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Circulating tumor cells (CTCs) are noninvasive biomarkers that can indicate the therapeutic response and prognosis. The study aimed to investigate the cellular characteristics of CTCs focusing on monitoring during atezolizumab and bevacizumab (Atezo-Bev) therapy in patients with hepatocellular carcinoma (HCC). Peripheral blood samples were collected from 10 healthy controls and 40 patients with HCC. CTCs enriched using RosetteSep™ Human CD45 depletion cocktail were analyzed by multiparametric flow cytometry. CTC isolation was based on PanCK(+)CD45(-) cells, and CTCs exhibiting markers CD90, CD133, EpCAM, or vimentin. The total number of CTCs and the number of CTCs expressing CD90, CD133, EpCAM, and vimentin were correlated with the BCLC stage of HCC. The change in total CTC count accurately reflected the initial response to Atezo-Bev therapy. The numbers and mean fluorescence intensity of the CTC subsets expressing CD90 and EpCAM molecules decreased in patients with partial response/stable disease, and increased in patients with progressive disease and were markedly correlated with overall survival. CD90(+) and EpCAM(+) CTCs may be candidate biomarkers for the early prediction of the treatment response and the overall survival of patients with HCC receiving Atezo-Bev therapy.
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Immune checkpoint inhibitors have promising outcomes in patients with hepatocellular carcinoma (HCC); however, there is no reliable biomarker for predicting disease progression. Circulating tumor cells (CTCs) derived from peripheral blood have attracted attention in monitoring therapeutic efficacy. In this study, CTCs were serially collected from HCC patients undergoing atezolizumab plus bevacizumab (Atezo+Bev), and changes in molecular expression and CTC numbers were analyzed to identify effective biomarkers. Changes in CTC numbers during Atezo+Bev reflected the tumor volume. Targeted RNA sequencing with next-generation sequencing (NGS) revealed that patients with elevated transforming growth factor (TGF)-ß signaling molecules had a poorer response, whereas those with elevated apoptosis signaling molecules had a favorable response. In addition, compared with changes in CTC counts, changes in TGF-ß signaling molecule expression in CTCs accurately and promptly predicted treatment response. Overall, NGS analysis of CTC-derived RNA showed that changes in TGF-ß signaling molecules predict treatment response earlier than changes in CTC counts. These findings suggest that changes in the expression of TGF-ß molecules in CTCs could serve as novel biomarkers for the early prediction of therapeutic response in patients with unresectable HCC undergoing Atezo+Bev.
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There remains no reliable biomarker of therapeutic efficacy in hepatocellular carcinoma (HCC) for the PD-L1 inhibitor atezolizumab and bevacizumab (Atezo/Bev). Circulating tumor cells (CTCs) enable the serial collection of living tumor cells. Pre-treatment and serial CTC gene expression changes and tumor histology were evaluated to identify predictors of response to Atezo/Bev. Peripheral blood from 22 patients with HCC treated with Atezo/Bev and 24 patients treated with lenvatinib was serially collected. The RNA expression in CTCs was analyzed using qRT-PCR. Higher PD-L1 expression in pre-treatment CTCs was associated with response and improved prognosis with Atezo/Bev treatment, but not with lenvatinib. There was no correlation between PD-L1 expression in CTCs and that in liver tumor biopsy specimens scored using imaging software. Furthermore, PD-L1 RNA expression in CTCs was dynamically altered by Atezo/Bev, decreasing during effective response and increasing upon progression. CTC-derived RNA collected during Atezo/Bev indicates that patients with higher PD-L1 expression in CTCs at baseline were 3.9 times more responsive to treatment. Therefore, PD-L1 RNA levels in CTCs are an accurate response predictor and may be a monitorable biomarker that changes dynamically to reflect the response during Atezo/Bev treatment.
