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1.
JCI Insight ; 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33621209

RESUMO

Studies of human hepatitis B virus (HBV) immune pathogenesis are hampered by limited access to liver tissues and technologies for detailed analyses. Here, utilizing imaging mass cytometry (IMC) to simultaneously detect 30 immune, viral and structural markers in liver biopsies from patients with HBeAg+ chronic hepatitis B, we provide novel comprehensive visualization, quantitation and phenotypic characterizations of hepatic adaptive and innate immune subsets that correlated with hepatocellular injury, histological fibrosis and age. We further show marked correlations between adaptive and innate immune cell frequencies and phenotype, highlighting complex immune interactions within the hepatic microenvironment with relevance to HBV pathogenesis.

2.
J Viral Hepat ; 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33305401

RESUMO

Pan and colleagues(1) used a prospective cohort and meta-analysis to investigate the role of caesarean section (CS) and non-breastfeeding on mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in the setting of high maternal viral load and absence of anti-viral therapy. The prospective cohort of 857 newborns found no significant benefit, yet the authors suggested "a tendency to reduce risk of infection". As the largest study to address this question and with adequate power to detect a meaningful benefit if present, this conclusion seems misplaced. The subsequent meta-analysis concluded there was benefit of CS and non-breastfeeding. However, the effect was modest; 23 women would need to undergo CS and 65 avoid breastfeeding to prevent one MTCT. Our concern is that the "costs" in terms of morbidity from CS and loss of infant benefits of breastfeeding are not emphasized.

3.
Hepatology ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33150599

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has exposed health care inequities in the United States and highlighted the importance of social conditions in shaping the health of individuals. In the field of hepatology, social determinants of health (SDOH) are closely linked to disparities in liver disease prevalence, outcomes, and access to treatment. The economic disruption and physical distancing policies brought on by the COVID-19 pandemic have further exacerbated these disparities, and may have long-lasting health consequences for marginalized patients with chronic liver disease. There are several ways that hepatology providers can bridge the gap in health equity through addressing SDOH, extending from the individual to the community and societal levels. Interventions at the individual level include implementation of systematic screening for social barriers in our hepatology practices to identify gaps in the care cascade. At the community and societal levels, interventions include creating collaborative partnerships with public health workers to expand health care access to the community, increasing funding for research investigating the association of SDOH, health disparities, and liver disease, engaging in advocacy to support policy reform that tackles the upstream social determinants, and addressing racism and implicit bias. As hepatology practices adapt to the "new normal," now is the time for us to address our patients' social needs within the context of health care delivery and reimagine ways in which to provide care to best serve our most vulnerable patients with liver disease in the COVID-19 era and beyond.

4.
Am J Gastroenterol ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33136566

RESUMO

INTRODUCTION: Young adults with alcohol-associated liver disease (ALD) are the fastest increasing demographic contributing to liver-related deaths; their outcomes after liver transplantation (LT) are understudied. METHODS: Using the United Network for Organ Sharing registry, we performed sex-specific analyses because of a significant interaction between sex and the explanatory variable, age. Cox regression was used with overall post-LT death as the primary outcome, adjusted for survival characteristics and center clustering. We calculated the absolute difference in adjusted 5-year post-LT survival between patient groups. Causes of death were supplemented by manual review of free-text entries. RESULTS: Among 42,014 LT recipients, 16,190 women (2,782 with ALD and 13,408 without ALD) and 25,824 men (9,502 with ALD and 16,322 without ALD), age of 40-50 years had the lowest risk of death. Women with ALD younger than 40 years had incrementally lower adjusted 5-year survival (95% confidence interval): 74% (63%-88%) for those aged 18-29 years, 82% (78%-87%) for those aged 30-39 years, and 90% (88%-92%) for those aged 40-49 years. Among women without ALD, men with ALD, and men without ALD, adjusted 5-year survival for ages 18-29, 30-39, and 40-49 years was similar. Among women, not men, there were significant interactions between younger age and ALD. Adjusted hazard for mortality for women with ALD vs without ALD was greater for those who aged 18-29 years (2.82 vs 1.09, P = 0.002) and 30-39 years (1.83 vs 1.09, P = 0.007 [reference age 40-49 years]). Among women with ALD, those aged 18-29 and 30-39 years had an absolute 17.7% and 9.5% excess in adjusted 5-year mortality vs similarly aged women without ALD. DISCUSSION: Young women (age < 40) with ALD have excess mortality beyond one-year post-LT. Recurrent disease or explicit mention of alcohol was the most common identified cause of death in this demographic.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33046891

