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BACKGROUND: Spontaneous bacterial peritonitis (SBP) is an ominous complication of decompensated cirrhosis. This study aimed to assess several epidemiological, clinical, microbiological and outcome characteristics in Greek patients with SBP, as no solid representative nationwide data of this type was available. METHODS: During a 3-year period, 77 consecutive patients with SBP (61 male; median age: 67 years; model for end-stage liver disease [MELD] score: 20), diagnosed and followed in 5 tertiary liver units, were prospectively recruited and studied. Various prognostic factors for disease outcome were studied. RESULTS: Thirty-eight patients had alcohol-related cirrhosis, 17 viral hepatitis, 6 non-alcoholic steatohepatitis, 6 autoimmune liver diseases, and 10 cryptogenic cirrhosis. Hepatocellular carcinoma (HCC) was present in 23 (29.9%), whereas 10 (13%) had portal vein thrombosis. The first SBP episode at baseline was community-acquired in 53 (68.8%), while in 24 (31.1%) was hospital-acquired, with predominant symptoms abdominal pain and encephalopathy. A positive ascitic culture was documented in 36% of patients in the initial episode, with almost equal gram (+) and gram (-) pathogens, including 3 multidrug-resistant pathogens. Significant factors for 6-month survival were: higher MELD score, previous b-blocker use, lower serum albumin, higher lactate on admission and need for vasopressors, while factors for 12-month survival were MELD score and lactate. For overall survival, higher MELD score and lactate along with HCC presence were negative predictive factors. CONCLUSIONS: MELD score, lactate, albumin, HCC and treatment with vasopressors were predictive of survival in SBP patients. In hospital-acquired SBP the prevalence of difficult-to-treat pathogens was higher.
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BACKGROUND: The accuracy of diagnosis and clinical implications of the hepatoadrenal syndrome, as currently diagnosed using total cortisol, remain to be validated. AIM: The aim of this study was to assess adrenal function using free cortisol in stable cirrhosis and study the potential implications of any abnormalities for renal and/or cardiac function. METHODS: Sixty-one stable consecutively enrolled patients with cirrhosis underwent assessment of adrenal function using the low-dose short Synacthen test, renal function by 51Cr-EDTA glomerular filtration rate (GFR), and cardiac function by two-dimensional echocardiography. RESULTS: Eleven patients (18%) had total peak cortisol (PC) < 500 nmol/L, but no patient had free PC < 33 nmol/L indicating that diagnosis of AI using total cortisol is not confirmed using free cortisol. Free cortisol did not correlate with GFR or parameters of cardiac function. Patients with higher Child-Pugh class had progressively lower free cortisol. Patients with low GFR < 60 mL/min (N = 22) had more frequently grade II-III diastolic dysfunction (66.7% vs. 17.6%; p = 0.005) and had higher Child-Pugh and MELD score compared to those with normal GFR. CONCLUSIONS: Diagnosis of AI using total cortisol is not confirmed using free cortisol and is thus considered unreliable in cirrhosis. Free cortisol is not associated with renal or cardiac dysfunction. Lower free cortisol in more advanced stages of liver disease might be secondary to decreased synthesis due to lower cholesterol levels. Irrespective of free cortisol, parameters of cardiac dysfunction are associated with renal impairment supporting the cardio-renal hypothesis.
