S. Tripi

Impact of liver steatosis on the antiviral response in the hepatitis C virus-associated chronic hepatitis.

Abstract: Background/Aim: Liver steatosis (LS) has been variably associated with chronic hepatitis C (CHC) but whether it affects sustained virological response to antiviral treatment and by what mechanisms is a question still under debate, at least for some genotypes. The aim of this work was to assess the frequency of LS, its relationship with host and viral factors and to what extent it can influence the response to antiviral combination therapy with pegylated interferon (INF)+ribavirin in a group of patients with CHC from a single center.

Percutaneous liver biopsy: A safe outpatient procedure?

Following the discovery of hepatitis C virus, more liver biopsies (LB) than before are being performed to assess the severity of liver disease. In this study, following the recommendations for outpatient LB made by the Patient Care Committee of the American Gastroenterological Association, we assessed the feasibility and benefits of LB performed as an outpatient versus inpatient procedure over the last 7 years in our centre. The study included 1,581 patients consecutively examined in our institute; all LBs were performed by a single operator with a 16-gauge needle using the Menghini technique, and in all cases the puncture site was determined using prebiopsy ultrasound. Liver lesions were classified using grading and staging scores. Ultrasound-guided LB of focal lesions were excluded from this study. LB was performed on 1,318 outpatients and 263 hospitalized patients. The mean age of the hospitalized patients was higher than that of the outpatients (p < 0.0001). As major side effects, one death and one haemoperitoneum requiring blood transfusion were recorded in the hospitalized patients. As minor side effects, one haemorrhage occurred in the hospitalized patients, whereas a case of haemobilia and 2 cases of subcapsular haematoma were recorded in the outpatients. In both groups pain at the puncture site was the most frequent minor complication which easily resolved after non-steroid drug administration. Severe histological diagnoses, both in terms of grading and staging, were significantly associated with hospitalized patients. In conclusion, by carefully selecting patients and using prebiopsy ultrasound to assess the puncture site, outpatient LB can be safely performed in most cases; this procedure should be more widely used, because it has met with the favour of patients who are able to return home the same day and reduces public health care service costs.

Ultrasound detection of abdominal lymph nodes in chronic liver diseases. A retrospective analysis

AIM To retrospectively evaluate the prevalence of lymph nodes of the hepato-duodenal ligament in a group of patients with chronic liver disease of various aetiologies and to investigate what clinical, aetiological and laboratory data may lead to their appearance. MATERIALS AND METHODS One thousand and three patients (554 men, 449 women) were studied, including 557 with chronic hepatitis and 446 with liver cirrhosis. The presence of lymph nodes near the trunk of the portal vein, hepatic artery, celiac axis, superior mesenteric vein and pancreas head was investigated using ultrasound. RESULTS Lymph nodes were detected in 394 out of the 1003 study patients (39.3%); their number ranged from one to four, with a diameter ranging between 0.8 and 4 cm. The highest prevalence was in the subgroup of patients with primary biliary cirrhosis (87.5%), followed by patients with hepatitis C virus (HCV; 42%), patients with HCV and hepatitis B virus (HBV; 41.3%), autoimmune hepatitis (40%), and HBV alone (21.2%). In the alcoholic and idiopathic subgroups prevalence was 9.5%, while in the non-alcoholic steatohepatitis and haemochromatosis subgroups it was 0%. HCV RNA was present in 97 out of 103 lymph node-positive patients and in 141 out of 168 lymph node-negative HCV-negative patients (p<0.003). Lymphadenopathy frequency increased as the liver disease worsened (chi(2) MH=74.3; p<0.0001). CONCLUSION Despite the limitations of a retrospective study, our data indicate a high prevalence of lymphadenopathy in liver disease patients; ultrasound evidence of lymph nodes of the hepato-duodenal ligament in a given liver disease may most likely suggest a HCV or an autoimmune aetiology and a more severe histological picture.

