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1.
JGH Open ; 6(1): 29-35, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35071785

RESUMO

Aims: There is a paucity of comparative data on the use of sorafenib and lenvatinib for unresectable hepatocellular carcinoma. We assessed the real-world treatment outcomes between using sorafenib and lenvatinib for unresectable hepatocellular carcinoma in the multiple molecular-targeted therapy era. Methods and Results: We enrolled 386 patients treated with sorafenib or lenvatinib as the first-line therapy for unresectable hepatocellular carcinoma at multiple centers. Propensity score matching was performed to adjust for differences in baseline and tumor characteristics between the two groups. Propensity score matching identified 110 patients in each treatment group. The median overall survival was similar between lenvatinib and sorafenib (14.8 and 13.0 months, respectively; P = 0.352). The median progression-free survival was longer with lenvatinib than with sorafenib (7.6 and 3.9 months, respectively; P < 0.001). The overall response rate (P < 0.001) and disease control rate (P = 0.015), as defined by the modified Response Evaluation Criteria in Solid Tumors, were significantly better with lenvatinib than with sorafenib. The median overall survival was longer in patients who received subsequent treatment than in those who did not in the sorafenib group (23.1 and 5.7 months, respectively; P < 0.001), whereas the median overall survival with or without subsequent treatment did not differ significantly in the lenvatinib group (17.8 and 14.7 months, respectively; P = 0.439). Conclusion: Overall survival with sorafenib and lenvatinib was not significantly different. However, patients who received subsequent treatments had longer overall survival than those who received only first-line treatment with sorafenib, whereas lenvatinib did not show this effect.

2.
Hepatol Res ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34861090

RESUMO

AIM: Direct-acting antivirals (DAAs) are currently available even for patients with decompensated cirrhosis. Reportedly, hepatic functional reserve improved in the short term after achievement of sustained virologic response (SVR). We aimed to clarify the outcomes after achievement of SVR in patients with decompensated cirrhosis who were treated by DAAs in real-world clinical practice. METHODS: A prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted in 86 patients with decompensated cirrhosis, who were evaluated for 48 weeks post-treatment. RESULTS: The cohort included 8 patients with Child-Pugh class A, 56 with B, and 22 with C. The proportion of Child-Pugh class A patients increased from 9.1% at baseline to 44.1% at 48 weeks post-treatment, while that of class B and C patients decreased from 66.2% to 35.1% and from 24.7% to 14.3%, respectively. Among the patients with Child-Pugh class B and C, univariate analysis identified low total bilirubin, Child-Pugh score, Child-Pugh class B, ALBI score, and high serum albumin as factors associated with improvement to Child-Pugh class A. The optimal cut-off value of the factors for predicting improvement to Child-Pugh class A were 1.4 mg/dL for total bilirubin, 2.9 g/dL for serum albumin, 8 points for Child-Pugh score, and -1.88 for ALBI score. CONCLUSION: Achievement of SVR with sofosbuvir/velpatasvir improved the liver functional reserve at 12 weeks post-treatment and maintained the stable effects until 48 weeks post-treatment in patients with decompensated cirrhosis. Specifically, the patients with less advanced conditions had the likelihood of improving to Child-Pugh class A at 48 weeks post-treatment. This article is protected by copyright. All rights reserved.

3.
Intern Med ; 2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34897151

RESUMO

We herein report a rare case of torsion of a wandering spleen in a patient with myeloproliferative disease. A 66-year-old Japanese woman presented to our hospital with abdominal pain and a fever. She had a medical history of polycythemia and secondary myelofibrosis. Abdominal enhanced computed tomography showed an enlarged spleen without enhancement in the lower pelvic region. The clinical diagnosis was severe torsion of a wandering spleen in a patient with myeloproliferative disease, necessitating surgical intervention. Splenectomy was performed after de-rotating to revascularize the spleen. After the operation, the platelet count gradually increased, and aspirin was administered to prevent thrombosis.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34953107

