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Background: Among patients with cirrhosis, it remains unclear whether there are racial/ethnic differences in cirrhosis complications and mortality. We examined the associations between race/ethnicity and risk for hepatocellular carcinoma (HCC), cirrhosis decompensation, and all-cause mortality overall and by cirrhosis etiology., Methods: US Veterans diagnosed with cirrhosis from 2001 to 2014 (n = 120,992), due to hepatitis C virus (HCV; n = 55,814), alcohol-associated liver disease (ALD; n = 36,323), hepatitis B virus (HBV; n = 1,972), nonalcoholic fatty liver disease (NAFLD; n = 17,789), or other (n = 9,094), were followed through 2020 for incident HCC (n = 10,242), cirrhosis decompensation (n = 27,887), and mortality (n = 81,441). Multivariable Cox proportional hazards regression was used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI)., Results: Compared with non-Hispanic White patients, Hispanic patients had higher risk for HCC overall (aHR, 1.32; 95% CI, 1.24-1.41) and by cirrhosis etiology, particularly for ALD- (aHR, 1.63; 95% CI, 1.42-1.87) and NAFLD-cirrhosis (aHR, 1.76; 95% CI, 1.41-2.20), whereas non-Hispanic Black patients had lower HCC risk in ALD- (aHR, 0.79; 95% CI, 0.63-0.98) and NAFLD-cirrhosis (aHR, 0.54; 95% CI, 0.33-0.89). Asian patients had higher HCC risk (aHR, 1.70; 95% CI, 1.29-2.23), driven by HCV- and HBV-cirrhosis. Non-Hispanic Black patients had lower risk for cirrhosis decompensation overall (aHR, 0.71; 95% CI, 0.68-0.74) and by cirrhosis etiology. There was lower risk for mortality among all other racial/ethnic groups compared with non-Hispanic White patients., Conclusions: Race/ethnicity is an important predictor for risk of developing HCC, decompensation, and mortality., Impact: Future research should examine factors underlying these racial/ethnic differences to inform prevention, screening, and treatment for patients with cirrhosis., (©2023 The Authors; Published by the American Association for Cancer Research.)

Disparities in hepatocellular carcinoma (HCC) incidence and survival have been observed between ethnic groups including African-Americans (AA) and European-Americans (EA). The evaluation of the changes in the levels of metabolites in samples stratified by race could provide a snapshot of ethnically diverse disease related pathways and identify reliable biomarkers. In this study, we considered AA and EA to investigate metabolites that may be associated with HCC in a race-specific manner. The levels of 46 metabolites in plasma samples, collected from patients recruited at MedStar Georgetown University Hospital, were analyzed by Agilent GC-qMS in selected ion monitoring (SIM) mode. A least absolute shrinkage and selection operator (LASSO) regression model was applied to select metabolites with significant changes in HCC vs. cirrhosis in three groups: (1) AA and EA combined; (2) AA separately; and (3) EA separately. In addition, metabolites that distinguish HCC cases from cirrhosis in these three groups were selected by excluding those without HCV infection. The performances of the metabolites selected by LASSO in each group were evaluated through a leave-one-out cross-validation. We identified race-specific metabolites that differentiated HCC cases from cirrhotic controls, yielding better area under the receiver operating characteristics (ROC) curve (AUC) compared to alpha-fetoprotein (AFP), the serological marker widely used for the diagnosis of HCC. This study sheds light on metabolites that could potentially be used as biomarkers for HCC by monitoring their levels in high-risk population of cirrhotic patients in a race-specific manner.

