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OBJECTIVE: To apply the new nomenclature for steatotic liver diseases (SLD), replacing nonalcoholic fatty liver disease (NAFLD) with metabolic dysfunction-associated steatotic liver disease (MASLD), in adolescents using National Health and Nutrition Examination Survey (NHANES) data. METHODS: Among 1410 adolescents (12-19 years) in NHANES (2017-March, 2020), the controlled attenuation parameter (CAP) of transient elastography (TE) was used to define steatosis and fibrosis (TE ≥ 7.4 kPa). Obesity and alanine aminotransferase (ALT) ≥ 80 U/L were used to identify adolescents qualifying for hepatology referral according to practice guidelines. NAFLD was defined as liver steatosis without a specific exposure; it has no cardiometabolic risk factor requirement, unlike MASLD. RESULTS: Steatosis (yes/no) is the first decision point in the new diagnostic protocol; however, criteria for steatosis are undefined. At the supplier (EchoSens)-recommended CAP threshold of 240 dB/m, 30.5% (95% confidence interval [CI]: 27.1%-34.0%) of adolescents had SLD and about 85% of adolescents with NAFLD met criteria for MASLD. The other 15% would receive an ambiguous diagnosis of either cryptogenic SLD or possible MASLD. At higher CAP thresholds, MASLD/NAFLD concordance increased and approached 100%. Among adolescents with MASLD-fibrosis, only 8.8% (95% CI: 0%-19.3%) had overweight/obese and ALT ≥ 80 U/L. CONCLUSIONS: The new nomenclature highlights the high prevalence of liver steatosis. At the CAP threshold of 240 dB/m, however, approximately 15% of adolescents would receive an ambiguous diagnosis, which could lead to confusion and worry. Fewer than 10% of adolescents with MASLD-fibrosis had overweight/obese and ALT ≥ 80 U/L. Revised guidelines are needed to ensure that the other 90% receive appropriate referral and liver disease care.
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Técnicas de Imagem por Elasticidade , Fígado Gorduroso , Cirrose Hepática , Inquéritos Nutricionais , Terminologia como Assunto , Humanos , Adolescente , Masculino , Feminino , Estados Unidos/epidemiologia , Criança , Adulto Jovem , Fígado Gorduroso/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Prevalência , Alanina Transaminase/sangueRESUMO
Chronic HCV infection induces interferon and dysregulates immune responses through inflammation and chronic antigenic stimulation. Antiviral drugs can cure HCV, providing a unique opportunity to examine the immunological restoration that does and does not occur when a chronic viral infection is eradicated. We quantified blood cytokines levels and used mass cytometry to immunophenotype peripheral blood mononuclear cells before and after HCV cure in 2 groups of patients and controls. At baseline, serum interferon α and soluble CD163 (a macrophage product) were elevated in both liver transplant and nonliver transplant patients compared to controls; the frequencies of several peripheral blood mononuclear cell populations differed from controls; and programmed death protein 1-positivity was increased in nearly all T cell subsets. Many abnormalities persisted after HCV cure, including elevated programmed death protein 1 expression on CD4 naïve and central memory T cells, elevated soluble CD163, and expansion of the plasmablast/plasma cell compartment. Several myeloid-lineage subsets, including Ag-presenting dendritic cells, remained dysregulated. In mechanistic studies, interferon α treatment increased programmed death protein 1 on human T cells and increased T cell receptor signaling. The data identify immunological abnormalities that persist after curative HCV treatment. Before cure, high levels of interferon α may stimulate programmed death protein 1 expression on human T cells, causing persistent functional changes.