RESUMO

BACKGROUND: Lusutrombopag effectively increases platelet count in patients with severe thrombocytopenia. However, no multicenter studies analyzing the effects of Lusutrombopag on patients with mild thrombocytopenia (platelet count > 50 000/µL) have been performed. In this study, we aimed to clarify the efficacy of Lusutrombopag on these patients by unifying background factors by propensity score matching. METHODS: A total of 139 patients with thrombocytopenia were enrolled, and matched for age, sex, etiology, disease, treatment, liver function, renal function, peripheral blood count, and spleen index. The primary endpoint was to compare the increase in platelet count from baseline between the high-platelet group (>50 000/µL) and the low-platelet group (<50 000/µL) after Lusutrombopag treatment, using propensity score matching. The secondary endpoint was to clarify platelet transfusion avoidance rate and adverse events, moreover, to identify independent predictors associated with the increase in platelet count. RESULTS: The mean increase in platelet count was 67 000/µL vs 48 000/µL in all patients (high- vs low-platelet group, P = .024), and 64 000/µL vs 48 000/µL (P = .12) after propensity score matching. The increase in platelet count and the platelet transfusion avoidance rate tended to be higher in the high-platelet group. There was no significant difference between adverse events. Predictors associated with an increase in platelet count were sex, estimated glomerular filtration rate, and spleen index by multivariate analysis. CONCLUSION: Lusutrombopag has a little stronger effect in patients with mild thrombocytopenia than those with severe thrombocytopenia and showed a more substantial effect in patients with impaired renal function and small spleen.

5.
Hepatol Res ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34755420

RESUMO

AIM: Sleep disorder is common in patients with chronic liver disease (CLD). Liver-related silent complications, including muscle cramps, covert hepatic encephalopathy (HE), and sarcopenia, often reduce the quality of life of patients with CLD and have been reported to cause sleep disorders. In this study, we clarified the prevalence of liver-related complications associated with sleep disorders in patients with CLD. METHODS: We conducted a multicenter cohort study of 271 patients with CLD. The Athens Insomnia Scale, muscle cramps questionnaires, and Stroop test were used to assess insomnia, muscle cramps, and covert HE, respectively. In addition, sarcopenia, dynapenia, and myopenia were diagnosed according to the guidelines of the Japan Society of Hepatology. RESULTS: In total, 136 patients (50.2%) had sleep disorders. Serum albumin and hemoglobin levels and prothrombin time activity were significantly lower in patients with sleep disorders than in those without sleep disorders. On univariate and multivariate analyses adjusted with inverse probability weighting, muscle cramps, covert HE, and dynapenia were associated with a sleep disorder. Sleep disorder was categorized as follows: cramp, covert HE, dynapenia, multiple complications, and others. In total, 106 of 136 patients (77.9%) with sleep disorder had at least one liver-related complication, whereas 75 patients had multiple liver-related complications. CONCLUSION: Sleep disorder in patients with CLD was classified into four categories (muscle cramp, covert HE, dynapenia, and others). Questionnaire for sleep disorder might be an easy primary step for surveillance of high-risk patients with silent complications associated CLD.

6.
Dig Dis ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34808618

RESUMO

BACKGROUND: Data regarding the influence of patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism for patients with liver cirrhosis (LC) are scarce. OBJECTIVE: This study assesses the role of the PNPLA3 polymorphism for the development of LC and its complications by the findings of genetic examinations. METHODS: Patients with LC caused by virus (n = 157), alcohol (n = 104), nonalcoholic fatty liver disease (NAFLD) (n = 106), or autoimmune disease (n = 33) and without LC (n = 128) were enrolled. LC were composed of the present and absent of complications, such as variceal bleeding, hepatic ascites, and/or hepatic encephalopathy. To assess the role of the PNPLA3 polymorphism, odds ratio (OR) for the rs738409 variant was calculated for the patients between (i) with LC and without LC in the entire cohort, and (ii) the present and absent of complications in the patients with LC. RESULTS: There was a significant difference among the patients without LC and those with alcohol, NAFLD related LC in the frequency of G alleles (p < 0.001, both). According to complications of LC, the OR for NAFLD related cirrhosis significantly increased in the presence of the two mutated alleles (OR = 3.165; p = 0.046) when the wild type was used as the reference. However, there were no significant risks for the complications in the virus and alcohol related cirrhosis unless there was a presence of G alleles. CONCLUSION: The PNPLA3 polymorphism was associated with the risk of NAFLD related LC and its complications.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34787743

