Randomized study of peginterferon-alpha2a plus ribavirin vs peginterferon-alpha2b plus ribavirin in chronic hepatitis C.

Background & Aims: Ribavirin (RBV) combined with either pegylated interferon (PegIFN) alpha2a or PegIFNalpha2b is the standard of care for chronic hepatitis C virus (HCV) infection. Due to the lack of head-to-head studies, the 2 PegIFNs have not been directly compared. The endpoints of our study were safety and antiviral efficacy of the 2 regimens.

A 28-year study of the course of hepatitis Delta infection: a risk factor for cirrhosis and hepatocellular carcinoma.

Background & Aims: Chronic infection with hepatitis Delta virus (HDV) is a risk factor for cirrhosis and hepatocellular carcinoma (HCC); predictors of disease outcome are, however, poorly defined. We tracked the course of HDV infection in 299 patients over a mean period of 233 months.

Methods: We analyzed data from patients who had been HDV positive for at least 6 months (230 males; mean age, 30 years) admitted from 1978 to 2006 to Maggiore Hospital, Milan.

Lack of rapid virological response predicts interferon-alpha2b/ribavirin therapy failure in HCV genotype 2 patients: a single-centre study.

Background: A minority of patients with HCV-2 chronic hepatitis does not attain a sustained virological response to interferon-based therapies. Registration trials have failed to identify the real proportion of HCV-2 non-responders, and predictors of non-response. The analysis of 'real-life' HCV-2 patients might help define the effectiveness of anti-HCV therapy and the role of response moderators.

Natural history and clinical impact of cryoglobulins in chronic hepatitis C: 10-year prospective study of 343 patients.

Background & Aims: Serum cryoglobulins (CGs) are present in patients with chronic hepatitis C virus (HCV) infection, but their long-term clinical importance has not been established. We assessed the development rates, morbidity, and influence on the evolutionary course of hepatitis C of CG.

Methods: A cohort of 343 HCV-RNA seropositive outpatients (173 men; age, 58 y; 82 with cirrhosis; 61 treated with interferon) with persistently increased aminotransferase levels and histologically defined liver disease was investigated.

Impaired response to interferon-alpha2b plus ribavirin in cirrhotic patients with genotype 3a hepatitis C virus infection.

Patients with chronic infection with the 3a genotype of hepatitis C virus (HCV) are considered as 'easy-to-treat' with interferon/ribavirin (IFN/RBV), independent of liver disease severity. However, patients with extensive fibrosis or cirrhosis were under-represented in all the registration Phase III trials performed so far. To assess the influence of liver fibrosis on the outcome of anti-HCV therapy, all patients with genotype 3a hepatitis C who were naive to IFN-based therapies, and received RBV combined with standard IFN or pegylated IFN-(alpha2b (peg-IFN-alpha2b) as standard of care for their disease, were investigated at our centre.

The natural history of compensated cirrhosis due to hepatitis C virus: A 17-year cohort study of 214 patients.

Large databases of consecutive patients followed for sufficiently long periods are needed to establish the rates, chronology, and hierarchy of complications of cirrhosis as well as the importance of other potential causes of liver disease. In accordance with this goal, a cohort of patients with compensated cirrhosis due to hepatitis C virus (HCV) was followed for 17 years. Two hundred and fourteen HCV RNA-seropositive patients with Child-Pugh class A cirrhosis who had no previous clinical decompensation were prospectively recruited and followed up with periodic clinical and abdominal ultrasound examinations.

The prevalence, clinical features and response to antiviral therapy of patients with chronic hepatitis C who are seropositive for liver-kidney microsome type 1 antibodies.

Background: Antibodies to liver-kidney microsome type 1 (anti-LKM-1), which are a marker of autoimmune hepatitis, are found in a minority of patients with chronic hepatitis C virus (HCV) infection. Whether interferon/ribavirin therapy is safe and effective in these patients is unclear.

Aim: To describe the prevalence, clinical features and response to interferon/ribavirin therapy of anti-LKM-1 seropositive patients with chronic hepatitis C.

Onset of inflammatory bowel diseases during combined alpha-interferon and ribavirin therapy for chronic hepatitis C: report of two cases.

We report two patients who developed an inflammatory bowel disease (IBD) shortly after beginning combined alpha-interferon and ribavirin treatment for HCV-related chronic hepatitis. The previous clinical history was negative for IBD in both patients, who developed diarrhoea and rectal bleeding 10 days and 6 months, respectively, after the initiation of therapy. The history, therapeutic management and the possible causal relationships of these cases are discussed.

