PWE-044 Inter-Tumour Heterogeneity in Hepatitis C Virus (HCV) Related Multi-Focal Hepatocellular Carcinoma (HCC) (original) (raw)
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Liver International, 2006
Background/Aim: Liver steatosis (LS) has been variably associated with chronic hepatitis C (CHC) but whether it affects sustained virological response to antiviral treatment and by what mechanisms is a question still under debate, at least for some genotypes. The aim of this work was to assess the frequency of LS, its relationship with host and viral factors and to what extent it can influence the response to antiviral combination therapy with pegylated interferon (INF)1ribavirin in a group of patients with CHC from a single center. Patients: One hundred and twelve patients with histologically proven CHC were treated with Peg INF-a 2a 180 mg a week subcutaneously for 48 weeks plus ribavirin 1000 or 1200 mg/day, according to the patient's body weight. Steatosis was graded according to Brunt et al. Results: Forty-six out of 112 patients (41.1%) were sustained virological responders (SVR). Seventy-two out of 112 (64.3%) presented with LS at histology; in this group, there were 24 patients (33.3%) with SVR compared with 22 (55%) of the non-steatosis group (w 2 5 6.5, Po0.02). Variables associated with the steatosis group were: higher serum levels of AST (Po0.04), alanine aminotransferase (Po0.02), g-GT (Po0.004), genotype 3a (Po0.03) and severity of histology (staging Po0.05) but at multiple linear regression analysis only genotype 3a and staging were significantly associated with LS. In the SVR group, age and body mass index (BMI) were significantly lower (Po0001 and Po0.03, respectively) compared with non-responders; moreover, genotype 1 was more frequent in the NR group, while genotype 3 was more frequent in the SVR group. At histology, grading and staging were also lower in the SVR group. Multiple logistic regression showed that only the grade of steatosis and genotype 3a were the variables independently associated with SVR. Conclusions: This study showed a frequency of LS on the higher side of the range so far reported in the literature and confirmed that it negatively influences response to therapy. Genotype1 was confirmed to be the most frequent type in our area. It is more frequent in patients with mild-moderate steatosis and seems to condition therapeutic response negatively, together with BMI and age. In contrast, genotype 3a is more frequent in patients with severe steatosis, but is a favorable predictor of successful therapy.
Hepatology, 2009
Hepatic steatosis is a common histologic feature in patients with chronic hepatitis C (CHC) but there are no large longitudinal studies describing the progression of steatosis in CHC. We examined changes in steatosis on serial biopsies among CHC patients participating in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. All 1050 patients in the trial had advanced fibrosis at baseline biopsy and were documented not to have had a sustained virological response to peginterferon and ribavirin. Most (94%) patients had genotype 1 infection. At least one protocol follow-up biopsy was read on 892 patients, and 699 had the last biopsy performed 3.5 years after randomization. At enrollment, 39% had cirrhosis and 61% had bridging fibrosis; 18%, 41%, 31%, and 10% had steatosis scores of 0, 1, 2, and 3 or 4, respectively. The mean steatosis score decreased in the follow-up biopsies in both the interferon-treated patients and controls with no effect of treatment assignment (P ؍ 0.66). A decrease in steatosis score by >1 point was observed in 30% of patients and was associated with both progression to cirrhosis and continued presence of cirrhosis (P ؍ 0.02). Compared to patients without a decrease in steatosis, those with a decrease in steatosis had worse metabolic parameters at enrollment, and were more likely to have a decrease in alcohol intake, improvement in metabolic parameters, and worsening liver disease (cirrhosis, esophageal varices, and deterioration in liver function). Conclusion: Serial biopsies demonstrated that in patients with CHC, steatosis recedes during progression from advanced fibrosis to cirrhosis. Decreased alcohol intake and improved metabolic parameters are associated with a decline in steatosis and may modulate hepatitis C progression.
Liver Transplantation, 2002
Chronic hepatitis C represents a major clinical problem after liver transplantation, but factors influencing the recurrent disease have not been well characterized. We analyzed the clinical records of all the patients transplanted for hepatitis C virus (HW-related liver disease in our Center between 1991 and 1997. Eighty consecutive HCV-positive (+) patients (60 men, ages 28 to 64) survived more than 1 month after transplantation and were followed for a median of 45 months. Diagnosis of recurrent chronic hepatitis C was made in 38 patients (47.5%), of whom 22 had moderate/severe chronic hepatitis. Decompensated cirrhosis occurred in six patients (7.5%).