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Antígenos CD , Antígenos de Diferenciação Mielomonocítica , Antivirais , Hepatite C Crônica , Interferon-alfa , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Antivirais/uso terapêutico , Pessoa de Meia-Idade , Feminino , Antígenos CD/imunologia , Antígenos CD/sangue , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/sangue , Antígenos de Diferenciação Mielomonocítica/imunologia , Hepatite C Crônica/imunologia , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/sangue , Hepatite C Crônica/cirurgia , Interferon-alfa/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Receptores de Superfície Celular/sangue , Receptores de Superfície Celular/imunologia , Adulto , Estudos de Casos e Controles , Idoso , Hepacivirus/imunologia , Hepacivirus/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Citocinas/sangue , Imunofenotipagem , Resultado do TratamentoRESUMO
BACKGROUND: Black patients have higher hepatocellular carcinoma (HCC)-related mortality than White patients and more often develop HCC in non-cirrhotic liver. HCC surveillance is primarily directed toward cirrhotic patients. We aimed to characterize HCC in non-cirrhotic patients and to identify factors associated with HCC beyond Milan criteria. METHODS: Demographic, imaging, laboratory, and pathology data of HCC patients at our institution, 2003-2018, were reviewed, retrospectively. Race/ethnicity were self-reported. Cirrhosis was defined as a Fibrosis-4 score ≥3.25. RESULTS: Compared to 1146 cirrhotic patients, 411 non-cirrhotic patients had larger tumors (median 4.7 cm vs. 3.1 cm, p < 0.01) and were less likely to be within Milan criteria (42.6% vs. 57.7%, p < 0.01). Among non-cirrhotic patients, Black patients had larger tumors (4.9 cm vs. 4.3 cm, p < 0.01) and a higher percentage of poorly differentiated tumors (39.4% vs. 23.1%, p = 0.02). Among cirrhotic patients, Black patients had larger tumors (3.3 cm vs. 3.0 cm, p = 0.03) and were less likely to be within Milan criteria (52.3% vs. 83.2%, p < 0.01). In multivariable analysis, lack of commercial insurance (OR 1.45 [CI 95% 1.19-1.83], p < 0.01), male sex (OR 1.34 [CI 95% 1.05-1.70], p < 0.01), absence of cirrhosis (OR 1.58 [CI 95% 1.27-1.98], p < 0.01) and Black race/ethnicity (OR 1.34 [CI 95% 1.09-1.66], p = 0.01) were associated with HCC beyond Milan criteria. Black patients had lower survival rates than other patients (p < 0.01). CONCLUSIONS: Non-cirrhotic patients had more advanced HCC than cirrhotic patients. Black patients (with or without cirrhosis) had more advanced HCC than comparable non-Black patients and higher mortality rates. Improved access to healthcare (commercial insurance) may increase early diagnosis (within Milan criteria) and reduce disparities.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Masculino , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Estudos Retrospectivos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Cirrose Hepática/complicaçõesRESUMO
BACKGROUND: Patients with advanced liver disease often have vitamin D deficiency, but the daily dosages of vitamin D3 needed to raise their serum 25-hydrodroxyvitamin D [25(OH)D] concentrations are unknown. OBJECTIVE: We aimed to establish the dose-response relationship between vitamin D3 and 25(OH)D in patients with liver cirrhosis. DESIGN: An open-label study of orally-administered vitamin D3 (gelcaps) was conducted in patients with liver cirrhosis using a tiered-dosing regimen: 4,000 IU/d for baseline 25(OH)D ≤ 15 ng/mL and 2,000 IU/d for baseline 25(OH)D > 15 to ≤ 25 ng/mL (NCT01575717). Supplementation continued for 6 months, or until liver transplantation. Changes in 25(OH)D were measured after ≥ 3 months. Dose-response data on 48 patients (21 receiving 4000 IU/d and 27 receiving 2,000 IU/d) reporting ≥ 80% adherence were analyzed using generalized estimating equations (GEE). RESULTS: Among the 48 patients, 39 (81%) had 25(OH)D > 20 ng/mL while on supplements, and none experienced hypercalcemia. The magnitude of the increase in 25(OH)D was approximately twofold greater in patients receiving the higher dose. The mean incremental increase was 5.1 ng/ml ± 3.9 of 25(OH)D per 1000 IU/d of vitamin D3. Multivariable models demonstrated a significant positive relationship between baseline 25(OH)D and serum albumin (p < 0.01) and hemoglobin (p = 0.01), and a negative relationship with the MELD score (p < 0.01) and total bilirubin (p < 0.01). CONCLUSIONS: A two-tiered dosing regimen of daily oral vitamin D3 supplementation safely raised 25(OH)D concentrations in the majority of adults with liver cirrhosis who were adherent to supplement use.
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Colecalciferol , Deficiência de Vitamina D , Adulto , Humanos , Estudos Prospectivos , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/tratamento farmacológico , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/induzido quimicamente , Suplementos Nutricionais , Vitamina DRESUMO
Objective: The Diabetes Prevention Program (DPP) is the gold standard lifestyle modification program that reduces incident type 2 diabetes mellitus. Patients with prediabetes and patients with non-alcoholic fatty liver disease (NAFLD) often share metabolic features; we hypothesized that the DPP could be adapted and used to improve outcomes in patients with NAFLD. Methods: NAFLD patients were recruited into a 1 year modified DPP. Demographics, medical comorbidities, and clinical laboratory values were collected at baseline, 6 and 12 months. The primary endpoint was change in weight at 12 months. Secondary endpoints were changes in hepatic steatosis, metabolic comorbidities, and liver enzymes (per-protocol basis) and retention at 6 and 12 months. Results: Fourteen NAFLD patients enrolled; three dropped out before 6 months. From baseline to 12 months, hepatic steatosis (p = 0.03), alanine aminotransferase (p = 0.02), aspartate aminotransferase (p = 0.02), high-density lipoprotein (p = 0.01) and NAFLD fibrosis score (p < 0.001) improved, but low-density lipoprotein worsened (p = 0.04). Conclusion: Seventy-nine percent of patients completed the modified DPP. Patients lost weight and had improvements in five out of six indicators of liver injury and lipid metabolism. Clinical Trial Registry Number: NCT04988204.
