAFLD and liver fibrosis. However, the synergistic effect between red meat consumption and the PNPLA3 gene polymorphism in NAFLD has not yet been evaluated. Objective: To evaluate the association between the presence of the polymorphism in the PNPLA3 gene and the consumption of macronutrients, including meat consumption and its cooking method among NAFLD patients. Methods: This was a cross-sectional study with 91 patients diagnosed with NAFLD by liver biopsy with genotyping for the polymorphism in the PNPLA3 gene were included. The consumption of calories and macronutrients was verified using the semi-quantitative food frequency questionnaire and the specific questionnaire on meat consumption. PNPLA3 gene polymorphism was analyzed by real-time polymerase chain reaction (RT-PCR) and anthropometric evaluation was realized. Results: The mean BMI was 32.38±4.58 kg/m² and the waist circumference was 107±10 cm. On liver biopsy, 42% of patients had significant fibrosis (F≥2). The odds ratio of F≥2 was 2.12 for the GG group and 1.54 for the CG group, compared to the CC group. The mean caloric intake was 1170±463.20 kcal/d. The odds ratio in the CC group concerning high red meat consumption in comparison to low consumption was 1.33. For white meat, the odds ratio was 0.8 when comparing high and low intake, also in the CC group. Conclusion: High red meat intake and PNPLA3 gene polymorphism seem to synergistically affect NAFLD and liver fibrosis, requiring confirmation in a larger number of patients and in different populations.

RESUMO Contexto: Estudos recentes mostram um aumento da doença hepática gordurosa não alcoólica (DHGNA) em populações com maior consumo de carne vermelha, processada e cozida em altas temperaturas. Por outro lado, o polimorfismo rs738409 no gene Patatin-like fosfolipase contendo 3 (PNPLA3) tem sido implicado na suscetibilidade à DHGNA e fibrose hepática. No entanto, o efeito sinérgico entre o consumo de carne vermelha e o polimorfismo no gene PNPLA3 na DHGNA ainda não foi avaliado. Objetivo: Avaliar a associação entre a presença do polimorfismo no gene PNPLA3 e o consumo de macronutrientes, incluindo o consumo de carne e seu modo de cozimento em pacientes com DHGNA. Métodos: Realizamos um estudo transversal com 91 pacientes diagnosticados com DHGNA por biópsia hepática e genotipados para o polimorfismo no gene PNPLA3. O consumo de calorias e macronutrientes foi verificado por meio do questionário de frequência alimentar semi-quantitativo (QFA) e do questionário específico sobre consumo de carnes. O polimorfismo no gene PNPLA3 foi analisado por reação em cadeia da polimerase em tempo real (RT-PCR) e a avaliação antropométrica foi realizada. Resultados: O índice de massa corporal médio foi de 32,38±4,58 kg/m² e a circunferência da cintura foi de 107±10 cm. Na biópsia hepática, 42% dos pacientes apresentavam fibrose significativa (F≥2). O odds ratio de F≥2 foi de 2,12 para o grupo GG e 1,54 para o grupo GC, comparado ao grupo CC. A ingestão calórica média foi de 1.170±463,20 kcal/d. O odds ratio para alto consumo de carne vermelha no grupo CC em comparação ao baixo consumo foi de 1,33. Para a carne branca, este valor foi de 0,8 ao comparar o alto e o baixo consumo, também no grupo CC. Conclusão: A alta ingestão de carne vermelha e o polimorfismo no gene PNPLA3 parecem afetar sinergicamente a DHGNA e a fibrose hepática, necessitando de confirmação em maior número de pacientes e em diferentes populações.