RESUMO

The management of viral hepatitis in the setting of pregnancy requires special consideration. There are five liver-specific viruses (hepatitis A, B, C, D, E), each with unique epidemiology, tendency to chronicity, risk of liver complications and response to antiviral therapies. In the setting of pregnancy, the liver health of the mother, the influence of pregnancy on the clinical course of the viral infection and the effect of the virus or liver disease on the developing infant must be considered. Although all hepatitis viruses can harm the mother and the child, the greatest risk to maternal health and subsequently the fetus is seen with acute hepatitis A virus or hepatitis E virus infection during pregnancy. By contrast, the primary risks for hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus are related to the severity of the underlying liver disease in the mother and the risk of mother-to-child transmission (MTCT) for HBV and HCV. The prevention of MTCT is key to reducing the global burden of chronic viral hepatitis, and prevention strategies must take into consideration local health-care and socioeconomic challenges. This Review presents the epidemiology of acute and chronic viral hepatitis infection in pregnancy, the effect of pregnancy on the course of viral infection and, conversely, the influence of the viral infection on maternal and infant outcomes, including MTCT.

7.
Transplantation ; 104(10): 2078-2086, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32969987

RESUMO

BACKGROUND: We evaluated trends and outcomes of liver transplantation (LT) recipients with/without HIV infection. METHODS: LT recipients between 2008 and 2015 from the United Network for Organ Sharing and Organ Procurement and Transplantation Network and European Liver Transplant Registry were included. Trends and characteristics related to survival among LT recipients with HIV infection were determined. RESULTS: Among 73 206 LT patients, 658 (0.9%) were HIV-infected. The proportion of LT HIV-infected did not change over time (P-trend = 0.16). Hepatitis C virus (HCV) as indication for LT decreased significantly for HIV-infected and HIV-uninfected patients (P-trends = 0.008 and <0.001). Three-year cumulative graft survival in LT recipients with and without HIV infection was 64.4% and 77.3%, respectively (P < 0.001), with improvements over time for both, but with HIV-infected patients having greater improvements (P-trends = 0.02 and 0.03). Adjusted risk of graft loss was 41% higher in HIV-infected versus HIV-uninfected (adjusted hazard ratio [aHR], 1.41; P < 0.001). Among HIV-infected, model of end-stage liver disease (aHR, 1.04; P < 0.001), body mass index <21 kg/m (aHR, 1.61; P = 0.006), and HCV (aHR, 1.83; P < 0.001) were associated with graft loss, whereas more recent period of LT 2012-2015 (aHR, 0.58; P = 0.001) and donor with anoxic cause of death (aHR, 0.51; P = 0.007) were associated with lower risk of graft loss. CONCLUSIONS: Patients with HIV infection account for only 1% of LTs in United States and Europe, with fewer LT for HCV disease over time. A static rate of LT among HIV-infected patients may reflect improvements in cirrhosis management and/or persistent barriers to LT. Graft and patient survival among HIV-infected LT recipients have shown improvement over time.

