M. A. Serra

Influence of age and date of infection on distribution of hepatitis C virus genotypes and fibrosis stage

Summary.  The objective of this study was to assess the influence of age and date of acquisition of hepatitis C virus (HCV) infection on the distribution of genotypes and the progression of fibrosis in HCV‐infected patients who were born in Spain and had their habitual place of residence in this country. Genotypic analysis was performed in 375 patients in whom it was possible to establish the year of HCV infection because the mode of transmission was known (transfusion, injection drug use, blood donor, or epidemic outbreak). In 298 patients with liver biopsy, fibrosis stage was related to age at infection, duration of infection, alcohol consumption, and HCV genotype. HCV subtype 1b was almost exclusively detected among transfusion recipients, but the onset of intravenous drug addiction was associated with the introduction of HCV genotypes other than 1b among injecting users with subsequent spread to other exposure risk groups. Fibrosis progression was influenced by alcohol consumption, increased duration of infection, and older age at infection. In summary, spread of intravenous drug use determined HCV infection by genotypes other than 1b. The risk of fibrosis progression was influenced more by age at viral acquisition and alcohol consumption than by the infecting genotype.

Immune response to hepatitis B vaccine in parenteral drug abusers

Responsiveness was assessed to a programme of vaccination of hepatitis B vaccine in a cohort of 197 intravenous drug addicts (mean age, 23.7 years) and their antibody response was compared with that of 271 healthy controls (mean age, 24.2 years). All participants were seronegative for hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs). The vaccination schedule consisted of three intramuscular injections (deltoid area) at months 0, 1 and 2. Although 70% of parenteral drug abusers received the three doses of vaccination, only 43.6% were evaluable for immune response. Fifty-eight per cent of heroin addicts and 80% of controls had evidence of anti-HBs seroconversion at 1 month after vaccination (chi 2 = 15.52, p less than 0.001). Geometric mean antibody titres were also significantly higher in controls (69.1 IU l-1; confidence interval 95%, 56.83 and 84.04) than in parenteral drug abusers (18.2 IU l-1; confidence interval 95%, 12.85 and 25.73) (F = 20.951, p less than 0.0001). The anti-HBs response was not influenced by coexistent anti-HBc, HCV antibody or HIV antibody seropositivity.

HTLV-III ANTIBODIES IN DRUG ADDICTS IN SPAIN

In drug addicts the prevalence of antibodies to HTLV-III has varied from 1.5% in the UK to 87% in some studies in the USA. We have used a commercial enzyme immunoassay (Abbott) to look for antibodies to HTLV-III in 303 drug addicts (in whom evidence of viral hepatitis B and delta infection was also sought by Abbott assays) and in 95 healthy blood donors. We found anti-HTLV-III in 112 drug addicts (37%) but in none of the controls. Antibodies were more common in samples taken in 1985 (48% of 75 cases) than in 1984 (40% of 174) or 1983 (11% of 58) samples and were more common when any hepatitis B virus marker was positive (42%) than when all markers were negative (14% p0.001). The frequency was 40% in sera that were seropositive for delta antibody and 33% in delta antibody negative cases (p 0.05). The prevalence of anti-HTLV-III in drug addicts in Spain is similar to that in Switzerland and less than the prevalence observed in Italy but greater than the figure for the UK. The prevalence of infection by HTLV-III has been increasing in Spain since 1983 and is linked to the length of the history of drug addiction. (full text)

Prevalence and incidence of gallstones in liver cirrhosis

BACKGROUND Our aim was to assess the prevalence and incidence of gallstone disease in patients with liver cirrhosis and to identify risk factors for cholecystolithiasis. METHODS We studied a cohort of 313 patients with liver cirrhosis confirmed by histology and/or laparoscopy and 357 patients free of liver disease, who had been referred for ultrasonographic examination of the upper abdomen. Hepatobiliary ultrasonography was performed when liver cirrhosis was diagnosed and every 6 months thereafter. Risk factors for cholelithiasis (age, gender, diet, pregnancy, diabetes, family history of cholelithiasis, etiology of cirrhosis, decompensated disease) were assessed. RESULTS The overall prevalence of gallstones in cirrhotic patients was 23.3%. In controls, the overall prevalence of cholecystolithiasis was 16.8%. After a median follow-up period of 65 months, 30 patients developed gallstones. The calculated annual incidence was 3.4%. CONCLUSIONS Given that the prevalence of gallstone disease is higher in cirrhotics than in noncirrhotic patients, cirrhosis of the liver may be considered a risk factor for cholecystolithiasis.

Oral Lichen Planus and Hepatic Cirrhosis

Excerpt To the Editor:Recent reports have described the association of chronic liver disease and lichen planus (13); however, there is uncertainty about the prevalence of chronic liver disease in p...