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Testes de Função do Córtex Suprarrenal , Córtex Suprarrenal/metabolismo , Insuficiência Adrenal/diagnóstico , Taxa de Filtração Glomerular , Síndrome Hepatorrenal/diagnóstico , Hidrocortisona/sangue , Rim/fisiopatologia , Cirrose Hepática/diagnóstico , Insuficiência Adrenal/sangue , Insuficiência Adrenal/epidemiologia , Insuficiência Adrenal/fisiopatologia , Adulto , Idoso , Biomarcadores/sangue , Feminino , Grécia/epidemiologia , Cardiopatias/diagnóstico , Cardiopatias/epidemiologia , Cardiopatias/fisiopatologia , Síndrome Hepatorrenal/sangue , Síndrome Hepatorrenal/epidemiologia , Síndrome Hepatorrenal/fisiopatologia , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/epidemiologia , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Prognóstico , Reprodutibilidade dos Testes , Adulto JovemRESUMO
BACKGROUND AND AIMS: Chronic viral hepatitis is a prevalent disease with major health implications. Its underlying pathophysiological mechanisms are not fully understood. IL-1ß and the NLRP3 inflammasome involvement has been suggested in recent years, from in vitro data and data from peripheral blood samples. Therefore, we investigated IL-1ß and the NLRP3 inflammasome in liver tissues in an effort to clarify their role in the pathophysiology of chronic viral hepatitis. METHODS: We studied liver biopsies from patients with a new diagnosis of either chronic hepatitis B (CHB) and chronic hepatitis C (CHC) or patients with chronic hepatitis B in remission (CHB-rem). The biopsies were separated in two parts. The first part was sent to histology to determine the grade of inflammation and fibrosis. From the second part, RNA was extracted and converted to cDNA used in semi-quantitative Real-Time PCR to measure the levels of IL1B, CASP1, NLRP3, ASC and IL1RA. The cell lines used in the in vitro experiments were Huh7.5, LX2 and THP-1 in variety of combinations of monocultures, co-cultures and triple cultures with one of the cell lines infected with the JFH-1 HCV clone. From the cell cultures RNA was extracted and converted to cDNA. For cell lines, we focused in the expression of IL1B and NLRP3. RESULTS: The expression of IL1B, CASP1 and NLRP3 were found significantly different between our groups (pâ¯=â¯0.001, pâ¯=â¯0.001 and pâ¯=â¯0.038, respectively). CHB patients displayed significantly higher IL1B and CASP1 mRNA levels compared to both CHB-rem and CHC patients. IL1B expression significantly correlates with liver biochemical data in CHB patients (AST: pâ¯=â¯0.006, râ¯=â¯0.457; ALT pâ¯=â¯0.002, râ¯=â¯0.497). Finally, mRNA levels of IL1B in CHB patients significantly correlate with the degree of inflammation (pâ¯=â¯0.016) but not the stage of fibrosis (pâ¯=â¯0.362). Interestingly, the relative expression of IL1B in triple culture experiments in vitro was below of 1.5-fold, suggesting no activation of IL1B. Moreover, no activation of NLRP3 was demonstrated in all investigated in vitro conditions. CONCLUSION: IL-1ß might play an important role in the pathogenesis of chronic hepatic inflammation from HBV, but not from HCV.
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Inflamassomos/metabolismo , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Fígado/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Adulto , Idoso , Caspase 1/metabolismo , Linhagem Celular , Feminino , Fibrose/metabolismo , Fibrose/virologia , Hepatite B Crônica/metabolismo , Hepatite B Crônica/virologia , Hepatite C Crônica/metabolismo , Hepatite C Crônica/virologia , Humanos , Inflamação/virologia , Fígado/virologia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Transdução de Sinais/fisiologia , Adulto JovemRESUMO
Interferon-based regimens for chronic hepatitis C (CHC) were often deferred in patients with ß-thalasaemia major (ß-TM) due to poor efficacy and tolerance. Current guidelines recommend direct-acting antivirals (DAAs) for these patients. The aim of this study was to assess the safety and efficacy of DAAs in patients with ß-TM and advanced liver disease due to CHC. Patients were recruited from eight liver units in Greece. The stage of liver disease was assessed using transient elastography and/or liver histology. Five regimens were used: sofosbuvir (SOF) + ribavirin (RBV); SOF + simeprevir ± RBV; SOF + daclatasvir ± RBV; ledipasvir/SOF ± RBV and ombitasvir/paritaprevir-ritonavir + dasabuvir ± RBV. Sixty-one patients (median age 43 years) were included. The majority of patients was previously treated for hepatitis C (75%) and had cirrhosis (79%). Viral genotype distribution was: G1a: n = 10 (16%); G1b: n = 22 (36%); G2: n = 2 (3%); G3: n = 14 (23%); G4: n = 13 (22%). The predominant chelation therapy was a combination of deferoxamine and deferiprone (35%). Overall sustained virological response rates were 90%. All treatment regimens were well tolerated and no major adverse events or drug-drug interactions were observed. Approximately half of the patients who received RBV (7/16, 44%) had increased needs for blood transfusion. Treatment of CHC with DAAs in patients with ß-TM and advanced liver disease was highly effective and safe.
