Hepatocellular Carcinoma In HIV-infected Patients Research Articles

Hepatocellular Carcinoma in HIV-Infected Patients: Clinical Presentation and Outcomes

Hepatocellular Carcinoma in HIV-Infected Patients: Clinical Presentation and Outcomes

Hepatocellular Carcinoma in HIV-Infected Patients: Clinical Presentation and Outcomes in a Racially Diverse Urban Population.

As life expectancy for HIV patients improve, hepatocellular carcinoma (HCC) has become a non-AIDS defining illness with a high impact on morbidity and mortality of HIV-infected individuals. We sought to compare outcomes in HIV- versus non-HIV-infected patients treated for HCC at a multiethnic academic medical health system. A retrospective chart review of patients diagnosed with HCC from 1/1/2005 to 12/31/2016 was performed. Differences in characteristics among HIV and non-HIV subjects were assessed. Associations between HIV status, viral load, CD4 count, and overall survival (OS) were also assessed. We identified 915 subjects (842 non-HIV and 73 with HIV). HIV-infected subjects were younger, predominantly male non-Hispanic Blacks, and more likely to have HBV and HCV co-infection, and alcohol use at diagnosis compared to non-HIV counterparts. Stage, MELD score, Child-Pugh, and ECOG performance status were similar. HIV-positive patients received systemic therapy at significantly higher rates and liver transplantation for HCC at significantly lower rates than those without HIV. The actuarial 3- and 5-year overall survival (OS) for all patients was 48.3% and 39.4%. For HIV-infected subjects, 3- and 5-year OS was significantly worse at 36.8% and 28.3% compared to 49.3% and 40.4%, respectively, for non-HIV subjects (log rank p = 0.033). HIV-infected HCC patients have lower survival rates compared to those without HIV. Despite younger age and similar stage, MELD, and ECOG at diagnosis, HIV portends worse outcomes in patients with HCC.

Liver Transplantation for HCC in HIV-Infected Patients: Long-Term Single-Center Experience.

Simple SummaryHCC are now emerging as leading causes of morbidity in HIV-infected patients since HAART has made it possible to achieve long life expectation by reducing AIDS-related complications. The results of liver transplantation for HCC in HIV-infected patients are still contradictory. In this paper we demonstrated in a cohort of 32 HIV-infected patients undergoing LT for HCC that the post-LT outcomes are comparable to the controlled cohort of uninfected recipients. Long survival rates were observed for HIV-infected LT patients with HCC.Background: HIV-infected patients now have long life expectation since the introduction of the highly active antiretroviral therapy (HAART). Liver diseases, especially cirrhosis and hepatocellular carcinoma (HCC), currently represent a leading cause of death in this setting of patients. Aim: To address the results of liver transplantation (LT) for HCC in HIV-infected patients. Methods: All patients with and without HIV infection who underwent LT for HCC (n = 420) between 2001 and 2021 in our center were analyzed with the intent of comparing graft and patient survival. Cox regression analysis was used to determine prognostic survival factors and logistic regression to determine the predictor factors of post-LT recurrence. Results: Among 1010 LT, 32 were HIV-infected recipients. With an average follow-up of 62 ± 51 months, 5-year overall survival in LT recipients with and without HIV-infection was 71.6% and 69.9%, respectively (p = ns), whereas 5-year graft survival in HIV-infected and HIV-non infected was 68.3% and 68.2%, respectively (p = ns). The independent predictive factor of survival in the study group was: HCV infection (HR 1.83, p = 0.024). There were no significant differences in the pathological characteristics of HCC between the two groups. The logistic regression analysis of the study population demonstrated that microvascular invasion (HR 5.18, p< 0.001), HCC diameter (HR 1.16, p = 0.028), and number of HCC nodules (HR 1.26, p = 0.003) were predictors of recurrence post-LT. Conclusion: Our study shows that HIV patients undergoing LT for HCC have comparable results in terms of post-LT survival. Excellent results can be achieved for HIV-infected patients with HCC, as long as a strategy of close surveillance and precise treatment of the tumor is adopted while on the waiting list.