Prevalence of liver disease and infection by hepatitis B, Delta virus, and human immunodeficiency virus in two Spanish penitentiaries

We studied the prevalence of liver disease and the carrier state for hepatitis B (HBV), delta virus (HDV) and HIV-1 infection in two Valencian penitentiaries, one for males and the other for females. Serological results were correlated with history of intravenous drug addiction, alcohol abuse, homosexuality or prostitution (high-risk groups), and duration and number of internments. A high prevalence of increased transaminase levels (52.2%) and serological markers for HBV infection (66.5%) was observed amongst the inmates, figures being higher amongst high-risk individuals and inmates confined for more than 6 months. No signs of HDV or HIV-1 infection were found amongst the prison staff. Anti-HIV-1 positivity was observed most frequently amongst individuals combining both drug abuse and homosexuality/and prostitution.

Clinical value of increased serum creatinine concentration as predictor of short-term outcome in decompensated cirrhosis.

Background: The purpose of this study was to assess whether serum creatinine concentration alone or associated with other biological parameters was an independent predictor of short-term mortality in patients with decompensated cirrhosis. Methods: A total of 212 consecutive episodes of decompensated cirrhosis in patients admitted to the hospital between January 1999 and December 2001 were reviewed retrospectively. Depending on a serum creatinine concentration equal to or greater than 1.5 mg/dL at the time of admission, patients were divided into decompensated cirrhosis with renal failure (101 episodes in 59 patients, aged 69.8 ± 10 years) and without renal failure (111 episodes in 61 patients, aged 64.5 ± 13 years). Outcome (alive, death) during the episode of decompensation of liver disease and outcome at 90 days after admission were assessed. Results: Differences in the frequency of variables according to outcome in the overall episodes of decompensated cirrhosis with and without renal failure showed significant differences between patients who died and those who were alive both at hospital discharge and at 90 days in serum bilirubin, Child-Pugh score, MELD (model for end-stage liver disease) score, and serum creatinine levels. In the multivariate analysis, serum creatinine was not an independent predictor of outcome. The prediction accuracy according to the area under the ROC (receiver operating characteristic) curve was greater for the MELD scale than for serum creatinine. Conclusions: Serum creatinine concentration is a parameter that should be included in the prognostic assessment of patients with decompensated cirrhosis, but should be combined with other specific parameters of liver function, such as bilirubin, albumin, and the international normalized ratio (INR) for prothrombin time.

Clinical significance of abdominal lymphadenopathy in chronic liver disease

The possibility of assessing the relationship of ultrasound (US)-detected abdominal lymphadenopathy with etiology, biochemical findings, and histologic data in patients with chronic liver disease was evaluated. US examination of the upper abdomen was performed in 321 consecutive patients with various chronic liver disorders and 56 control patients. The prevalence of lymphadenopathy in chronic liver disease was 38%. This prevalence varied according to etiology of liver disease, from 50% in chronic hepatitis C virus (HCV) to less than 10% in alcoholic cirrhosis and hepatitis B-virus (HBV)-related chronic liver disease. Patients with lymphadenopathy showed significantly higher serum levels of AST and ALT, as well as greater histopathological severity on liver biopsy specimens. In anti-HCV positive patients, there were no differences in the prevalence of lymphadenopathy according to HCV genotypes, whereas lymphadenopathy occurred less frequently in responders to interferon therapy than in nonresponders.

Altered modulation of soluble guanylate cyclase by nitric oxide in patients with liver disease

The glutamate–nitric oxide–cGMP pathway is impaired in brain in vivo in animal models of chronic moderate hyperammonemia either with or without liver failure. The impairment occurs at the level of activation of soluble guanylate cyclase by nitric oxide (NO). It has been suggested that the impairment of this pathway may be responsible for some of the neurological alterations found in hyperammonemia and hepatic encephalopathy. Soluble guanylate cyclase is also present in lymphocytes. Activation of guanylate cyclase by NO is also altered in lymphocytes from hyperammonemic rats or from rats with portacaval anastomosis. We assessed whether soluble guanylate cyclase activation was also altered in human patients with liver disease. We studied activation of soluble guanylate cyclase in lymphocytes from 77 patients with liver disease and 17 controls. The basal content of cGMP in lymphocytes was decreased both in patients with liver cirrhosis and in patients with chronic hepatitis. In contrast, cGMP concentration was increased in plasma from patients with liver disease. Activation of guanylate cyclase by NO was also altered in liver disease and was higher in lymphocytes from patients with cirrhosis or hepatitis than that in lymphocytes from controls. Successful treatment with interferon of patients with hepatitis C reversed all the above alterations. Altered modulation of soluble guanylate cyclase by NO in liver disease may play a role in the neurological and hemodynamic alterations in these patients.

Effect of L-Carnitine Upon Ammonia Tolerance Test in Cirrhotic Patients

In a group of liver cirrhosis (LC) patients subjected to a rectal ammonium overload test, the effect of L-carnitine on ammoniemia and on the type A numerical connection and star clock psychomotor tests has been evaluated. On comparing 40 LC patients given L-carnitine with 40 control cirrhotics given a placebo, no significant differences were observed in ammonium levels after performing the overload test in both groups. However, on studying the patients with the greatest liver involvement, those given L-carnitine showed smaller elevations in ammoniemia and better responses to the psychometric tests than those receiving the placebo. The results obtained emphasize the need to continue testing the effect of L-carnitine using either similar tests or carrying out long-term evaluations to determine its protective effect in the appearance of hepatic encephalopathy, perhaps even including its evaluation in the treatment of established encephalopathy.