ABSTRACT
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Subject(s)
Humans , Male , Middle Aged , Liver Failure, Acute/ethnology , Carcinoma, Neuroendocrine/diagnostic imaging , Carcinoma, Neuroendocrine/pathology , Carcinoma, Neuroendocrine/surgery , Immunohistochemistry/methods , Lymphadenopathy/diagnostic imaging , Lymphadenopathy/pathology , Hepatomegaly/diagnostic imaging , Hepatomegaly/pathologySubject(s)
Hepatitis B, Chronic/therapy , Liver Failure, Acute/therapy , Liver, Artificial , Asian People , China/epidemiology , Health Status Disparities , Healthcare Disparities , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/ethnology , Hepatitis B, Chronic/virology , Humans , Liver Failure, Acute/diagnosis , Liver Failure, Acute/ethnology , Liver Failure, Acute/virology , Risk Factors , Treatment OutcomeABSTRACT
BACKGROUND: The impact of ethnicity on outcomes after orthotopic liver transplantation (OLT) is unclear. The British Indo-Asian population has a high incidence of liver disease but its contribution to the national deceased donor pool is small. We evaluated access to and outcomes of OLT in Indo-Asians. METHODS: We compared 182 Indo-Asians with white patients undergoing OLT. Matching criteria were transplantation year, liver disease, age, sex. Donor and recipient characteristics, postoperative outcomes, including patient and graft survival, OLT era (early, 1987-2001; late, 2002-2011) were compared. Survival was also analyzed by underlying disease-acute liver failure (ALF) and chronic liver failure. RESULTS: Indo-Asians had higher diabetes incidence. There were no differences in waiting time for transplantation, despite smaller body size and more uncommon blood groups (B, AB) among Indo-Asians. In the early era, patient survival for Indo-Asians with ALF was worse when compared to whites. In the late era, graft and patient survival at 1, 2, and 5 years were similar between groups. CONCLUSION: This study demonstrates that Indo-Asian patients have equal access to OLT and comparable outcomes to whites in the United Kingdom. Survival has improved among Indo-Asian patients; this may be attributable to careful patient selection in case of ALF, though improvement of patient management may have contributed.
Subject(s)
Asian People , End Stage Liver Disease/ethnology , End Stage Liver Disease/surgery , Liver Failure, Acute/ethnology , Liver Failure, Acute/surgery , Liver Transplantation , Adolescent , Adult , Aged , Chi-Square Distribution , Databases, Factual , End Stage Liver Disease/diagnosis , End Stage Liver Disease/mortality , England/epidemiology , Female , Graft Survival , Health Services Accessibility , Healthcare Disparities/ethnology , Humans , Incidence , India/ethnology , Kaplan-Meier Estimate , Liver Failure, Acute/diagnosis , Liver Failure, Acute/mortality , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Male , Middle Aged , Odds Ratio , Proportional Hazards Models , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Waiting Lists , White People , Young AdultABSTRACT
BACKGROUND: We sought to compare liver transplant waiting list access by demographics and geography relative to the pool of potential liver transplant candidates across the United States using a novel metric of access to care, termed a liver wait-listing ratio (LWR). METHODS: We calculated LWRs from national liver transplant registration data and liver mortality data from the Scientific Registry of Transplant Recipients and the National Center for Healthcare Statistics from 1999 to 2006 to identify variation by diagnosis, demographics, geography, and era. RESULTS: Among patients with ALF and CLF, African Americans had significantly lower access to the waiting list compared with whites (acute: 0.201 versus 0.280; pre-MELD 0.201 versus 0.290; MELD era: 0.201 versus 0.274; all, P<0.0001) (chronic: 0.084 versus 0.163; pre-MELD 0.085 versus 0.179; MELD 0.084 versus 0.154; all, P<0.0001). Hispanics and whites had similar LWR in both eras (both P>0.05). In the MELD era, female subjects had greater access to the waiting list compared with male subjects (acute: 0.428 versus 0.154; chronic: 0.158 versus 0.140; all, P<0.0001). LWRs varied by three-fold by state (pre-MELD acute: 0.122-0.418, chronic: 0.092-0.247; MELD acute: 0.121-0.428, chronic: 0.092-0.243). CONCLUSIONS: The marked inequity in early access to liver transplantation underscores the need for local and national policy initiatives to affect this disparity.
