Risk of hepatocellular carcinoma in chronic hepatitis B: Assessment and modification with current antiviral therapy

SummaryIn the treatment of chronic hepatitis B (CHB), the ultimate goal is preventing hepatitis B virus (HBV)-associated liver disease, including hepatocellular carcinoma (HCC). Recently published studies show that in CHB patients treated with the currently recommended first-line nucleos(t)ide analogs (NAs) entecavir or tenofovir, annual HCC incidences range from 0.01% to 1.4% in non-cirrhotic patients, and from 0.9% to 5.4% in those with cirrhosis. In Asian studies including matched untreated controls, current NA therapy consistently resulted in a significantly lower HCC incidence in patients with cirrhosis, amounting to an overall HCC risk reduction of ∼30%; in non-cirrhotic patients, HCC risk reduction was overall ∼80%, but this was only observed in some studies. For patients of Caucasian origin, no appropriate comparative studies are available to date to evaluate the impact of NA treatment on HCC. Achievement of a virologic response under current NA therapy was associated with a lower HCC risk in Asian, but not Caucasian studies. Studies comparing entecavir or tenofovir with older NAs generally found no difference in HCC risk reduction between agents, except for one study which used no rescue therapy in patients developing lamivudine resistance. Overall, these data indicate that with the current, potent NAs, HCC risk can be reduced but not eliminated, probably due to risk factors that are not amenable to change by antiviral therapy, or events that may have taken place before treatment initiation. Validated pre- and on-therapy HCC risk calculators that inform the best practice for HCC surveillance and facilitate patient counseling would be of great practical value

Blood Cell Salvage and Autotransfusion Does Not Worsen Oncologic Outcomes Following Liver Transplantation with Incidental Hepatocellular Carcinoma: A Propensity Score-Matched Analysis

BACKGROUND: Intraoperative blood cell salvage and autotransfusion (IBSA) during liver transplantation (LT) for hepatocellular carcinoma (HCC) is controversial for concern regarding adversely impacting oncologic outcomes. OBJECTIVE: We aimed to evaluate the long-term oncologic outcomes of patients who underwent LT with incidentally discovered HCC who received IBSA compared with those who did not receive IBSA. METHODS: Patients undergoing LT (January 2001-October 2018) with incidental HCC on explant pathology were retrospectively identified. A 1:1 propensity score matching (PSM) was performed. HCC recurrence and patient survival were compared. Kaplan-Meier survival analyses were performed, and univariable Cox proportional hazard analyses were performed for risks of recurrence and death. RESULTS: Overall, 110 patients were identified (IBSA, n = 76 [69.1%]; non-IBSA, n = 34 [30.9%]). Before matching, the groups were similar in terms of demographics, transplant, and tumor characteristics. Overall survival was similar for IBSA and non-IBSA at 1, 3, and 5 years (96.0%, 88.4%, 83.0% vs. 97.1%, 91.1%, 87.8%, respectively; p = 0.79). Similarly, the recurrence rate at 1, 3, and 5 years was not statistically different (IBSA 0%, 1.8%, 1.8% vs. non-IBSA 0%, 3.2%, 3.2%, respectively; p = 0.55). After 1:1 matching (26 IBSA, 26 non-IBSA), Cox proportional hazard analysis demonstrated similar risk of death and recurrence between the groups (IBSA hazard ratio [HR] of death 1.26, 95% confidence interval [CI] 0.52-3.05, p = 0.61; and HR of recurrence 2.64, 95% CI 0.28-25.30, p = 0.40). CONCLUSIONS: IBSA does not appear to adversely impact oncologic outcomes in patients undergoing LT with incidental HCC. This evidence further supports the need for randomized trials evaluating the impact of IBSA use in LT for HCC

Genetic Association of Multiple Sclerosis with the Marker rs391745 near the Endogenous Retroviral Locus HERV-Fc1: Analysis of Disease Subtypes

We have previously described the occurrence of multiple sclerosis (MS) to be associated with human endogenous retroviruses, specifically the X-linked viral locus HERV-Fc1. The aim of this study was to investigate a possible association of the HERV-Fc1 locus with subtypes of MS. MS patients are generally subdivided into three categories: Remitting/Relapsing and Secondary Progressive, which together constitute Bout Onset MS, and Primary Progressive. In this study of 1181 MS patients and 1886 controls we found that Bout Onset MS was associated with the C-allele of the marker rs391745 near the HERV-Fc1 locus (p = 0.003), while primary progressive disease was not. The ability to see genetic differences between subtypes of MS near this gene speaks for the involvement of the virus HERV-Fc1 locus in modifying the disease course of MS

Toronto HCC Risk Index::A validated scoring system to predict 10-year risk of HCC in patients with cirrhosis