Intravenous natural β-interferon in white patients with chronic hepatitis C who are nonresponders to α-interferon

Objectives: α-Interferons (α-IFN) have been shown to be effective in the treatment of chronic viral C hepatitis, but their efficacy remains unsatisfactory. Recently natural β-interferon (β-IFN) administered by intravenous infusion has been used successfully. Methods: To evaluate the efficacy and safety of intravenous β-IFN administration we treated 20 patients with histologically proven chronic hepatitis C who were nonresponders to at least two previous courses of α-IFN treatment. All patients received 6 million units (MU) of natural human fibroblast β-IFN by drip infusion, 6 times per wk for 8 wk and were followed up for 6 months after suspension of treatment. Results: Five patients (25%) had response at the end of treatment; of these patients only one had sustained response. Patients who responded to therapy had lower, although not significantly, baseline levels of HCV RNA, compared with nonresponders. Whereas mean viral load decreased during therapy, only two patients were HCV RNA negative at the end of treatment, but none were at the end of the follow-up period. Genotype 1 was found in 17 cases, genotype 2 was found in one case, and a combination of genotypes 1b and 2a was found in the remaining two cases. Therapy was well tolerated and β-IFN administration was neither interrupted nor its dosage reduced due to side effects in any of the patients. Conclusions: Our study shows that intravenous β-IFN is well tolerated and that the modest results obtained may depend on the brevity of treatment. Consequently, further studies are needed to define the optimum dose, schedule, and duration of treatment to eradicate HCV infection.

Reliability of the bright liver echo pattern in diagnosing steatosis in patients with cryptogenic and HCV-related hypertransaminasaemia.

AIM To evaluate the reliability of the bright liver (BL) echo pattern on ultrasound to detect histological steatosis in chronic cryptogenic hypertransaminasaemia (CCH) and hepatitis C virus (HCV)-related forms of hypertransaminasaemia. MATERIALS AND METHODS One hundred and fifty patients, 54 with CCH and 96 with HCV hypertransaminasaemia (76 genotype 1/2 and 20 genotype 3), were enrolled. Histological steatosis was measured as the percentage of hepatocytes involved. The reliability of the BL sign was estimated using the sensitivity, specificity, positive and negative predictive values. RESULTS Histological steatosis was present in 102/150 patients (68%) divided into 59/96 (62%) in the HCV group and 43/54 (79.6%) in the CCH group (chi(2)=4.4; p=0.035). In a multivariate analysis, the variable associated with the BL echo pattern was steatosis percentage (p=0.0018). Steatosis percentage was higher in CCH group than in the HCV genotype 1/2 and 3 groups (p=0.02). The sensitivity of the BL echo pattern was 88% in the CCH group [confidence interval (CI) 95% 74-95] versus 61% (CI 95% 44-73) in the HCV genotype 1/2 group. The CI indicates that ultrasound can provide evidence for steatosis in a statistically significant way in the CCH versus HCV genotype 1/2 patients. In the genotype 3 group, the sensitivity was high (90%), but the limited number of cases limited the statistical significance due to the high CI. CONCLUSION In CCH the BL echo pattern has excellent reliability in diagnosing steatosis, better than in HCV hypertransaminasaemia because of the higher prevalence and extent of steatosis.

Anti-hepatitis a virus seroprevalence and seroconversion in a cohort of patients with chronic viral hepatitis

BACKGROUND Patients with chronic hepatitis C infected by hepatitis A virus have a substantial risk of fulminant hepatitis or death, while the course of hepatitis A virus is uncomplicated in most subjects with chronic hepatitis B. AIM To evaluate the prevalence of anti-hepatitis A virus antibodies and the incidence of hepatitis A virus seroconversion in a nationwide sample of 530 patients with chronic hepatitis B and/or hepatitis C infection initially susceptible to this infection after a follow-up of some years. RESULTS The overall anti-hepatitis A virus prevalence was 85.7%, with no difference between males and females. By the age of 50 years, almost all patients were found to have been exposed to hepatitis A virus. After a mean follow-up period of 76 months the overall anti-hepatitis A virus seroconversion rate in the 76 initially susceptible individuals was 1.2 per 100 person/years. However, it was 0.3 per 100 person/years in those hepatitis B surface antigen positive but 3.36 per 100 person/years in those anti-hepatitis C virus positive. None of the seroconverters was affected by a clinically evident disease or showed deterioration of underlying chronic liver disease. CONCLUSIONS The present study shows that Italian patients >50 years of age with chronic liver disease have already been exposed to hepatitis A virus suggesting that anti-hepatitis A virus screening is not advisable in these subjects.