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Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Talassemia beta/complicações , Adulto , Carbamatos , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Imidazóis/efeitos adversos , Imidazóis/uso terapêutico , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Pirrolidinas , Ribavirina/efeitos adversos , Ribavirina/uso terapêutico , Índice de Gravidade de Doença , Simeprevir/efeitos adversos , Simeprevir/uso terapêutico , Sofosbuvir/efeitos adversos , Sofosbuvir/uso terapêutico , Valina/análogos & derivadosRESUMO
OBJECTIVES: Although animal studies demonstrated that Smad7 induction ameliorates TGF-ß/SMAD-mediated fibrogenesis, its role in human hepatic diseases is rather obscure. Our study explored the activation status of TGF-ß/activin pathway in patients with chronic liver diseases, and how it is affected by successful antiviral treatment in chronic HBV hepatitis (CHB). METHODS: Thirty-seven CHB patients (19 with active disease, 14 completely remitted on long-term antiviral treatment and 4 with relapse after treatment withdrawal), 18 patients with chronic HCV hepatitis, 12 with non-alcoholic fatty liver disease (NAFLD), and 3 controls were enrolled in the study. Liver mRNA levels of CTGF, all TGF-ß/activin isoforms, their receptors and intracellular mediators (SMADs) were evaluated using qRT-PCR and were correlated with the grade of liver inflammation and fibrosis staging. The expression and localization of pSMAD2 and pSMAD3 were assessed by immunohistochemistry. RESULTS: TGF-ß signalling is activated in CHB patients with active disease, while SMAD7 is up-regulated during the resolution of inflammation after successful treatment. SMAD7 overexpression was also observed in NAFLD patients exhibiting no or minimal fibrosis, despite the activation of TGF-ß/activin signaling. CONCLUSIONS: SMAD7 overexpression might represent a mechanism limiting TGF-ß-mediated fibrogenesis in human hepatic diseases; therefore, SMAD7 induction likely represents a candidate for novel therapeutic approaches.
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Hepatite B/metabolismo , Proteína Smad7/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Adulto , Idoso , Antivirais/uso terapêutico , Doença Crônica , Feminino , Fibrose , Hepatite B/tratamento farmacológico , Hepatite B/genética , Hepatite B/patologia , Hepatite C/genética , Hepatite C/metabolismo , Hepatite C/patologia , Humanos , Fígado/metabolismo , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , RNA Mensageiro/metabolismo , Transdução de Sinais , Proteína Smad7/genética , Fator de Crescimento Transformador beta/genética , Adulto JovemRESUMO
BACKGROUND AND AIM: T cell expression of PD1 and inhibition of T effector cells by Foxp3(+)-T regulatory cells are among the most powerful mechanisms for achieving a balanced immune response. Our aim was to investigate, how liver FOXP3 and PD1/PDL1 expression is regulated in chronic HBV hepatitis (CHB) on maintained long-term remission in comparison with active disease, and whether they are correlated to the expression of pro- and anti-inflammatory cytokines and apoptosis mediators, along with the degree of histological inflammation and markers of T cell effector restoration. METHODS: Fifty-three HBeAg-negative CHB patients with both active (30) and completely remitted disease on long-term antiviral treatment (23) and four controls (submitted to liver biopsy due to a mild increase of aminotransferases but without liver necroinflammatory and architecture changes) were enrolled in the study. Liver mRNA levels of immunoregulatory genes (FOXP3, IL10, TGFB1, and those of PD1/PDL1/PDL2 pathway), major apoptosis mediators (FAS, FASL, TNFA, TRAIL), cytokines of effector T cell restoration (IL2, IFNG), and those of IL1B, CD4, and CD8, were evaluated by quantitative real-time reverse-transcriptase PCR and were correlated with each other, along with the intensity of liver inflammation and fibrosis staging. The expression and localization of FOXP3, PD1, PDL1, CD4, and CD8 were also assessed by immunohistochemistry. RESULTS: The expression of FOXP3, IL10, TGFB1, PD1, PDL1, FASL, and CD8 was significantly down-regulated in the remission state. In contrast, liver expression of IL2 and IFNG, along with CD4, IL1B, TNFA, and FAS did not change significantly. Moreover, FOXP3, PD1, PDL1, and CD8 transcripts were positively correlated to the intensity of liver inflammation. CONCLUSION: Our data indicate that in the CHB disease model, the immunosuppressive liver environment is down-regulated in the maintained on-treatment long-term remission state and correlates with the intensity of liver inflammation, but not liver T cell restoration.