Introduction and Aim: HCV-infected immigrants contribute to the total prevalence in Canada and other developed nations. Little is known about engagement in care, access to service, and treatment outcomes in recipients of Direct Acting Antiviral (DAA) HCV therapies among immigrants living with HCV., Material and Methods: HCV patients assessed at The Ottawa Hospital Viral Hepatitis Clinic between 2000-2016 were identified. Immigration history, race, socioeconomic status, HCV work-up, treatment and outcome data were evaluated. HCV fibrosis assessment, treatment and sustained virologic response (SVR) were compared using logistic regression., Results: 2,335 HCV-infected patients were analyzed with 91% (2114) having data on immigration (23% immigrants). A median 16 years (Quartiles: 5, 29) passed from immigration to referral. Access to diagnostic procedures (Fibroscan/liver biopsy) was greater among immigrants compared to Canadian-born (78% vs. 68%, p = 0.001) and immigrants had an odds ratio of 1.72 (95% CI: 1.18-2.51) of receiving a FibroScan compared to Canadians after adjustment for demographic characteristics, HCV risk factors, and socioeconomic status. No differences in SVR were found between immigrants for IFN recipients. Among DAA recipients, rates of SVR were > 94% among all patients, 93% in Canadian-born and 98% among immigrants (p = 0.14)., Conclusion: Nearly 80% of immigrants in this setting had access to fibrosis assessment which was higher than Canadian-born patients. Under half of both groups had initiated HCV therapy. Delays in accessing HCV care represent a missed opportunity to engage, treat and cure HCV patients. HCV screening and health care engagement at the time of immigration would optimize HCV care and therapeutic outcomes.

Objectives: Hepatitis C virus (HCV) infection is a well-documented risk factor for hepatocellular carcinoma (HCC). Seven HCV genotypes have been classified, and the genotypes show a great variety of geographic distribution. HCV genotype 6 is prevalent in Southeast Asia and has been less studied than the other genotypes., Methods: This follow-up study was designed to evaluate the natural history of HCV genotype 6. The cohort enrolled 851 Asian patients consisting of 222 with HCV genotype 6 and 629 with other genotypes. The incidence of HCC per 1,000 person-years of various HCV genotypes was estimated by dividing the new HCC cases to the person-years of follow-up. The adjusted hazards ratios (HRs) with 95% confidence intervals (CIs) were estimated by Cox's proportional hazards models., Results: After 4072 person-years of follow-up, there were 96 newly-developed HCC cases, confirming an incidence of 23.6 per 1000 person-years. By stratifying cirrhosis at study entry, the cumulative risk of HCC among HCV genotype 6 vs. non-6 was 2.9 vs. 2.2% for those without cirrhosis (P=0.45) and 76.2% (95% CI: 55.6-96.8%) vs. 36.2% (95% CI: 28.7-39.1%) for those with cirrhosis (P<0.05), respectively. Among patients with cirrhosis, HCV genotype 6 was significantly associated with HCC compared to patients with non-6 genotypes, with the adjusted HR=2.12 (1.33-3.39), P<0.05. In a model treating patients with genotypes other than 1 or 6 as the reference, the adjusted HR for HCC for HCV genotypes 1 and 6 were 1.13 (0.56-2.27) and 2.34 (1.12-4.86), respectively., Conclusions: Among patients with cirrhosis, those with HCV genotype 6 infection should be given high priority for antiviral therapy to decrease HCC risk and for vigilant adherence to HCC surveillance.

Background: Many HIV antiretroviral medications have been associated with chronic liver injury. HIV-infected patients frequently develop HIV and highly active antiretroviral treatment-associated lipodystrophy syndrome (HALS), characterized by accumulation of intra-abdominal fat, insulin resistance, and hepatic steatosis. We sought to determine whether long-term exposure to specific antiretroviral medications or the presence of HALS predispose HIV-infected patients to the development of cirrhosis., Methods: HIV-infected patients with cirrhosis who received care in the Veterans Affairs Healthcare System nationally in 2009 were matched by hepatitis C virus (HCV) coinfection status and year of first visit for HIV to the Veterans Affairs Healthcare System with HIV-infected patients without cirrhosis in a 1 : 3 ratio., Results: Among HIV/HCV coinfected patients (593 with cirrhosis and 1591 matched controls), HALS was associated with a significantly increased risk for cirrhosis (adjusted odds ratio 1.6, 95% confidence interval 1.1-2.3), especially among Black patients (adjusted odds ratio 2.9, 95% confidence interval 1.6-5.2). In addition, among HIV/HCV coinfected patients, longer cumulative exposures to all antiretroviral medications, all nucleoside reverse transcriptase inhibitors, all protease inhibitors, and selected individual medications (didanosine, stavudine, and nelfinavir) were found to be significantly associated with cirrhosis. In contrast, among HIV-infected patients not coinfected with HCV (245 with cirrhosis and 658 matched controls), HALS or exposure to antiretroviral medications was found not to be significantly associated with cirrhosis, with the exception of didanosine., Conclusion: HALS and cumulative exposure to nucleoside reverse transcriptase inhibitors and protease inhibitors, especially stavudine, didanosine, and nelfinavir, were found to be associated with the development of cirrhosis in HIV/HCV coinfected patients, but not in HIV-monoinfected patients.