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BACKGROUND: Successful treatment of hepatitis C reduces liver inflammation and fibrosis; however, patients remain at risk of developing hepatocellular carcinoma (HCC). AIMS: To identify risk factors for new-onset HCC in patients cured of hepatitis C. METHODS: Imaging, histological, and clinical data on patients whose first HCC was diagnosed >12 months of post-SVR were analyzed. Histology of 20 nontumor tissues was analyzed in a blinded manner using the Knodel/Ishak/HAI system for necroinflammation and fibrosis/cirrhosis stage and the Brunt system for steatosis/steatohepatitis. Factors associated with post-SVR HCC were identified by comparison with HALT-C participants who did not develop post-SVR HCC. RESULTS: Hepatocellular carcinoma was diagnosed in 54 patients (45 M/9F), a median of 6 years of post-SVR [interquartile range (IQR) =1.4-10y] at a median age of 61 years (IQR, 59-67). Approximately one-third lacked cirrhosis, and only 11% had steatosis on imaging. The majority (60%) had no steatosis/steatohepatitis in histopathology. The median HAI score was 3 (1.25-4), indicating mild necroinflammation. In a multivariable logistic regression model, post-SVR HCC was positively associated with non-Caucasian race (p = 0.03), smoking (p = 0.03), age > 60 years at HCC diagnosis (p = 0.03), albumin<3.5 g/dL (p = 0.02), AST/ALT>1 (p = 0.05), and platelets <100 × 103 cells/µL (p < 0.001). Alpha fetoprotein ≥4.75 ng/mL had 90% specificity and 71% sensitivity for HCC occurrence. Noncirrhotic patients had larger tumors (p = 0.002) and a higher prevalence of vascular invasion (p = 0.016) than cirrhotic patients. CONCLUSIONS: One-third of patients with post-SVR HCC did not have liver cirrhosis; most had no steatosis/steatohepatitis. Hepatocellular carcinomas were more advanced in noncirrhotic patients. Results support AFP as a promising marker of post-SVR HCC risk.
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Carcinoma Hepatocelular , Fígado Gorduroso , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Humanos , Pessoa de Meia-Idade , Idoso , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Antivirais/uso terapêutico , Resposta Viral Sustentada , Fatores de Risco , Hepatite C/complicações , Cirrose Hepática/complicações , Fígado Gorduroso/complicações , Fígado Gorduroso/tratamento farmacológico , HepacivirusRESUMO
Background & Aims: The prevalence and aetiology of liver fibrosis vary over time and impact racial/ethnic groups unevenly. This study measured time trends and identified factors associated with advanced liver fibrosis in the United States. Methods: Standardised methods were used to analyse data on 47,422 participants (≥20 years old) in the National Health and Nutrition Examination Survey (1999-2018). Advanced liver fibrosis was defined as Fibrosis-4 ≥2.67 and/or Forns index ≥6.9 and elevated alanine aminotransferase. Results: The estimated number of people with advanced liver fibrosis increased from 1.3 million (95% CI 0.8-1.9) to 3.5 million (95% CI 2.8-4.2), a nearly threefold increase. Prevalence was higher in non-Hispanic Black and Mexican American persons than in non-Hispanic White persons. In multivariable logistic regression analysis, cadmium was an independent risk factor in all racial/ethnic groups. Smoking and current excessive alcohol use were risk factors in most. Importantly, compared with non-Hispanic White persons, non-Hispanic Black persons had a distinctive set of risk factors that included poverty (odds ratio [OR] 2.09; 95% CI 1.44-3.03) and susceptibility to lead exposure (OR 3.25; 95% CI 1.95-5.43) but did not include diabetes (OR 0.88; 95% CI 0.61-1.27; p =0.52). Non-Hispanic Black persons were more likely to have high exposure to lead, cadmium, polychlorinated biphenyls, and poverty than non-Hispanic White persons. Conclusions: The number of people with advanced liver fibrosis has increased, creating a need to expand the liver care workforce. The risk factors for advanced fibrosis vary by race/ethnicity. These differences provide useful information for designing screening programmes. Poverty and toxic exposures were associated with the high prevalence of advanced liver fibrosis in non-Hispanic Black persons and need to be addressed. Impact and Implications: Because liver disease often produces few warning signs, simple and inexpensive screening tests that can be performed by non-specialists are needed to allow timely diagnosis and linkage to care. This study shows that non-Hispanic Black persons have a distinctive set of risk factors that need to be taken into account when designing liver disease screening programs. Exposure to exogenous toxins may be especially important risk factors for advanced liver fibrosis in non-Hispanic Black persons.