RESUMO

This review focuses on ultrasonography (US) to diagnose patients with complications in portal hypertension. Clinicians first use US to evaluate patients with suspected portal hypertension, because US is quick, simple, and radiation free. US is necessary for grading and performing paracentesis for ascites. Doppler US-based detection of reverse splanchnic vein flow or the presence of a spontaneous portosystemic shunt is highly specific in patients with cirrhosis. Since it is important to estimate spleen size in patients with portal hypertension, spleen size is usually measured by US. Spleen volume can be more accurately measured with 3D-US. Estimation of viable residual splenic volume after partial splenic embolization should be limited to cases with total splenic volume less than 1000 ml. Portal vein thrombosis is often detected during the US examination performed when symptoms first appear or during the follow-up. Two-dimensional transthoracic echocardiography is an excellent noninvasive screening test in patients with pulmonary portal hypertension who can undergo it. By measuring the maximum and minimum diastolic blood flow velocities in the renal arteries using renal color Doppler US, the pulsatility index (PI) and resistive index (RI) can be calculated. The PI and RI in cirrhotic patients were significantly higher than those in healthy subjects and patients with chronic hepatitis, and showed a significant positive correlation with the Child-Pugh Score. In conclusion, US is an essential tool for the diagnosis and treatment of patients with portal hypertension.

8.
Hepatol Res ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34761470

RESUMO

PURPOSE: To assess the impact of clinical factors on the safety and efficacy of atezolizumab plus bevacizumab (ATZ + BV) treatment in patients with unresectable hepatocellular carcinoma (u-HCC). METHOD: Ninety-four u-HCC patients who were treated with ATZ + BV at multiple centers were enrolled. We defined Child-Pugh (CP)-A patients who received ATZ + BV treatment as a first line therapy as the 'meets the broad sense of the IMbrave150 criteria' group (B-IMbrave150-in, n = 46), and patients who received ATZ + BV treatment as a later line therapy or CP-B patients (regardless of whether ATZ + BV was a first line or later line therapy) as the B-IMbrave150-out group (n = 48). Patients were retrospectively analyzed for adverse events (AEs) and treatment outcomes according to their clinical characteristics, including neutrophil lymphocyte ratio (NLR) at baseline. RESULTS: The overall incidence of AEs was 87.2% (82/94 patients). The frequency of interruption of ATZ + BV treatment due to fatigue was higher in CP-B than CP-A patients (p = 0.030). Objective response (OR) rates of the B-IMbrave150-in group (28.3%, 39.1%) were significantly higher than those of the B-IMbrave150-out group (8.3%, 18.8%; p = 0.0157, 0.0401) using Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST, respectively. In multivariate analysis, NLR (hazard ratio (HR), 4.591; p = 0.0160) and B-IMbrave150 criteria (HR, 4.108; p = 0.0261) were independent factors associated with the OR of ATZ + BV treatment using RECIST. CONCLUSION: In real-world practice, ATZ + BV treatment might offer significant benefits in patients who meet B-IMbrave150 criteria or have low NLR.