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AIM: To present the characteristics and the course of a series of anti-hepatitis B virus core antibody (HBc) antibody positive patients, who experienced hepatitis B virus (HBV) reactivation after immunosuppression. METHODS: We retrospectively evaluated in our tertiary centers the medical records of hepatitis B virus surface antigen (HBsAg) negative patients who suffered from HBV reactivation after chemotherapy or immunosuppression during a 3-year period (2009-2011). Accordingly, the clinical, laboratory and virological characteristics of 10 anti-HBc (+) anti-HBs (-)/HBsAg (-) and 4 anti-HBc (+)/antiHBs (+)/HBsAg (-) patients, who developed HBV reactivation after the initiation of chemotherapy or immunosuppressive treatment were analyzed. Quantitative determination of HBV DNA during reactivation was performed in all cases by a quantitative real time polymerase chain reaction kit (COBAS Taqman HBV Test; cut-off of detection: 6 IU/mL). RESULTS: Twelve out of 14 patients were males; median age 74.5 years. In 71.4% of them the primary diagnosis was hematologic malignancy; 78.6% had received rituximab (R) as part of the immunosuppressive regimen. The median time from last chemotherapy schedule till HBV reactivation for 10 out of 11 patients who received R was 3 (range 2-17) mo. Three patients (21.4%) deteriorated, manifesting ascites and hepatic encephalopathy and 2 (14.3%) of them died due to liver failure. CONCLUSION: HBsAg-negative anti-HBc antibody positive patients can develop HBV reactivation even 2 years after stopping immunosuppression, whereas prompt antiviral treatment on diagnosis of reactivation can be lifesaving.
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Anticorpos Monoclonais Murinos/efeitos adversos , Artrite Reumatoide/terapia , Hepatite B Crônica/imunologia , Fatores Imunológicos/efeitos adversos , Anticorpos Monoclonais Murinos/imunologia , Anticorpos Monoclonais Murinos/uso terapêutico , Artrite Reumatoide/imunologia , Feminino , Hepatite B Crônica/virologia , Humanos , Fatores Imunológicos/imunologia , Fatores Imunológicos/uso terapêutico , Pessoa de Meia-Idade , Recidiva , RituximabRESUMO
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome (MetS), is common and accounts for 80% of cases of elevated liver function tests (LFTs). We assessed the long-term effects of multifactorial intervention on LFTs and their association with cardiovascular disease (CVD) events in patients with MetS without diabetes mellitus or CVD. MATERIAL AND METHODS: This prospective, randomized, open label study included 1,123 patients (aged 45-65 years). Patients received intensive lifestyle intervention and pharmacotherapy: atorvastatin in all patients (low density lipoprotein cholesterol [LDL-C] targets of<100 mg/dl [group A] or<130 mg/dl [group B]), inhibitors of the renin-angiotensin-aldosterone axis for hypertension, metformin for dysglycaemia and orlistat for obesity. RESULTS: Among participants, 326 had modestly elevated LFTs and ultrasonographic (US) evidence of NAFLD (165 patients in group A2 and 161 patients in group B2). The NAFLD resolved during the 42-month treatment period in 86% of patients in group A2 and in 74% of patients in group B2 (p<0.001). In both groups nearly 90% of patients attained lipid goals. Mean LDL-C and TG levels were higher in group B2 than in group A2 (p<0.001). There were no CVD events in group A2 whereas 5 non-fatal events occurred in group B2 (log-rank-p = 0.024). There were no major side-effects. CONCLUSIONS: Attaining multiple treatment targets is safe and beneficial in primary prevention patients with MetS and NAFLD. Lipid levels and LFTs normalized, US findings associated with NAFLD resolved and no CVD events occurred in patients with LDL-C levels<100 mg/dl (group A2). Resolution of NAFLD might have contributed to the prevention of CVD events.