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BACKGROUND & AIMS: Genetic variants affecting liver disease risk vary among racial and ethnic groups. Hispanics/Latinos in the United States have a high prevalence of PNPLA3 I148M, which increases liver disease risk, and a low prevalence of HSD17B13 predicted loss-of-function (pLoF) variants, which reduce risk. Less is known about the prevalence of liver disease-associated variants among Hispanic/Latino subpopulations defined by country of origin and genetic ancestry. We evaluated the prevalence of HSD17B13 pLoF variants and PNPLA3 I148M, and their associations with quantitative liver phenotypes in Hispanic/Latino participants from an electronic health record-linked biobank in New York City. METHODS: This study included 8739 adult Hispanic/Latino participants of the BioMe biobank with genotyping and exome sequencing data. We estimated the prevalence of Hispanic/Latino individuals harboring HSD17B13 and PNPLA3 variants, stratified by genetic ancestry, and performed association analyses between variants and liver enzymes and Fibrosis-4 (FIB-4) scores. RESULTS: Individuals with ancestry from Ecuador and Mexico had the lowest frequency of HSD17B13 pLoF variants (10%/7%) and the highest frequency of PNPLA3 I148M (54%/65%). These ancestry groups had the highest outpatient alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and the largest proportion of individuals with a FIB-4 score greater than 2.67. HSD17B13 pLoF variants were associated with reduced ALT level (P = .002), AST level (P < .001), and FIB-4 score (P = .045). PNPLA3 I148M was associated with increased ALT level, AST level, and FIB-4 score (P < .001 for all). HSD17B13 pLoF variants mitigated the increase in ALT conferred by PNPLA3 I148M (P = .006). CONCLUSIONS: Variation in HSD17B13 and PNPLA3 variants across genetic ancestry groups may contribute to differential risk for liver fibrosis among Hispanic/Latino individuals.
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Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica , Humanos , Predisposição Genética para Doença , Hispânico ou Latino/genética , Cirrose Hepática/enzimologia , Cirrose Hepática/genética , Hepatopatia Gordurosa não Alcoólica/enzimologia , Hepatopatia Gordurosa não Alcoólica/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND & AIMS: A number of genetic polymorphisms have been associated with susceptibility to or protection against non-alcoholic fatty liver disease (NAFLD), but the underlying mechanisms remain unknown. Here, we focused on the rs738409 C>G single nucleotide polymorphism (SNP), which produces the I148M variant of patatin-like phospholipase domain-containing protein 3 (PNPLA3) and is strongly associated with NAFLD. METHODS: To enable mechanistic dissection, we developed a human pluripotent stem cell (hPSC)-derived multicellular liver culture by incorporating hPSC-derived hepatocytes, hepatic stellate cells, and macrophages. We first applied this liver culture to model NAFLD by utilising a lipotoxic milieu reflecting the circulating levels of disease risk factors in affected individuals. We then created an isogenic pair of liver cultures differing only at rs738049 and compared NAFLD phenotype development. RESULTS: Our hPSC-derived liver culture recapitulated many key characteristics of NAFLD development and progression including lipid accumulation and oxidative stress, inflammatory response, and stellate cell activation. Under the lipotoxic conditions, the I148M variant caused the enhanced development of NAFLD phenotypes. These differences were associated with elevated IL-6/signal transducer and activator of transcription 3 (STAT3) activity in liver cultures, consistent with transcriptomic data of liver biopsies from individuals carrying the rs738409 SNP. Dampening IL-6/STAT3 activity alleviated the I148M-mediated susceptibility to NAFLD, whereas boosting it in wild-type liver cultures enhanced NAFLD development. Finally, we attributed this elevated IL-6/STAT3 activity in liver cultures carrying the rs738409 SNP to increased NF-κB activity. CONCLUSIONS: Our study thus reveals a potential causal link between elevated IL-6/STAT3 activity and 148M-mediated susceptibility to NAFLD. IMPACT AND IMPLICATIONS: An increasing number of genetic variants manifest in non-alcoholic fatty liver disease (NAFLD) development and progression; however, the underlying mechanisms remain elusive. To study these variants in human-relevant systems, we developed an induced pluripotent stem cell-derived multicellular liver culture and focused on a common genetic variant (i.e. rs738409 in PNPLA3). Our findings not only provide mechanistic insight, but also a potential therapeutic strategy for NAFLD driven by this genetic variant in PNPLA3. Our liver culture is therefore a useful platform for exploring genetic variants in NAFLD development.
