Outcome of liver disease in a large cohort of histologically proven chronic hepatitis C: influence of HCV genotype.

OBJECTIVE: To assess the influence of hepatitis C virus (HCV) genotypes on the clinical outcome of liver disease, we analysed 2,307 patients. RESULTS: The most frequently represented genotypes were 1b (40%) and 2 (28.1%). Patients with these genotypes had a median age higher than patients with other genotypes (P< 0.01). The overall survival of subjects with genotype 1b was poorer than the survival of patients with other genotypes (P< 0.01). Liver cirrhosis was found in 280 patients (12.1%), and type 1b was the most represented isolate among them (P< 0.01). Sixty-two patients (22%) developed hepatocellular carcinoma (HCC) during a follow-up of 1481.8 cumulative years (estimated crude incidence rate, 4.1 cases per 100 person-years for all cirrhotics; 5.9 cases for genotype 1a; 4.5 cases for genotype 1b; and 2.8 cases for genotypes non-1). Considering the whole population of 2,307 patients, only genotype 1b was associated significantly with both cirrhosis and the development of HCC. One hundred and nineteen cirrhotic patients underwent treatment with interferon in uncontrolled studies. Interferon therapy was associated with both better survival (P< 0.01) and a lower cumulative hazard for HCC (P< 0.01). CONCLUSIONS: Genotype 1b was associated with a poorer prognosis, probably because it leads to cirrhosis and consequently to HCC development. However, our data did not confirm genotype 1b as an independent risk factor for HCC in liver cirrhosis, which plays a major role in carcinogenesis. Interferon should be considered as a useful strategy in cirrhosis for improvement of survival and reduction of HCC risk.

HCV genotypes in Northern Italy: a survey of 1368 histologically proven chronic hepatitis C patients.

BACKGROUND/AIMS: Hepatitis C virus (HCV) easily undergoes genomic changes, thus accounting for the presence of different genotypes, with different geographic distributions and different outcomes of chronic hepatitis. Type 1b is frequently found in advanced diseases; however, since this genotype is the most prevalent in older patients, the association with advanced age and severity of the disease is confounding. The aim of this study was to assess changes in the prevalence of HCV genotypes by surveying a large population of chronic hepatitis C patients in Northern Italy, and to assess if the high prevalence of genotype 1b in older patients with advanced diseases simply reflects the duration of HCV infection, rather than intrinsic biological properties of HCV. METHODS: We studied 1368 HCV-RNA positive patients, with histologically proven chronic hepatitis. Drug addiction, blood transfusions and sporadically acquired infections represented the risk factors. RESULTS: Genotype 1b, the most prevalent isolate, and genotype 2a were associated with older age, cirrhosis, sporadically-acquired infections and blood transfusion, while types 1a, 3a, and 4 were associated with younger age, chronic persistent hepatitis and drug addiction. Patients with a history of transfusions were divided into four groups depending on the period of transfusion. The prevalence of genotype 1b decreased with time. Type 3a appeared only after 1979. CONCLUSION: The severity of chronic hepatitis C could be related more to the duration of the infection rather than to the intrinsic pathogenicity of HCV genotypes.

Ultrastructural alterations and virus-like particles in lymph nodes of drug addicts with lymphadenopathy syndrome (LAS).

Lymph node biopsies from 16 cases of intravenous drug addicts with lymphadenopathy syndrome (LAS) have been examined at the electron microscope. The main ultrastructural alterations observed in the lymphocytes, dendritic reticulum cells and endothelial cells were tubulo-reticular structures (TRS), test tube and ring shaped forms (TRF) and nuclear pockets (NP). Images suggesting virus budding from lymphocytes and virus-like particles have also been found in 9 out of the 16 cases. The possibility to correlate the latter findings with a better knowledge of LAS evolution and prognosis is discussed.

AIDS-like immunologic alterations in clinically unaffected drug users.

Peripheral blood lymphocyte subpopulations (PBLS) and HLA-DR phenotype have been evaluated in 30 IV drug users who were not affected by acquired immune deficiency syndrome (AIDS). A strongly significant reduction in helper/suppressor ratio was found in these subjects as compared to the control population. When the group under study was subdivided according to the presence or absence of signs of lymphadenopathy syndrome (LAS), the apparently unaffected individuals still had significant modifications in PBLS when compared with controls. These modifications were more marked in subjects within the LAS+ subgroup, who also showed a greater DR5 frequency than those belonging to the LAS- subgroup. The authors concluded that AIDS-like laboratory alterations are present in clinically unaffected IV drug users; the possible role of DR5 in conditioning different individual susceptibility is considered.