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Arachidonic acid 5-lipoxygenase (5-LOX), an enzyme that synthesizes leukotrienes (LTs), is involved in cancer development including proliferation, invasion, metastasis and drug resistance. However, the functional role of 5-LOX in hepatocellular carcinoma (HCC) remains to be elucidated. In this study, we analyzed the contribution of 5-LOX in HCC progression and investigated the potential of targeted therapy. Analysis of 86 resected HCC specimens and the clinical data of 362 cases of liver cancer from The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset, showed that 5-LOX expression was associated with postoperative survival. The cancer proliferative and stem cell potential were correlated with the levels of 5-LOX in CD163(+) tumor-associated macrophages (TAMs). In an HCC mouse model, CD163(+) TAMs expressed 5-LOX and produced LTB4 and LTC/D/E4; the 5-LOX inhibitor, zileuton, suppressed HCC progression. LTB4 and LTC/D/E4 promoted cancer proliferation and stem cell capacity via phosphorylation of extracellular signal-regulated kinase 1/2 and stem cell-associated genes. Taken together, we identified a novel mechanism of HCC progression in which CD163(+) TAMs express 5-LOX and produce LTB4 and LTC/D/E4, thereby enhancing the proliferative and stem cell potential of HCC cells. Furthermore, inhibition of 5-LOX activity regulates HCC progression, suggesting it has potential as a new therapeutic target.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Camundongos , Animais , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Araquidonato 5-Lipoxigenase/metabolismo , Macrófagos Associados a Tumor/metabolismo , Leucotrieno B4/metabolismoRESUMO
Cancer immunotherapy using immune checkpoint inhibitors can cause immune reactions at various sites as a side effect called immune-related adverse events (irAEs). The gastrointestinal tract is susceptible to irAEs, however, the degree and presentation vary considerably from case to case. A 76-year-old woman was diagnosed with anal mucosal melanoma. She underwent radical surgery and received postoperative adjuvant therapy. However, because new metastases were also found in bilateral inguinal lymph nodes, immunotherapy with nivolumab was performed. Approximately 10 months after the initiation of nivolumab administration, she presented with epigastric discomfort and nausea, and her laboratory data showed severe eosinophilia (1938/mm3). Computed tomography demonstrated a diffuse thickening of the gastric wall. Esophagogastroduodenoscopy and endoscopic ultrasonography showed mucosal thickening due to edema, and histologic examination revealed severe invasion of eosinophils in the lamina propria. Subsequently, she was diagnosed with eosinophilic gastritis due to irAEs induced by nivolumab. Oral administration of prednisolone rapidly normalized her endoscopic and histologic findings, dramatically reducing her symptoms. This is a very rare and important case report of nivolumab-induced severe eosinophilic gastritis. Although gastric lesions as IrAEs is rare, it is necessary to differentiate eosinophilic gastritis if unexplained nausea occurred during the administration of immune checkpoint inhibitors.
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Antineoplásicos Imunológicos , Eosinofilia , Melanoma , Segunda Neoplasia Primária , Neoplasias Cutâneas , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Enterite , Eosinofilia/induzido quimicamente , Feminino , Gastrite , Humanos , Inibidores de Checkpoint Imunológico , Melanoma/tratamento farmacológico , Melanoma/patologia , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Nivolumabe/efeitos adversos , Prednisolona/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
AIM: Curing hepatitis B virus (HBV) infection requires elimination of covalently closed circular DNA (cccDNA). Interferon (IFN)-γ has noncytolytic antiviral potential; however, elimination of cccDNA could not be achieved. To enhance the regulatory effect, we comprehensively analyzed the host factors associated with cccDNA amplification and IFN-γ and IFN-α effects using an in vitro HBV infection system showing various transcription levels. METHODS: Primary human hepatocytes were infected with HBV using genomic plasmids carrying the basic core promoter mutation A1762T/G1764A and/or the precore mutation G1896A and treated with IFN-γ and IFN-α. Comprehensive and functional studies involving microarray and small interfering RNA analysis revealed the host factors related to cccDNA regulation. RESULTS: The HBV infection system reproduced the HBV life cycle and showed various propagation levels. Microarray analysis revealed 53 genes correlated with the cccDNA levels. Of the 53 genes, expression of IFN-induced protein 44-like (IFI44L) was significantly upregulated by IFN-γ and IFN-α. The anti-HBV effect of IFI44L is exerted regardless of IFN-γ or IFN-α by inhibiting the activation of nuclear factor-κB and signal transducer and activator of transcription 1 pathways. CONCLUSIONS: Using the in vitro HBV infection system, an IFN-inducible molecule, IFI44L, associated with cccDNA amplification, was identified. These results suggest an innovative molecular strategy for the regulation of HBV cccDNA by controlling a novel host factor, IFI44L.