ABSTRACT COVID-19 is commonly associated with high serum levels of pro-inflammatory cytokines, and the post-infection status can disturb self-tolerance and trigger autoimmune responses. We are reporting a 45-year-old male who was admitted with fatigue, jaundice, elevated liver enzymes (with cholestatic pattern), and acute kidney injury two weeks after recovering from a mild SARS-CoV-2 infection. Serologies for viral hepatitis and anti-mitochondrial antibody were negative, while anti-nuclear and anti-smooth muscle antibodies were positive. There were no signs of chronic liver disease, and a magnetic resonance cholangiography showed no dilatation of biliary ducts. Histologic evaluation of the liver evidenced numerous foci of lobular necrosis without ductopenia or portal biliary reaction. Considering the autoantibody profile and histologic changes, the medical team started oral prednisone, but there was a suboptimal biochemical response in the outpatient follow-up. Two months later, a second liver biopsy was performed and revealed non-suppurative destructive chronic cholangitis, extensive areas of confluent necrosis with hepatocytes regenerating into pseudorosettes, and numerous plasma cells. According to the Paris Criteria, the patient was then diagnosed with an autoimmune hepatitis-primary biliary cholangitis overlap syndrome (AIH-PBC-OS). After adding azathioprine and ursodeoxycholic acid to the treatment, there was a satisfactory response. This is the second worldwide report of an AIH-PBC-OS triggered by COVID-19, but the first case with a negative anti-mitochondrial antibody. In this setting, histologic evaluation of the liver by an experienced pathologist is a hallmark of achieving the diagnosis and correctly treat the patient.

RESUMO Contexto: A Síndrome Hepatorrenal (SHR) é a forma mais grave de lesão renal aguda em pacientes com cirrose avançada, estando diretamente associada a alta taxa de mortalidade. Normalmente é diagnosticada seguindo critérios definidos pela International Ascites Club (IAC). Atualmente, as terapias farmacológicas mais indicadas no tratamento da SHR são a combinação de vasoconstritores esplâncnicos (terlipressina ou norepinefrina) associados à albumina. Com o aumento progressivo dos gastos em saúde, torna-se relevante realizar uma análise de custo-efetividade do tratamento farmacológico em pacientes com diagnóstico de SHR. Objetivo: Realizar avaliação de custo-efetividade do uso da terlipressina associada à albumina no tratamento da SHR em pacientes com cirrose. Métodos: Avaliação econômica de custo-efetividade, com base em dados secundários de estudos publicados com resultado da eficácia da terapia com terlipressina, em comparação com norepinefrina combinada com albumina ou apenas albumina. A análise de custo-efetividade foi calculada usando a razão de custo-efetividade incremental (RCEI) e uma análise de sensibilidade foi desenvolvida variando os valores das terapias e probabilidades. O real foi a moeda utilizada na análise. Resultados: Após a seleção, elegibilidade e avaliação da qualidade das publicações, os resultados demonstraram que a administração da associação de terlipressina ou norepinefrina com albumina em pacientes diagnosticados com SHR tipo 1 possui eficácia comprovada. Os custos do tratamento com a terapia combinada de terlipressina com albumina foram de USD $1,644.06, administração de somente albumina USD $912.02 e norepinefrina mais albumina USD $2,310.78. Considerando as terapias combinadas com efetividade terapêutica comprovada, isto é, terlipressina e norepinefrina associada a albumina, o custo incremental foi de USD $666.73 e efetividade de 0,570 para o grupo da terlipressina associada a albumina e de 0,200 para o grupo da norepinefrina associada a albumina. A efetividade incremental foi de 0,370 e o valor da RCEI foi de USD $1,801.97. Assim, os fatores de incremento do custo por terapia e razão de custo-efetividade incremental definem que a terapia combinada de terlipressina mais albumina é custo efetiva quando comparada a administração de somente albumina ou norepinefrina no cenário do sistema único de saúde. Conclusão: O estudo demonstrou por meio de uma análise de custo-efetividade que a terlipressina associada à albumina quando administrada concomitantemente a pacientes com diagnóstico de SHR tipo 1 é custo-efetiva quando comparada à albumina sozinha e com norepinefrina associada à albumina administrada em um ambiente controlado.