The impact of hepatic steatosis on the natural history of chronic hepatitis C infection
Journal of Viral Hepatitis, 2009
Summary. Since patients with hepatitis C virus (HCV) often have hepatic steatosis, this retrospective analysis aimed to assess whether steatosis influences fibrosis progression. We studied 112 HCV RNA positive subjects (median age 44, IQR 39–51 years), who had two liver biopsies performed (median biopsy interval 50, 34–74 months). Fibrosis was staged using the Ishak method and steatosis by the Kleiner system (<5% steatosis = S0, 5–33% = S1, 33–66% = S2, and >66% = S3). The subjects were untreated because they had mild fibrosis (n = 59), declined therapy (n = 48), or had co-existing disease precluding treatment (n = 5). On first liver biopsy, 60 (54%) had S0, 34 (30%) had S1, 12 (11%) had S2, and 6 (5%) had S3. Steatosis was associated with genotype 3, odds ratio 4.8 (95% CI 1.3–16.7, P = 0.02). Twenty-three patients (21%) had disease progression on the second biopsy, defined as an increase in Ishak score by ≥1 stage. On univariate analysis, fibrosis progression was associated with older age (P = 0.004), higher AST (P = 0.04), and steatosis (P = 0.005) but on multivariate analysis, only baseline steatosis was significant, odds ratio 14.3 (2.1–111.1, P = 0.006). Kaplan-Meier analysis demonstrated that steatosis impacted on time to progression to both significant fibrosis (Ishak ≥F3) and cirrhosis (Ishak F5-6) (P = 0.001 and P = 0.049, respectively). The finding that steatosis was significantly associated with fibrosis progression indicates that, independent of baseline fibrosis stage, patients should be considered for anti-viral treatment if steatosis is present. Furthermore, strategies to reduce steatosis may have a beneficial effect on fibrosis progression and, therefore, patient outcome.
Long-Term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C
Hepatology, 2003
Data on the long-term outcome of nonalcoholic steatohepatitis (NASH)-associated cirrhosis are few, and most reports describe cases of cryptogenic cirrhosis associated with risk factors for NASH but without histologic definition. In this prospective cohort study, we describe the longterm morbidity and mortality of 23 patients with NASH-associated cirrhosis defined by strict clinicopathologic criteria. Outcomes were compared with 46 age-and gender-matched patients with cirrhosis from chronic hepatitis C virus (HCV) infection: 23 untreated and 23 nonresponders to antiviral therapy. During follow-up (mean, 84 months; median, 60 months; range, 5-177 months), 9 of the 23 NASH-associated cirrhosis cases developed liver-related morbidity (8 ascites and/or encephalopathy, 1 variceal bleeding). The probability of complication-free survival was 83%, 77%, and 48% at 1, 3, and 10 years, respectively, and the cumulative probability of overall survival was 95%, 90%, and 84% at 1, 3, and 10 years, respectively. Five deaths were from liver failure, 1 from a non-liver-related cause. By multivariate analysis, bilirubin (P ؍ .02) and platelet (P ؍ .04) were independent predictors of complication-free survival; bilirubin (P ؍ .05) was the only predictor for overall survival. After controlling for these factors, there was no difference in complication-free or overall survival between the NASH-cirrhosis cohort and either group of HCV-cirrhosis. However, 8 cases of liver cancer occurred in the HCV-cirrhosis groups compared with none among NASH cases. In conclusion, liver failure is the main cause of morbidity and mortality in NASH-associated cirrhosis. The prognosis is either similar or less severe than HCV-cirrhosis, except that HCC appears less common. (HEPATOLOGY 2003;38:420-427.) Abbreviations: NASH, nonalcoholic steatohepatitis; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; BMI, body mass index; ALT, alanine aminotransferase; AST, aspartate aminotransferase; HR, hazard ratio. From the
Steatosis as a predictive factor for treatment response in patients with chronic hepatitis C
Gastroenterology, 2003