8.
Hepatology ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32926749

RESUMO

Organs from HCV-viremic donors have been used in HCV-uninfected recipients (D+/R-) but the optimal treatment approach has not been defined. We evaluated the kinetics of HCV infection post-transplant in D+/R- kidney (KT) and liver transplant (LT) recipients when a preemptive antiviral strategy was used. Six U.S. transplant programs prospectively treated D+/R- primary LT and KT recipients with sofosbuvir-velpastasvir for 12 weeks starting once viremia was confirmed post-transplant and the patient judged to be clinically stable including eGFR >30 ml/min. Primary endpoints were sustained virologic response at 12 weeks post-transplant (SVR12) and safety (assessed by proportion of treatment-related adverse and serious adverse events). Of 24 patients transplanted (13 liver of whom 2 had prior treated HCV infection, 11 kidney), 23 became viremic post-transplant. The median (IQR) time from transplant to start of antiviral therapy was 7.0 (6.0,12.0) vs. 16.5 (9.8,24.5) days and the median (IQR) HCV RNA level 3 days after transplant was 6.5 (3.9,7.1) vs. 3.6 (2.9,4.0) log10 IU/mL in LT vs. KT recipients, respectively. By week four of treatment, 10/13 (77%) LT, but only 2/10 (20%) KT had undetectable HCV RNA (p=0.01). At the end of treatment, all LT recipients were HCV RNA undetectable, while three (30%) of the kidney recipients still had detectable, but not quantifiable, viremia. All achieved SVR12 (lower 95% CI bound 85%). Serious adverse events considered possibly related to treatment were antibody-mediated rejection, biliary sclerosis, cardiomyopathy and graft-versus-host-disease, with the latter associated with multiorgan failure, premature treatment discontinuation and death. We conclude that despite differing kinetics of early HCV infection in liver versus non-liver recipients, a preemptive antiviral strategy is effective. Vigilance for adverse immunologic events is warranted.

9.
Hepatology ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32946672

RESUMO

This first Practice Guidance on Reproductive Health from the American Association for the Study of Liver Diseases (AASLD) is intended to be a comprehensive reference on adolescents and adults with chronic liver disease. The Guidance specifically (1) addresses management of reproductive health in women and men from puberty to senescence and (2) summarizes the natural history, risk factors, evaluation, and optimal management of liver diseases during pregnancy and after birth.

10.
Semin Thromb Hemost ; 46(6): 682-692, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32820479

RESUMO

Thrombocytopenia is one of the most common hematologic complications in cirrhosis. Despite limited data linking platelet count and bleeding risk in patients with cirrhosis, the use of platelets transfusions for invasive procedures has been a common practice. Recently, thrombopoietin (TPO) receptor agonists have been approved for use in patients with chronic liver disease (CLD) undergoing invasive procedures. The aim of this study was to review current literature on bleeding risk in patients with cirrhosis and the use of platelet transfusions and TPO receptor agonists in the context of invasive procedures. PubMed search was conducted to find articles relating to cirrhosis, thrombocytopenia, and new novel treatments for this condition. Search terms included CLD, cirrhosis, thrombocytopenia, bleeding, thrombosis, coagulopathy, hemostasis, and TPO receptor agonists. Romiplostim, eltrombopag, avatrombopag, and lusutrombopag are approved TPO receptor agonists, with avatrombopag and lusutrombopag specifically approved for use in patients with CLD undergoing invasive procedures. In patients with platelet counts < 50,000/mm3, avatrombopag and lusutrombopag increased the platelet counts above this threshold in the majority of treated patients and reduced the frequency of platelet transfusions. At the approved doses, incidence of thrombosis was not increased and therapies were well tolerated. Studies were not powered to assess whether risk of bleeding complications was reduced and the fundamental question of whether correction of thrombocytopenia is warranted in patients undergoing invasive procedures remains unanswered. The use of TPO receptor agonists has resulted in less requirement for platelet transfusions. In patients with cirrhosis undergoing invasive procedures for whom platelet transfusion is planned, TPO receptor agonists are an alternative and avoid the risks associated with transfusions. However, there is need for a thoughtful approach to manage bleeding risk in patients with cirrhosis undergoing procedures, with the consideration of a comprehensive hemostatic profile, the severity of portal hypertension, and the complexity of the invasive procedure to guide decisions regarding transfusions or use of TPO receptor agonists.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32801014