ABSTRACT Background Hepatorenal syndrome (HRS) is the most severe form of acute kidney injury in patients with advanced cirrhosis, and it is associated with high mortality. It is usually diagnosed according to criteria defined by the International Ascites Club. Currently, the most frequently indicated pharmacological therapy for the treatment of HRS is a combination of splanchnic vasoconstrictors (terlipressin or norepinephrine) in combination with albumin. With the progressive increase in healthcare spending, it is important to conduct a cost-effectiveness analysis of pharmacological treatment in patients who are diagnosed with HRS. Objective: To perform a cost-effectiveness assessment for the use of terlipressin in combination with albumin to treat HRS in patients with cirrhosis. Methods: Economic evaluation of cost-effectiveness based on secondary data from studies showed the efficacy of terlipressin therapy compared with norepinephrine combined with albumin or albumin alone. The cost-effectiveness analysis was calculated using an incremental cost-effectiveness ratio (ICER), and a sensitivity analysis was developed by varying the values of therapies and probabilities. The Brazilian real was the currency used in the analysis, and the results were converted to US dollars. Results: After selection, eligibility, and evaluation of the quality of publications, the results demonstrated that administration of terlipressin or norepinephrine in combination with albumin in patients diagnosed with HRS type 1 was efficacious. The cost of treatment with terlipressin in combination with albumin was USD $1,644.06, administration of albumin alone was USD $912.02, and norepinephrine plus albumin was USD $2,310.78. Considering that the combination therapies demonstrated effectiveness, the incremental cost of terlipressin and norepinephrine in combination with albumin was USD $666.73, and an effectiveness of 0.570 was found for terlipressin in combination with albumin and 0.200 for norepinephrine in combination with albumin. The incremental effectiveness was 0.370, and the ICER was USD $1,801.97. Thus, the parameters of increasing cost per therapy and ICER indicated that the combined therapy of terlipressin plus albumin was cost effective compared to albumin alone or norepinephrine plus albumin in a public single-payer healthcare system. Conclusion: A cost-effectiveness analysis showed that terlipressin in combination with albumin when administered concomitantly to patients who were diagnosed with type 1 HRS is cost-effective compared to norepinephrine in combination with albumin administered in a controlled environment.

ABSTRACT Despite recent advances in therapy for chronic hepatitis C (CHC), the disease caused by genotype 3 virus (GEN3) is still considered a treatment challenge in certain patient subgroups. The aim of this retrospective study was to evaluate the effectiveness and safety of the peginterferon (Peg-IFN) and ribavirin (RBV) combination treatment for GEN3/CHC patients, and to evaluate sustained virological response (SVR) indicators and early treatment interruption due to serious adverse events (SAE). This was a retrospective observational study of GEN3/CHC patients, co-infected or not by HIV and treated with Peg-IFN/RBV in nine Brazilian healthcare centers. The study sample included 184 GEN3/CHC patients; 70 (38%) were co-infected with HIV. The overall SVR rate was 57.1% (95% CI 50-64). Among co-infected and mono-infected patients, the SVR rate was 51.4% (36/70) and 60.5% (69/114), respectively (p=0.241). Thirty-four (18.5%) patients experienced SAE and interrupted treatment. SVR was negatively associated with the use of Peg-IFN alpha 2b (PR 0.75; 95% CI 0.58-0.99; p=0.045) and to early treatment interruption due to SAE (PR 0.36; 95% CI 0.20-0.68; p=0.001). Early treatment interruption due to SAE was associated with age (PR 1.06; 95% CI 1.02-1.10; p<0.001) and occurrence of liver cirrhosis (PR 2.06; 95% CI 1.11-3.83; p=0.022). In conclusion, Peg-IFN/RBV might represent an adequate treatment option, mainly in young patients without advanced liver disease or when the use of direct-action drugs is limited to specific patient groups.