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Hepatopatia Gordurosa não Alcoólica , Fosfolipases A2 Independentes de Cálcio , Humanos , Predisposição Genética para Doença , Interleucina-6/genética , Interleucina-6/metabolismo , Fígado/patologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Fosfolipases A2 Independentes de Cálcio/genética , Polimorfismo de Nucleotídeo Único , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismoRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) incidence and mortality vary by race/ethnicity and both are higher in Black patients than in Whites. For HCC surveillance, all cirrhotic patients are advised to undergo lifelong twice-annual abdominal imaging. We investigated factors associated with surveillance and HCC incidence in a diverse HCC risk group, cirrhotic patients recently cured of hepatitis C virus (HCV) infection. METHODS: In this observational cohort study, all participants (n = 357) had advanced fibrosis/cirrhosis and were cured of HCV with antiviral treatment. None had Liver Imaging Reporting and Data System (LI-RADS) 2-5 lesions prior to HCV cure. Ultrasound, computed tomography, and/or magnetic resonance imaging were used for surveillance. RESULTS: At a median follow-up of 40 months [interquartile range (IQR) = 28-48], the median percentage of time up-to-date with surveillance was 49% (IQR) = 30%-71%. The likelihood of receiving a first surveillance examination was not significantly associated with race/ethnicity, but was higher for patients with more advanced cirrhosis, for example, bilirubin [odds ratio (OR) = 3.8/mg/dL, p = 0.002], private insurance (OR = 3.4, p = 0.006), and women (OR = 2.3, p = 0.008). The likelihood of receiving two or three examinations was significantly lower for non-Hispanic Blacks and Hispanics versus non-Hispanic Whites (OR = 0.39, and OR = 0.40, respectively, p < 0.005 for both) and for patients with higher platelet counts (OR = 0.99/10,000 cells/µl, p = 0.01), but higher for patients with private insurance (OR = 2.8, p < 0.001). Incident HCC was associated with higher bilirubin (OR = 1.7, p = 0.02) and lower lymphocyte counts (OR = 0.16, p = 0.01). CONCLUSIONS: Contrary to best practices, HCC surveillance was associated with sociodemographic factors (insurance status and race/ethnicity) among patients cured of HCV. Guideline-concordant surveillance is needed to address healthcare disparities.
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Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Antivirais/uso terapêutico , Bilirrubina , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Feminino , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C Crônica/complicações , Humanos , Incidência , Cirrose Hepática/complicações , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologiaRESUMO
Guidelines recommend hepatitis B (HBV) testing in individuals from endemic areas, and if positive, screening for hepatocellular carcinoma (HCC). While screening programs are well established in the Asian immigrant population in New York City (NYC), less is known about the characteristics of HBV/HCC among the African immigrant community. A retrospective review was performed of HCC cases from 2005 to 2018 at our institution. Country of origin was not documented in the electronic medical record; therefore, African immigrant status was approximated using self-identified race/ethnicity, positive HBV status, and an online registry to determine country of origin based on last name. Surnames with the greatest prevalence or density in an African country were considered. Among 4400 patients with HCC, 472 identified as non-Hispanic Black; of these, 86 were HBV+. Based on surname, it was estimated that 33 individuals were likely immigrants from Africa. In this group, median age of HCC diagnosis was 48 years (IQR 43-55). In patients with an available date of HBV diagnosis (n = 24), 17 (71%) were unaware of their HBV status when they presented with HCC. Zero patients were diagnosed with HCC through routine screening, most patients (66%) were diagnosed upon imaging evaluation of symptoms. Twelve patients (36%) underwent resection or transplantation; the remaining 64% were ineligible for surgical treatment. Of the 26 patients with follow-up data, 18 (69%) died of disease or were critically ill at last encounter, and of these, 14 (77%) died within 1 year of HCC diagnosis. In conclusion, African immigrants in NYC with HBV/HCC are at high risk of HCC related mortality at a young age. Most were unaware of their hepatitis status at the time of HCC diagnosis. No patients were enrolled in routine HCC screening; the majority were diagnosed based on imaging obtained for symptoms. Most individuals presented with inoperable disease, and the majority died within months of diagnosis. Awareness of these findings may help healthcare providers improve patient outcomes.
