Jaime Enríquez

Selective intestinal decontamination prevents spontaneous bacterial peritonitis

In a prospective randomized study, selective intestinal decontamination with norfloxacin was performed during hospitalization in 32 cirrhotic patients with low ascitic fluid total protein levels. The incidence of infections was compared with that in a control group of 31 nontreated cirrhotic patients of similar characteristics. We found a significantly lower incidence of infections [1/32 (3.1%) vs. 13/31 (41.9%); P less than 0.005] and spontaneous bacterial peritonitis [0/32 (0%) vs. 7/31 (22.5%); P less than 0.05] in patients receiving norfloxacin. The lower incidence of extraperitoneal infections [1/32 (3.1%) vs. 7/31 (22.5%); P = 0.052] in the treated group did not reach statistical significance. The incidence of infections [1/28 (3.6%) vs. 9/22 (40.9%); P less than 0.01] and spontaneous bacterial peritonitis [0/28 (0%) vs. 5/22 (22.7%); P less than 0.05] in cirrhotic patients admitted because of ascites was also significantly lower in the treated group. The decrease in the rate of mortality observed in the group undergoing selective intestinal decontamination did not reach statistical significance. These data show that selective intestinal decontamination is useful to prevent spontaneous bacterial peritonitis and extraperitoneal infections in hospitalized cirrhotic patients with low ascitic fluid total protein levels.

Controlled trial of tamoxifen in patients with advanced hepatocellular carcinoma

Thirty-six consecutive patients with advanced hepatocellular carcinoma and chronic liver disease were randomly allocated to two groups: group I included 20 patients who were treated with 10 mg bid. tamoxifen and group II with 16 non-treated patients. The two groups were homogeneous according to clinical and analytical data. Survival curves in the tamoxifen-treated patients improved significantly when compared with the non-treated group (p = 0.01). Cumulative survival at the end of the first year was 48.5% in the treated patients and 9.1% in controls. Median survival was 261 days in the treated group vs. 172 in the non-treated group (p < 0.05). Complications of cirrhosis and worsening of the performance status test occurred less in the treated patients than in the controls, but not significantly so. Tamoxifen was well tolerated and no marked side effects were observed. In this series, tamoxifen improved survival in patients with advanced hepatocellular carcinoma.

Low C3 in cirrhotic ascites predisposes to spontaneous bacterial peritonitis

The risk of developing spontaneous bacterial peritonitis (SBP) in relation to the concentration of C3 in ascitic fluid (AF) has been studied prospectively in 33 patients with cirrhosis of the liver, seven of whom had one or more episodes of SBP during hospitalization. C3 concentrations in the AF of patients who developed infection (9.0 +/- 2.67 mg/dl) were significantly lower than in those who did not (18.26 +/- 8.11 mg/dl) (P less than 0.01). C4 concentrations were similar in both groups. A direct correlation was found between AF C3 and total protein concentrations (P less than 0.001). We conclude that a low C3 concentration in AF may predispose to SBP.

Prevalence of thyroid autoantibodies is not increased in blood donors with hepatitis C virus infection

Serum autoimmune reactions are found in many patients with hepatitis C. A high prevalence of thyroid dysfunction and antithyroid antibodies in patients with chronic hepatitis C was recently reported. We have compared the prevalence of thyroid dysfunction and antithyroid peroxidase antibodies in blood donors with hepatitis C virus (HCV) infection (study group) and in seronegative anti-HCV donors (control group). One hundred and ninety-two blood donors were studied: 96 were anti-HCV positive by ELISA 2 (48 males and 48 females; age 48 +/- 12.9 years, mean +/- SD), and 96 were HCV seronegative (55 males and 41 females; age 37 +/- 14.8 years). In all patients, serum TSH (0.25-4.2 mU/l) and fT4 (9-23 pmol/l) were measured by immunochemiluminiscent assays and antithyroid peroxidase antibodies (normal < 100 U/ml) by RIA. In all anti-HCV positive donors, hepatitis C viremia was tested using the nested polymerase chain reaction. Thyroid dysfunction was found in three females (3.1%) in the anti-HCV positive group (three cases of hypothyroidism), and in four (4.1%) anti-HCV negative blood donors (three cases of hypothyroidism, two females and one male; one case of hyperthyroidism, a female), (p = NS). Antithyroid peroxidase antibody titers were above normal values in 5 (5.2%) anti-HCV positive individuals and in eight (8.3%) anti-HCV negative blood donors (p = NS). These results do not show an increase prevalence of thyroid dysfunction and antithyroid peroxidase antibodies in blood donors with HCV infection when compared with a control group.