Subject(s)
End Stage Liver Disease/surgery , Health Services Accessibility/trends , Healthcare Disparities/trends , Liver Failure, Acute/surgery , Liver Transplantation/trends , Tissue and Organ Procurement/trends , Waiting Lists , Adult , Black or African American , Aged , End Stage Liver Disease/diagnosis , End Stage Liver Disease/ethnology , End Stage Liver Disease/mortality , Female , Health Care Rationing/trends , Health Services Needs and Demand/trends , Healthcare Disparities/ethnology , Hispanic or Latino , Humans , Liver Failure, Acute/diagnosis , Liver Failure, Acute/ethnology , Liver Failure, Acute/mortality , Male , Middle Aged , Registries , Residence Characteristics , Risk Factors , Sex Factors , Time Factors , United States/epidemiology , Waiting Lists/mortality , White People , Young AdultABSTRACT
BACKGROUND: The sexual dimorphism of hepatitis B virus (HBV) -related liver diseases is related with estrogen and its receptors. Recent reports indicate that abnormal expression of estrogen receptor alpha (ESR1) may be a hallmark for the progression of liver disease and HBV carriers presenting variant ESR1 have an extremely aggressive clinical course. Here we examine whether the ESR1 polymorphisms or its haplotypes are related to HBV-related acute liver failure (ALF) risk among chronic HBV carriers in a Chinese population. METHODS: A total of 1216 unrelated Han Chinese HBV carriers were recruited in this hospital-based case-control study, including 359 HBV surface antigen (HBsAg) carriers affected with ALF and 857 asymptomatic HBsAg carriers. Two ESR1 haplotype tagging polymorphisms, c.30 T > C (rs2077647) and c.453-397 T > C (rs2234693), were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: We observed a significantly increased susceptibility to HBV-ALF associated with the c.30 C allele (P = 8.65 × 10-4), c.453-397 C allele (5.37 × 10-4) and [c.30 C; c.453-397 C] haplotype (Dominant model, P =0.0004, odds ratio = 1.53, 95% CI 1.23 ~ 1.96) compared with the T alleles and [c.30 T; c.453-397 T] haplotype of c.30 T > C and c.453-397 T > C polymorphisms, respectively. CONCLUSIONS: Our study suggests that [c.30 C; c.453-397 C] haplotype may be a risk factor for genetic susceptibility to HBV-related ALF in the Chinese population. It also emphasizes the importance of ESR1 in the pathophysiology of HBV-related ALF on the population level.
Subject(s)
Estrogen Receptor alpha/genetics , Hepatitis B virus/genetics , Hepatitis B/complications , Liver Failure, Acute/ethnology , Liver Failure, Acute/genetics , Liver Failure, Acute/virology , Polymorphism, Genetic , Adult , Alleles , Case-Control Studies , China , Female , Haplotypes , Humans , Male , Middle Aged , Polymorphism, Restriction Fragment Length , Receptors, Antigen/chemistryABSTRACT
BACKGROUND & AIMS: Keratins 8 and 18 (K8/K18) provide anti-apoptotic functions upon liver injury. The cytoprotective function of keratins explains the overrepresentation of K8/K18 variants in patients with cirrhosis. However, K8/K18 variant-associated susceptibility to acute liver injury, which is well-described in animal models, has not been studied in humans. METHODS: We analyzed the entire coding regions of KRT8 and KRT18 genes (15 total exons and their exon-intron boundaries) to determine the frequency of K8/K18 variants in 344 acute liver failure (ALF) patients (49% acetaminophen-related) and 2 control groups (African-American [n = 245] and previously analyzed white [n = 727] subjects). RESULTS: Forty-five ALF patients had significant amino-acid-altering K8/K18 variants, including 23 with K8 R341H and 11 with K8 G434S. K8 variants were significantly more common (total of 42 patients) than K18 variants (3 patients) (P < .001). We found increased frequency of variants in white ALF patients (9.1%) versus controls (3.7%) (P = .01). K8 R341H was more common in white (P = .01) and G434S was more common in African-American (P = .02) ALF patients versus controls. White patients with K8/K18 variants were less likely to survive ALF without transplantation (P = .02). K8 A333A and G434S variants associated exclusively with African Americans (23% combined frequency in African American but none in white controls; P < .0001), while overall, K18 variants were more common in non-white liver-disease subjects compared to whites (2.8% vs 0.6%, respectively; P = .008). CONCLUSIONS: KRT8 and KRT18 are important susceptibility genes for ALF development. Presence of K8/K18 variants predisposes to adverse ALF outcome, and some variants segregate with unique ethnic and race backgrounds.
Subject(s)
Black or African American/genetics , Chemical and Drug Induced Liver Injury/genetics , Keratin-18/genetics , Keratin-8/genetics , Liver Failure, Acute/genetics , White People/genetics , Acetaminophen/adverse effects , Adult , Analgesics, Non-Narcotic/adverse effects , Asian/genetics , Chemical and Drug Induced Liver Injury/ethnology , Chemical and Drug Induced Liver Injury/mortality , Chi-Square Distribution , Female , Gene Frequency , Genetic Predisposition to Disease , Hispanic or Latino/genetics , Humans , Indians, North American/genetics , Liver Failure, Acute/chemically induced , Liver Failure, Acute/ethnology , Liver Failure, Acute/mortality , Logistic Models , Male , Middle Aged , Odds Ratio , Phenotype , Prognosis , Prospective Studies , Risk Assessment , Risk Factors , United States/epidemiology , Young AdultABSTRACT
Autoimmune hepatitis has diverse presentations that may mask its identity, affect its clinical behavior, and confound its management. The objectives of this report are to characterize the populations that are underdiagnosed or difficult to manage and to provide guidelines for meeting their challenges. The elderly have an aggressive, indolent liver disease that responds well to conventional corticosteroid treatment, but the diagnosis of this disease can be hampered by concurrent illnesses and medication. Genetic factors affect the expression and outcome of autoimmune hepatitis in different genders, and they may influence the nature and reactivity to triggering antigens or hormonal imbalances. Pregnancy can ameliorate autoimmune hepatitis, whereas delivery can exacerbate it. Asymptomatic patients and those with mild laboratory derangements may not require immediate therapy, but they commonly require treatment later. Centrilobular zone 3 necrosis can characterize an acute, severe, or fulminant presentation, and corticosteroid therapy can be lifesaving if effective within 2 weeks. Region-specific etiological agents, host-dependent susceptibility factors, and socioeconomic conditions may diversify the presentation in different ethnic groups. The special clinical challenges are essential to recognize and treat properly, and they may also extend hypotheses of pathogenesis.