Background. Hepatic steatosis has been described in 31-72% of chronic hepatitis C virus (HCV) liver biopsies. Steatosis has been related to disease progression and suggested as a predictor of treatment response in chronic HCV. This study aims to evaluate the presence and degree of steatosis in liver histology of patients with chronic HCV prior to combination therapy with interferon (INF) and ribavirin (RBV), and how it influences treatment response. Methods. The medical charts of patients with chronic HCV who received treatment at the San Juan Veterans Affairs (VA) Medical Center from 1998 to 2002 were reviewed. Selected patients completed therapy, had a pre-treatment liver biopsy, genotype determination, and pre and post treatment HCV-RNA levels. Patient's age, sex and body mass index (BMI) were determined. Pre-treatment liver biopsy slides were reviewed and graded for steatosis by a hepatopathologist blinded to the treatment outcome. Steatosis was graded by the presence of fat in total biopsy area as: mild (<33%), moderate (33-66%), severe (>66%) or absent. Treatment response was defined as virological clearance measured by HCV RNA at the end of treatment and 24 weeks after completion of treatment. The presence of steatosis was compared to BMI, HCV genotype and treatment response. Results. 46 patients met the inclusion criteria. All patients were male of Hispanic origin. Mean age: 52.7 years (range: 40-68). Mean BMI: 27.5 kg/m2 (range: 21.1-35.9). HCV genotype 1 was present in 67% of patients. 82.6% (38/46) of the patients had hepatic steatosis: 29 (63%) mild, 7 (15%) moderate and 2(4%) severe. 16.6% (8/46) of the biopsies did not show steatosis. Overall, the response rate for those with steatosis was 31.6% (12/38): 10/29 (34.5%) mild, 1/7 (14.3%) moderate and 1/2 (50%) of severe. 75% (6/8) of those without steatosis responded to treatment. This difference (31.6% vs.75%) was statistically significant (p=.042). The mean BMI of both groups was similar (27.7 kg/m2 for those with steatosis and 26.6 kg/m2 for those without steatosis). This difference was not statistically significant (p=.308). Conclusions. The results of our study show a high prevalence of steatosis in the liver histology of patients with chronic HCV. The presence and degree of steatosis in our HCV patients appears to be unrelated to either genotype or BMI. Furthermore, the response to therapy is negatively influenced by the presence of steatosis regardless of genotype. Hepatic steatosis, mild, moderate or severe, appears to be an independent predictor of poor response to therapy.
Journal of Hepatocellular Carcinoma, 2021
Background: Direct-acting antivirals (DAA) have revolutionized the therapy of chronic hepatitis C (CHC) and have replaced previous PEG-interferon/ribavirin (PEG-IFN/RBV) treatment. Patients with CHC and advanced liver disease are at increased risk for hepatocellular carcinoma (HCC). However, the effects of DAA-based CHC treatment on subsequent HCC incidence remain poorly understood. Patients and Methods: This retrospective single-institution cohort study included 243 consecutive patients after PEG-IFN/RBV and 263 patients after DAA treatment. Multivariable cause-specific Cox proportional hazards models were used to compare time to HCC between treatment types, censoring patients who died or had an orthotopic liver transplantation (OLT) at the time of the competing event. Age, gender, BMI, viral load, cirrhosis, fibrosis stage, diabetes, virus genotype and previous PEG-IFN/RBV (before DAA) were used as covariates. In addition, we performed a propensity score-matched analysis. Results: Nineteen HCC cases were observed after DAA therapy compared to 18 cases after PEG-IFN/RBV treatment. Patients were followed for a median of 4.1 years (IQR: 3.5-4.7) for DAA and 9.3 years (IQR: 6.6-12.4) for the PEG-IFN/RBV group. In an unadjusted Cox model, a hazard ratio (HR) of 6.40 (CI: 2.20-18.61, p=0.006) for HCC following DAA vs PEG-IFN/RBV was estimated. In multivariable Cox proportional hazard models, age and liver cirrhosis were identified as further HCC risk factors but the HR estimates for DAA vs PEG-IFN/RBV still indicate a considerably increased hazard associated with DAA treatment (HR between 7.23 and 11.52, p≤0.001, depending on covariates). A HR of 6.62 (CI: 2.01-21.84, p=0.002) for DAA vs PEG-IFN/RBV was estimated in the propensity score-matched analysis. The secondary outcomes death and OLT did not differ between treatment groups. Conclusion: In a cohort study from a tertiary care hospital rates of HCC after the start of DAA treatment were higher compared to PEG-IFN/RBV treatment. Our data reinforce the recommendation that surveillance should be continued after successful CHC treatment.