RESUMO

BACKGROUND & AIMS: Despite apparent differences between men and women in the prevalence and incidence of nonalcoholic fatty liver disease (NAFLD), there are limited epidemiologic data regarding the associations of reproductive and hormone-related factors with NAFLD. We examined the associations of these factors and exogenous hormone use with NAFLD risk in African American, Japanese American, Latino, Native Hawaiian, and white women. METHODS: We conducted a nested case-control study (1861 cases and 17,664 controls) in the Multiethnic Cohort Study. NAFLD cases were identified using Medicare claims data; controls were selected among participants without liver disease and individually matched to cases by birth year, ethnicity, and length of Medicare enrollment. Reproductive and hormone-related factors and covariates were obtained from the baseline questionnaire. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% CIs. RESULTS: Later age at menarche was associated inversely with NAFLD (Ptrend = .01). Parity, regardless of number of children or age at first birth, was associated with increased risk of NAFLD (OR, 1.25; 95% CI, 1.05-1.48). Oral contraceptive use also was linked to increased risk of NAFLD (OR, 1.14; 95% CI, 1.01-1.29; duration of use Ptrend = .04). Compared with women with natural menopause, those with oophorectomy (OR, 1.41; 95% CI, 1.18-1.68) or hysterectomy (OR, 1.33; 95% CI, 1.11-1.60) had an increased risk of NAFLD. A longer duration of menopause hormone therapy (only estrogen therapy) was linked with an increasing risk of NAFLD (OR per 5 years of use, 1.08, 95% CI, 1.01-1.15). CONCLUSIONS: Findings from a large multiethnic study support the concept that menstrual and reproductive factors, as well as the use of exogenous hormones, are associated with the risk of NAFLD.

12.
Gastroenterology ; 159(5): 1752-1762.e10, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32781083

RESUMO

BACKGROUND & AIMS: The incidence of cirrhosis is increasing among women of childbearing age. Contemporary outcomes of pregnant women with cirrhosis and their infants, as well as liver-related complications, have not been described in North America, to our knowledge. We investigated the association between cirrhosis and perinatal outcomes and evaluated perinatal liver-related events. METHODS: We performed a retrospective cohort study using population-based administrative health care data from Ontario, Canada (2000-2017). We identified pregnant women with compensated cirrhosis (n = 2022) using validated case definitions and routine mother-infant linkage; the women were matched to 10,110 pregnant women in the general population (1:5) based on birth year and socioeconomic status. Maternal and infant outcomes up to 6 weeks postpartum and liver-related complications up to 1 year postpartum were evaluated by using multivariate log-binomial regression. RESULTS: After we adjusted for demographic and metabolic risk factors, cirrhosis was independently associated with intrahepatic cholestasis of pregnancy (relative risk [RR], 10.64; 95% confidence interval [CI], 7.49-15.12), induction of labor (RR, 1.15; 95% CI, 1.03-1.28), puerperal infections (RR, 1.32; 95% CI, 1.02-1.70), preterm birth (RR, 1.60; 95% CI, 1.35-1.89), infants who were large for gestational age (RR, 1.24; 95% CI, 1.05-1.46), and neonatal respiratory distress (RR, 1.20; 95% CI, 1.02-1.42). Fewer than 2% of pregnant women with cirrhosis had liver-related complications, but these occurred in a significantly higher proportion of women with a history of hepatic decompensation (13%) than women with compensated cirrhosis (1.2%) (P < .001). CONCLUSIONS: In a population-based study, we found that cirrhosis is an independent risk factor for adverse perinatal outcomes. However, liver-related complications are rare. Multidisciplinary teams are needed to coordinate care for pregnant women with cirrhosis during pregnancy and postpartum to optimize outcomes.

13.
Am J Surg ; 220(3): 566-579, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32600846

RESUMO

BACKGROUND: As obesity prevalence grows, more end-stage organ disease patients will be precluded from transplant. Numerous reports suggest bariatric surgery in end-stage organ disease may help patients achieve weight loss sufficient for transplant listing. METHODS: We performed a systematic review/meta-analysis of studies of bariatric surgery to achieve solid organ transplant listing. RESULTS: Among 82 heart failure patients, 40.2% lost sufficient weight for listing, 29.3% were transplanted, and 8.5% had sufficient improvement with weight loss they no longer required transplantation. Among 28 end-stage lung disease patients, 28.6% lost sufficient weight for listing, 7.1% were transplanted, and 14.3% had sufficient improvement following weight loss they no longer required transplant. Among 41 cirrhosis patients, 58.5% lost sufficient weight for listing, 41.5% were transplanted, and 21.9% had sufficient improvement following weight loss they no longer required transplant. Among 288 end-stage/chronic kidney disease patients, 50.3% lost sufficient weight for listing and 29.5% were transplanted. CONCLUSIONS: Small sample size and publication bias are limitations; however, bariatric surgery may benefit select end-stage organ disease patients with obesity that precludes transplant candidacy.


