There appears to be some controversy about this but several studies listed below suggest disease progression may be worse in genotype 1 than 2.

  The natural course of chronic hepatitis C: a comparison between patients with genotypes 1 and 2 hepatitis C viruses
M Kobayashi, E Tanaka, T Sodeyama, A Urushihara, A Matsumoto and K Kiyosawa

The Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.  

This study was conducted to clarify if the long-term histological outcome among patients with chronic hepatitis C differs according to whether they are infected with genotype 1 or 2 hepatitis C virus (HCV). We examined 140 patients with chronic hepatitis C. The HCV genotype was determined by the enzyme-linked immunosorbent assay (ELISA) based on genotypes 1 and 2 specific recombinant proteins; genotype 1 was found in 100 patients (96 were 1b and 4 were indeterminate) and genotype 2 in 36. The two groups showed no significant difference for any clinical background features.

Deterioration of the grade of liver histology during the follow-up period was seen in 68.0 percent of the patients with genotype 1 as compared with 41.7 percent of those with genotype 2 (P < .01). Similarly, the deterioration of the stage of liver histology was more common in the former group than in the latter (63.0 percent and 38.9 percent respectively; P < .05). The mean serum HCV-RNA titer was significantly higher in the patients with genotype 1 than in those with genotype 2 (P < .001), and multivariate analysis showed the titer was one of the independent factors of the deterioration of the stage (P = .0044). This phenomenon may be related in part to the difference in pathogenicity between the two HCV genotypes. In conclusion, our results suggest that more severe progression of chronic hepatitis C is seen in patients showing genotype 1b compared with those with genotype 2.


Effects of interferon treatment on the antiviral T-cell response in hepatitis C virus genotype 1b- and genotype 2c-infected patients

G Missale, E Cariani, V Lamonaca, A Ravaggi, A Rossini, R Bertoni, M Houghton, Y Matsuura, T Miyamura, F Fiaccadori and C Ferrari  Cattedra Malattie Infettive, Universita di Parma, Italy

The T-cell response to HCV peptides and recombinant core protein detected throughout the follow-up was significantly more vigorous in genotype 2c- than in genotype 1b- infected patients. This difference was the result of a greater enhancement of the T-cell response caused by IFN treatment in genotype 2c- compared with genotype 1b-infected patients. The different IFN modulatory effect on T cells from genotype 1b- and genotype 2c-infected patients illustrates an aspect of the virus-host interaction, which may contribute toward the explanation of why different genotypes differ in responsiveness to IFN treatment.

The T-cell response to HCV core protein was sequentially analyzed before and during IFN treatment in two groups of patients chronically infected with HCV genotype 1b (eight patients) or 2c (eight patients). Overlapping 20 mer peptides corresponding to the amino acid sequence of the prevalent viral population identified in the serum of each patient were used for the analysis of the T-cell proliferative response to avoid possible problems caused by amino acid differences between infecting virus and HCV proteins used in vitro. Recombinant HCV core antigen was used in parallel. The level of viremia was monitored by competitive polymerase chain reaction (PCR).

My take: The following study suggests individuals with cirrhosis don't progress more quickly whether they have genotype 1 or 2. This does not mean that genotype 1 or 2 may not affect progression prior to cirrhosis developing.

Lack of correlation between hepatitis C virus genotypes and clinical course of hepatitis C virus-related cirrhosis 

L Benvegnu, P Pontisso, D Cavalletto, F Noventa, L Chemello and A Alberti Clinica Medica Second, University of Padova, Italy.  

The influence of the hepatitis C virus (HCV)-genotype on liver disease severity was evaluated in 429 consecutive patients with chronic hepatitis C, including 109 with cirrhosis who were followed up prospectively, allowing for the assessment of the role of the HCV- genotype on disease outcome and on the development of hepatocellular carcinoma (HCC). HCV-1 was detected in 147 (46%) patients without cirrhosis and in 47 (43%) with cirrhosis

(P: not significant), being mainly HCV-1b. HCV-2 was found in 103 (32%) cases without cirrhosis and in 30 (27.5) with cirrhosis (P: not significant), being mainly HCV-2a. HCV-3 was detected in 32 (10%) patients without cirrhosis and in 2 (2%) with cirrhosis (P < 0.005). Infection with more than one genotype (HCV- 1/HCV-2 and HCV-1/HCV-3) was observed only in cirrhotic patients (6 of 109; 5.5%). During a mean follow-up of 67 +/- 22 months, 21 (19%) patients with cirrhosis showed worsening in Child's stage, 5 (4.5%) underwent liver transplantation, 23 (21%) developed HCC, and 24 (22%) died of complication of liver disease; the overall incidence of at least one of these events was 38.5%. By the Kaplan-Meier method and log-rank test, the cumulative probability of developing each or at least one of the above events did not differ in relation to the genotype of infecting HCV, apart from patients with mixed genotype infection who showed a significantly higher incidence of death (P < .05). These data indicate that HCV-genotypes do not have a significant effect on the severity and outcome of liver disease in patients with chronic HCV- infection. Patients with cirrhosis who are also infected by HCV-1 and HCV-2 had a similar prognosis and progression to HCC, while patients infected by more than one genotype showed the most unfavorable course of disease.

