Fabiana Roberto Lima

S-nitroso-N-acetylcysteine attenuates liver fibrosis in experimental nonalcoholic steatohepatitis

S-Nitroso-N-acetylcysteine (SNAC) is a water soluble primary S-nitrosothiol capable of transferring and releasing nitric oxide and inducing several biochemical activities, including modulation of hepatic stellate cell activation. In this study, we evaluated the antifibrotic activity of SNAC in an animal model of nonalcoholic steatohepatitis (NASH) induced in Sprague-Dawley rats fed with a choline-deficient, high trans fat diet and exposed to diethylnitrosamine for 8 weeks. The rats were divided into three groups: SNAC, which received oral SNAC solution daily; NASH, which received the vehicle; and control, which received standard diet and vehicle. Genes related to fibrosis (matrix metalloproteinases [MMP]-13, -9, and -2), transforming growth factor β-1 [TGFβ-1], collagen-1α, and tissue inhibitors of metalloproteinase [TIMP-1 and -2] and oxidative stress (heat-shock proteins [HSP]-60 and -90) were evaluated. SNAC led to a 34.4% reduction in the collagen occupied area associated with upregulation of MMP-13 and -9 and downregulation of HSP-60, TIMP-2, TGFβ-1, and collagen-1α. These results indicate that oral SNAC administration may represent a potential antifibrotic treatment for NASH.

Graft-versus-host disease after liver transplantation

Graft-versus-host disease (GVHD) following liver trans-plantation (LT) is an uncommon complication but has highmortality and represents a major diagnostic challenge.GVHD occurs when immunocompetent donor lymphocytesoriginating from the transplanted liver undergo activationand clonal expansion, allowing them to mount a destructivecellular immune response against recipient tissues.Humoral GVHD is usually seen after an ABO-mismatchedliver transplant, but cellular GVHD is directed against themajor histocompatibility complex and often results in severemultisystem disease with high mortality.

Large-for-size liver transplantation: a flowmetry study in pigs.

BACKGROUND Ischemia-reperfusion injury is partly responsible for morbidity in pediatric liver transplantation. Large-for-size (LFS) liver transplantation has not been fully studied in the pediatric population, and the effects of reperfusion injury may be underestimated. MATERIALS AND METHODS Thirteen Landrace-Large white pigs weighing 23 kg (range, 17-38 kg) underwent orthotopic liver transplantation. They were divided into two groups according to the size of the donor body: LFS and control (CTRL). After transplantation, the abdominal cavity of the recipient was kept open and portal venous flow (PVF) was measured after 1 h. The ratio of recipient PVF (PVFr) to donor PVF was used to establish correlations with ischemia and reperfusion parameters. Liver biopsies were taken 1 h after transplantation to assess ischemia and reperfusion and to quantify the gene expression of endothelial nitric oxide synthase, interleukin 6, BAX, and BCL. RESULTS Recipient weight, total ischemia time, and warm ischemia time were similar between groups. Among hemodynamic and metabolic analyses, pH, central arteriovenous PCO2 difference, and AST were statistically worse in the LFS group than in the CTRL group. The same was found with endothelial nitric oxide synthase (0.41 ± 0.18 versus 1.56 ± 0.78; P = 0.02) and interleukin 6 (4.66 ± 4.61 versus 16.21 ± 8.25; P = 0.02). In the LFS group, a significant decay in the PVFr was observed in comparison with the CTRL group (0.93 ± 0.08 and 0.52 ± 0.11, respectively; P < 0.001). CONCLUSIONS The implantation of a graft was responsible for poor hemodynamic status of the recipient 1 h after transplantation. Furthermore, the LFS group demonstrated markers of ischemia and reperfusion that were worse when compared with the CTRL group and exhibited a more significant decrease in PVF from donor to recipient.

Congenital intrahepatic arterioportal fistula presenting as severe undernutrition and chronic watery diarrhea in a 2-year-old girl

Intrahepatic arterioportal fistula (IAPF) is a rare cause of portal hypertension in young children. We report the case of a 2-year-old girl with severe undernutrition, chronic watery diarrhea, and gastrointestinal bleeding because of a congenital intrahepatic arterioportal fistula. Radiographic embolization and surgical ligation of the left hepatic artery were attempted, with no resolution of the symptoms. So, a left lobectomy was performed, with excellent results and prompt disappearance of the diarrhea. Hepatectomy should be considered as a definitive and reliable therapy for congenital IAPF.