Background/aims: Within Europe, Italy has the highest incidence of HCV. PROPHESYS was a large, non-interventional, multinational cohort study of patients treated with peginterferon alfa-2a or -2b/ribavirin for CHC; 22.4% of patients were from Italian centers. This sub-analysis evaluates real-life practice and treatment outcomes in Italy., Methodology: The PROPHESYS 2 cohort included 1604 HCV mono-infected, treatment-naive patients. All patients were prescribed peginterferon alfa/ribavirin at the discretion of the treating physician according to country-specific requirements., Results: The majority of G1-3 patients were White/Caucasian and 48.4% had HCV G1 infection. Overall, SVR24 rates of 44.9%, 81.4% and 69.1% were achieved in G1-, 2- and 3-infected patients. In G1 patients, SVR24 rates declined with increasing FIB-4 score; this trend was not observed for G2/3-infected patients. Virologic response by Week 2 and 4 was highly predictive of SVR24 (G1: 91.7%, 84.8%; G2: 91.1%, 89.7%; G3: 92.9%, 86.7%, respectively). Absence of virologic response by Week 12 had the highest negative predictive value across genotypes., Conclusions: In Italian patients, a virologic response by Week 2 or 4 was highly predictive of SVR24 across genotypes. These data demonstrate the importance of monitoring on-treatment response to help guide treatment decisions. FIB-4 score correlated well with SVR24 in G1 patients.

Background: Black recipients undergoing liver transplantation (LT) for hepatitis C virus (HCV) have decreased patient and graft survival compared with white recipients, a finding that is primarily limited to black recipients of livers from white donors. The cause(s) for these discrepant outcomes are unclear but may be related to HCV disease recurrence. The rates of HCV-related disease recurrence and liver fibrosis progression among black and white liver transplant recipients have not been investigated., Methods: In this study, we compared liver fibrosis progression between 105 black and 364 white recipients after HCV-related LT in a multisite cohort study and assessed the impact of donor race., Results: At 6, 12, and 24 months after LT, there was a significantly higher percentage in the black recipient/white donor (B/W) group with severe fibrosis, defined as stage 3 or 4 (F3/F4), compared with all other recipient/donor race combinations. The adjusted odds ratio of developing F3/F4 for the B/W group was 2.54 (1.49-4.69; reference group, white recipient/white donor). Black recipients with black donors demonstrated a similar rate of progression to F3/F4 as white recipients. Patient survival was also decreased in the B/W group compared with other recipient/donor race combinations., Conclusion: African American recipients with white donors have more severe fibrosis progression after HCV-related LT. The mechanisms responsible for accelerating fibrosis progression in this high-risk race-mismatched group need to be investigated.

The ethnicity and socioeconomic status of the host may affect the progression of hepatitis C virus (HCV). We aimed to compare survival and fibrosis progression in Hispanic white (HW) and non-Hispanic white (NHW) recipients of liver transplantation (LT) with HCV. All HW and NHW patients with HCV who underwent transplantation between January 2000 and December 2007 at 2 centers were retrospectively assessed. The primary outcomes were the time to death, death or graft loss due to HCV, and significant fibrosis [at least stage 2 of 4]. Five hundred eleven patients were studied (159 HW patients and 352 NHW patients), and the baseline demographics were similar for the 2 groups. NHW patients were more likely to be male, to have attended college, and to have private insurance, and they had a higher median household income (MHI). The unadjusted rates of survival (log-rank P = 0.93), death or graft loss due to HCV (P = 0.89), and significant fibrosis (P = 0.95) were similar between groups. In a multivariate analysis controlling for center, age [hazard ratio (HR) per 10 years = 1.43, P = 0.01], donor age (HR per 10 years = 1.25, P < 0.001), and rejection (HR = 1.47, P = 0.048) predicted death, whereas HW ethnicity (HR = 1.06, P = 0.77) was not significant. Independent predictors of significant fibrosis were HW ethnicity (HR = 2.42, P = 0.046), MHI (HR per $10,000 = 1.11, P = 0.01), donor age (HR per 10 years = 1.13, P = 0.02), cold ischemia time (HR = 1.06, P = 0.03), and the interaction between ethnicity and MHI (HR = 0.82, P = 0.03). In conclusion, there is no difference in post-LT survival or graft loss due to HCV between HW patients and NHW patients. Socioeconomic factors may influence disease severity; this is suggested by our findings of more significant fibrosis in HW patients with a low MHI., (Copyright © 2012 American Association for the Study of Liver Diseases.)