Background: Current guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in all patients with cirrhosis, regardless of etiology. However, HCC incidence is not well established for many causes of cirrhosis. Aim: To assess the disease-specific incidence of HCC in a large cohort of patients with cirrhosis and to develop a scoring system to predict HCC risk. Methods: A derivation cohort of patients with cirrhosis diagnosed by biopsy or non-invasive measures was identified through retrospective chart review. The disease-specific incidence of HCC was calculated according to etiology of cirrhosis. Factors associated with HCC were identified through multivariable Cox regression and used to develop a scoring system to predict HCC risk. The scoring system evaluated in an external cohort for validation. Results: Of 2,079 patients with cirrhosis and ≥6 months follow-up, 226 (10.8%) developed HCC. The 10-year cumulative incidence of HCC varied by etiologic category from 22% in patients with viral hepatitis, to 16% in those with steatohepatitis and 5% in those with autoimmune liver disease (p<0.001). By multivariable Cox regression, age, sex, etiology and platelets were associated with HCC. Points were assigned in proportion to each hazard ratio to create the Toronto HCC Risk Index (THRI). The 10-year cumulative HCC incidence was 3%, 10% and 32% in the low (<120 points) medium (120-240) and high (>240) risk groups respectively, values that remained consistent after internal validation. External validation was performed on a cohort of patients with PBC, HBV and HCV cirrhosis (n= 1,144) with similar predictive ability (Harrell’s c-statistic 0.77) in the validation and derivation cohorts. Conclusion: HCC incidence varies markedly by etiology of cirrhosis. The THRI, using readily available clinical and laboratory parameters, has good predictive ability for HCC in patients with cirrhosis, and has been validated in an external cohort. This risk score may help to guide recommendations regarding HCC surveillance among patients with cirrhosis

Erythrocyte Inosine triphosphatase activity: A potential biomarker for adverse events during combination antiretroviral therapy for HIV

The purine analogues tenofovir and abacavir are precursors of potential substrates for the enzyme Inosine 5’-triphosphate pyrophosphohydrolase (ITPase). Here, we investigated the association of ITPase activity and ITPA genotype with the occurrence of adverse events (AEs) during combination antiretroviral therapy (cART) for human immunodeficiency virus (HIV) infection. In 393 adult HIV-seropositive patients, AEs were defined as events that led to stop of cART regimen. ITPase activity 4 mmol IMP/mmol Hb/hour was considered as normal. ITPA genotype was determined by testing two ITPA polymorphisms: c.94C>A (p. Pro32Thr, rs1127354) and c.124+21A>C (rs7270101). Logistic regression analysis determined odds ratios for developing AEs. In tenofovir-containing regimens decreased ITPase activity was associated with less AEs (p = 0.01) and longer regimen duration (p = 0.001). In contrast, in abacavir-containing regimens decreased ITPase activity was associated with more AEs (crude p = 0.02) and increased switching of medication due to AEs (p = 0.03). ITPA genotype wt/wt was significantly associated with an increase in the occurrence of AEs in tenofovir-containing regimens. Decreased ITPase activity seems to be protective against occurrence of AEs in tenofovir-containing cART, while it is associated with an increase in AEs in abacavir-containing regimens

Increased hepatitis E virus seroprevalence correlates with lower CD4+ cell counts in HIV-infected persons in Argentina

Hepatitis E virus (HEV) is a single-stranded RNA virus that can cause hepatitis in an epidemic fashion. HEV usually causes asymptomatic or limited acute infections in immunocompetent individuals, whereas in immunosuppressed individuals such as transplant recipients, HEV can cause chronic infections. The risks and outcomes of HEV co-infection in patients infected with human immunodeficiency virus (HIV) are poorly characterized. We used a third generation immunoassay to measure serum IgG antibodies specific for HEV in 204 HIV-infected individuals from Argentina and a control group of 433 HIV-negative individuals. We found 15 of 204 (7.3%, 95%CI 3.74-10.96%) individuals in the HIV-positive group to have positive HEV IgG levels suggestive of previous infection, compared to 19 of 433 (4.4%, 95% CI 2.5-6.3%) individuals in the HIV-negative control group (p = 0.12). Among HIV-positive individuals, those with HEV seropositivity had lower CD4 counts compared to those that were HEV seronegative (average CD4 count of 234 vs 422 mm3, p = 0.01), indicating that patients with lower CD4 counts were more likely to be HEV IgG positive. Moreover, HEV seropositivity in patients with CD4 counts 200 mm3 (p = 0.012). We found a positive PCR result for HEV in one individual. Our study found that increased seroprevalence of HEV IgG correlated with lower CD4 counts in HIV-infected patients in Argentina

Long-term effects of treatment and response in patients with chronic hepatitis C on quality of life. An international, multicenter, randomized, controlled study

Background: Hepatitis C decreases health related quality of life (HRQL) which is further diminished by antiviral therapy. HRQL improves after successful treatment. This trial explores the course of and factors associated with HRQL in patients given individualized or standard treatment based on early treatment response (Ditto-study). Methods: The Short Form (SF)-36 Health Survey was administered at baseline (n = 192) and 24 weeks after the end of therapy (n = 128). Results: At baseline HRQL was influenced by age, participating center, severity of liver disease and income. Exploring the course of HRQL (scores at follow up minus baseline), only the dimension general health increased. In this dimension patients with a relapse or sustained response differed from non-responders. Men and women differed in the dimension bodily pain. Treatment schedule did not influence the course of HRQL. Conclusions: Main determinants of HRQL were severity of liver disease, age, gender, participating center and response to treatment. Our results do not exclude a more profound negative impact of individualized treatment compared to standard, possibly caused by higher doses and extended treatment duration in the individualized group. Antiviral therapy might have a more intense and more prolonged negative impact on females