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Carcinoma Hepatocelular , Emigrantes e Imigrantes , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Adulto , Carcinoma Hepatocelular/epidemiologia , Hepatite B/epidemiologia , Hepatite B Crônica/diagnóstico , Humanos , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Prevalência , Fatores de RiscoRESUMO
There is mounting evidence that Black patients develop more advanced liver cancers with less advanced liver disease. These findings have important implications for the future of liver cancer screening.
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Negro ou Afro-Americano , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etnologia , Detecção Precoce de Câncer/normas , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etnologia , Programas de Rastreamento/normas , Humanos , Guias de Prática Clínica como Assunto/normasRESUMO
There is constant remodeling in a cirrhotic liver resulting in cirrhosis being spatially heterogeneous. The Laennec system, and, more recently the Beijing classification, have been used to sub-classify various degrees of cirrhosis. It is unknown how these two schemes compare with each other, how they are impacted by geographic variation, and how they correlate with clinical outcomes. Five needle biopsies were obtained from 20 explanted cirrhotic HCV livers at the time of transplantation. Collagen proportionate area (CPA) was measured by computerized quantitative morphometry. The Laennec system (4A-4C indicating increasing degrees of cirrhosis) and Beijing classification (P-progressive, R-regressive, I-indeterminate) were assessed and then correlated with CPA. Geographical variation using CPAs was calculated by the coefficient of variation (CoV). CPA of Laennec 4C cirrhosis was higher than 4A (p = 0.00008) or 4B (p = 0.0002). The CPA of the P pattern was greater than the R (p = 0.002) or I patterns (p = 0.037). The mean CoV of the five CPAs was 47.3 ± 4.5%, suggesting a significant degree of geographic variation. There was 100% overlap between the Beijing R pattern and Laennec 4A, and 80% overlap between the P pattern and Laennec 4C. Patients' platelet counts of P pattern were lower than R pattern (p = 0.008) or I pattern (p = 0.024), while Laennec 4C was lower than 4A (p = 0.036) and 4B patients (p = 0.7). There was no correlation between CPA, Laennec stage, or Beijing classification and MELD score, liver weights, total bilirubin, or albumin levels. The Laennec system and the Beijing classification are highly correlated with CPA in cirrhosis. This study confirms that there is a significant degree of geographic variation in terms of fibrosis content and cirrhosis morphology throughout the liver.
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Cirrose Hepática/patologia , Fígado/patologia , Idoso , Biópsia por Agulha , Feminino , Hepatite C/complicações , Humanos , Fígado/cirurgia , Fígado/virologia , Cirrose Hepática/classificação , Cirrose Hepática/cirurgia , Cirrose Hepática/virologia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
BACKGROUND AND AIMS: Although chronic HCV infection increases mortality, thousands of patients remain diagnosed-but-untreated (DBU). We aimed to (1) develop a DBU phenotyping algorithm, (2) use it to facilitate case finding and linkage to care, and (3) identify barriers to successful treatment. APPROACH AND RESULTS: We developed a phenotyping algorithm using Java and SQL and applied it to ~2.5 million EPIC electronic medical records (EMRs; data entered January 2003 to December 2017). Approximately 72,000 EMRs contained an HCV International Classification of Diseases code and/or diagnostic test. The algorithm classified 10,614 cases as DBU (HCV-RNA positive and alive). Its positive and negative predictive values were 88% and 97%, respectively, as determined by manual review of 500 EMRs randomly selected from the ~72,000. Navigators reviewed the charts of 6,187 algorithm-defined DBUs and they attempted to contact potential treatment candidates by phone. By June 2020, 30% (n = 1,862) had completed an HCV-related appointment. Outcomes analysis revealed that DBU patients enrolled in our care coordination program were more likely to complete treatment (72% [n = 219] vs. 54% [n = 256]; P < 0.001) and to have a verified sustained virological response (67% vs. 46%; P < 0.001) than other patients. Forty-eight percent (n = 2,992) of DBU patients could not be reached by phone, which was a major barrier to engagement. Nearly half of these patients had Fibrosis-4 scores ≥ 2.67, indicating significant fibrosis. Multivariable logistic regression showed that DBUs who could not be contacted were less likely to have private insurance than those who could (18% vs. 50%; P < 0.001). CONCLUSIONS: The digital DBU case-finding algorithm efficiently identified potential HCV treatment candidates, freeing resources for navigation and coordination. The algorithm is portable and accelerated HCV elimination when incorporated in our comprehensive program.