Background: Hispanics have much higher cirrhosis mortality rates than non-Hispanic Blacks and Whites. Although heavy alcohol use and hepatitis C virus (HCV) infection are two major risk factors for cirrhosis, no studies have systematically assessed the contribution of alcohol- and HCV-related cirrhosis deaths to the total cirrhosis mortality for Hispanics as a whole and its variations across Hispanic subgroups. To fill this gap, this study presents the latest data on total cirrhosis mortality as well as its component alcohol- and HCV-related cirrhosis mortality for all Hispanics and for Hispanic subgroups., Methods: The multiple-cause approach was used to analyze data from the U.S. Multiple Cause of Death Data Files for 28,432 Hispanics and 168,856 non-Hispanic Whites (as a comparison group) who died from cirrhosis as the underlying or a contributing cause during 2000-2004. Four major Hispanic subgroups were defined by national origin or ancestry, including Mexicans, Puerto Ricans, Cubans, and Other Hispanics. The cirrhosis deaths were divided into four distinctive cause-of-death categories: alcohol-related, HCV-related, both alcohol- and HCV-related, and neither alcohol- nor HCV-related. Age-adjusted total cirrhosis death rates and percentage shares of the cause-specific categories were compared across Hispanic subgroups and non-Hispanic Whites., Results: Compared with non-Hispanic Whites, all Hispanic subgroups except Cubans had much higher cirrhosis mortality. The age-adjusted total cirrhosis death rates were twice as high for Puerto Ricans and Mexicans as for non-Hispanic Whites. Alcohol-related and HCV-related cirrhosis death rates also were higher for most Hispanic subgroups than for non-Hispanic Whites., Conclusions: Heavy alcohol use and hepatitis C viral infection are two important factors contributing to the high cirrhosis mortality among Hispanics. However, their relative contributions to total cirrhosis mortality varied by gender and Hispanic subgroup. This information is useful for targeted prevention and intervention efforts to address the excessive cirrhosis mortality in the Hispanic population., (Copyright © 2010 by the Research Society on Alcoholism. No claim to original U.S. government works.)

Objective: The inter-individual difference in response to liver injury appears to be important in the progression of liver fibrosis. Interleukin 10 (IL-10) is an anti-inflammatory cytokine, and several functional gene polymorphisms have been found. The aim of this study was to examine the possible association of IL-10 polymorphisms with the progression of liver fibrosis in hepatitis C virus (HCV)-related chronic liver disease patients., Methods: We examined the IL-10 -1087 A/G and -824 T/C gene polymorphisms in 184 Japanese patients with HCV-related chronic liver disease: 94 chronic hepatitis (CH) and 90 with liver cirrhosis (LC)., Results: There were no significant differences in the genotype distributions or allele frequencies of IL-10 -824 T/C and -1087 A/G between the CH and LC groups. However, among the cirrhotic patients, the lower transcriptional allele, -824 T homozygotes had significantly lower serum albumin and platelet counts, and a higher Child-Pugh score than the -824 C carriers, and the lower transcriptional allele, -1087 A homozygotes had a higher ICG-R 15 compared with -1087 G carriers. Haplotype analysis of IL-10 -1087/-824 showed no significant difference between the CH and LC groups, but the combinations of AT and AC haplotypes (AT/AT, AT/AC and AC/AC) had a significantly higher ICG-R 15 than the GC carriers., Conclusion: IL-10 lower transcriptional -824 T allele, -1087 A allele, and -1087/-824 haplotypes AT and AC are risk factors for the progression of liver fibrosis in HCV-related chronic liver disease.