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AIM: Spur cell anemia (SCA) is a form of acquired hemolytic anemia seen in patients with advanced cirrhosis and particularly in patients with alcoholic cirrhosis. The aim of the present study was to evaluate the incidence of spur cells and spur cell anemia in patients with advanced liver disease and to correlate the presence of spur cell anemia with survival. METHODS: During a 33-month period, all patients with advanced cirrhosis (Child-Pugh-Turcott score [CPT]>/=7] who were hospitalized in our department for various reasons were included in this study. RESULTS: A total of 54 patients were included in the study; 26 patients had spur cells on peripheral blood smear (median 4, range 1-14). Patients with spur cells had more advanced liver disease compared with those without spur cells (CPT score, P < 0.0001 and MELD score, P < 0.0001), lower hemoglobin levels (P < 0.0001), higher bilirubin levels (total/unconjugated, P < 0.0001), higher reticulocyte count (P < 0.0001) and more prolonged international normalized ratio (INR; P < 0.0001). Patients with 5% spur cells or more had more advanced disease compared with patients with 1-4% spur cells (CPT score, P = 0.004 and MELD score, P = 0.003), lower hemoglobin levels (P = 0.033), more elevated bilirubin levels (total/unconjugated, P = 0.006) and more prolonged INR (P = 0.04). Three-month survival was lower in patients with spur cells compared with patients without spur cells (P = 0.017 and P = 0.104, respectively). Patients with 5% spur cells or more had lower 3-month survival compared with those with 1-4% spur cells (P = 0.014). CONCLUSION: Presence of spur cells in patients with advanced cirrhosis is not always accompanied by spur cell anemia. The presence of 5% spur cells or more and/or hemolytic anemia is associated with poor prognosis and these patients might have to be given priority for liver transplantation.
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BACKGROUND AND AIM: Adefovir dipivoxil (ADV) is effective in lamivudine (LAM)-resistant hepatitis B e antigen-negative (HBeAg(-)) chronic hepatitis B (CHB). However, it is unclear whether LAM treatment should be continued in these patients. We aimed to compare the long-term efficacy of adding ADV to ongoing LAM treatment versus switching to ADV monotherapy in LAM-resistant HBeAg(-) CHB. METHODS: Sixty LAM-resistant patients with HBeAg(-) CHB were randomly assigned (3:1) to combination therapy (10 mg ADV once daily plus ongoing LAM at 100 mg once daily [n = 45]) or 10 mg ADV monotherapy once daily (n = 15). Virological and biochemical responses were defined as hepatitis B virus (HBV)-DNA <400 copies/mL and as normalization of alanine aminotransferase levels, respectively. RESULTS: The median follow-up time was 53 months (range 20-60 months). A virological response was observed in 38/45 (84.4%) and 11/15 (73.3%) patients in the ADV/LAM and ADV monotherapy groups, respectively (P = 0.56). Biochemical response rates were higher in the ADV/LAM group than in the ADV monotherapy group (90.9% vs 57.1%, respectively; P = 0.01). In the ADV/LAM group, serum HBV-DNA remained undetectable in all patients who achieved a virological response (n = 38). In the ADV monotherapy group, virological breakthrough occurred in four of the 11 patients who achieved a virological response (36.4%; P < 0.001 vs the ADV/LAM group, log-rank test). In addition, two patients in each group who did not achieve a virological response eventually developed ADV resistance. CONCLUSIONS: Adding ADV to LAM is more effective than switching to ADV monotherapy in LAM-resistant patients with HBeAg(-) CHB.
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Adenina/análogos & derivados , Antivirais/uso terapêutico , Farmacorresistência Viral Múltipla , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Organofosfonatos/uso terapêutico , Adenina/efeitos adversos , Adenina/uso terapêutico , Adulto , Idoso , Alanina Transaminase/sangue , Antivirais/efeitos adversos , Biomarcadores/sangue , DNA Viral/sangue , Farmacorresistência Viral Múltipla/genética , Quimioterapia Combinada , Feminino , Genótipo , Hepatite B/genética , Hepatite B/imunologia , Hepatite B Crônica/diagnóstico , Humanos , Lamivudina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Organofosfonatos/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
We report a case of a 33-year-old female patient with Budd-Chiari syndrome because of polycythemia vera. A transjugular intrahepatic portal-systemic shunt was performed because of refractory ascites 7 months after diagnosis. She had a stable hepatic function receiving anticoagulants until 3 years later when she presented with bloody diarrheas, liver function deterioration with prolonged prothrombin time and hypoalbuminemia, encephalopathy, and ascites. Colonoscopy revealed ulcerative pancolitis and the patient was treated with corticosteroids and antibiotics. Hepatic function was stabilized in parallel to controlling ulcerative colitis and the patient is in good health until now receiving maintenance therapy for ulcerative colitis and anticoagulants for Budd-Chiari syndrome.