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Idiopathic portal hypertension (IPH) is one of the background diseases causing nodular regenerative hyperplasia (NRH). Furthermore, IPH patients accompanied with autoimmune diseases, such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), are more likely to form NRH in the liver. A 76-year-old woman had been aware of the Raynaud's phenomenon and scleroderma for the past 30 years. In this case, she presented with abdominal fullness, and her imaging analysis revealed ascites and multiple liver nodules. On Gd-EOB-DTPA enhanced magnetic resonance imaging (EOB-MRI), donut-like uptake was observed in the nodules in the hepatobiliary phase. Liver biopsy of a nodule demonstrated that it was composed of hyperplastic hepatocytes without fibrous septa, and dilated sinusoids were observed beside the nodule. Conversely, background liver showed that peripheral portal veins appeared stenotic with dense fibrosis in the portal area. The final diagnosis was that multiple NRH of the liver developed in SSc patient accompanying IPH. This case suggests that NRH may be unexpectedly diagnosed in patients with autoimmune diseases accompanying IPH.
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Hipertensão Portal , Escleroderma Sistêmico , Idoso , Feminino , Humanos , Hiperplasia/patologia , Hipertensão Portal/complicações , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/patologia , Pancitopenia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/patologia , Esplenomegalia , Hipertensão Portal não Cirrótica IdiopáticaRESUMO
Owing to effective treatments and sanitary improvements, the incidence of latent tuberculosis infection (LTBI) has decreased. However, approximately one-quarter of the world's population is thought to have LTBI, and the reactivation of tuberculosis (TB) sometimes occurs in immunocompromised hosts. A 54-year-old man presented with a fever. The patient had past histories of alcoholic and hepatitis C virus-related cirrhosis and hepatocellular carcinoma (HCC). He was treated with drug-eluting beads transarterial chemoembolization (DEB-TACE) for HCC three times, beginning 10 months before his current visit. A computed tomography scan showed enlarged intraabdominal lymph nodes with calcification, and the interferon-gamma release assay for TB infection was positive. The patient was diagnosed with tuberculous reactivation. Anti-TB therapy was administered to the patient, after which we restarted TACE and the TB infection remains controlled. In this case, we presumed that DEB-TACE is associated with the reactivation of TB infection and that anthracycline increases the risk of reactivating TB infection. In summary, we experienced a case of TB reactivation during the clinical course of a patient with HCC who was treated with DEB-TACE. When patients with HCC are treated with TACE, their symptoms, laboratory data, and imaging results should be monitored when latent TB infections are suspected.
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Carcinoma Hepatocelular/tratamento farmacológico , Quimioembolização Terapêutica/efeitos adversos , Tuberculose Latente/virologia , Neoplasias Hepáticas/tratamento farmacológico , Tuberculose Gastrointestinal/virologia , Tuberculose dos Linfonodos/virologia , Ativação Viral , Quimioembolização Terapêutica/métodos , Meios de Contraste , Humanos , Tuberculose Latente/diagnóstico por imagem , Masculino , Microesferas , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X/métodos , Tuberculose Gastrointestinal/diagnóstico por imagem , Tuberculose dos Linfonodos/diagnóstico por imagemRESUMO
OBJECTIVES: Rheumatoid arthritis (RA) patients often take non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids as supportive drugs. In this study, we investigated the prevalence of endoscopic gastric damage and their prescribed medications under an actual clinical condition. METHODS: We collected the data of 1704 RA patients who underwent upper gastrointestinal fiberscopy. Gastric mucosal erosion and ulcer were classified using modified LANZA score. We analyzed these data with a multiple regression analysis. RESULTS: The prevalence of endoscopic gastric mucosal damage in these RA patients was 16.7% (285 cases). A multiple regression analysis indicated that prednisolone (PSL), NSAIDs and proton pump inhibitors (PPIs) were independent risk factors associated with the modified LANZA score. PSL and NSAIDs were positively correlated with the score, while the administration of PPIs was inversely correlated with the score. The modified LANZA score in RA patients treated with both PSL and NSAIDs was significantly higher than that in those treated with PSL alone (no NSAIDs use). CONCLUSIONS: Our findings suggest that PSL and NSAIDs were exacerbating factors for gastric mucosal damage, while PPIs usage was a protective factor. And, the combined usage of corticosteroids and NSAIDs may induce the development of gastric ulcers.