PD-3 Hepatocellular carcinoma in HIV-infected patients: Clinical presentation and outcomes in a racially diverse urban population

As life expectancy for HIV patients improves in the highly active antiretroviral treatment (HAART) era, hepatocellular carcinoma (HCC) has become a non-AIDS-defining illness with a high impact on morbidity and mortality of HIV-infected patients. We sought to compare outcomes in HIV versus non-HIV patients diagnosed with and treated for HCC at a multiethnic urban academic medical center. A retrospective chart review of patients diagnosed with HCC from 1/1/2005 to 12/31/2016 was performed. Subjects included had at least one-week of follow-up and were censored at last point of contact. Variables collected included HIV status, HIV viral load, CD4 count, Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection, TMN stage, ECOG performance status, MELD score, and AFP level at diagnosis, as well as treatments received. Bivariate associations comparing characteristics between HIV and non-HIV subjects were assessed using t-tests or non-parametric equivalents for continuous variables and chi-square tests for categorical variables. Associations between HIV status, viral load and CD4 count, and overall survival (OS) were assessed using Cox proportional hazards regression as well as the Kaplan-Meier method with log-rank test. We identified 819 non-HIV and 73 HIV-infected subjects. Race was 17.3% white and 26.7% black for non-HIV versus 2.7% white and 43.8% black for HIV subjects (p=0.001). Ethnicity was 34.1% Hispanic in non-HIV versus 26.0% in HIV subjects. Mean age was 64.2 versus 57.2 years in non-HIV versus HIV subjects (p< 0.001). Rates of HBV (6.7 versus 17.8%, p< 0.001), HCV (59.8 versus 75.3%, p=0.022), and alcohol use (17.6 versus 38.4%, p< 0.001) were lower in non-HIV compared to HIV subjects. Of non-HIV subjects, 34.7% had AFP level >100 at diagnosis versus 49.3% of HIV subjects (p=0.015). Stage, MELD, and ECOG score at diagnosis showed no significant associations with HIV status. While rates of resection and regional treatments were similar, transplantation occurred more often in non-HIV compared to HIV subjects (10.4 versus 2.7%, p< 0.022). Median follow-up was 18.2 months. The 3-year actuarial OS for all patients was 49.7%, and significantly worse for those with HIV infection (37.0 vs. 50.9%, p=0.024). Patients with HIV also had worse OS on multivariable analysis (HR=1.90, p=0.001) when adjusting for age, MELD, AFP, stage and performance status. Viral load, but not CD4 count showed a significant association with survival (p=0.017 and p=0.070, respectively by log-rank test). HIV-infected HCC subjects have lower survival rates compared with those without HIV. Despite younger age and similar MELD, ECOG, and stage at diagnosis, HCC subjects with HIV have worse outcomes compared to non-HIV counterparts. In our study, HIV-infected subjects had significantly higher rates of HBV, HCV, alcohol use, and lower rates of transplantation--all factors that could mediate the increased mortality observed in these subjects. While the etiology of survival differences between HIV and non-HIV patients with HCC remains unclear, robust efforts should be made to offer the subset of those with HIV not only transplants but also novel systemic therapies, given the profound potential for benefit.

Impact of HIV on the survival of hepatocellular carcinoma in hepatitis C virus-infected patients.

Previous studies have suggested that hepatocellular carcinoma (HCC) has an aggressive presentation and a shorter survival in people with HIV (PWH). This could be due to later diagnosis or lower rates of HCC treatment, and not to HIV infection itself. AIM: :: To assess the impact of HIV on HCC survival in hepatitis C virus (HCV)-infected patients. Multicenter cohort study (1999-2018) of 342 and 135 HCC cases diagnosed in HIV/HCV-infected and HCV-monoinfected patients. Survival after HCC diagnosis and its predictors were assessed. HCC was at Barcelona-Clinic Liver-Cancer (BCLC) stage 0/A in 114 (33%) HIV/HCV-coinfected and in 76 (56%) HCV-monoinfected individuals (P < 0.001). Of them, 97 (85%) and 50 (68%) underwent curative therapies (P = 0.001). After a median (Q1-Q3) follow-up of 11 (3-31) months, 334 (70%) patients died. Overall 1 and 3-year survival was 50 and 31% in PWH and 69 and 34% in those without HIV (P = 0.16). Among those diagnosed at BCLC stage 0/A, 1 and 3-year survival was 94 and 66% in PWH whereas it was 90 and 54% in HIV-negative patients (P = 0.006). Independent predictors of mortality were age, BCLC stage and α-fetoprotein levels. HIV infection was not independently associated with mortality [adjusted hazard ratio (AHR) 1.57; 95% confidence interval: 0.88-2.78; P = 0.12]. HIV coinfection has no impact on the survival after the diagnosis of HCC in HCV-infected patients. Although overall mortality is higher in HIV/HCV-coinfected patients, this seem to be related with lower rates of early diagnosis HCC in HIV-infected patients and not with HIV infection itself or a lower access to HCC therapy.

