HCV genotype 3 is associated with a higher hepatocellular carcinoma incidence in patients with ongoing viral C cirrhosis

J Viral Hepat. 2011 Oct;18(10):e516-22. doi: 10.1111/j.1365-2893.2011.01441.x.

HCV genotype 3 is associated with a higher hepatocellular carcinoma incidence in patients with ongoing viral C cirrhosis.

Nkontchou G, Ziol M, Aout M, Lhabadie M, Baazia Y, Mahmoudi A, Roulot D, Ganne-Carrie N, Grando-Lemaire V, Trinchet JC, Gordien E, Vicaut E, Baghad I, Beaugrand M.

Source
Department of Hepatogastroenterology Pathology Unit Hôpital Jean Verdier (Assistance Publique-Hôpitaux de Paris), Bondy, France PatUnit the Unit of Clinical Research Hôpital Lariboisiere URC Department of Virology, Hôpital Avicenne (Assistance Publique-Hôpitaux de Paris), France.

Nkontchou G et al. – In multivariate analysis, infection with a genotype 3 was independently associated with an increased risk of hepatocellular carcinoma occurrence, even after adjustment for prothrombin activity and alcohol abuse. For patients with hepatitis C virus cirrhosis and ongoing infection, infection with genotype 3 is independently associated with an increased risk of hepatocellular carcinoma development.

Abstract
Summary. 
Liver steatosis is a main histopathological feature of Hepatitis C (HCV) infection because of genotype 3. Steatosis and/or mechanisms underlying steatogenesis can contribute to hepatocarcinogenesis.

The aim of this retrospective study was to assess the impact of infection with HCV genotype 3 on hepatocellular carcinoma (HCC) occurrence in patients with ongoing HCV cirrhosis.

Three hundred and fifty-three consecutive patients (193 men, mean age 58 ± 13 years), with histologically proven HCV cirrhosis and persistent viral replication prospectively followed and screened for HCC between 1994 and 2007.

Log-rank test and Cox model were used to compare the actuarial incidence of HCC between genotype subgroups.

The patients infected with a genotype 3 (n = 25) as compared with those infected with other genotypes (n = 328) had a lower prothrombin activity [78 (interquartile range 60-85) vs 84 (71-195) %, P = 0.03] and higher rate of alcohol abuse (48%vs 29%, P = 0.046).

During a median follow-up of 5.54 years [2.9-8.6], 11/25 patients (44%) and 87/328 patients (26%) with a genotype 3 and non-3 genotype, respectively, develop a HCC. HCC incidences were significantly different among the genotype subgroups (P = 0.001).

The 5-year occurrence rate of HCC was 34% (95% CI, 1.3-6.3) and 17% (95% CI, 5.7-9.2) in genotype 3 and non-3 genotype groups, respectively (P = 0.002).

In multivariate analysis, infection with a genotype 3 was independently associated with an increased risk of HCC occurrence [hazard ratio 3.54 (95% CI, 1.84-6.81), P = 0.0002], even after adjustment for prothrombin activity and alcohol abuse [3.58 (1.80-7.13); P = 0.003].

For patients with HCV cirrhosis and ongoing infection, infection with genotype 3 is independently associated with an increased risk of HCC development.
© 2011 Blackwell Publishing Ltd.

In Case You Missed It

European Journal of Gastroenterology & Hepatology:

September 2011 - Volume 23 - Issue 9
p 747–753 doi: 10.1097/MEG.0b013e3283488aba
Original Articles:

Hepatitis Response to antiviral therapy in patients with genotype 3 chronic hepatitis C: fibrosis but not race encourages relapse

Shoeb, Daniaa; Rowe, Ian A.b; Freshwater, Dennisb; Mutimer, Davidb; Brown, Ashleyc; Moreea, Sullemand; Sood, Ruchitd; Marley, Richarda; Sabin, Caroline A.e; Foster, Graham R.a

Abstract Background and aims:
We completed a retrospective analysis of patients with genotype 3 hepatitis C virus (HCV) undergoing therapy in four UK centres with large populations of patients from the Indian subcontinent.

Materials and methods:
Notes on all patients treated with pegylated interferon and ribavirin were reviewed and factors that influenced the response were examined. Results: Six hundred and four patients with genotype 3 HCV were studied, of whom 299 were Asians. Median age was 43 years, 65% were men and 24% had cirrhosis. Overall, 457 (76%) patients achieved sustained virological response (SVR).

By multivariable analysis it was found that ethnicity was not associated with an impaired response but age, cirrhosis and diabetes were significantly associated with a reduced SVR, the likelihood of a response was reduced by 25% per 10-year increment in age, by 59% among individuals with cirrhosis and by 62% among individuals with diabetes mellitus. Most patients who did not achieve an SVR relapsed (15%) rather than failing to achieve an end of treatment response.

Conclusion:
The response to antiviral therapy in genotype 3 HCV is not affected by South Asian (vs. Caucasian) ethnicity, but age, cirrhosis and diabetes reduce the response. Treatment failure most often is due to relapse.

Viral clearance is associated with improved insulin resistance in genotype 1 chronic hepatitis C but not genotype 2/3
Published Online First 26 August 2011

Abstract
Genotype-specific associations between hepatitis C virus (HCV) and insulin resistance (IR) have been described, but a causal relationship remains unclear. This study investigated the association between a sustained virological response (SVR) and IR after chronic HCV therapy.

Methods
2255 treatment-naive patients with chronic HCV genotype 1 or 2/3 were enrolled in two phase 3 trials of albinterferon alpha-2b versus pegylated interferon alpha-2a for 48 or 24 weeks, respectively. IR was measured before treatment and 12 weeks after treatment using homeostasis model assessment (HOMA)-IR.

Results
Paired HOMA-IR measurements were available in 1038 non-diabetic patients (497 with genotype 1; 541 with genotype 2/3). At baseline the prevalence of HOMA-IR >3 was greater in patients with genotype 1 than 2/3 (33% vs 27%; p=0.048). There was a significant reduction in the prevalence of IR in patients with genotype 1 achieving SVR (δ 10%; p<0.001), but not in genotype 1 non-responders or those with genotype 2/3. Multivariate analysis indicated that SVR was associated with a significant reduction in mean HOMA-IR in patients with genotype 1 (p=0.004), but not in those with genotype 2/3, which was independent of body mass index, alanine transaminase, γ-glutamyl transpeptidase and lipid level changes.

Conclusions
SVR is associated with a reduction in HOMA-IR in patients with HCV genotype 1 but not in those with genotype 2/3. Genotype 1 may have a direct effect on the development of IR, independent of host metabolic factors, and may be partially reversed by viral eradication

Telaprevir Alone or with Peginterferon, Ribavirin Reduces HCV RNA
In a study appearing in Gastroenterology, doctors evaluated antiviral activity of two weeks of therapy with telaprevir alone, peginterferon alfa-2a and ribavirin, or all three drugs in treatment-naïve patients with chronic hepatitis C virus (HCV) genotype 2 or 3 infections. They found that telaprevir monotherapy for two weeks reduces levels of HCV ribonucleic acid in patients with chronic HCV genotype 2 infections, but has limited activity in patients with HCV genotype 3.
Gastroenterology 2011; 141(3): 881-889.e1