9.
Cureus ; 13(10): e18449, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34650837

RESUMO

Objectives Considering that pathogens resistant to initial antibiotic therapies for cholangitis can affect mortality rates, appropriate initial empiric antibiotic therapy is important. However, evidence regarding the influence of pathogens resistant to initial antibiotics in patients with cholangitis who have undergone early endoscopic retrograde cholangiopancreatography (ERCP) is limited, and the conditions in several cases can improve with early ERCP even when pathogens resistant to initial antibiotics are detected on time. Therefore, this study aimed to assess the influence of pathogens resistant to initial antibiotics on the course of cholangitis in patients undergoing early ERCP. Materials and methods Patients (n=266) with positive blood or bile culture results treated with early ERCP were divided into those with cultures that were resistant to the initial antibiotics (antibiotic-resistant group; n=66; 24.8%) and those with cultures that were sensitive to the initial antibiotics (antibiotic-sensitive group; n=200; 75.2%). The duration of hospitalization, in-hospital mortality rates due to cholangitis, rates of increased disease severity, and complications during hospitalization were studied. Results Enterococcus, Enterobacter, Citrobacter, and Pseudomonas species showed high resistance to several antibiotics. No significant between-group differences were found in the duration of hospitalization, in-hospital mortality rates due to cholangitis, and rates of increased disease severity. However, the rate of post-ERCP cholecystitis was significantly higher in the antibiotic-resistant group than in the antibiotic-sensitive group (p=0.0245). Conclusions Even if the initial antibiotics were ineffective, the rate of fatal outcomes did not increase among patients with cholangitis who had undergone early ERCP. However, when initial antibiotics were ineffective, the frequency of post-ERCP cholecystitis increased even after early bile duct decompression.

10.
BMC Gastroenterol ; 21(1): 401, 2021 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34689751

RESUMO

BACKGROUND: Bleeding can be a serious adverse event of endoscopic sphincterotomy (EST). However, the risk of EST bleeding between direct oral anticoagulant (DOAC) users and those who received no antithrombotic agents has not been clarified. This study analyzed the risk factors for bleeding after EST in patients on DOAC and evaluated the Japan Gastroenterological Endoscopy Society (JGES) guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment. METHODS: We retrospectively analyzed 524 patients treated with EST who received DOAC or no antithrombotic drug from May 2016 to August 2019. We investigated the risk factors for bleeding. DOAC was typically discontinued for ≤ 1-day based on the JGES guideline. Although DOAC therapy recommenced the next morning after EST in principle, the duration of DOAC cessation and heparin replacement were determined by the attending physician based on each patient's status. RESULTS: The number of patients on DOAC (DOAC group) and those not on antithrombotic drug (no-drug group) was 42 (8.0%) and 482 (92.0%), respectively. DOAC was discontinued for ≤ 1-day in 17 (40.0%) patients and for > 1-day in 25 (60.0%). Of the 524 patients, 21 (4.0%) had EST bleeding. The bleeding rate was higher in the DOAC group (14.0%) (p = 0.004). Multivariate analysis showed that bleeding occurred more frequently in patients on DOAC (odds ratio [OR] 3.95, 95% confidence interval [CI] 1.37-11.4, p = 0.011), patients with low platelet counts (< 100,000/µl) (OR 6.74, 95% CI 2.1-21.6, p = 0.001), and elderly patients (> 80 years old) (OR 3.36, 95%CI 1.17-9.65, p = 0.024). CONCLUSIONS: DOAC treatment, low platelet count, and old age (> 80 years old) are risk factors for EST bleeding. Although the bleeding incidence increased in patients on DOAC who received antithrombotic therapy according to the JGES guidelines, successful hemostasis was achieved with endoscopy in all cases, and no thrombotic events occurred after cessation of DOAC. Thus, the JGES guidelines are acceptable.


Assuntos
Anticoagulantes , Esfinterotomia Endoscópica , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Fibrinolíticos/efeitos adversos , Heparina , Humanos , Estudos Retrospectivos , Esfinterotomia Endoscópica/efeitos adversos
12.
Hepatol Res ; 51(9): 968-978, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34269502