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Síndrome de Budd-Chiari/complicações , Colite Ulcerativa/complicações , Adulto , Ascite/tratamento farmacológico , Ascite/etiologia , Colite Ulcerativa/tratamento farmacológico , Feminino , Humanos , Policitemia Vera/complicaçõesRESUMO
Idiopathic portal hypertension belongs to the group of non-cirrhotic portal hypertension, its etiology is still unknown but its prognosis is excellent. We report a case of 45 year old female with inactive hepatitis B virus (HBV) carrier status and persistently elevated alpha-fetoprotein (AFP), presented with features of portal hypertension and without evidence of cirrhosis or fibrosis on liver biopsy.
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Inflammatory pseudotumor of the liver is a rare, benign lesion characterized by a well-circumscribed mass of chronic inflammatory cell infiltration and proliferating fibrous tissue. Its etiology remains unclear, although inflammatory processes have been proposed. It is often misdiagnosed as a malignant tumor, and the management has been traditionally surgical. We report the case of a 16-year-old boy who was referred from another hospital with a fever of >38 degrees C with rigor and right upper quadrant pain which he had suffered from for 5 days. The ultrasonographic computed tomography and MRI findings were not diagnostic, and we performed a needle biopsy from the lesion that was consistent with inflammatory pseudotumor (of liver, mixed fibrous tissue and chronic inflammatory cell infiltration). The patient was treated with nonsteroidal anti-inflammatory drugs and had an uneventful clinical course. During follow-up, the lesion subsequently shrank to completely vanish 1 year later.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Granuloma de Células Plasmáticas/diagnóstico , Hepatopatias/diagnóstico , Naproxeno/uso terapêutico , Adolescente , Biópsia por Agulha , Meios de Contraste , Diagnóstico Diferencial , Seguimentos , Granuloma de Células Plasmáticas/tratamento farmacológico , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Hepatopatias/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios X , Resultado do Tratamento , UltrassonografiaRESUMO
BACKGROUND AND AIM: Monotherapy has been proven insufficient in achieving sustained control of chronic hepatitis B. We aimed to assess the efficacy of combined sequential administration of lamivudine and pegylated interferon alfa-2b in patients with hepatitis Be antigen (HBeAg)-negative chronic hepatitis B. METHODS: Eighteen patients were given sequential combination treatment starting with 3 months of lamivudine monotherapy followed by 9 months of pegylated interferon alfa-2b (after a 3-month period of concomitant administration of the two drugs) and 24 patients received lamivudine monotherapy. RESULTS: At the end of treatment, 88.9% of the patients who received sequential combination treatment and 70.8% of those who received lamivudine monotherapy had hepatitis B virus (HBV) DNA levels below 400 copies/mL (P = not significant). At the end of treatment, 72.2% of the patients who received sequential combination treatment and 70.8% of those who received lamivudine monotherapy achieved alanine aminotransferase normalization (P = not significant). After 12 months of follow up, 33.3% of the patients who received sequential combination treatment and 16.7% of those who received lamivudine monotherapy had HBV-DNA levels below 400 copies/mL (P = 0.4). After 12 months of follow up, 72.2% of the patients who received sequential combination treatment and 25.0% of those who received lamivudine monotherapy had normal alanine aminotransferase levels (P < 0.01). Twenty-five percent of the patients in the lamivudine monotherapy group had virological breakthrough compared to none in the sequential combination treatment group (P = 0.06). CONCLUSIONS: Sequential combination treatment is able to improve sustained biochemical response rates and prevent the emergence of lamivudine-resistant mutants in patients with HBeAg-negative chronic hepatitis B.