Screening for Hepatocellular Carcinoma in HIV-Infected Patients: Current Evidence and Controversies.

This review aims to summarize evidence regarding hepatocellular carcinoma (HCC) screening in the specific context of HIV infection and discuss areas of uncertainty. It has not been definitely established if HCC incidence in HIV/HCV-coinfected patients with cirrhosis is above the 1.5%/year threshold that makes screening cost-effective. Outside cirrhosis or HBV infection, available data do not support surveillance. The performance of currently recommended ultrasound (US) screening strategy is poor in HIV-infected patients, as rates of early-stage HCC detection are low. Magnetic resonance imaging-based surveillance strategies or liquid biopsy are innovative approaches that should be specifically tested in this setting. HIV-infected patients with cirrhosis are at risk of HCC. US surveillance identifies patients with early-stage HCC who will benefit of curative therapies, although the quality of the evidence supporting screening remains limited. The HIV population should be a priority group to assess and validate new surveillance strategies.

Which curative treatment for stages 0-A hepatocellular carcinoma in HIV-infected patients ? An intention-to-treat analysis

Introduction: Liver transplantation (LT) has become a consensual treatment for hepatocellular carcinoma (HCC) in human immunodeficiency virus (HIV)-carriers. However, high drop-out rates raise questions to the role of alternative treatments. Our aim was to address the Results of resection in this setting and to compare them against survival after LT in an intention-to-treat analysis. Patients and Methods: Records from all patients with HIV and HCC listed for LT (liver transplant candidates = LTc+) or resection (LR+) between 2000 and 2017 at our tertiary centre were analysed and compared for overall survival (OS) and disease-free survival (DFS). Result: The LTc+ group (n=43) presented with higher MELD scores and more advanced portal hypertension and HCC stages than the LR+ group (n=15), with no differences in epidemiological or co-infection rates. One-, 3- and 5-year intention-to-treat survival rates were: 81%, 60% and 44%, versus 86%, 58% and 58% in the LTc+ and LR+ groups, respectively (p=0.746). Eleven patients dropped out (in all cases before LT). After LT, OS was 81%, 68% and 59% (no difference versus the LR+ group; p=0.844). There tended to be better DFS after LT, reaching 78%, 68% and 56% versus 53%, 33% and 33% in the LR+ group (p=0.062). Time-to-recurrence was significantly longer in the LT+ group (p=0.001). Conclusion: This was the largest series of resections for HCC in HIV+ patients and the first intention-to-treat analysis. Although LT and resection do not always concern the same population, they enable equivalent survival. At the price of a high recurrence rate, resection could be integrated in the global armoury of liver surgeons.

Comparative analysis of outcomes after liver resection and liver transplantation for early stages hepatocellular carcinoma in HIV-infected patients. An intention-to-treat analysis

BackgroundTo address the results of resection for hepatocellular carcinoma (HCC) in human immunodeficiency virus (HIV)-carriers, and to compare them against survival after liver transplantation (LT). MethodsAll patients with HIV and HCC listed for LT (candidates = LTc+) or resection (LR+) between 2000 and 2017 in our centre were analysed and compared for overall survival (OS) and disease-free survival (DFS). ResultsThe LTc + group (n = 43) presented with higher MELD scores and more advanced portal hypertension and HCC stages than LR + group (n = 15). One-, 3- and 5-year intention-to-treat survival rates were: 81%, 60% and 44%, versus 86%, 58% and 58% in the LTc+ and LR + groups, respectively (p = 0.746). Eleven LTc + patients dropped out. After LT, OS was 81%, 68% and 59% (no difference with LR + group; p = 0.844). There tended to be better DFS after LT, reaching 78%, 68% and 56% versus 53%, 33% and 33% in the LR + group (p = 0.062). ConclusionThis was the largest series of resections for HCC in HIV + patients and the first intention-to-treat analysis. Although LT and resection do not always concern the same population, they enable equivalent survival. At the price of higher recurrence rate, resection could be integrated in the global armoury of liver surgeons.