Hepatitis C reactivation in patients with chronic infection with genotypes 1b and 2c: a retrospective cohort study of 206 untreated patients.

Background: We previously described hepatitis reactivation in two carriers of the hepatitis C virus (HCV) genotype 2c.

Aim: To assess the relationship between HCV genotypes and risk of hepatitis reactivation, we studied the course of aminotransferases in patients infected with the two relevant genotypes in Italy.

Patients: A cohort of 100 patients with genotype 2c chronic hepatitis and 106 with genotype 1b were subjected to surveillance.

Serum levels of hepatitis C virus core antigen as a marker of infection and response to therapy.

Objectives: Hepatitis C virus (HCV) core antigen is a recently developed marker of hepatitis C infection. We compared the predictive power of HCV core antigen with reverse transcription polymerase chain reaction (RT-PCR) and branched DNA assay for HCV-RNA as markers of infection and response to interferon therapy.

Methods: Four hundred and forty-four sera from 111 patients (65 men, 52 yr) with chronic hepatitis C, receiving ribavirin together with standard interferon (n = 61) or pegylated interferon (n = 50) were retrospectively investigated.

Increased survival of cirrhotic patients with a hepatocellular carcinoma detected during surveillance.

Background & Aims: Significant improvements in management of hepatocellular carcinoma (HCC) have occurred in the last years, but their impact on surveillance outcome is unknown. To clarify this, we compared survival of HCC patients identified along 3 consecutive quinquennia of surveillance.

Methods: A cohort of 417 HCC-free outpatients with compensated cirrhosis was prospectively followed for 148 months (range, 1-213 months) with periodic ultrasound examinations.

A prospective study of blood alpha-fetoprotein messenger RNA as a predictor of hepatocellular carcinoma in patients with cirrhosis.

Blood alpha-fetoprotein messenger RNA (AFP mRNA) is thought to be a marker of hepatocellular carcinoma (HCC). Its value as a predictor of HCC in patients at risk is not known. A series of 201 patients with compensated cirrhosis (114 men, mean age 58 years) underwent surveillance with semi-annual ultrasound and serum alpha-fetoprotein measurements.

Treatment of chronic hepatitis C in Europe.

The lifetime cumulative risk of developing cirrhosis and hepatocellular carcinoma is the rationale for treating patients with chronic hepatitis C with antivirals. The standard treatment is combination therapy with interferon-alfa and ribavirin. In patients with high transaminases and histologic signs of chronic hepatitis, 6- to 12-month therapy with 3 mega units (MU) interferon-alfa thrice weekly, combined with ribavirin, yielded up to 30% sustained responders, and this was increased to 50% with pegylated interferon combined with ribavirin.

The clinical and pathogenetic significance of estrogen receptor-beta expression in chronic liver diseases and liver carcinoma.

Background: Estrogen receptor-alpha (ERalpha) is variably expressed in hepatocellular carcinoma (HCC) and is believed to be correlated with prognosis and survival. Recently, another estrogen receptor (ERbeta) has been identified, but its relevance in liver diseases is unknown.

Methods: The expression of ERbeta in the liver of 42 patients with HCC (10 with paired extratumoral tissues) and 26 with chronic liver disease without HCC was studied by a reverse transcriptase-polymerase chain reaction method, and correlated with the expression of ERalpha and severity of the liver disease.

Long-term suppression of hepatitis B e antigen-negative chronic hepatitis B by 24-month interferon therapy.

To assess whether extended treatment with interferon improves the outcome of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B, 101 consecutive patients were treated with 6 MU of interferon alfa 2b 3 times weekly for 24 months. During the 68-month study, 30 patients (30%) had a sustained response (i.e.

Segmental transcatheter arterial chemoembolization treatment in patients with cirrhosis and inoperable hepatocellular carcinomas.

Purpose: To establish whether segmental transcatheter arterial chemoembolization (TACE) treatment may improve the rates of survival in patients with compensated cirrhosis and inoperable hepatocellular carcinoma (HCC).

Materials And Methods: Fifty-six patients with compensated cirrhosis and inoperable HCC were treated with segmental TACE. One hundred forty treatments (mean, 2.

Progressive hepatic fibrosis in healthy carriers of hepatitis C virus with a transaminase breakthrough.