Latinos in the US experience a 60% higher death rate from primary hepatocellular carcinoma (HCC) when compared to Non-Latinos. The goal of this study was to examine risk factors that are associated with ethnic disparities among HCC patients seen at the transplant center of a metropolitan medical center in New York City. We compared HCC risk factors in 140 Non-Latino and 55 Latino patients that presented with HCC from 1995 to 2003. Surnames were used to define Latino and Non-Latino HCC patients in a retrospective analysis. Latino and Non-Latino HCC patients did not vary by gender or age at presentation (mean Latino age 60.8). Latino HCC patients had a higher frequency of presentation with advanced disease, defined as patients with unresectable HCC, than non Latino HCC patients (Latino 52.7%; 95% CI 39.1-66.3 vs. Non-Latino vs. 36.4%; 95% CI 28.3-44.4). Latinos were more likely than Non Latinos to have underlying HCV (34.5 vs. 22.1%, P < .0001; adjusted odds ratio [Siegel, 2008 #564], 3.69; 95% CI, 1.16-11.7) and cryptogenic liver diseases (7.2 vs. 3.5%, P < .0001; OR 8.86; 95% CI, 1.21-65.0) after adjusting for age, gender and alfa-fetoprotein levels. Although more advanced disease may signal delay in access to care or more aggressive disease, HCV infection and cryptogenic cirrhosis at presentation are likely key factors for the greater burden of HCC among Latinos in New York City.

Objectives: The recurrence of hepatitis C virus infection after liver transplant is common and may endanger both graft and patient survival. We investigated the frequency and outcome of and risk factors for the recurrence of that virus after living-donor liver transplant in hepatitis C virus positive recipients., Materials and Methods: Seventy-four adult hepatitis C virus positive subjects were monitored for 36 months after living-donor liver transplant and demographic and laboratory data for the recipients and donors were evaluated. Recurrent hepatitis C virus infection was diagnosed on the basis of viral replication revealed by polymerase chain reaction after transplant, elevated levels of transaminases, and the results of liver biopsy., Results: Hepatitis C virus recurrence was identified in 31.1% of the patients studied. Histopathologic recurrence was mild, and 91% of the subjects had a fibrosis score of < or = F2. No recipient exhibited cirrhosis or clinical decompensation during followup. Recurrent hepatitis C virus infection was associated with pretransplant and posttransplant viral load and antibody positive to hepatitis B core antigen. No other risk factors (sex, donor or recipient age, pretransplant Child-Pugh or Model for End-Stage Liver Disease scores, immunosuppressive drug therapy, and treatment with pulse steroids) were significantly correlated with the frequency of hepatitis C virus recurrence, the grade of the histologic activity index, or the stage of fibrosis., Conclusions: In living-donor liver transplant recipients, patient and graft survival rates associated with hepatitis C virus (genotype 4) related cirrhosis were comparable to those in deceased-donor liver transplant recipients reported in the literature. Recurrent infection with hepatitic C virus after living-donor liver transplant was mild. After transplant, a higher viral load and the presence of antibody to hepatitis B core antigen could be risk factors for hepatitis C virus recurrence. Long-term follow-up in a large number of patients is required.

Background and Aim: The natural history of alcoholic cirrhosis, especially in Asian countries, has not been completely understood thus far., Methods: We retrospectively compared the outcomes of compensated cirrhosis between Japanese alcoholic and hepatitis C virus (HCV)-infected patients., Results: A total of 227 patients (75 alcoholic and 152 HCV-infected patients) with compensated cirrhosis were enrolled. The median follow-up period was 4.9 years. The cumulative rates of hepatocellular carcinoma (HCC) development were significantly lower in the alcoholic patients than in the HCV-infected patients (6.8% vs 50.3% at 10 years, P = 0.0003), while the cumulative rates of hepatic decompensation (37.4% vs 51.7% at 10 years) and survival (53.8% vs 47.4% at 10 years) did not significantly differ between the two groups (Kaplan-Meir analysis). The main causes of death were hepatic failure and non-hepatic diseases in the alcoholic patients and HCC and hepatic failure in the HCV-infected patients. Multivariate analyses using the Cox proportional hazard model revealed that the risk of HCC was lower in alcoholic cirrhosis than in HCV-related cirrhosis (hazard ratio (HR), 0.46), while the risk of hepatic decompensation and mortality was the same. Predictors of decreased survival were non-abstinence (HR, 2.53) in the alcoholic patients and low serum albumin level (1.58) in the HCV-infected patients., Conclusions: Survival of patients with alcoholic cirrhosis was similar to that of patients with HCV-related cirrhosis. The risk of HCC development was lower in alcoholic cirrhosis than in HCV-related cirrhosis. Abstinence from alcohol was important for improving the survival of patients with alcoholic cirrhosis.