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Artrite Reumatoide/patologia , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/patologia , Gastroscopia , Idoso , Anti-Inflamatórios não Esteroides/farmacologia , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico por imagem , Inibidores de Ciclo-Oxigenase 2/farmacologia , Feminino , Mucosa Gástrica/efeitos dos fármacos , Humanos , Masculino , Prevalência , Fatores de Risco , Úlcera Gástrica/complicaçõesRESUMO
Background and study aims Duplication cysts of the ileum are rare and present with non-specific clinical manifestations such as abdominal pain, vomiting, melena, and intussusception. Therefore, preoperative diagnosis is difficult. Here, we report a case of duplication cyst of the small intestine that was diagnosed preoperatively using double-balloon enteroscopy. A 19-year-old man presented with severe iron deficiency anemia, abdominal pain, and exertional dyspnea. Gastroscopy and colonoscopy revealed no remarkable findings. Abdominal computed tomography revealed a cystic structure in the ileum. Therefore, we performed double-balloon enteroscopy via the anal route. The intestinal tract was bifurcated, with one segment ending in a blind sac containing normal villi and an ulceration. Tc-99âm pertechnetate scintigraphy showed no accumulation in the lesion. Accordingly, we diagnosed a duplication cyst and suspected that this was the cause of severe anemia. Following small bowel resection with cyst excision and anastomosis, the anemia and presenting symptoms resolved. This report highlights the usefulness of double-balloon enteroscopy of the small intestine for preoperative diagnosis of the obscure gastrointestinal bleeding, including duplication cysts .
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Factor XIII is one of the twelve coagulation factors and also known as a fibrin-stabilizing factor. In 2012, we encountered a male RA patient with hemorrhagic factor XIII deficiency who had been treated with tocilizumab for two years. There are few reports regarding the relationship between tocilizumab (a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R)) and factor XIII. We measured the factor XIII activity levels in the plasma of 40 RA patients (10 patients treated without biologics, 30 patients treated with biologics (15 patients treated with necrosis factor inhibitors and 15 patients treated with tocilizumab)) and 19 healthy controls. Consequently, the tocilizumab group exhibited lower levels than the other three groups according to the Steel-Dwass test (P<0.01). Furthermore, we compared the plasma factor XIII activity levels and the plasma factor XIII concentrations in the RA patients treated with biologics. Pearson's correlation test was used to assess the relationship between the factor XIII activity levels and the plasma factor XIII concentrations (r=0.449, P=0.019). According to the multiple regression analysis, the treatment with tocilizumab is an independent risk factor for plasma factor XIII reduction in RA patients. In conclusion, RA patients treated with tocilizumab, an IL-6R blocker, are at risk of developing acquired factor XIII deficiency. The mechanisms underlying the reduced factor XIII activity observed in RA patients treated with tocilizumab may result from the quantitative reduction in the plasma. These data imply that IL-6 plays an important role in maintaining the factor XIII activity level.
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Anticorpos Monoclonais Humanizados/farmacologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Fator XIII/metabolismo , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/sangue , Feminino , Humanos , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
Urea breath test (UBT) using an infrared spectral analyzer is widely used for non-invasive and rapid detection of gastric Helicobacter spp. in human, but not veterinary medicine. The main purposes of this study were to determine the reference range of the UBT in dogs and to evaluate its clinical usefulness. To address the first aim, 6 healthy laboratory beagles were subjected to UBT and upper gastrointestinal endoscopy. Gastric endoscopic biopsy samples from the antrum, corpus and fundus were examined for Helicobacter spp. by polymerase chain reaction (PCR) testing, rapid urease test (RUT), histology and cytology. Amoxicillin, metronidazole and omeprazole were given to infected dogs for 14 days, and dogs that became Helicobacter-negative were used to determine the reference range for UBT. To address the second aim, 32 canine patients underwent UBT before upper gastrointestinal endoscopy, and the sensitivity and specificity of UBT were calculated based on our newly determined reference range using PCR as the gold standard for detection of Helicobacter spp. Initially, all 6 laboratory beagles were infected in all gastric regions and became uninfected after eradication. The mean ± 2 SD UBT value after eradication was 0.6 ± 1.8, and the reference range for UBT was determined to be less than 2.5. UBT was completed successfully in 27 patients. Using our reference range, UBT displayed 89% (16/18) sensitivity and 89% (8/9) specificity, indicating that UBT was quite useful for the detection of gastric Helicobacter spp. infection in dogs.