Hepatocellular Carcinoma in HIV-Infected Patients: Clinical Characteristics and Prognostic Factors

Hepatocellular Carcinoma in HIV-Infected Patients: Clinical Characteristics and Prognostic Factors

Peculiarities of HIV-positive patients coinfection with hepatitis C virus

The review of publications on human immunodeficiency virus (HIV) «satellite» infections - hepatitis B and C was made. 1329 articles published in the last 10 years concerning the problem of HIV and hepatitis B and C co-infection were found in PubMed database. The problem of viral hepatitis in HIV-infected patients remains extremely relevant nowadays. Results of numerous European studies indicate that chronic hepatitis C is ranked fifth in the list of death causes of HIV-infected patients. Most researchers agree on a more severe course of chronic hepatitis C in HIV-infected patients. Viral hepatitis is found in 7 out of 10 HIV-infected patients. The problem of antiretroviral drugs hepatotoxicity is still not resolved. Hepatitis C viral load is generally higher in HIV-infected patients than that of HIV-negative, and the probability of progression to cirrhosis, liver failure and hepatocellular carcinoma in HIV-infected patients is 3 times higher. So the problem of HIV and viral hepatitis co-infection requires a better understanding of co-infection treatment features, the definition of clear criteria for effectiveness and safety of therapy of HIV-infected patients co-infected with viral hepatitis B and C.

Do the epidemiology, physiological mechanisms and characteristics of hepatocellular carcinoma in HIV-infected patients justify specific screening policies?

Reducing the incidence of hepatocellular carcinoma (HCC) in HIV-infected patients has become a serious problem when managing these patients. There are many explanations for this disease evolution, which notably include their longer survival under effective antiviral therapy and also the more rapid evolution of chronic liver disease. Despite recent advances in the management of hepatitis B (HBV) and hepatitis C (HCV) viral diseases, which will probably increase the number of patients achieving a virological response, HIV-infected patients with cirrhosis are still at risk of the onset of HCC. This evolution to HCC is also correlated to other comorbidities such as excessive alcohol consumption and nonalcoholic steatohepatitis (NASH). HCC thus remains a public health issue in this population. The poor prognosis and aggressiveness of HCC have been fully demonstrated, but the mechanisms underlying this aggressiveness are not yet well defined. As well as underlying mechanisms that contribute to accelerating hepatocarcinogenesis in HIV-infected patients, there are other reasons why HIV-infected patients should be considered a higher risk population. This review discusses the principal epidemiological determinants; the mechanisms of pathogenesis; and the treatment of HCC in HIV/HBV and HIV/HCV coinfected patients. It also discusses the probable need to develop a specific screening policy for HCC in this population in order to prevent the rapid development and to make them more amenable to a curative treatment.

Incidence of Hepatocellular Carcinoma in HIV-Infected Patients With Cirrhosis

: This study assesses the incidence of hepatocellular carcinoma (HCC) in a prospective cohort of HIV-infected patients, the majority receiving antiretroviral therapy, with liver cirrhosis from different etiologies, enrolled between 2004 and 2005 with median follow-up of 5 years. We followed 371 patients, 25.6% with decompensated cirrhosis at baseline. The incidence rate of HCC was 6.72 per 1000 person-years [95% confidence interval (CI): 2.6 to 10.9]. There was a trend toward a higher cumulative probability of developing HCC at 6 years of follow-up (considering death and liver transplant as competing risks) in patients with decompensated versus compensated cirrhosis at baseline (6% vs. 2%, P < 0.06).

