Effect of Liver Steatosis on Therapeutic Response in Chronic Hepatitis C Virus Genotype 1 Infected Patients in Hungary (original) (raw)
Related papers
Arquivos de Gastroenterologia, 2011
CONTEXT: Chronic hepatitis C as well as non-alcoholic fatty liver disease are recognized as the main cause of liver disease in Western countries. It is common to see the concomitance of the diseases and the influence of steatosis in the sustained virological response of patients with hepatitis C virus. OBJECTIVE: Assess the sustained virological response in chronic hepatitis C patients according to the presence of liver steatosis. METHODS: One hundred sixty patients with chronic hepatitis C were retrospectively evaluated. Demographic data such as gender, age, body mass index, presence of diabetes mellitus and systemic arterial hypertension, virus genotype and use of pegylated interferon were analyzed, as was the staging of fibrosis and the presence of steatosis at histology. RESULTS: Most patients were male (57.5%), with a mean age of 48 ± 9.7 years. The most frequent genotype observed was 3 (56.9%) and, in the histological evaluation, steatosis was observed in 65% of the patients (...
Steatosis in chronic hepatitis C: Relative contributions of obesity, diabetes mellitus, and alcohol
Hepatology, 2002
Steatosis has emerged as a histologic finding of importance to the progression of hepatitis C virus (HCV)-associated liver disease. However, most studies of HCV-associated steatosis have excluded alcohol drinkers and individuals with diabetes and thus have not addressed the relative contribution of known causes of steatosis to liver injury in HCV-associated disease. To address this issue, we studied 297 consecutive patients with HCV who met inclusion criteria. Alcohol consumption, demographics, and serologic tests were correlated with degrees of steatosis and fibrosis on liver biopsy. Liver biopsy specimens were also examined for evidence of significant alcohol or nonalcoholic steatohepatitis (NASH) injury. In univariate analysis, steatosis correlated with type 2 diabetes mellitus (P ؍ .005) and body mass index (BMI) (P ؍ .0001) but not with the intensity of alcohol intake (in grams per day). In multivariate analysis, BMI (P ؍ .0002) and genotype 3a infection (P ؍ .02) were independent predictors of steatosis. When patients with risk factors for NASH were excluded, genotype 3a infection was the only independent predictor of steatosis. Steatosis (P ؍ .04) and inflammation (P < .0001) scores on liver biopsy were the only independent predictors of fibrosis. Significant alcohol or NASH injury was found in only 6% of biopsy specimens. In conclusion, steatosis in HCV infection is associated with risk factors for NASH, particularly obesity, rather than alcohol consumption. (HEPATOLOGY 2002;36:729-736.) Abbreviations: HCV, hepatitis C virus; NASH, nonalcoholic steatohepatitis; BMI, body mass index. From the
Liver International, 2009
Background: Hepatic steatosis is common in patients infected with hepatitis C virus (HCV). The effect of steatosis on anti-HCV therapy efficacy is unclear. Methods: We studied host and viral factors associated with steatosis and the effect of steatosis on treatment efficacy using the database of a large prospective trial in patients with HCV genotypes 2 and 3. Results: Out of 885 patients assessed for steatosis, a total of 614 patients or 69% had steatosis. Patients with genotype 3 were more likely to have steatosis than those with genotype 2 (79 vs. 59%, P o 0.001). Using the logistic regression model, steatosis was associated with genotype 3 (P o 0.0001), older age (P = 0.0025), heavier weight (P o 0.0001), higher HCV RNA (P o 0.0001), and higher ALT levels (P = 0.015). By univariate analysis, steatosis was associated with lower sustained virological response (SVR) in patients with genotype 3, but not in patients with genotype 2. When all factors associated with steatosis and SVR were evaluated by logistic regression analysis; genotype, age, bodyweight, histological diagnosis, ALT quotient, baseline HCV RNA and treatment duration were associated with the probability of SVR, but gender, race and steatosis were not. Further analysis showed that steatosis remained a non-significant factor while baseline viral load was significantly associated with the probability of an SVR. Conclusions: Steatosis did not influence the efficacy of treatment in our study population. Baseline viral load is a confounding factor, particularly in patients infected with genotype 3 and once baseline viral load was accounted for, the association between steatosis and SVR was not relevant.
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.
Hepatitis C and hepatic steatosis
QJM, 2010
Hepatic steatosis is commonly seen in patients with chronic hepatitis C infection, and the two together have a greater association than by chance alone. Hepatitis C virus is closely associated with lipid metabolism throughout its lifecycle. Hepatic steatosis is more common in genotype 3 infection, due to direct viral effects including through microsomal triglyceride transfer protein, peroxisome proliferator activating receptor, and sterol regulatory element binding protein. In non-genotype 3 infection, hepatic steatosis is considered largely to be due to alterations in host metabolism, particularly through insulin resistance. The clinical relevance of this association has yet to be fully explored. Hepatic steatosis is associated with increased hepatic fibrosis and a reduced level of sustained virological response to pegylated interferon and ribavirin. Small studies trialing adjuvant anti-diabetic therapies or HMG-CoA reductase inhibitors with pegylatedinterferon and ribavirin have shown an improved sustained virological response and reduced viral titer. Furthermore, simple lifestyle alterations showed positive effects on parameters of disease activity. These insights raise the possibility of novel treatment options.
Evolutive peculiarities in chronic hepatitis C
Journal of Hepatology, 1998
Since 1995 at the Infectious Disease unit HDF there was an intensive focus on HCV patients due to the fact that our department open for the public as weiI for military patients we joined the ongoing hepatitis treatment program. In 19% and 1997 we treated 16 patients (assumed: infected by HCV-lb genom) with serum positive HCV RNA (measured by bDNA /Quantiplex TM, Chiron) and bistologicaly veriRed chronic hepatitis (8M and 7F, mean age:42,4 years). 13 patients received 3 MU TIW for 3 months and 3 patients 5 MU TIW for 3 months recombinant aifa-2b interferon (Intron-A, Scbering-Plot@) subcutaneously, and we were studied blood examinations monthly. 14 patients were considered responders according to their serum ALAT levels oormaIiiation and HCV viremia disappearence and them we treated for 1 year 3 MU TIW according to the actual OfBciai Hungarian Hepatits Protocol. Our results are reported as follows: Sustained response(SR) 4pts (HCV-, ALAT norm. after 1 year) Partial response (PR) lpts (HCV+, ALAT norm., Hist. Impr.) Relapser RL) 4pts Responder (R) Spts (after 3 months treatment) Non-responders (NR) 2pts (after 3 months treatment) Conclusion: &Our findings strongIy correlate to the literature and the average Hungarian data.& We recommend to our interferon relapser patients or non-responders to interferon to treat by study "IFN + Ribavirin combination therapy".&. HCV RNA levels seem to be predictors of subsequent response to IFN in our patients with chronic IICV hepatitis.
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.
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.