A precise understanding of the source of infection and modes of transmission of hepatitis C virus (HCV) is a worldwide priority in terms of public health. This is more evident where multi-ethnic customs cohabit. Despite the knowledge on risk factors for HCV transmission, nearly 50% of infected patients do not have a history suggesting a parenteral route of acquisition. In the present paper, the authors, focusing on ethnic and cultural aspects of HCV transmission, emphasize the need for health education in order to avoid the acquisition and the diffusion of the infection. With the current globalization and large-scale migrations, only by following a preventive strategy based on disseminate information risk behaviours may be modified.

Background: We address the independent and interactive roles of habitual betel quid chewing and other known risk factors for biochemical dysfunction and cirrhosis of the liver., Methods: To determine the prevalence rates and risk factors associated with biochemical dysfunction of the liver, a total of 3,010 adult residents in an Atayal Aboriginal community were invited to participate in the study. Abdominal ultrasonography was used to diagnose liver cirrhosis., Results: There were 2,063 Atayal Aboriginal and 947 non-Aboriginal in this study. The result showed overall prevalence rates for hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) were 21.2 % and 2.9 %, respectively. There were 16.5 %, 15.1 % and 22.4 % subjects with abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transpeptidase (GGT), accordingly. Multiple logistic regression analysis showed that combined infections with HBV and HCV presented with the highest risks with OR (odds ratio) and 95% CI (confidence interval) of 4.2 (1.2-17.4) and 3.8 (1.0-14.1), respectively for elevation of ALT and AST; followed by alcohol (1.7 and 3.1), male gender (1.7 and 1.6), betel quid (1.5 and 1.3), smoking (1.4 and 1.8), and aboriginal (1.4 and 1.3). There is effect-measure modification between viral infection and betel quid chewing for increased severity of abnormal ALT elevation. Among 1,382 subjects consenting to abdominal ultrasonography, 41(3.0%) were found to have liver cirrhosis with the same factors associated with higher risks., Conclusion: In addition to infections with viral hepatitis B and/or C, we found Atayal Aboriginal, males, current smokers, drinkers and betel quid chewers were independently associated with biochemical dysfunction and probably cirrhosis of the liver. Further study is needed to corroborate the above hypothesis.

Aim: To assess hepatic fibrosis and factors associated with its progression in children with HCV infection., Methods: At the Hepatology Unit, Cairo University Children's Hospital, a single liver biopsy was performed to 43 children with HCV infection after an informed consent between 1998-2004. Their mean age at liver biopsy was 8.67 +/- 4.3 years., Results: Among the 43 patients' biopsies, 12 (27.9%) were having no fibrosis, 20 (46.5%) mild fibrosis and 11 (25.6%) moderate to severe fibrosis. The median time for development of fibrosis was estimated to be 5.5 years. Developing fibrosis was significantly associated with shorter duration from first detected ALT elevation to biopsy (12 mo vs 1.2 mo, P=0.015) and having higher levels of direct serum bilirubin (0.3 mg/dL vs 0.5 mg/dL, P=0.048). No association was found between fibrosis stage and the presence of co-morbid conditions (P=0.33)., Conclusion: Hepatic fibrosis was present in 72.1% of children with HCV infection. The development of fibrosis was associated with higher levels of direct serum bilirubin. There was no significant association between fibrosis and age, duration of infection, risk factors, co-morbid conditions and most biochemical parameters.