Multicenter Italian Experience in Liver Transplantation for Hepatocellular Carcinoma in HIV-Infected Patients

The aim of our work is to assess the clinical outcomes of liver transplantation (LT) for hepatocellular carcinoma (HCC) in HIV-coinfected patients. This is a multicenter study involving three Italian transplant centers in northern Italy: University of Modena, University of Bologna, and University of Udine. We compared 30 HIV-positive patients affected by HCC who underwent LT with 125 HIV-uninfected patients who received the same treatment from September 2004 to June 2009. At listing, there were no differences between HIV-infected and -uninfected patients regarding HCC features. Patients outside the University of California, San Francisco criteria (UCSF) were considered eligible for LT if a down-staging program permitted a reduction of tumor burden. HIV-infected patients were younger, they were more frequently anti-HCV positive, and a higher number of HIV-infected patients presented a coinfection HBV-HCV. Pre-LT treatments (liver resection and or locoregional treatments) were similar between the two groups. Histological characteristics of the tumor were similar in patients with and without HIV infection. No differences were observed in terms of overall survival and HCC recurrence rates. LT for HCC is a feasible procedure and the presence of HIV does not particularly affect the post-LT outcome.

Could anti-HCV treatment prevent recurrence of hepatocellular carcinoma in HIV-infected patients? Two case reports

Highly active antiretroviral therapy (HAART) has proven long-term efficacy in human immunodeficiency virus (HIV) infection. Combination therapy with pegylated interferon and ribavirin has become the standard of care in patients with both hepatitis C virus (HCV) chronic hepatitis and HIV/HCV co-infection. Data on the safety and efficacy of combination therapy in chronic hepatitis C patients with hepatocellular carcinoma (HCC) is scarce and even more so in HIV/HCV co-infected subjects. We report the successful administration of both HAART and anti-HCV therapies in two HIV/HCV co-infected patients after HCC eradication. These encouraging results might argue for the feasibility of an aggressive approach in the management of co-infected patients with HCC.

Increasing Incidence of Hepatocellular Carcinoma in HIV-Infected Patients in Spain

To report the clinical and epidemiological characteristics of hepatocellular carcinoma (HCC) diagnosed in a cohort of human immunodeficiency virus (HIV)-infected patients in Spain. All HIV-infected patients diagnosed of HCC in 18 hospitals in Spain before 31 December 2010 were included. The main characteristics of HCC cases are described and comparisons between cases according to the year of diagnosis are presented. Eighty-two cases of HCC in HIV-infected patients were included, all of them related to viral hepatitis coinfection: hepatitis C virus (HCV) in 66 (81%), hepatitis B virus (HBV) in 6 (7%), and HBV/HCV in 10 (12%). From 1999, when the first case of HCC was diagnosed, a progressive increment in the incidence of HCC in the cohort has occurred. In patients coinfected with HIV/HCV-coinfected patients, the incidence HCC increased from 0.2 to 2.8 cases per 1000 person-years between 2000 and 2009. Death occurred in 65 patients (79%), with a median survival of 91 days (interquartile range, 31-227 days). Three of 11 patients (28%) who received potentially curative therapy died, compared with 62 of 71 patients (87%) who did not receive curative therapy (P = .0001). Compared with cases of HCC diagnosed before 2005, cases diagnosed later did not show a higher survival rate. HCC is an emerging complication of cirrhosis in HIV-infected patients. A sharp increase in its incidence has occurred in those also infected by HCV in the recent years. Unfortunately, HCC is frequently diagnosed at an advanced stage, and mortality continues to be very high, with no significant changes in recent years. Earlier diagnosis, which may allow potentially curative therapy, is necessary.

Is it justifiable to transplant infected livers into haemophilia recipients?

Is it justifiable to transplant infected livers into haemophilia recipients?

First-time use of bevacizumab for aggressive, metastatic hepatocellular carcinoma in an HIV/hepatitis B virus coinfected patient: a case report

We present a case of an HIV-1 infected patient with history of chronic hepatitis B and chronic alcohol use without cirrhosis, who presented with aggressive hepatocellular carcinoma with multiple metastases. Systemic chemotherapy combined with use of bevacizumab (anti-vascular endothelium growth factor monoclonal antibody) was without effect and the patient succumbed to his disease within few weeks. To our knowledge, this is the first report in the English literature of bevacizumab use for metastatic hepatocellular carcinoma in HIV-infected patients.