Diffuse large B-cell lymphoma presenting in the leukemic phase.

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma comprising a heterogeneous group of disorders with variable histological and clinical behavior. Although other lymphomas may present in the leukemic phase more frequently, this appearance is unusually observed among DLBCL cases. Diagnosing lymphoma is not always easy, and the patients clinical status quite often may hamper invasive procedures for diagnosis pushing the clinician to look for alternatives to reach the nearest possible accurate diagnosis. The authors report the case of a middle-aged man who presented the history of malaise, weight loss, and low-grade fever. The peripheral blood count showed leukocytosis with the presence of blasts and thrombocytopenia. The cytological morphology and immunophenotyping of the peripheral blood and bone marrow aspirate, as well as the bone marrow biopsy accompanied by a thorough immunohistochemical analysis, rendered the diagnosis of DLBCL in the leukemic phase. The patient was prescribed R-CHOP with a favorable outcome. Intra-abdominal lymph node biopsy was avoided because of the patients critical medical condition. The authors highlight this rare form of presentation of DLBCL as well as the combination of peripheral blood, bone marrow aspirate, and bone marrow biopsy for reaching the diagnosis in cases were a lymph node sample is unavailable for the diagnostic work-up.

Imatinib-induced fulminant liver failure in chronic myeloid leukemia: role of liver transplant and second-generation tyrosine kinase inhibitors: a case report

BackgroundThere is a worldwide problem of acute liver failure and mortality associated with remaining on the waiting for a liver transplant. In this study, we highlight results published in recent years by leading transplant centers in evaluating imatinib-induced acute liver failure in chronic myeloid leukemia and follow-up in liver transplantation.Case presentationA 36-year-old brown-skinned woman (mixed Brazilian race) diagnosed 1 year earlier with chronic myeloid leukemia was started after delivery of a baby and continued for 6 months with imatinib mesylate (selective inhibitor of Bcr-Abl tyrosine kinase), which induced liver failure. We conducted a literature review using the PubMed database for articles published through September 2017, and we demonstrate a role of liver transplant in this situation for imatinib-induced liver failure. We report previously published results and a successful liver transplant after acute liver failure due to imatinib-induced in chronic myeloid leukemia treatment.ConclusionsWe report a case of a successful liver transplant after acute liver failure resulting from imatinib-induced chronic myeloid leukemia treatment. The literature reveals the importance of prompt acute liver failure diagnosis and treatment with liver transplant in selected cases.

Biochemical profile in an infant with neonatal hemochromatosis shows evidence of impairment of mitochondrial long-chain fatty acid oxidation

Dear Editor, Neonatal hemochromatosis (NH) is a severe, progressive, lifethreatening disorder that leads to hepatic failure during the first weeks of life and is associated with massive iron deposits. Although its exact etiology remains to be better clarified, it has been hypothesized that maternal alloimmunity and mitochondrial dysfunction might play important roles in this disease. This condition differs from the main disorders that present with liver iron deposits, such as HFE-related hemochromatosis (autosomal recessive disorder caused by biallelic mutations in HFE gene in which iron deposits lead to adult-onset liver, heart, testicular and pancreatic involvement; OMIM#235200), juvenile hereditary hemochromatosis (autosomal recessive condition associated with biallelic mutations in HJV and HAMP genes and clinically similar to HFE-related hemochromatosis, but earlier onset and fast progression; OMIM#602390 and 613313), TFR2-related hereditary hemochromatosis (autosomal recessive condition associated with biallelic mutations in TFR2 gene and clinically similar to HFE-related hemochromatosis, but earlier onset and slow progression; OMIM#604250) and ferroportin (SLC40A1)-related iron overload (autosomal dominant condition associated with monoallelic mutations in SLC40A1 gene; OMIM#606069). Our male infant was born at term (39 weeks of gestation, birth weight: 2,615 g), after an uneventful pregnancy. His parents were healthy, caucasian, non-consanguineous and have not reported any familial history of liver, genetic, metabolic or syndromic conditions. His general conditions deteriorated after delivery and he required intensive care unit admission for anemia, bleeding, hypoglycemia, hypoactivity and unconjugated hyperbilirubinemia. During the following days, he developed recurrent hypoglycemia, cholestatic jaundice, hepatomegaly and hepatic dysfunction. He was then transferred to our tertiary-care unit at the 33rd day of life. Laboratory tests demonstrated anemia (hemoglobin 9.1 g/dL; hematocrit 26.3%), thrombocytopenia (platelet count: 49,000/μL), abnormal synthetic liver function (International Normalised Ratio Biochemical profile in an infant with neonatal hemochromatosis shows evidence of impairment of mitochondrial long-chain fatty acid oxidation