In short-term studies, patients with chronic hepatitis C virus (HCV) infection, consistently normal serum aminotransferase (ALT) levels, and minimal or mild necro-inflammatory changes in the liver, did not progress to histologically severe hepatitis. There are no data on longer term outcome of liver disease in these patients. We describe two patients with HCV infection (genotype 2c) with a rise in serum ALT values greater than 10 times the upper normal value that occurred after an 8- and 15-year period of persistently normal or minimally elevated ALT levels.

High rates of hepatocellular carcinoma in cirrhotic patients with high liver cell proliferative activity.

The prevalence, risk factors, and clinical significance of high liver cell proliferative activity were investigated in 208 well-compensated cirrhotic patients (150 men; 50 years; 135 with chronic hepatitis C) who had been under prospective surveillance for hepatocellular carcinoma (HCC) with annual abdominal ultrasound (US) and serum alpha-fetoprotein (AFP) determination. Immunostaining for proliferating cell nuclear antigen (PCNA) was employed to assess liver cell proliferative activity in formalin-fixed, paraffin-embedded liver specimens. The percentage of reactive nuclei was calculated by a computer-assisted image analysis system.

Serum levels of hepatitis C virus RNA predict non-response to interferon therapy: comparison of two commercial assays.

We compared two commercial assays for quantification of serum hepatitis C virus (HCV) RNA to investigate whether pretreatment levels of serum HCV RNA could predict the outcome of interferon (IFN) therapy. The Amplicor HCV Monitor test is based on a single, combined reverse transcription and amplification reaction carried out by the Tth DNA polymerase using specific primers for the 5' untranslated (UTR) region. The Quantiplex HCV RNA 2.

Prevalence and risk factors for the presence of serum cryoglobulins in patients with chronic hepatitis C.

To assess the prevalence and risk factors for cryoglobulinaemia associated with hepatitis C virus (HCV) infection, we studied 360 consecutive patients with chronic hepatitis C (191 men, median age 57 years; 86 [24%] with cirrhosis). One-hundred and sixty-eight (47%) had circulating cryoglobulins (mean levels 208 +/- 256 mg l-1), predominantly of type III (80%; and 20% type II). Cryoglobulins were more common in women than in men (56% vs 39%, P=0.

High prevalence of multinodular hepatocellular carcinoma in patients with cirrhosis attributable to multiple risk factors.

To see whether or not there is an association between the cause of cirrhosis and the number of hepatocellular carcinoma (HCC) nodules, we analyzed 178 consecutive patients in whom HCC was detected during a prospective screening by abdominal ultrasound (US). The relevant information was obtained from the database of the screening programs operating at four hospitals in the Milan area. One hundred twenty-nine (72%) patients had a single tumor nodule detected by US and 49 (28%) patients had multinodular disease.

Chronic unexplained hypertransaminasemia may be caused by occult celiac disease.

In a subset of patients attending liver units, a chronic increase in serum transaminases may remain of undetermined cause despite thorough investigations. On the other hand, elevated levels of serum transaminases have been reported in about 40% of adult celiac patients. To evaluate the prevalence of subclinical celiac disease in patients with chronic unexplained hypertransaminasemia in comparison with that in the general population (0.

High prevalence but low pathogenicity of hepatitis G virus infection in Italian patients with genetic haemochromatosis.

Background: Various environmental factors have been shown to hasten cirrhosis and hepatocellular carcinoma in patients with genetic haemochromatosis.

Aim: To assess the prevalence and the role of the recently identified hepatitis G virus in 70 patients with genetic haemochromatosis in comparison with 40 patients with cryptogenic chronic hepatitis and 200 regular blood donors.

Patients: Six patients with genetic haemochromatosis (9%) had serum hepatitis B surface antigen, 14 (20%) had serum hepatitis C virus RNA.

A randomized, controlled trial of a 24-month course of interferon alfa 2b in patients with chronic hepatitis B who had hepatitis B virus DNA without hepatitis B e antigen in serum.

Short-term interferon treatment of serum hepatitis B e antigen (HBeAg)-negative carriers with serum hepatitis B virus (HBV) DNA and histological features of chronic hepatitis B has been largely unsuccessful. In a pilot study of long-term treatment, 42 such patients were randomly assigned to 6 million units of interferon alfa 2b (IFN-alpha2b) three times per week for 24 consecutive months (n = 21, 4 with cirrhosis) or to no therapy (n = 21, 3 with cirrhosis). Five patients (24%) discontinued therapy because of treatment-related adverse reactions.