Leucocyte Interferon-alpha for Patients with Chronic Hepatitis C Intolerant to Other alpha-Interferons

BackgroundAlpha-interferon (α-IFN) is the treatment of choice for chronic hepatitis C but most patients experience adverse effects which sometimes lead to the suspension of therapy. Recently, higher doses of α-IFN or prolonged therapy have increased the number of cases of intolerance.Study DesignIn this open study we evaluated the efficacy and safety of leucocyte interferon-alpha (IFNα) [6MU three times a week] in 43 patients with chronic hepatitis C who had been intolerant to previous treatment courses with recombinant or lymphoblastoid IFNα. All patients were treated for 6 months and followed-up for an additional 6 months.End of treatment responders were patients in whom hepatitis C virus (HCV)-RNA had been eradicated from the blood by the end of treatment, sustained responders were those patients who maintained negative HCV-RNA at the end of follow-up, and the remaining patients were considered non-responders. Adverse effects were monitored by interviews, laboratory and clinical examinations.ResultsFive patients (11.6%) discontinued the treatment, four due to the reappearance of previous adverse effects, and one due to an ex novo adverse effect. In six patients the dose had to be halved. At the end of treatment 11 patients (25.6%) had negative serum HCV-RNA. After discontinuation of therapy, disease flared in four patients, thus seven patients were sustained responders.ConclusionsThis study shows that leucocyte IFNα at a dose of 6MU three times a week is well tolerated in patients previously intolerant to recombinant or lymphoblastoid IFNα, allowing a high percentage of them to complete a course of treatment in terms of duration and dose.

Interfreron-α Alone versus Interferon-α plus Ribavirin in Patients with Chronic Hepatitis C Not Responding to Previous Interferon-α Treatment

AbstractObjective: To study the effects of monotherapy with leucocyte interferon-α (IFNα) versus IFNα + ribavirin in patients with chronic hepatitis C who were nonresponders to previous courses of recombinant or lymphoblastoid IFNα. Design and setting: This was a nonblind randomised study of outpatients at 3 centres in Palermo, Sicily, Italy. Patients and participants: We recruited 72 patients (48 males, 24 females), mean age 48.8 ± 6.6 years (range 31 to 63 years), with biopsy-proven chronic hepatitis C, predominantly genotype lb. Interventions: 24 patients (group A) received IFNα 6MU 3 times weekly for 6 months, and 48 patients (group B) received IFNα 6MU 3 times weekly + ribavirin 1200 mg/day for 6 months. ALT levels and adverse effects were monitored monthly, and hepatitis C virus (HCV) RNA levels were measured at study entry, at the end of treatment and after a 6-month follow-up. Results: At baseline all patients were HCV-RNA positive and had ALT levels greater than twice normal. Mean post-treatment serum HCV-RNA levels were below baseline in group A, but the virus was eradicated in only 1 patient; 6 patients had normalised serum ALT levels. In group B at end of treatment, 12 patients were negative for HCV-RNA and serum ALT levels were normal in 18. At follow-up, all group A patients had elevated ALT levels and positive HCV-RNA. In group B, 3 patients were still negative for HCV-RNA and 4 had normal ALT. In 4 patients in group B, therapy was suspended because of anaemia, depression and decrease in neutrophil count; a flu-like syndrome was recorded with no frequency difference between groups. Conclusions: These results suggest that patients with chronic hepatitis C unresponsive to IFNα monotherapy could benefit from combination therapy with IFNα + ribavirin.