Successful Liver Transplantation Case Report from a Deceased Donor with Sickle Cell Anemia

There is a worldwide problem of waiting time and mortality rate associated with remaining on the waiting list for a liver transplant. However, some situations have been encouraging in terms of determining appropriate recipients and expanding the donor criteria. We herein report a case of useful liver donor with sickle cell anemia for liver transplantation. Here we described a case of liver transplantation from a donor with sickle cell anemia to a recipient with hepatocellular carcinoma who was deemed to be at risk of tumor growth and at risk of being dropped from the waiting list. The literature reveals the importance of using safe donors, and we describe the benefits of using a safe, deceased liver donor with sickle cell anemia who was an adequate option for liver transplantation.

Histological remission of autoimmune hepatitis after the addition of allopurinol and azathioprine dose reduction

The standard therapy for some autoimmune diseases consists of a combination of corticosteroids and thiopurines. In non-responders to thiopurine drugs, the measurement of the metabolites of azathioprine, 6-thioguanine, and 6-methylmercaptopurine, can be a useful tool. The measurement has been used during the treatment of inflammatory bowel diseases and, less commonly, in autoimmune hepatitis. Many patients preferentially metabolize thiopurines to 6-methylmercaptopurine (6-MMP), which is potentially hepatotoxic, instead of 6-thioguanine, the active immunosuppressive metabolite. The addition of allopurinol shifts the metabolism of thiopurine towards 6-thioguanine, improving the immunosuppressive effect. We present the case of a 51-year-old female with autoimmune hepatitis who had a biochemical response after azathioprine and prednisone treatment without histological remission, and who preferentially shunted to 6-MMP. After the addition of allopurinol, the patient’s 6-thioguanine levels increased, and she reached histological remission with a reduction of 67% of the original dose of azathioprine. The patient did not develop clinical manifestations as a consequence of her increased immunosuppressive state. We also review the relevant literature related to this issue. In conclusion, the addition of allopurinol to thiopurine seems to be an option for those patients who do not reach histological remission and who have a skewed thiopurine metabolite profile.

Abdominal and pelvic actinomycosis due to longstanding intrauterine device: a slow and devastating infection

Actinomycosis is a chronic or subacute bacterial infection characterized by large abscess formation, caused mainly by the gram-positive non-acid-fast, anaerobic, or microaerophilic/capnophilic, obligate parasites bacteria from the Actinomyces genus. Although pelvic inflammatory disease is an entity associated with the longstanding use of intrauterine devices (IUDs), actinomycosis is not one of the most frequent infections associated with IUDs. We present the case of a 43-year-old female patient who was referred to the emergency facility because of a 20-day history of abdominal pain with signs of peritoneal irritation. Imaging exams revealed collections confined to the pelvis, plus the presence of an IUD and evidence of sepsis, which was consistent with diffuse peritonitis. An exploratory laparotomy was undertaken, and a ruptured left tubal abscess was found along with peritonitis, and a huge amount of purulent secretion in the pelvis and abdominal cavity. Extensive lavage of the cavities with saline, a left salpingo-oophorectomy, and drainage of the cavities were performed. The histopathological examination of the surgical specimen revealed an acute salpingitis with abscesses containing sulfur granules. Therefore, the diagnosis of abdominal and pelvic actinomycosis was made. The postoperative outcome was troublesome and complicated with a colocutaneous fistula, which drained through the surgical wound. A second surgical approach was needed, requiring another extensive lavage and drainage of the recto-uterine pouch, plus the performance of a colostomy. Broad-spectrum antibiotics added to ampicillin were the first antimicrobial regimen followed by 4 weeks of amoxicillin during the outpatient follow-up. The patient satisfactorily recovered and is already scheduled for the intestinal transit reconstitution.