RESUMO

AIM: There are limited data from prospective studies showing the clinical usefulness of the new criteria for sarcopenia in liver disease produced by the Japan Society of Hepatology. Therefore, we aimed to evaluate the clinical usefulness of this new criteria for prognosis in cirrhotic patients. METHODS: This prospective study was performed at six centers. The 300 enrolled patients, aged more than 20 years with liver cirrhosis, were evaluated over a 3-year period for skeletal muscle mass index and grip strength. Sarcopenia was defined according to the Japan Society of Hepatology criteria by grip strength and computed tomography-based skeletal muscle mass index values. We investigated the correlation between sarcopenia and the survival rate of cirrhotic patients. RESULTS: Among the 300 assessed patients there were 99 (33%) patients with sarcopenia. The number of deaths in the sarcopenia and non-sarcopenia groups was 34 (34.3%) and 38 (18.9%), respectively (p = 0.002). Multivariate analysis confirmed that sarcopenia, decompensated phase, albumin-bilirubin grade, and hepatocellular carcinoma (HCC) stage 3/4 were independent factors correlated with death in patients with liver cirrhosis during the observation period. The interaction between sarcopenia and the presence of HCC was statistically significant (p < 0.001), and the presence of HCC had the highest hazard ratio of 6.665 for deaths in cirrhotic patients when non-sarcopenia and the absence of HCC were used as references. CONCLUSIONS: The new Japan Society of Hepatology criteria for sarcopenia are accurate predictors of poor prognosis in patients with liver cirrhosis.

13.
Liver Int ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34309184

RESUMO

BACKGROUND & AIMS: Tolvaptan, vasopressin V2-receptor antagonist, has been used for patients with difficult-to-treat ascites in Japan. In this study, we conducted a genome-wide association study (GWAS) in the Japanese population to identify genetic variants associated with tolvaptan's efficacy for patients with hepatic ascites. METHODS: From 2014 through 2018, genomic DNA samples were obtained from 550 patients who were treated with tolvaptan. Of those, 80 cases (non-responder; increase of body weight [BW]) and 333 controls (responder; >1.5 kg decrease of BW) were included in the GWAS and replication study. RESULTS: Genome-wide association study showed 5 candidate SNPs around the miR818, KIAA1109, and SVEP1 genes. After validation and performing a replication study, an SNP (rs2991364) located in the SVEP1 gene was found to have a significant genome-wide association (OR = 3.55, P = 2.01 × 10-8 ). Multivariate analyses showed that serum sodium (Na), blood urea nitrogen (BUN) and SVEP1 SNP were significantly associated with the response (OR = 0.92, P = .003; OR = 1.02, P = .02 and OR = 3.98, P = .000008, respectively). Based on a prediction model of logistic regression analysis in a population with the rs2991364 risk allele, the failure probability (=exp (score: 22.234 + BUN*0.077 + Na*-0.179) (1 + exp (score)) was determined for the detection of non-responders. Assuming a cutoff of failure probability at 38.6%, sensitivity was 84.4%, specificity was 70% and AUC was 0.774. CONCLUSION: SVEP1 rs2991364 was identified as the specific SNP for the tolvaptan response. The prediction score (>38.6%) can identify tolvaptan non-responders and help to avoid a lengthy period of futile treatment.

14.
Hepatol Commun ; 5(7): 1290-1299, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34278176

RESUMO

Hepatocellular carcinoma (HCC) can de novo develop in patients with chronic hepatitis C even after the achievement of sustained virologic response (SVR). We characterized de novo HCC after SVR, comparing it with HCC that developed in patients during persistent hepatitis C virus (HCV) infection. Characteristics, survival rates, and recurrence rates after curative treatment in 178 patients who developed initial HCC after SVR diagnosed between 2014 and 2020 were compared with those of 127 patients with initial HCC that developed during persistent HCV infection diagnosed between 2011 and 2015; HCC was detected under surveillance in both groups. HCC was less advanced and liver function worsened less in patients with SVR than in patients with persistent HCV. The survival rate after diagnosis was significantly higher for patients with SVR than for patients with persistent HCV (1-, 3-, and 5-year survival rates, 98.2%, 92.5%, and 86.8% versus 89.5%, 74.7%, and 60.8%, respectively; P < 0.001). By contrast, the recurrence rate after curative treatment was similar between groups (1-, 3-, and 5-year recurrence rates, 11.6%, 54.6%, and 60.4% versus 24.0%, 46.7%, and 50.4%, respectively; P = 0.7484). Liver function improved between initial HCC diagnosis and recurrence in patients with SVR (P = 0.0191), whereas it worsened in the control group (P < 0.001). In addition, patients with SVR could receive curative treatment for recurrence more frequently than patients with persistent HCV (80.4% versus 47.8%, respectively; P = 0.0008). Conclusion: Survival of patients with de novo HCC after SVR was significantly higher than that of patients in whom HCC developed during persistent HCV infection, despite similar rates of recurrence after curative treatment. A higher prevalence of curative treatment for recurrent HCC and improved liver function contributed to this result.