Acetylcysteine Therapy for Chronic Hepatitis C Are its Effects Synergistic with Interferon Alpha? A Pilot Study

AbstractObjective: This trial reports the 6-month results of a pilot study using lymphoblastoid interferon alpha (IFNα) and acetylcysteine (N-acetylcysteine) separately and in combination in patients with chronic hepatitis C, genotype 1b, who were nonresponders to previous treatment with recombinant IFNα alone. Patients and Methods: 21 patients were randomly divided into three groups of seven each. Group A was treated with lymphoblastoid IFNα 6MU three times a week for 6 months; group B received the same schedule of lymphoblastoid IFNα as group A plus acetylcysteine 1200 mg/day per os in two administrations, and group C received only acetylcysteine 1200 mg/day per os in two administrations. Results: Mean serum alanine aminotransferase (ALT) levels at 6 months in groups A and B, but not in group C, were significantly lower than baseline values (p < 0.05 and p < 0.03, respectively). Two patients in group A (28.6%) and three in group B (42.9%), but none in group C, had normalised ALT levels at 6 months. During follow-up, levels flared in one group A and in one group B patient. Thus, at the end of follow-up one group A and two group B patients were sustained responders. At the end of therapy and follow-up, hepatitis C virus (HCV)-RNA was negative in one patient in group A and two patients in group B. As no serious adverse effects were observed, therapy was never interrupted or suspended. Conclusion: Acetylcysteine alone had no effect on hepatic cytolysis and viral replication; lymphoblastoid IFNα showed a modest, but better, response than recombinant IFNα, and the combination therapy, although in a limited number of patients, appeared to be more efficient than lymphoblastoid IFNα alone.

Randomised Trial of Two Different Daily Doses of Interferon-α versus Classical Therapy in Treatment-Naïve Patients with Chronic Hepatitis C

ObjectiveTo evaluate the efficacy and tolerability of two different daily doses of interferon-α (lymphoblastoid-IFNα-N1, Wellferon®) [IFNα] for 2 months, followed by the same dose on alternate days for up to 1 year, versus administration on alternate days for 1 year.Patients and methodsA non-blind, randomised study of outpatients with chronic hepatitis C at five centres in Sicily, Italy. Ninety-seven consecutive treatment-naive patients [72 patients with hepatitis C virus (HCV) genotype 1b infection] with histological chronic hepatitis C were included in the study and randomised to receive IFNα subcutaneously: 5 million international units (MIU) daily for 2 months, followed by the same dose on alternate days for up to 1 year (n = 33, group A); 3 MIU for 2 months, followed by the same dose on alternate days for up to 1 year (32, group B); 5 MIU on alternate days for 12 months (32, group C). Adverse effects were monitored through interviews and by clinical and biochemical check-ups at 1-month intervals.ResultsThere were no significant differences between the three groups with regard to age, gender, HCV genotype distribution, or severity of histological findings. Seven patients dropped out of the study because of severe adverse effects: three from group A, two from group B, and three from group C. Approximately 30% of the 97 patients, equally distributed between the three groups, had a ‘flu-like syndrome of mild-to-moderate intensity. Dosage reduction of IFNα from 5 MIU to 3 MIU daily was necessary in two patients in group A during the first month of treatment. Overall, 88 patients completed treatment as scheduled. After the induction phase, HCV was eradicated from the bloodstream in 27 patients (81.8%) from group A versus 15 (46.9%) from group B (p < 0.001) and 15 (46.9%) from group C (p < 0.001). The switch to maintenance dosages caused some infection breakthroughs, with the result that at the end of treatment 16 patients in group A, 12 in group B and 14 in group C had undetectable serum levels of HCV-RNA. After treatment discontinuation, however, five patients in group A, four in group B and six in group C became HCV-RNA positive. Thus, at the end of follow-up, 11 patients in group A, eight in group B and eight in group C had a sustained virological response.ConclusionThe present study shows that induction therapy with 5 MIU of IFNα administered daily for 2 months is well tolerated and that the percentage of patients with viral eradication at the end of this phase is higher than the percentage obtained with traditional therapy. Unfortunately, this good initial response decreases as treatment continues with conventional therapy, thus nullifying the benefits of the induction phase.