Assuntos
Cirurgia Bariátrica , Transplante de Órgãos , Humanos , Obesidade Mórbida/cirurgia , Seleção de Pacientes , Perda de Peso
14.
Ann Hepatol ; 19(4): 388-395, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32507734

RESUMO

INTRODUCTION AND OBJECTIVES: Universal vaccination at birth and in infancy is key to the elimination of chronic hepatitis B infection. We aimed to assess hepatitis B immune-prophylaxis and perinatal transmission knowledge, in a large and ethnically diverse cohort of previously pregnant North American women, chronically infected with hepatitis B. MATERIALS AND METHODS: The Hepatitis B Research Network (HBRN) is comprised of 28 Clinical Centers in the United States and Canada. Female cohort participants were administered a questionnaire to assess: (1) their assertion of knowledge regarding HBV prophylaxis at birth, testing, and diagnosis of hepatitis B in their children, and (2) the percentage of affirmative to negative responses for each of the HBV-related interventions her child may have received. The relationship between asserted knowledge, actions taken and maternal demographics were assessed. RESULTS: A total of 351 mothers with 627 children born in or after 1992 were included. Median age at enrollment was 39.8 years. Mothers were mostly foreign-born with the largest percentage from Asia (73.4%) and Africa (11.7%). Of the 627 children, 94.5% had mothers who asserted that they knew whether their child had received HBIG or HBV vaccine at birth, for 88.8% of the children, their mothers indicated that they knew if their child was tested for HBV and for 84.5% of children, their mothers knew if the child was diagnosed with HBV infection. Among children whose mothers asserted knowledge of their HBV management, 95.3% were reported to have received HBIG or HBV vaccine, 83.4% of children were said to have been tested for HBV, and 4.8% of children were said to have been diagnosed with HBV. Younger maternal age was the only factor significantly associated with higher percentage of children for whom mothers reported knowledge of testing (p=0.02) or diagnosis of HBV (p=0.02). CONCLUSIONS: While high percentages of North American children had mothers asserting knowledge of HBV prophylaxis and testing, knowledge gaps remain, with mothers of 5.5-15.5% of children lacking knowledge of key components of the HBV prevention and diagnosis in the perinatal setting. Targeted education of HBsAg-positive mothers may aid in closing this gap and reducing vertical transmission.

15.
Aliment Pharmacol Ther ; 52(2): 382-389, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32432816

RESUMO

BACKGROUND: Chronic hepatitis B infection is an important contributor to mortality in the United States, yet impact of available and effective oral antivirals on mortality among infected individuals is unknown. AIMS: To compare risks and predictors of mortality in a recent time period between those with chronic, prior and no hepatitis B infection. METHODS: This is a population-based cohort study of National Health and Nutrition Examination Surveys participants between 1999 and 2014 linked to National Death Index data. Adults aged 20 years or older with hepatitis B serologic testing were included. Outcomes of all-cause and liver-related mortality were evaluated using Cox regression. RESULTS: Of 39 206 participants, 192 (0.5%) had chronic and 2694 (6.9%) had prior hepatitis B infection. The all-cause age/sex-standardised mortality rates for chronic, prior and uninfected were 21.4, 15.1 and 11.8 per 1000 person-years respectively. Liver-related mortality occurred at respective rates of 4.1, 0.3 and 0.1 per 1000 person-years. In multivariable analyses, those with chronic infection had 1.9-fold (95% CI 1.1-3.3) increased hazard of all-cause mortality and 13.3-fold (95% CI 3.9-45.5) increased hazard of liver-related mortality compared to uninfected. Predictors of all-cause mortality among chronic infection included heavy alcohol use (HR 18.3, 95% CI 3.3-100.6) and higher alanine aminotransferase (HR 1.02, 95% CI 1.00-1.03). CONCLUSIONS: Mortality among adults living with chronic hepatitis B infection still exceeds that of uninfected despite availability of improved therapeutics. Identification of chronic infection, initiation of treatment among eligible and modulation of co-factors for disease progression are needed to improve survival.