15.
Intern Med ; 60(21): 3427-3433, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33967143

RESUMO

We herein report a rare case of cartilage-hair hypoplasia (CHH) complicated with liver cirrhosis. A 20-year-old Japanese man with CHH was found incidentally to have liver cirrhosis and an esophageal varix. This patient had been treated for infections due to immunodeficiency since early childhood. He ultimately died of liver failure at 31 years of age. An autopsy revealed an abnormality of the interlobular bile ducts and intrahepatic cholestasis. Liver cirrhosis was thought to have been caused by chronic intrahepatic cholestasis due to biliary duct hypoplasia and changes in the intestinal microbiome. Therefore, CHH may cause biliary cirrhosis due to multiple effects.


Assuntos
Colestase Intra-Hepática , Doença de Hirschsprung , Doenças da Imunodeficiência Primária , Adulto , Colestase Intra-Hepática/complicações , Colestase Intra-Hepática/diagnóstico , Evolução Fatal , Cabelo/anormalidades , Humanos , Cirrose Hepática/complicações , Masculino , Osteocondrodisplasias/congênito , Adulto Jovem
16.
Clin J Gastroenterol ; 14(4): 1233-1239, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34024039

RESUMO

In November 2020, atezolizumab plus bevacizumab became available for the treatment of hepatocellular carcinoma (HCC), and its efficacy is expected as a new treatment option for HCC. However, the occurrence of immune-related adverse events (irAEs) associated with the administration of immune checkpoint inhibitors is a major concern in clinical practice. We reported a case of irAE-induced myocarditis after the treatment for HCC. Based on the symptoms and echocardiographic findings, we suspected irAE-induced myocarditis and acute heart failure, and the patient was admitted to the hospital for further investigation and treatment. From starting the patient on therapy with methylprednisolone succinate sodium, the laboratory data and symptoms tended to improve. The patient was discharged to home on the 25th day of treatment. Because the number of patients with irAE myocarditis is expected to increase in clinical practice in the near future, further accumulation and investigation of cases are necessary.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Miocardite , Anticorpos Monoclonais Humanizados , Bevacizumab/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas/tratamento farmacológico , Miocardite/induzido quimicamente
18.
Hepatology ; 74(2): 656-666, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33706421

RESUMO

BACKGROUND AND AIMS: Real-world data for treatment effectiveness and renal outcomes in chronic hepatitis B (CHB) patients who were switched to the new and safer prodrug tenofovir alafenamide (TAF) from tenofovir disoproxil fumarate (TDF) are limited. Therefore, we aimed to evaluate treatment and renal outcomes of this population. APPROACH AND RESULTS: We analyzed 834 patients with CHB previously treated with TDF for ≥12 months who were switched to TAF in routine practice at 13 US and Asian centers for changes in viral (HBV DNA < 20 IU/mL), biochemical (alanine aminotransferase [ALT] < 35/25 U/L for male/female), and complete (viral+biochemical) responses, as well as estimated glomerular filtration rate (eGFR; milliliters per minute per 1.73 square meters) up to 96 weeks after switch. Viral suppression (P < 0.001) and ALT normalization (P = 0.003) rates increased significantly after switch, with a trend for increasing complete response (Ptrend = 0.004), while the eGFR trend (Ptrend  > 0.44) or mean eGFR (P > 0.83, adjusted for age, sex, baseline eGFR, and diabetes, hypertension, or cirrhosis by generalized linear modeling) remained stable. However, among those with baseline eGFR < 90 (chronic kidney disease [CKD] stage ≥2), mean eGFR decreased significantly while on TDF (P = 0.029) but not after TAF switch (P = 0.90). By week 96, 21% (55/267) of patients with CKD stage 2 at switch improved to stage 1 and 35% (30/85) of CKD stage 3-5 patients improved to stage 2 and 1.2% (1/85) to stage 1. CONCLUSIONS: Overall, we observed continued improvement in virologic response, ALT normalization, and no significant changes in eGFR following switch to TAF from TDF.