Presentation and outcome of hepatocellular carcinoma in HIV-infected patients: A U.S.–Canadian multicenter study

HIV-infected patients now live longer and often have complications of liver disease, especially with hepatitis B or C virus coinfection. Limited data are available on those with hepatocellular carcinoma (HCC). A retrospective analysis from 1992 to 2005 in 6 centers identified 63 HIV-infected HCC patients. Controls were 226 consecutive HIV-negative HCC patients from four sites. HIV-positive patients were younger than controls (52 vs. 64 years, p<0.001), more commonly had chronic hepatitis B or C (97% vs. 73%, p<0.001), were more frequently symptomatic (51% vs. 38%, p=0.048), had a higher median alfa-fetoprotein level (227 vs. 51 ng/ml, p=0.005), but a similar mean Child-Turcotte-Pugh score (7.0 vs. 7.5, p=0.05) and HCC staging score (Barcelona-Clínic-Liver-Cancer stages C+D in 50% vs. 58%, p=0.24). HCC developed faster in HIV/HCV-coinfected than in HCV-monoinfected patients (mean, 26 vs. 34 years after HCV infection, p=0.002). HIV-positive patients received proven therapy more often (48% vs. 31%, p=0.017), but median survival was similar (6.9 vs. 7.5 months, p=0.44). Independent factors predicting survival were symptomatic presentation (hazard ratio [HR], 0.437; p<0.001), any proven therapy (HR, 2.19; p<0.001), diagnosis after 01-Jan-2002 (HR, 1.52; p=0.010), Barcelona-Clínic-Liver-Cancer stages C+D (HR, 0.491; p<0.001), AST/ALT >or= 2.00 (HR, 0.597; p=0.001), AFP >or= 400 ng/mL (HR, 0.55, p=0.003), and platelets >or= 100,000/mm3 (HR, 0.651; p=0.012), but not HIV-serostatus (p=0.19). In HIV-infected patients without HCC therapy (n=33), median survival was longer with undetectable HIV RNA (<400 copies/mL) than with HIV viremia (6.5 vs. 2.6 months, p=0.013). HIV-positive HCC patients are younger and more frequently symptomatic and infected with HCV or HBV than HIV-negative patients. Tumor staging and survival are similar. In untreated patients, undetectable HIV RNA independently predicts better survival.

Hepatocellular carcinoma in HIV-infected patients

Hepatocellular carcinoma (HCC) is an increasing cause of mortality in HIV-seropositive individuals. The aim of the study was to compare the main features of HCC in HIV-seropositive individuals with those in to HIV-negative patients. All HIV-infected subjects with a diagnosis of HCC included in three cancer registry databases were enrolled in the study as cases. HCC cases that occurred in the province of Brescia, North Italy, in the period 1995-1998 and all cases reported at the Italian Liver Cancer Project were enrolled as controls. All data were collected using a standardized case report form. The main clinical and epidemiological characteristics of patients with HCC and their survival were compared between HIV-positive and uninfected subjects. Forty-one HIV-infected subjects with HCC were identified. Multivariate analysis adjusted for age and sex identified an association between HIV infection and HCV infection [odds ratio (OR), 11; P = 0.005], and infiltrating tumours and/or extranodal metastasis at presentation (OR = 11.8; P < 0.001). HIV infection was independently associated with shorter survival (hazard ratio, 1.63; P = 0.015). HCC in HIV-infected patients is mainly associated with underlying chronic hepatitis C and has a more aggressive clinical course. Thus, preventative strategies (including the treatment of hepatitis C) should be implemented in the management of HIV/HCV-coinfected patients.

Hepatitis viruses and hepatocellular carcinoma in HIV-infected patients.

Hepatocellular carcinoma, the most common primary cancer of the liver, results in significant morbidity and mortality. Several disease entities have been shown to predispose to hepatocellular carcinoma. In most cases, however, hepatitis B virus, hepatitis C virus, and cirrhosis are the principal etiologic factors. In HIV-positive patients, a significant increase in the incidence of certain malignancies has been noted. Although HIV and the hepatitis viruses share common modes of transmission, an increase in the incidence of hepatocellular carcinoma in the patients with HIV has not been observed. This finding may be a function of premature death in patients with HIV before the advent of effective antiretroviral therapy. The introduction of such therapy may alter the epidemiology of hepatocellular carcinoma and strain health services, because current treatment options targeting both the underlying causative viruses and liver cancer itself are unsatisfactory and are the subject of ongoing research.