Assuntos
Hepatite B Crônica/mortalidade , Alanina Transaminase/sangue , Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/mortalidade , Estudos de Coortes , Feminino , Hepatite B Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia
16.
Cancer Lett ; 480: 39-47, 2020 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-32229190

RESUMO

The hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC), partly driven by viral integration and specific oncogenic HBV variants. However, the biological significance of HBV genomes within lymphoid cells (i.e., peripheral blood mononuclear cells, PBMCs) is unclear. Here, we collected available plasma, PBMC, liver, and tumor from 52 chronic HBV (CHB) carriers: 32 with HCC, 19 without HCC, and one with dendritic cell sarcoma, DCS. Using highly sensitive sequencing techniques, next generation sequencing, and AluPCR, we demonstrate that viral genomes (i.e., HBV DNA, RNA, and cccDNA), oncogenic variants, and HBV-host integration are often found in all sample types collected from 52 patients (including lymphoid cells and a DCS tumor). Viral integration was recurrently identified (n = 90 such hits) in genes associated with oncogenic consequences in lymphoid and liver cells. Further, HBV genomes increased in PBMCs derived from 7 additional (treated or untreated) CHB carriers after extracellular mitogen stimulation. Our study shows novel HBV molecular data and replication not only liver, but also within 63.8% of lymphoid cells analysed (including a representative lymphoid cell malignancy), that was enhanced in ex vivo stimulated PBMC.

17.
J Hepatol ; 73(3): 540-548, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32243960

RESUMO

BACKGROUND & AIMS: Direct-acting antiviral (DAA) therapy is used in patients with HCV-related decompensated cirrhosis with the expectation of improving hepatic function. However, little is known about the long-term hepatic benefit of successful antiviral treatment. METHODS: Patients with advanced/decompensated cirrhosis (model for end-stage liver disease [MELD] ≥10), in whom NS5A-containing DAA therapy was initiated prior to September 2018, were included (from the HCV-TARGET cohort). Treatment outcomes and the impact of treatment on short-term and long-term hepatic function were examined. RESULTS: A total of 642 patients were analyzed. The mean age was 60 years, 68% were male. The median baseline MELD was 12 (range 10-39) and 64% had prior decompensation. Among patients with available virologic outcomes, 90.5% achieved a sustained virologic response at 12 weeks (SVR12). Eighty (24%) patients achieved a clinically significant decrease in MELD by ≥3 points during short-term follow-up (9-26 weeks after the end of treatment). However, in long-term follow-up (median of 4 years after treatment), mean changes in MELD (-0.30 points), total bilirubin (+0.23 mg/dl) and albumin (+0.36 g/dl) were marginal. Fifty-one patients died and 22 underwent liver transplant. In long-term follow-up, a clinically meaningful decrease in MELD of ≥3 occurred in 29% and a final MELD score of <10 was achieved in 25%. CONCLUSION: In a large real-world experience of patients with advanced/decompensated HCV-related cirrhosis treated with DAAs, there were only marginal improvements in MELD, total bilirubin, or albumin at long-term follow-up (after achieving SVR12). These patients may remain at high risk of decompensation and must continue to be closely monitored. CLINICALTRIALS.GOV: NCT01474811. LAY SUMMARY: Hepatitis C virus infection can now be cured with medications, even in patients who have advanced scarring of the liver (cirrhosis). In this study, we evaluated whether liver function improves or deteriorates in the long-term, following successful treatment of hepatitis C in patients with cirrhosis. We found that overall liver function was relatively stable with only 29% of patients achieving a clinically meaningful improvement in liver function, and we therefore believe that these patients require ongoing monitoring.