Prednisolone withdrawal therapy enhances the effect of human lymphoblastoid interferon in chronic hepatitis B

BACKGROUND/AIMS The aim of this multicentre, randomised, controlled, clinical trial was to evaluate the effect of prednisolone followed by lymphoblastoid interferon treatment in chronic hepatitis B. METHODS Two hundred and thirteen patients with chronic hepatitis B were randomised to either prednisolone (2 weeks of 0.6 mg/kg/day, 1 week of 0.45 mg/kg/day and 1 week of 0.25 mg/kg/day) or matching placebo followed by a 2-week rest phase and then human lymphoblastoid interferon 10 MU daily for 5 days followed by 10 MU thrice weekly for 11 weeks. Of 200 evaluable patients, 33 (16.5%) were females, and 50 (25%) were male homosexuals. Thirty three patients (16.5%) had chronic persistent hepatitis, 145 (72.5%) had chronic active hepatitis and 22 (11%) had active cirrhosis. RESULTS Survival analysis disclosed statistically significant effects of prednisolone pre-treatment on both HBeAg disappearance and HBeAg to anti-HBe seroconversion (log-rank test statistics 5.43; p = 0.02 and 4.75; p = 0.03). Observed HBeAg disappearance and HBeAg to anti-HBe seroconversion rates (placebo vs. prednisolone patients) were 28% vs. 44% and 23% vs. 38%. Six months after stopping interferon, HBV DNA was negative in 51% of prednisolone patients vs. 28% of placebo patients (Chi-square test statistic 6.13; p = 0.013). Prednisolone pre-treatment tended to be more effective in patients with higher transaminase levels and in patients with low levels of HBV DNA. Fifteen patients (7.5%) (13 within 1 year of follow-up) eventually lost HBsAg; 14 of these subsequently developed anti-HBs. Interferon treatment was modified in 102 patients (51%). Three out of 22 patients with cirrhosis (14%), one of whom received prednisolone pre-treatment, developed hepatic decompensation with a fatal outcome while on interferon treatment. CONCLUSIONS Prednisolone pre-treatment significantly enhanced the treatment effect of lymphoblastoid interferon in terms of HBeAg clearance and seroconversion to anti-HBe. Treatment should be used with caution in patients with cirrhosis and avoided in patients showing signs, or with a history, of decompensated cirrhosis.

Biochemical liver abnormalities in Turner's syndrome

BACKGROUND Turners syndrome is a chromosomal abnormality (45X0) which may be associated with various autoimmune disorders and disease conditions; however, association with liver pathology has rarely been reported. OBJECTIVES The aim of this work was to assess liver function abnormalities in a group of adult patients with Turners syndrome. DESIGN AND METHODS Liver function tests were performed in 16 women with Turners syndrome all of whom had been previously treated with oestrogens. Patients with liver abnormalities were further studied with hepatic ultrasonography, serological markers of viral hepatitis and autoantibody determinations. RESULTS Seven women (43.7%) presented with asymptomatic liver cholestasis; these patients were older than those with normal biochemical values (33.4+/-5.2 vs 24.7+/-5.7 years, P<0.05). Liver function abnormalities appeared 7.8+/-4.9 years after starting oestrogen therapy; however, no improvement of liver function was observed 20+/-17.7 months after stopping treatment. All of these women were anti-HCV and HBsAg negative, and autoimmune hepatitis was ruled out in all cases. Liver ultrasound only disclosed homogeneous liver enlargement in one case and cholelithiasis without bile duct abnormalities in another. Four patients underwent a percutaneous liver biopsy of which two were normal and two showed minimal non-specific changes. CONCLUSIONS The incidence of biochemical liver cholestasis in this group of patients with Turners syndrome is high. Oestrogen therapy and autoimmune disorders do not seem to be the responsible causes. It appears that this is a benign condition which does not seem to reflect any substantial liver dysfunction. The aetiology remains uncertain.

Pre-treatment with prednisolone does not improve the efficacy of subsequent alpha interferon therapy in chronic hepatitis C

BACKGROUND/AIMS Alpha interferon administration is quite disappointing as a single therapy in chronic hepatitis C. A brief course of corticosteroid therapy might increase the effectiveness of subsequent alpha interferon administration, but data on this issue are controversial. METHODS One hundred and fifty-six consecutive patients with chronic hepatitis C were randomly assigned to be treated blind with tapering doses of oral prednisolone or placebo for 4 weeks. Two weeks after cessation of therapy, patients received alpha interferon (3 MU t.i.w.) for 48 weeks and were followed for 24 additional weeks. Response was defined by the presence of normal alanine aminotransferase (ALT) and negative HCV-RNA in serum. RESULTS ALT activity decreased during prednisolone administration and rebounded upon withdrawal in 38% of the patients treated with this drug. Significant changes in serum bilirubin were not observed. HCV-RNA serum concentration tended to increase during prednisolone administration and to decrease upon withdrawal. ALT and HCV-RNA did not change during administration of placebo. At the end of interferon administration, 33% of patients treated with prednisolone and 25% of those treated with placebo presented biochemical and virological response. At the end of post-treatment follow-up, response was maintained in 12% and 13% of patients treated with prednisolone or placebo respectively. Response was not related to ALT or HCV-RNA changes observed during the pre-interferon phase of the study. No adverse events related to prednisolone administration were observed. CONCLUSIONS Prednisolone administration and withdrawal induced a rebound in ALT activity and a decrease in HCV-RNA serum concentration in about one third of the patients with chronic hepatitis C. However, these changes did not enhance the effectiveness of subsequent alpha interferon therapy.