CONTEXTO: Os hormônios tireoidianos podem interferir na regulação do metabolismo de lipídios e carboidratos e também na gravidade da doença hepática gordurosa não-alcoólica (DHGNA), porém os resultados ainda são debatidos. OBJETIVOS: Avaliar retrospectivamente correlações clínicas e metabólicas entre hipotireoidismo e DHGNA. MÉTODOS: Em 103 pacientes com DHGNA confirmada por biopsia e também hipotireoidismo recebendo tratamento, procedeu-se à investigação clínica, bioquímica e histológica. RESULTADOS: A esteatose foi observada em 32,0% e a esteatohepatite não-alcoólica em 68,0% da população. O sexo feminino foi mais frequente nas duas circunstâncias, com idade média de 50,0 ± 1,5 e 56,0 ± 1,1 anos, respectivamente. O hipotireoidismo não foi raro (15,5%), sendo que na análise multivariada insulina (r = 0,213, P = 0,03), índice de homeostase glicídica HOMA (r = 0,221, P = 0,02), aspartato aminotransferase (r = 0,234, P = 0,01) e triglicerídeos acima de 150 mg/dL (r = 0,233, P = 0,01) foram correlacionados positivamente com hipotireoidismo. A associação entre hipotireoidismo e esteatohepatite não pôde ser estabelecida neste estudo. CONCLUSÃO: O hipotireoidismo vinculou-se à piora de alguns marcadores do metabolismo glicolipídico, porém não a lesões histológicas mais avançadas. A falta de correlação com a biopsia do fígado requer maiores estudos.

CONTEXT: Thyroid hormones may interfere with regulation of lipid and carbohydrate metabolism as well as with severity of nonalcoholic fatty liver disease (NAFLD), however results are still debated. OBJECTIVES: Retrospective evaluation of clinical and metabolic correlations between hypothyroidism and NAFLD was the target. METHODS: Clinical, biochemical and histological investigation of 103 NAFLD patients exhibiting drug-treated hypothyroidism was conducted. RESULTS: Steatosis was present in 32.0% of the population and nonalcoholic steatohepatitis in 68.0%. Females were the majority in both groups, with age of 50.0 ± 1.5 and 56.0 ± 1.1 years, respectively. Hypothyroidism was not rare (15.5%), and multivariate analysis confirmed positive correlation with this disease for insulin (r = 0.213, P = 0.03), glucose homeostasis index "HOMA" (r = 0.221, P = 0.02), aspartate aminotransferase (r = 0.234, P = 0.01) and triglycerides above 150 mg/dL (r = 0.233, P = 0.01). No association between hypothyroidism and steatohepatitis could be established. CONCLUSION: A link could be identified between hypothyroidism and markers of glucose and lipid homeostasis, but not with severity of NAFLD. The lack of correlation with liver biopsy requires further studies.

Na maioria dos mamíferos a atividade da enzima lactase diminui na parede intestinal após o desmame, caracterizando a hipolactasia primária que provoca sintomas de intolerância à lactose. A intensidade dos sintomas de distensão, flatulência, dor abdominal e diarreia variam, dependendo da quantidade de lactose ingerida, e aumentam com o passar da idade. A hipolactasia é determinada geneticamente, porém uma mutação ocorreu para que fizesse parte da humanidade tolerar o leite na idade adulta. O diagnóstico é feito por teste de tolerância, empregando a lactose como desafio. Com a descoberta dos finlandeses do polimorfismo associado com a persistência da lactase, principalmente no norte da Europa, o exame genético passou a ser outra ferramenta diagnóstica mais confortável para o intolerante. No Brasil, 43% dos brancos e dos mulatos têm alelo de persistência da lactase, sendo a hipolactasia mais frequente entre os negros e japoneses. Entretanto, na prática clínica indivíduos com hipolactasia podem ser orientados a consumir alguns derivados do leite e alimentos contendo lactose sem apresentar sintomas de intolerância, enquanto que outros terão que fazer restrição de lactose na dieta.

In most mammals, lactase activity declines on the intestinal wall after weaning, characterizing primary hypolactasia that provokes symptoms of lactose intolerance. The intensity of symptoms of distention, flatulence, abdominal pain and diarrhea varies, according to the amount of ingested lactose, and increases with age. Hypolactasia is genetically determined; nonetheless, a mutation occurred that had made a part of mankind tolerate milk in adulthood. Diagnosis is made by a tolerance test, using the lactose challenge. With the discovery made by the Finns of polymorphism associated with lactase persistence, mainly, in Northern Europe, the genetic test was incorporated as a more comfortable diagnostic tool for the intolerant. In Brazil, 43% of Caucasian and Mulatto groups have lactase persistence allele, with hipolactasia more frequently found among Blacks and Japanese. However, in clinical practice people with hypolactasia may be advised to consume certain dairy products and food containing lactose without developing intolerance symptoms, whereas others will need a lactose restriction diet.