18.
Am J Kidney Dis ; 75(5): 665-683, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32279907

RESUMO

The first KDIGO (Kidney Disease: Improving Global Outcomes) guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection was published in 2008. The ensuing decade bore witness to remarkable advances in the treatment of HCV infection following the approval of direct-acting antiviral (DAA) agents that deliver cure rates routinely >95%. In this context, the KDIGO organization correctly recognized the need for an updated HCV guideline that would be relevant to the treatment of HCV-infected patients with kidney disease in the DAA era. The current NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) commentary provides an in-depth review and perspective on the 2018 KDIGO guideline. Of note, the KDIGO work group made significant updates to guideline chapters 2 and 4 as a direct result of the availability of DAAs. The intent of this commentary is to provide useful interpretation for nephrologists and other practitioners caring for HCV-infected patients with chronic kidney disease, including dialysis patients and kidney transplant recipients. The availability of DAA agents that are safe and highly effective has created new opportunities, such as the transplantation of kidneys from HCV-infected kidney donors. The ability to treat HCV infection in patients with kidney disease will have a significant impact on the care of our patients and should favorably influence long-term outcomes as well.


Assuntos
Hepatite C , Guias de Prática Clínica como Assunto , Antivirais/farmacologia , Antivirais/uso terapêutico , Infecção Hospitalar/diagnóstico , Gerenciamento Clínico , Seleção do Doador , Diagnóstico Precoce , Contaminação de Equipamentos , Previsões , Genótipo , Hepacivirus/genética , Hepatite B/complicações , Hepatite B/diagnóstico , Hepatite C/complicações , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C/prevenção & controle , Humanos , Controle de Infecções/métodos , Transplante de Rim , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Programas de Rastreamento , Diálise Renal/efeitos adversos , Diálise Renal/instrumentação , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Pesquisa
19.
Ann Hepatol ; 19(4): 437-445, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32139262

RESUMO

INTRODUCTION AND OBJECTIVES: The prevalence of alcohol, tobacco, and coffee use and association with liver health among North Americans with Chronic Hepatitis B (CHB) infection has not been well described. MATERIALS AND METHODS: The Hepatitis B Research Network includes an observational study of untreated CHB adults enrolled at 21 sites in the United States and Canada. Alcohol use was categorized as none, moderate, and at-risk based on the definition from the National Institute on Alcohol Abuse and Alcoholism; tobacco use as never, current and former; coffee use as none, 1-2 cups/day, and ≥3 cups/day. Linear regression and linear mixed models were used to associate lifestyle behaviors with ALT and FIB-4 values. RESULTS: 1330 participants met eligibility: 53% males, 71% Asian and the median age was 42 years (IQR: 34-52). Median ALT was 33U/L (IQR: 22-50), 37% had HBV DNA <103IU/mL, 71% were HBeAg negative, and 65% had a FIB-4 <1.45. At baseline, 8% of participants were at-risk alcohol drinkers, 11% were current smokers and 92% drank <3 cups of coffee/day. Current tobacco and 'at-risk' alcohol use, were significantly associated with elevated ALT levels in univariable analyses, however, these associations were not statistically significant when controlling for sociodemographic and HBV characteristics. CONCLUSIONS: In this large diverse cohort of untreated CHB participants, at-risk alcohol use, current tobacco use and limited coffee consumption did not have an association with high ALT and FIB-4 values. In contrast, significant associations were found between the frequency of these lifestyle behaviors and sociodemographic factors.

20.
Expert Rev Gastroenterol Hepatol ; 14(3): 175-184, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32077333

RESUMO

Introduction: Severe alcohol-associated hepatitis (sAH) portends high morbidity and mortality and there are no effective therapies for those ineligible or unresponsive to corticosteroids. Early liver transplantation (LT) defined as transplantation without a mandated period of sobriety, for sAH, is being increasingly considered as a rescue therapy.Areas covered: PubMed and manual searches were combined and last performed on 28 October 2019. Key search terms were 'alcoholic hepatitis', 'abstinence', 'alcohol relapse', and 'liver transplantation'. Terms were combined within each database. General reviews and references from published trials were also used.Expert opinion: Early LT is indicated in highly selected patients with sAH. While long-term data are sparse, 1 and 3-year survival post-transplantation are excellent and comparable to other liver diseases. Alcohol relapse is uncommon but approaches 10-25% at 3 years and if use is heavy and/or sustained leads to reduced survival. Thus, for continued application of transplantation for this indication, there is a need to further refine selection criteria and to optimize management of alcohol use disorder (AUD) in the transplant setting. Integral to advancing these objectives is the elimination of societal stigmatization and an acknowledgment that AUD is a medical condition that requires long-term management.

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