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Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Lamivudina/uso terapêutico , Adulto , Idoso , Antivirais/administração & dosagem , DNA Viral/sangue , Quimioterapia Combinada , Feminino , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/imunologia , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Lamivudina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis , Reação em Cadeia da Polimerase , Estudos Prospectivos , Proteínas Recombinantes , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
AIM: To investigate the role of pegylated-interferon (IFN) alpha-2b in the management of patients with lamivudine-resistant chronic hepatitis B. METHODS: Twenty consecutive anti-HBe positive patients were treated with pegylated IFN alpha-2b (100 mug sc once weekly) for 12 mo. There was no interruption in lamivudine therapy. Hematology, liver biochemistry, serum HBV DNA levels were detected by PCR, and vital signs were also assessed. Liver histology was assessed in some patients at entry and at wk 52 for comparison. RESULTS: Nine patients (45%) had a partial virological end-treatment response; seven patients (35%) showed complete virological end-treatment response. Eight patients (40%) showed biochemical end-treatment response. There was a trend for higher virological response rates in patients who had previously responded to IFN and relapsed compared to IFN non-responders (four out of seven patients vs none out of six patients, respectively; P=0.1). Patients without virological end-treatment response showed significant worsening of fibrosis [median score 2 (range, 1 to 3) vs median score 3 (range, 1 to 4)], in the first and second biopsy respectively (P=0.014), whereas necroinflammatory activity was not significantly affected. Patients with complete or partial virological end-treatment response did not show any significant changes in histological findings, possibly due to the small number of patients with paired biopsies (n=5). Nevertheless, after 12 mo of follow-up, only one patient (5%) showed sustained virological response and only 2 patients (10%) showed sustained biochemical response. Two patients (10%) discontinued pegylated IFN both after 6 mo of treatment due to flu-like symptoms. CONCLUSION: Pegylated IFNalpha-2b, when added to ongoing lamivudine therapy in patients with lamivudine-resistant chronic hepatitis B, induces sustained responses only in a small minority of cases.
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Antivirais/administração & dosagem , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Lamivudina/administração & dosagem , Adulto , Idoso , DNA Viral/sangue , Farmacorresistência Viral , Feminino , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Interferon alfa-2 , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis , Proteínas RecombinantesRESUMO
The congenital dyserythropoietic anemias comprise a group of rare hereditary disorders of erythropoiesis, characterized by ineffective erythropoiesis as the predominant mechanism of anemia and by characteristic morphological aberrations of the majority of erythroblasts in the bone marrow. Congenital dyserythropoietic anemia type II is the most frequent type. All types of congenital dyserythropoietic anemias distinctly share a high incidence of iron loading. Iron accumulation occurs even in untransfused patients and can result in heart failure and liver cirrhosis. We have reported about a patient who presented with liver cirrhosis and intractable ascites caused by congenital dyserythropoietic anemia type II. Her clinical course was further complicated by the development of autoimmune hemolytic anemia. Splenectomy was eventually performed which achieved complete resolution of ascites, increase of hemoglobin concentration and abrogation of transfusion requirements.
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Anemia Diseritropoética Congênita/cirurgia , Anemia Diseritropoética Congênita/complicações , Anemia Diseritropoética Congênita/patologia , Anemia Hemolítica Autoimune/complicações , Ascite/etiologia , Ascite/cirurgia , Feminino , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Pessoa de Meia-Idade , EsplenectomiaRESUMO
Congenital hepatic fibrosis belongs to the fibrocystic diseases of the liver and represents ductal plate malformation of interlobular bile ducts, along with a destructive cholangiopathy associated with fibrosis. Four patients with congenital hepatic fibrosis are described. Their median age at presentation was 25 years; none of them had a family history of liver or renal disease. Variceal bleeding was the initial manifestation in three patients. All of them required frequent endoscopic variceal ligation sessions and distal splenorenal shunting was also performed in two, almost obviating the need for further variceal ligation. Variceal bleeding did not recur during follow-up. One of these three patients rarely exhibited acute cholangitis; administration of ursodeoxycholic acid resulted in complete remission. In contrast, the fourth patient showed frequent severe episodes of acute cholangitis but normal cholangiographic findings. He underwent liver transplantation but died 2 months later. Laboratory findings disclosed pancytopenia in all patients whereas hepatic synthetic capacity was well preserved. Renal function was unaffected despite the presence of polycystic kidneys in two patients. In summary, congenital hepatic fibrosis can also be diagnosed in older ages, might have strikingly different manifestations and is associated with prominent portal hypertension necessitating aggressive management in order to prevent variceal bleeding.