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Algoritmos , Antivirais/uso terapêutico , Registros Eletrônicos de Saúde/estatística & dados numéricos , Hepatite C Crônica/diagnóstico , Armazenamento e Recuperação da Informação/métodos , Idoso , Estudos de Viabilidade , Feminino , Hepatite C Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: In this study, we describe the patterns of hepatocellular carcinoma (HCC) screening with imaging and factors associated with imaging modality selection in a tertiary care transplant center. METHODS: This was a retrospective study where all adult patients with cirrhosis and/or chronic hepatitis B virus infection referred for HCC screening with ultrasound (US), CT or MRI were identified during 2017. The association between imaging methods, demographic/clinical data were analyzed by uni- and multivariate analysis. RESULTS: A total of 1437 patients were included (median age 61y, 59% male, median BMI 27.5 kg/m2, median AFP 3.4 ng/mL, 37% with HCV and 87% with cirrhosis). Index screening imaging method utilization included MRI (51%), US (33%) and CT (16%). Use of US as the index imaging modality for screening was significantly associated with race/ethnicity [Odds Ratio (OR) 1.71-2.01, all p < 0.05] in multivariate analysis. Presence of cirrhosis (OR 0.29, p < 0.001) and referral by a hepatologist (OR 0.23, p < 0.001) were associated with screening with MRI in the multivariate analysis; while gender, age, BMI, etiology and income at ZIP code of residence were not significantly associated with imaging modality selection. HCC was observed in 62 patients (prevalence 4.3%). Rate of HCC detection was significantly higher with MRI vs US (5.9% vs. 1.5%, p = 0.001). CONCLUSION: MRI was the most frequently used modality (> 50%) for HCC screening in our tertiary care center, in contrast with the current practice guidelines. Race/ethnicity, cirrhosis and referral by a hepatologist were associated with the imaging method used for HCC screening.
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Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Adulto , Carcinoma Hepatocelular/diagnóstico por imagem , Feminino , Humanos , Cirrose Hepática/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Atenção Terciária , Atenção Terciária à Saúde , alfa-FetoproteínasRESUMO
BACKGROUND: The World Trade Center (WTC) attack exposed thousands of workers to toxic chemicals that have been linked to liver diseases and cancers. This study examined the relationship between the intensity of WTC dust exposure and the risk of hepatic steatosis in the WTC General Responders Cohort (GRC). METHODS: All low-dose computed tomography (CT) scans of the chest performed on the WTC GRC between September 11, 2001 and December 31, 2018, collected as part of the World Trade Center Health Program, were reviewed. WTC dust exposure was categorized into five groups based on WTC arrival time. CT liver density was estimated using an automated algorithm, statistics-based liver density estimation from imaging. The relationship between the intensity of WTC dust exposure and the risk of hepatic steatosis was examined using univariate and multivariable regression analyses. RESULTS: Of the 1788 WTC responders, 258 (14.4%) had liver attenuation less than 40 Hounsfield units (HU < 40) on their earliest CT. Median time after September 11, 2001 and the earliest available CT was 11.3 years (interquartile range: 8.0-14.9 years). Prevalence of liver attenuation less than 40 HU was 17.0% for arrivals on September 11, 2001, 16.0% for arrivals on (September 12, 2001 or September 13, 2001), 10.9% for arrivals on September 14-30, 2001, and 9.0% for arrivals on January 10, 2001 or later (p = 0.0015). A statistically significant trend of increasing liver steatosis was observed with earlier arrival times (p < 0.0001). WTC arrival time remained a significant independent factor for decreased liver attenuation after controlling for other covariates. CONCLUSIONS: Early arrival at the WTC site was significantly associated with increasing hepatic steatosis.
Assuntos
Fígado Gorduroso , Ataques Terroristas de 11 de Setembro , Estudos de Coortes , Poeira , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/epidemiologia , Fígado Gorduroso/etiologia , Humanos , Cidade de Nova Iorque , PrevalênciaRESUMO
We previously reported a higher incidence of non-albumin proteinuria and a small but significant decline in estimated glomerular filtration rate (eGFR) among HIV-negative adults randomized to emtricitabine/tenofovir disoproxil fumarate preexposure prophylaxis (FTC/TDF PrEP) versus placebo. In a nested case--control study among participants randomized to FTC/TDF PrEP, established kidney injury biomarkers measured at 12âmonths were not significantly different between participants who subsequently experienced one of these kidney endpoints and randomly selected controls who did not.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Adulto , Fármacos Anti-HIV/efeitos adversos , Biomarcadores , Emtricitabina/efeitos adversos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Humanos , Rim , Tenofovir/efeitos adversosRESUMO
New therapies offer hope for a cure to millions of persons living with hepatitis C virus (HCV) infection. HCV elimination is a global goal that will be difficult to achieve using the traditional paradigms of diagnosis and care. The current standard has evolved toward universal HCV screening and treatment, to achieve elimination goals. There are several steps between HCV diagnosis and cure with major barriers along the way. Innovative models of care can address barriers to better serve hardly reached populations and scale national efforts in the United States and abroad. Herein, we highlight innovative models of HCV care that aid in our progress toward HCV elimination.