Terapia de inducción con interferón alfa-2a en la cirrosis por el virus de la hepatitis C compensada. Estudio multicéntrico aleatorizado

Fundamento Aunque el tratamiento con interferon (IFN) a las dosis estandar solo consigue unarespuesta persistente en el 5% de los pacientes con cirrosis debida al virus de la hepatitis C(CVHC), se ha planteado que podria disminuir el riesgo de complicaciones y la incidencia dehepatocarcinoma. Teniendo en cuenta los estudios cineticos del virus de la hepatitis C (VHC),la terapia de induccion con IFN podria aumentar las tasas de respuesta al tratamiento. Pacientes y metodo Cuarenta pacientes con CVHC compensada fueron distribuidos al azar pararecibir (grupo I = 19) o no (grupo II = 21) tratamiento con IFN (4,5 MU/dia durante 6 meses,seguidos de 4,5 MU/dias alternos durante 6 meses mas, solo si la ALT se habia normalizado). Resultados El tratamiento con IFN hubo de reducirse o interrumpirse por efectos adversos en11 (58%) y seis (31,5%) casos, respectivamente. La respuesta al final del tratamiento se observoen 4 pacientes del grupo I (21%), que fue persistente en dos (10,5%), y en ninguno delgrupo II (p = 0,04 y NS, respectivamente). La probabilidad global de presentar ascitis, hepatocarcinomay/o muerte o trasplante hepatico fue menor en el grupo I que en el II (el 6 frenteal 27% a los tres anos; p = 0,05). Conclusiones Aunque la terapia de induccion con IFN en la CVHC compensada se asocia a frecuentesefectos adversos e induce una respuesta persistente en una proporcion baja de pacientes,podria mejorar el pronostico a medio plazo de los pacientes.

Comparative study of two high doses of lymphoblastoid interferon in the treatment of chronic hepatitis C: influence on the levels of ALT, viraemia and histologic activity.

Summary. Ninety consecutive patients with chronic hepatitis C were included in a randomized, uncontrolled trial to compare the efficacy of two treatment regimens, 10 MU (group A) vs 5 MU (group B), of lymphoblastoid interferon, in a step‐down schedule for 24 weeks. All of the patients had antibodies against the hepatitis C virus, and all but one were HCV RNA positive in serum. The origin of the infection was attributed to blood transfusion in 30 patients and classified as sporadic in 60 patients. During treatment reduction in the ALT levels as well as the elimination of viraemia was observed in both treated groups, although these changes did not correlate significantly with the interferon dose. Nine months after the end of therapy, a sustained response was achieved in 13.6% (12/88) of the patients. Relapse in group B (87.5%) was significantly higher than in group A (59.1%). The percentage of cases which remained with undetectable HCV RNA was significantly higher for the sustained responders (66.7%) than for the non‐responders (11.8%) and relapser patients (2.4%). Repeated liver biopsies showed an overall significant reduction of all the subindices of histological activity from patients with sustained response, except for fibrosis. In short: the 10 MU dosing regimen of lymphoblastoid interferon was as efficient as the 5 MU dose as it brought about a similar improvement in ALT levels, histological activity and elimination of viraemia, albeit 10 MU proved significantly more effective in the prevention of a relapse among the responders after 24 weeks therapy.

Demonstration of HCV-RNA and HBV-DNA in the serum of HBsAg negative patients with hepatocellular carcinoma

Forty patients with chronic liver disease and HCC were analyzed for infection with hepatitis C (HCV) and hepatitis B (HBV) viruses. All patients were negative for HBsAg, 16 were alcoholics, 6 had previous blood transfusions and 18 had sporadic chronic hepatitis. Antibodies to HCV were determined by EIA 2nd generation. HBV-DNA was detected by PCR using primers of the precore region. Analysis of HCV-RNA was done with nested PCR amplifying the 5′ non-coding region of the HCV genome, using primers complementary to nucleotides 1–20 and 305–320 and nested primers complementary to nucleotides 21–31 and 271–286 of the HCV-J1. Anti-HCV were positive in 35/40 patients (87.5%). HCV-RNA was detected by PCR in 34 patients (85%) all of them positive for the anti-HCV. HCV-RNA was detected in 70.5% of the alcohol abusers, in 100% of patients with history of transfusion(s) and 94.1% of patients with cryptogenic chronic liver disease. HBV-DNA was detected in only 2 patients. In conclusion, there is a high rate of HCV and a low rate of HBV viremia detected by PCR in Spanish patients with HCC HBsAg negative. No patient without anti-HCV presents HCV-RNA. Our results suggest that persistent HCV replication may play a role in hepatic carcinogenesis, as HBV-DNA could be found in only 5% of our HCC patients.