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Testes Respiratórios/métodos , Doenças do Cão/diagnóstico , Doenças do Cão/microbiologia , Infecções por Helicobacter/veterinária , Estômago/microbiologia , Animais , Isótopos de Carbono/análise , Primers do DNA/genética , Cães , Endoscopia , Infecções por Helicobacter/diagnóstico , Reação em Cadeia da Polimerase , Valores de Referência , Sensibilidade e Especificidade , Espectrofotometria Infravermelho , Estatísticas não Paramétricas , Ureia/análiseRESUMO
OBJECTIVE: The diagnostic criteria for primary biliary cirrhosis (PBC) in Japan were revised in 2004. The prevalence and prognosis of PBC using the revised criteria have not been reported. This study investigated the prevalence and prognosis of "newly-diagnosed" symptomatic-PBC (ns-PBC), which was defined as asymptomatic PBC (a-PBC) in Japan until 2004. PATIENTS AND METHODS: The clinical features and the prognosis of 207 patients with PBC were retrospectively investigated according to clinical stage. RESULTS: The prevalence of ns-PBC was 3.4% and 9.7%, at the time of diagnosis and final evaluation, respectively. The prognosis of ns-PBC was poorer than a-PBC. A total of 7.2% of the patients with a-PBC progressed to ns-PBC during the observation period. These patients had a poorer prognosis than patients who remained asymptomatic. CONCLUSION: Approximately 10% of the PBC patients presented with signs of portal hypertension as an initial symptom. The signs of portal hypertension should therefore be carefully investigated in patients with PBC at the time of diagnosis and during the observation.
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Hipertensão Portal/diagnóstico , Hipertensão Portal/epidemiologia , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/epidemiologia , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos RetrospectivosRESUMO
PURPOSE: Among patients with asymptomatic primary biliary cirrhosis (a-PBC), a substantial portion ultimately develop symptoms suggestive of liver injury. Prognostic variables to distinguish patients likely to become symptomatic from patients who will remain asymptomatic need to be identified. We examined the impact of biochemical response to ursodeoxycholic acid in the development of symptoms in patients with a-PBC. METHODS: Subjects comprised 83 patients with a-PBC treated using ursodeoxycholic acid (UDCA). All patients were followed regularly every 1-3 months. Response to treatment with UDCA was defined as a decrease in gamma-glutamyl transpeptidase (GGT) > or = 70% of pretreatment or normal levels from 6 months after start of treatment. RESULTS: During the follow-up period (62.1 +/- 52.7 months), 12 patients (14.5%) developed liver-related symptoms. Incidence of the development of liver-related symptoms was significantly higher in UDCA non-responders than in responders (p < 0.001). Multivariate analysis showed that response to UDCA (improvement of GGT) represents an independent factor for predicting symptom development in patients with a-PBC. CONCLUSIONS: Patients with a-PBC showing lack of biochemical response to UDCA by 6 months after treatment commencement should be considered for further treatments.
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Colagogos e Coleréticos/uso terapêutico , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/tratamento farmacológico , Ácido Ursodesoxicólico/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Fígado/patologia , Cirrose Hepática Biliar/sangue , Cirrose Hepática Biliar/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Autoimmune hepatitis is a chronic liver disease, and both genetic background and environmental factors are related to its pathogenesis. Here, we report that out of five members of a family with similar human leukocyte antigen haplotypes, two developed autoimmune hepatitis, one was positive for antinuclear antibody, and the remaining two had no features of autoimmunity. The two patients with autoimmune hepatitis had a history of medication use, whereas the other family members did not. Our familial study suggests that in addition to genetic background, medication use and other environmental factors may be related to the onset of autoimmune hepatitis.
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Hepatite Autoimune/diagnóstico , Hepatite Autoimune/genética , Linhagem , Adulto , Idoso , Biópsia , Feminino , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Haplótipos , Hepatite Autoimune/patologia , Humanos , Fígado/patologia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The course of primary biliary cirrhosis (PBC) is determined by clinical symptoms and histological findings. The present study examined the prognostic importance of imaging parameters in PBC. METHODS: The volumes of the liver and spleen of patients with PBC were assessed by computed tomography (CT). The volume ratio of liver to spleen (LV/SV ratio) was evaluated and used for further analyses. RESULTS: The prognosis was significantly poorer in PBC patients with a low, rather than high, LV/SV ratio. The Cox proportional hazard regression model showed that the serum bilirubin level and the LV/SV ratio could predict the prognosis of PBC patients. In addition, the LV/SV ratio was significantly lower in patients who developed symptoms (s-PBC) than in those who remained asymptomatic (a-PBC) during the observation period. CONCLUSIONS: The LV/SV ratio is of prognostic importance in patients with PBC.