Results from following study correlate genotype 1 with developing liver cancer

Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: a prospective study

S Bruno, E Silini, A Crosignani, F Borzio, G Leandro, F Bono, M Asti, S Rossi, ALarghi, A Cerino, M Podda and MU Mondelli Divisione di Medicina Generale III, Cattedra di Medicina Interna, Istituto di Scienze Biomediche San Paolo, Universita di Milano, Italy.

A prospective study was performed to establish whether infection with specific hepatitis C virus (HCV) genotypes was associated with an increased risk of development of hepatocellular carcinoma (HCC) in cirrhosis. A cohort of 163 consecutive hepatitis C virus antibody (anti- HCV)-positive cirrhotic patients was prospectively evaluated for the development of HCC at 6-month intervals by ultrasound (US) scan and alpha-fetoprotein (AFP) concentration. HCV genotypes were determined according to Okamoto. Risk factors associated with cancer development were analyzed by univariate and multivariate statistics. At enrollment, 101 patients (62%) were infected with type 1b, 48 (29.5%) were infected with type 2a/c, 2 (1.2%) were infected with type 3a, 1 (0.6%) was infected with type 1a, 3 (1.8%) had a mixed-type infection, and, in 8 patients (4.9%), genotype could not be assigned. After a 5- to 7-year follow-up (median, 68 months), HCC developed in 22 of the patients, 19 infected with type 1b and 3 with type 2a/c (P < .005). Moreover, HCC developed more frequently in males (P < .01), patients with excessive alcohol intake (P < .01), those over 60 years of age (P < .02), and in patients who did not receive interferon treatment (P < .02). Multivariate analysis showed that type 1b was the most important risk factor associated with tumor development (odds ratio 6.14, 1.77-21.37 95% confidence interval). Other independent risk factors were older age and male sex. Cirrhotic patients infected with HCV type 1b carry a significantly higher risk of developing HCC than patients infected by other HCV types. The latter may require a less intensive clinical surveillance for the early detection of neoplasia.

This study also suggests genotype 1 is more associated with disease severity than genotype 2.

Influence of different hepatitis C virus genotypes on the course of asymptomatic hepatitis C virus infection

D Prati, C Capelli, A Zanella, F Mozzi, P Bosoni, M Pappalettera, F Zanuso, L Vianello, E Locatelli, C de Fazio, G Ronchi, E del Ninno, M Colombo and G Sirchia  Centro Trasfusionale e di Immunologia dei Trapianti, Ospedale Maggiore, Milano, Italy.

BACKGROUND & AIMS: The association of liver disease with hepatitis C virus (HCV) genotypes mainly refers to patients with serious liver damage; little information is available on symptomless carriers. The aim of this study was to investigate the correlation of genotypes with clinical course, risk factors for infection, and antibody to HCV reactivity in asymptomatic subjects. METHODS: One hundred nine viremic blood donors with at least 1 year of follow-up were studied; 41 underwent liver biopsy. Genotypes were determined by line-probe assay. RESULTS: Genotype 1 was found in 47 (43.1%), genotype 2 in 48 (44%), genotype 3 in 8 (7.3%), genotype 4 in 2 (1.8%), and coinfections in 4 (3.7%). The relative risk (RR) for a raised pattern of alanine amino-transferase, aspartate aminotransferase, and gamma- glutamyl-transpeptidase was 2.1 (confidence interval [CI], 1.4-3.2), 1.7 (CI, 1.2-2.4), and 2.8 (CI, 1.6-4.9) in subjects with genotype 1 vs. 0.4 (CI, 0.2-0.7), 0.4 (CI, 0.3-0.7), and 0.4 (CI, 0.2-0.8) in subjects with genotype 2. Chronic hepatitis was found in 68%; the RR of chronic hepatitis was similar for genotypes 1 and 2 (RR, 1.1 [CI, 0.8-1.7] vs. RR, 1.0 [CI, 0.7-1.6]). Reactivity to NS4-derived antigens was infrequent in type 2-infected subjects. CONCLUSIONS: Genotype 2 was as frequent as genotype 1 but associated with less liver function impairment. The high prevalence of chronic hepatitis should be considered in counseling viremic asymptomatic donors.