19.
JGH Open ; 5(1): 34-40, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33490611

RESUMO

Background and Aim: Although tenofovir alafenamide (TAF), as well as entecavir (ETV), is widely used as first-line treatment for patients with chronic hepatitis B, there are only a few studies comparing sequential therapy from ETV to TAF and continuous ETV monotherapy in patients with maintained virologic response to ETV. Methods: In a retrospective multicenter study, we investigated the efficacy and safety of sequential therapy from ETV to TAF (ETV-TAF group) and compared them with continuous ETV monotherapy (ETV group), using propensity score matching, in chronic hepatitis B patients. Results: From 442 patients, we analyzed 142 patients from each group comprising 71 patients matched for several data, including age, HBV genotype, hepatitis B envelope antigen, cirrhosis, alanine aminotransferase, platelet count, prior ETV monotherapy period, and hepatitis B surface antigen (HBsAg) change during prior ETV monotherapy. In the ETV-TAF group, HBsAg levels significantly decreased from baseline to 48 weeks after switching to TAF (-0.02 log IU/mL, P = 0.038). HBcrAg levels also significantly decreased after switching to TAF (-0.1 log IU/mL, P = 0.004). However, there were no significant differences in the reduction of HBsAg and HBcrAg levels between the ETV-TAF and ETV groups. There was no significant difference in the change of estimated glomerular filtration rate levels from baseline to 48 weeks between the two groups. Conclusions: The present study indicated that the efficacy, especially of the HBsAg-reducing action, and safety of sequential therapy from ETV to TAF were similar to those of continuous ETV monotherapy among chronic hepatitis B patients with maintained virologic response to ETV.

20.
Dig Dis ; 39(3): 225-233, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32731217

RESUMO

BACKGROUND: We aimed to elucidate the characteristics and prognosis of autoimmune hepatitis (AIH) patients with immunoglobulin (Ig) G4-positive plasma cell infiltration. METHODS: We enrolled 84 AIH patients. The number of IgG- and IgG4-positive plasma cells was immunohistochemically counted per high-power field in the portal area. Patients with 3 or more IgG4-positive plasma cells on average and a ratio of IgG4 to IgG-positive plasma cells ≥5% were defined as IgG4-associated AIH (IgG4-AIH), and their clinicopathological characteristics and prognosis were compared to those of the remaining classical-AIH patients. RESULTS: Ten (11.9%) and 74 patients (88.1%) were categorized as IgG4-AIH and classical-AIH patients, respectively. The median age of the IgG4-AIH patients was 67 years, the majority was female (80.0%), and the distribution was similar to that of the classical-AIH patients. The IgG4-AIH patients exhibited significantly more severe phenotypes in portal inflammation, interface hepatitis, fibrosis, and rosette formation. All clinical laboratory data were similar except for serum IgG4 levels, which were higher in IgG4-AIH patients (168.5 vs. 22.9 mg/dL, p = 0.014). During a median follow-up period of 139 months, the relapse rate was significantly lower in the IgG4-AIH group than in the classical-AIH group (11.1 vs. 49.2%; p = 0.048). Twelve (16.2%) and 6 (8.1%) classical-AIH patients underwent liver-related events and liver-related deaths, respectively. In contrast, none of the IgG4-AIH patients progressed to severe liver disease. CONCLUSIONS: The IgG4-AIH patients had more severe inflammation and advanced fibrosis in the liver. However, their prognosis was not poor compared to that of classical-AIH patients. IgG4-AIH may have a phenotype distinct from classical-AIH.


Assuntos
Hepatite Autoimune/imunologia , Hepatite Autoimune/patologia , Imunoglobulina G/imunologia , Plasmócitos/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hepatite Autoimune/diagnóstico , Humanos , Hepatopatias/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
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