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Cirrose Hepática Biliar/diagnóstico por imagem , Fígado/diagnóstico por imagem , Baço/diagnóstico por imagem , Progressão da Doença , Feminino , Seguimentos , Humanos , Hipertensão Portal/diagnóstico por imagem , Hipertensão Portal/etiologia , Cirrose Hepática Biliar/complicações , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Esplenomegalia/diagnóstico por imagem , Esplenomegalia/etiologia , Fatores de Tempo , Tomografia Computadorizada por Raios XAssuntos
Antibacterianos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas , Testes de Função Hepática , Acetaminofen/efeitos adversos , Analgésicos/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , Cromanos/efeitos adversos , Anticoncepcionais Orais Hormonais/efeitos adversos , Fármacos Gastrointestinais/efeitos adversos , Humanos , Hepatopatias/diagnóstico , Hepatopatias/epidemiologia , Hepatopatias/terapia , Psicotrópicos/efeitos adversos , Tiazolidinedionas/efeitos adversos , Fatores de Tempo , TroglitazonaRESUMO
It is controversial whether steroid therapy should be continued to prevent the recurrence of autoimmune hepatitis (AIH) in patients who have undergone liver transplantation (LTx) due to AIH. We report a case of recurrent autoimmune hepatitis after LTx despite a persistently normal range of alanine aminotransferase (ALT). A 50-year-old woman was admitted to our hospital because of jaundice and severe liver dysfunction, where she was diagnosed with liver failure due to AIH. Steroid therapy was not effective enough and the patient received living-donor LTx in 1999. Following the operation, the level of ALT was maintained within a normal range and anti-nuclear antibody (ANA) became negative, however, the serum level of IgG gradually elevated and ANA became positive, while platelets decreased. A liver biopsy performed 6 years after LTx showed histological findings of AIH and she was diagnosed with recurrent AIH. A recurrence of AIH may occur after LTx even if the level of ALT remains within a normal range. We consider that a protocol liver biopsy should be performed in patients who undergo LTx due to AIH to decide the indication for steroid therapy.
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Alanina Transaminase/sangue , Hepatite Autoimune/sangue , Hepatite Autoimune/diagnóstico , Transplante de Fígado/efeitos adversos , Contraindicações , Feminino , Hepatite Autoimune/imunologia , Hepatite Autoimune/prevenção & controle , Humanos , Falência Hepática/imunologia , Falência Hepática/cirurgia , Falência Hepática/terapia , Transplante de Fígado/imunologia , Doadores Vivos , Pessoa de Meia-Idade , Recidiva , EsteroidesRESUMO
BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) is an inflammatory disease of the liver that usually develops in middle-aged women. However, due to the increasing aging of the population and better diagnostic facilities, AIH is now diagnosed in older patients as well. This analysis compared the clinical and pathologic characteristics of older and middle-aged patients with AIH. PATIENTS AND METHODS: Thirteen older patients with AIH (mean age, 75.0+/-5.3 years; range, 70-89 years) and 27 middle-aged patients (mean age, 51.3+/-5.8 years; range, 41-60 years) were included in this study. In addition, the use of different treatment regimens, including prednisolone therapy and ursodeoxycholic acid (UDCA), was examined. RESULTS: There were no significant differences in gender, complications of other autoimmune diseases, and liver function tests between groups. However, the degree of hepatic fibrosis was significantly higher in older patients compared with middle-aged patients (P<0.05). Four patients with AIH in the older age group were successfully managed by UDCA alone. CONCLUSION: This study shows that older patients with abnormal liver function should be checked for AIH. In addition, UDCA may be an effective drug for management of older patients with AIH.
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BACKGROUND: Esophageal varices (EV), one feature of portal hypertension, have been regarded as a late complication of liver diseases. However, accumulating evidence indicates that EV sometimes develop early during the course of primary biliary cirrhosis (PBC). The prognosis is usually poorer for patients with symptomatic PBC than for those with asymptomatic PBC. Nevertheless, the clinical features and prognosis of patients with PBC whose initial symptoms are EV have not been clarified. METHODS: The clinical features and the prognosis of patients who initially developed EV without other symptoms (v-PBC) were retrospectively investigated in 54 patients with symptomatic PBC. RESULTS: The leukocyte and platelet counts were lower in patients with v-PBC than in those with PBC accompanied by other symptoms (s-PBC). Liver function tests, autoantibodies, and histological stage did not differ between patients with v-PBC and those with s-PBC. Although the prognosis did not differ, the incidence of hepatocellular carcinoma was significantly higher in v-PBC than in s-PBC (P = 0.0037). CONCLUSIONS: These data indicate that v-PBC is a hypercarcinogenic state and constitutes a new subgroup of PBC.