Assuntos
Erradicação de Doenças/organização & administração , Acessibilidade aos Serviços de Saúde , Hepatite C/prevenção & controle , Programas de Rastreamento/organização & administração , Inovação Organizacional , Antivirais/uso terapêutico , Erradicação de Doenças/métodos , Hepacivirus , Hepatite C/epidemiologia , Humanos , Programas de Rastreamento/métodosRESUMO
BACKGROUND: In the United States, mortality after a diagnosis of hepatocellular carcinoma (HCC) is higher in patients who are Black than in patients of other racial groups. The objective of this study was to clarify factors contributing to this disparity by analyzing liver and tumor characteristics in patients with HCC who have a history of hepatitis C virus (HCV) infection. METHODS: Records of patients with HCV and HCC at the authors' institution from 2003 to 2018 were retrospectively reviewed. Race and ethnicity were self-identified. Imaging, laboratory, and pathologic features were compared between Black and non-Black cohorts. RESULTS: Among 1195 individuals with HCC, 390 identified as Black. At the time of HCC diagnosis, Black patients had better liver function, as measured by Child-Pugh score, Model of End-Stage Liver Disease score, histology of nontumor tissue, and fibrosis-4 (FIB-4) score (all P < .05). FIB-4 scores were <3.25 in 31% of Black patients. In addition, Black patients had less early stage HCC (20.2% vs 32.3%; P < .05), larger tumors (median [interquartile range]: 3.5 cm [2.2-6.2 cm] vs 3.1 cm [2.1-5.1 cm]; P < .01), more multiple tumors (median, [interquartile range]: 1 tumor [1-3 tumors] vs 1 tumor [1-2 tumors]; P = .03), more poorly differentiated tumors (30.3% vs 20.5%; P < .05), and more microvascular invasion (67.2% vs 56.5%; P < .05). CONCLUSIONS: Black patients with HCV exposure develop HCC at earlier stages of liver disease than members of other racial groups. Nearly one-third would not qualify for HCC screening using the common FIB-4 cirrhosis threshold. Practice guidelines that stress HCC surveillance for cirrhotic patients with HCV may need to be revised to be more inclusive for Black patients. In addition, tumors in Black patients carry worse prognostic features, and molecular studies are needed to characterize their biologic properties.
Assuntos
População Negra , Carcinoma Hepatocelular/patologia , Hepatite C/etnologia , Neoplasias Hepáticas/patologia , Idoso , Carcinoma Hepatocelular/etnologia , Carcinoma Hepatocelular/virologia , Doença Hepática Terminal , Feminino , Infecções por HIV/complicações , Hepacivirus , Hepatite B/complicações , Hepatite C/complicações , Humanos , Cirrose Hepática/patologia , Neoplasias Hepáticas/etnologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Carga TumoralRESUMO
Viral hepatitis leads to immune-mediated liver injury. The rate of disease progression varies between individuals. We aimed to phenotype immune cells associated with preservation of normal liver function during hepatitis C virus (HCV) infection. Clinical data and specimens were obtained from 19 HCV-infected patients undergoing liver transplantation. Liver and peripheral blood mononuclear cells were isolated and eight subsets of innate immune cells were delineated by multiparameter flow cytometry. Cytokine assays and microarrays were performed. Intrahepatic CD56Bright/CD16- natural killer (NK) cells comprised the only subset correlating with better liver function, i.e., lower bilirubin (p = 0.0002) and lower model for end stage of liver disease scores (p = 0.03). The signature of liver NK cells from HCV-infected patients included genes expressed by NK cells in normal liver and by decidual NK cells. Portal vein blood had a higher concentration of interleukin (IL)-10 than peripheral blood (p = 0.03). LMCs were less responsive to toll-like receptor (TLR) stimulation than PBMCs, with fewer pro-inflammatory gene-expression pathways up-regulated after in vitro exposure to lipopolysaccharide and a TLR-7/8 agonist. Hepatic CD56Bright/CD16- NK cells may be critical for maintaining liver homeostasis. Portal vein IL-10 may prime inhibitory pathways, attenuating TLR signaling and reducing responsiveness to pro-inflammatory stimuli.