Portal decompression by transjugular intrahepatic portosystemic shunt and changes in serum-ascites albumin gradient.

The serum ascites albumin gradient (SAAG) is widely used to help determine the cause of ascites formation. A serum ascites albumin gradient of > or = 1.1 g/dL reliably distinguishes portal hypertension-related ascites from other causes. To date, there are no published data on the impact of portal decompression on this gradient. The recent development of transjugular intrahepatic portosystemic shunt (TIPS) allows for nonsurgical decompression of portal hypertension by radiologically creating a portosystemic shunt. This study examines the short-term impact of portal decompression on the serum ascites albumin gradient (SAAG) in patients with portal hypertension-related ascites undergoing transjugular intrahepatic portosystemic shunt. Portal pressure measurements were obtained before and after TIPS placement. Serum ascites albumin gradient was determined before and at 6 and 24 hours post-TIPS placement. Fifteen patients were enrolled in the study. The mean portosystemic gradient (PSG) before TIPS was 21.0 +/- 9.2 mmHg, whereas the post-TIPS mean PSG was reduced to 11.0 +/- 6.3 mmHg, consistent with portal decompression (p = 0.005). The mean pre-TIPS serum ascites albumin gradient was 1.9 +/- 0.5 g/dL and was reduced to 1.7 +/- 0.5 g/dL at 6 hours (p = 0.003) and 1.4 +/- 0.4 g/dL at 24 hours (p = 0.002) after TIPS placement. These findings further solidify the association between the SAAG and portal hypertension.

Is there an optimal time to measure quantitative HCV RNA to predict non-response following interferon treatment for chronic HCV infection?

BACKGROUND/AIMS: Current criteria to predict sustained response for a patient with chronic hepatitis C virus during interferon treatment are not consistent. The aim of this study was to determine a reliable point in time to predict non-response to therapy, as a theoretical basis for early cessation of treatment. METHODS: Sera (-70 degrees C) from 66 patients treated with interferon (3 million units three times a week for 6 months) were assayed with a quantitative polymerase chain reaction (sensitivity < or =100 copies per milliliter). Evaluations were made at baseline, during treatment at weeks 1, 2, 4, 12, and 24, and at follow-up week 48. Biochemical response was defined using standard alanine aminotransferase criteria. Virologic response was defined as: sustained if loss of HCV RNA persisted through therapy and follow-up; relapse if HCV RNA became undetectable but reappeared during treatment or follow-up; and non-response if HCV RNA remained detectable during the study period. Alanine aminotransferase and HCV RNA results were analyzed at defined time intervals to determine a predictive value for non-response and sustained response. RESULTS: HCV RNA results are a more accurate predictor than alanine aminotransferase for both non-response and sustained response. Serum HCV RNA predicted non-response better than sustained response. The optimal time to predict non-response with serum HCV RNA was treatment week 12. CONCLUSIONS: Treatment week 12 results indicate that HCV RNA was a more accurate predictor for non-response than serum alanine aminotransferase. This prediction would have theoretically permitted stopping treatment for 75% of the patients in this study at treatment week 12 allowing an overall cost savings of 28%.

Hepatitis C and G co-infection: response to interferon therapy and quantitative changes in serum HGV-RNA.

Hepatitis G virus (HGV), a positive sense RNA virus, is distantly related to hepatitis C virus (HCV): its genetic organization and identity are consistent with the Flaviviridae family. Coinfection with HGV occurs in 10% to 20% of HCV-infected subjects. These similarities raise two theoretical questions. First, could HGV coinfection play any role in the response of HCV to antiviral therapy and second, would this coinfected population have changes in serum HGV-RNA induced by interferon. To address these questions, 98 patients with documented chronic HCV underwent interferon therapy (3 million units three times a week) for 6 months. Response to therapy was categorized using standard biochemical criteria. Changes in HGV-RNA levels were evaluated before, during, and after interferon therapy by a quantitative branched DNA amplification research-based assay. Eleven of 98 (11%) patients with HCV infection had detectable serum HGV-RNA. There was no difference between the groups (HGV+ vs. HGV-) when baseline alanine aminotransferase (ALT) values, HCV-RNA levels, HCV genotype, histological severity, or other demographic features were analyzed. Interferon response was similar in both groups and HGV was not associated with outcome following therapy. Antiviral therapy appeared to induce a reduction in HGV-RNA load in five of nine patients coinfected with HCV serially tested. In two patients, the fall in serum HGV-RNA correlated with biochemical response, independent of changes in HCV-RNA. These observations indicate that a larger study of an HGV population is required to more clearly define the relationship between HCV and HGV coinfection and their response to antiviral therapy.

Fluctuations in viral load (HCV RNA) are relatively insignificant in untreated patients with chronic HCV infection.

A recently available assay to quantify serum viral load in hepatitis C virus (HCV) infection has been used to evaluate the effects of anti-viral therapies. However, variability in HCV RNA levels in untreated patients with HCV infection has not yet been established. We therefore prospectively measured the biological fluctuations of HCV RNA in sera from untreated patients with chronic HCV infection. Sera were collected from seven patients at 8 am and 4 pm on the same day to assess the effect of diurnal variation, daily for 5 days in a further 10 patients, biweekly for 6 weeks in nine patients and monthly for 3 months in 11 patients. All patients had biopsy-proven chronic liver disease with elevated alanine aminotransferase (ALT) values and had not received anti-viral treatment. HCV RNA was measured blinded, in duplicate, using the quantitative branched (bDNA) amplification assay (Quantiplex HCV RNA, Chiron Co. Emeryville, CA) 36 of the 37 patients studied had measurable HCV RNA throughout the study. There was no significant correlation between HCV RNA levels and ALT values or histological activity. HCV RNA levels did not appear to vary significantly within any of the groups studied and there did not appear to be a change associated with diurnal variation. All individual patients demonstrated less than a threefold fluctuation in HCV RNA throughout the study period. Hence HCV RNA levels remain relatively stable in untreated individuals with chronic HCV infection. Changes of a magnitude of threefold (0.5 log) or greater in HCV RNA levels were not observed in untreated patients.