In patients with chronic hepatitis C who relapse after treatment with interferon, therapy with interferon and oral ribavirin results in higher rates of sustained virologic, biochemical, and histologic response than treatment with interferon alone.

FOR THE HEPATITIS INTERVENTIONAL THERAPY GROUP 10This international, randomized, active-controlled, parallel-group, double-blind dose-finding study compared peginterferon alfa-2b (PegIntron ™ ) to interferon alfa-2b for the initial treatment of compensated chronic hepatitis C. We randomly assigned 1,219 subjects to receive either the standard three-times-weekly (TIW) interferon alfa-2b dose (3 MIU) or the once-weekly (QW) peginterferon alfa-2b (0.5, 1.0, or 1.5 g/kg). Subjects were treated for 48 weeks and then followed for an additional 24 weeks. All 3 peginterferon alfa-2b doses significantly (P < .042) improved virologic response rates (loss of detectable serum HCV RNA) after treatment and after follow-up, as compared with interferon alfa-2b. Unlike the end-of-treatment virologic response, the sustained virologic response rate was not doserelated above 1.0 g/kg peginterferon alfa-2b because of a higher relapse rate among patients treated with 1.5 g/kg peginterferon alfa-2b, particularly among patients infected with genotype 1. All 3 peginterferon alfa-2b doses decreased liver inflammation to a greater extent than did interferon alfa-2b, particularly in subjects with sustained responses. No new adverse events were reported, and the majority of adverse events and changes in laboratory values were mild or moderate. In conclusion, peginterferon alfa-2b maintained (0.5 g/kg) or surpassed (1.0, 1.5 g/kg) the clinical efficacy of interferon alfa-2b while preserving its safety profile. The higher rate of virologic response during treatment with 1.5 g/kg peginterferon alfa-2b in patients infected with genotype 1 and high viral levels warrants further evaluation. (HEPATOLOGY 2001;34:395-403.)The current international standard of care treatment for chronic hepatitis C, interferon alfa-2b in combination with ribavirin, has proven highly effective, achieving sustained viral eradication in approximately 40% of patients. 1,2 Interferon alfa-2b is administered as a fixed dose 3 times per week, but this schedule is burdensome to patients and may be associated with virologic breakthrough infections. 3,4 To maintain constant pressure on the virus and reduce the frequency of drug administration, a pegylated formulation of interferon alfa-2b has been developed. The advantages of protein pegylation are well established, having been described for many clinically applicable proteins. [5][6][7][8] Covalently attached polyethylene glycol (peg) delays protein clearance and reduces immunogenicity. 8 The resulting longer plasma half-life increases exposure to the drug and therefore may improve efficacy and allow for less frequent dosing. Less frequent dosing, in turn, may improve patient compliance and quality of life.Peginterferon alfa-2b (PegIntron ™ ), a protein-conjugate containing a single straight-chain peg with a molecular weight of 12,000 daltons and interferon alfa-2b in a 1:1 ratio, maintains its antiviral activity but has an approximately 10-fold longer plasma half-life than interferon alfa-2b in humans (29-34 hours vs. 3.6 ho...

Background and Aims: The outcome of patients with hepatocellular carcinoma (HCC) remains poor because of late diagnosis. The aim of this study was to compare the accuracy of alpha fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) in the early diagnosis of HCC. Methods: Among 1031 patients randomized in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) Trial, a nested case-control study of 39 HCC cases (24 early stage) and 77 matched controls was conducted to compare the performance of AFP and DCP. Testing was performed on sera from 12 months prior (month −12) to the time of HCC diagnosis (month 0). Results: The sensitivity and specificity of DCP at month 0 was 74% and 86% at a cutoff of 40 mAU/mL and 43% and 100% at a cutoff of 150 mAU/mL. The sensitivity and specificity of AFP at month 0 was 61% and 81% at a cutoff of 20 ng/mL and 22% and 100% at a cutoff of 200 ng/mL. At month −12, the sensitivity and specificity at the low cutoff was 43% and 94% for DCP and 47% and 75% for AFP. Combining both markers increased the sensitivity to 91% at month 0 and 73% at month 12 but the specificity decreased to 74% and 71%. Diagnosis of early HCC was triggered by surveillance ultrasound in 14, doubling of AFP in 5 and combination of tests in 5 patients. Conclusions: Biomarkers are needed to complement ultrasound in the detection of early HCC but neither DCP nor AFP is optimal.

A prospective study identified 45 patients with malignancy-related ascites among 448 ascites patients (10% of the total). Patients were categorized into five subgroups based on the pathophysiology of ascites formation. Each subgroup had a distinctive ascitic fluid analysis. Patients with peritoneal carcinomatosis but without massive liver metastases (53.3% of the patients with malignancy-related ascites) had a uniformly positive ascitic fluid cytology, high ascitic fluid protein concentration and low serum-ascites albumin gradient. Patients with massive liver metastases and no other cause for ascites formation (13.3% of the series) had a negative cytology, low ascitic fluid protein concentration, high serum-ascites albumin gradient and markedly elevated serum alkaline phosphatase. Those with peritoneal carcinomatosis and massive liver metastases (13.3% of the series) had a nearly uniformly positive ascitic fluid cytology, variable protein concentration, high serum-ascites albumin gradient and markedly elevated serum alkaline phosphatase. Chylous ascites (6.7%) was characterized by a milky appearance, negative cytology and an elevated ascitic fluid triglyceride concentration. Patients with hepatocellular carcinoma superimposed on cirrhosis (13.3%) had negative ascitic fluid cytology, low ascitic fluid protein concentration, high serum-ascites albumin gradient and elevated serum and ascitic fluid alpha-fetoprotein concentration. Two-thirds of patients with malignancy-related ascites had peritoneal carcinomatosis; 96.7% of patients with peritoneal carcinomatosis had positive ascitic fluid cytology. Ascitic fluid analysis is helpful in identifying and distinguishing the subgroups of malignancy-related ascites.