[High dose repeat therapy in previously treated patients with chronic hepatitis C].
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Amantadine↗
Biomedical subjects
G Teuber
Publications and source records attributed to G Teuber.
Impaired health-related quality of life in patients with chronic hepatitis C and persistently normal aminotransferase levels.
A significant impact of hepatitis C virus (HCV) infection on health-related quality of life (HRQOL) has been previously described. However, comprehensive data on the quality of life in patients with chronic hepatitis C and persistently normal aminotransferase levels (PNAL) are currently not available. One hundred fifteen patients with chronic hepatitis C (45 with persistently normal aminotransferases and 70 with elevated aminotransferases) and 50 healthy subjects were enrolled. Emotional and psychological states were assessed by Profile of Mood States (POMS) scale and HRQOL was assessed by the 'Everyday Life' questionnaire (EDLQ), a validated questionnaire related to the SF-36 Health Survey. An impairment in HRQOL was observed in patients with chronic hepatitis C showing PNAL compared with healthy subjects with significant differences for the factor scores depression and anger in the POMS scale as well as for the items body, relationship to partner, self-confidence and zest of life in the EDLQ. No differences in any questionnaire were observed between patients with chronic hepatitis C showing PNAL or elevated aminotransferase levels except of a worse mean level for factor score anger in POMS scale in patients with persistently normal aminotransferases. No association of quality of life with severity of liver disease was found. Impairment of HRQOL by chronic infection with HCV is similar in patients with PNAL and those with elevated aminotransferase levels.
Adult↗
Sonographic characterisation of hepatocellular carcinoma at time of diagnosis.
BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant liver tumour with a high prevalence world-wide. For screening procedures conventional transabdominal B-mode ultrasound and AFP determination are commonly used. We investigated 100 consecutive patients with histologically proven hepatocellular carcinoma in order to evaluate sonographic characteristics in unselected patients and to compare native and contrast-enhanced ultrasonographic techniques. PATIENTS AND METHODS: We investigated 100 consecutive patients with hepatocellular carcinoma at time of diagnosis with respect to echogenicity, patterns of vascularity, and portal/hepatic vein thrombosis. In addition to B-mode and native power Doppler sonography, contrast-enhanced power Doppler sonography with SHU 508A was used in 65 patients. RESULTS: The ultrasound appearance with conventional B-mode of hepatocellular carcinoma was hypoechoic in 48 % of the cases, isoechoic in 9 %, hyperechoic in 19 %, and in 25 % a mixture between hyper- and hypoechoic appearance was found compared to the surrounding liver tissue. Contrast-enhanced power Doppler sonography with SHU 508A changed the pattern of tumour vascularity in 27 % of patients into hypervascular, mainly in small lesions. DISCUSSION: At the time of diagnosis, the most commonly observed finding in hepatocellular carcinoma is that they appear hypervascular, independent of their size. The use of ultrasound contrast media should be considered to achieve characterisation of liver nodules in cirrhotic livers because they can improve the evaluation of tumour vascularity. Hypovascular HCC are found in about 10 % even after the administration of a contrast agent.
Adenoma↗
[Hepatic hydrothorax].
Hepatic hydrothorax is a rare complication of portal hypertension secondary to liver cirrhosis affecting approximately 5-10% of cirrhotic patients with ascites. Hepatic hydrothorax results from an accumulation of fluid migrating through a diaphragmatic defect from the abdominal cavity into the pleural cavities. The effusion of hepatic hydrothorax is typically transudative whereas the effusion of spontaneous bacterial empyema (SBEM) is exudative. The clinical management of hepatic hydrothorax is equivalent to that of ascites. Patients with persistent hepatic hydrothorax despite fluid and sodium restriction as well as the use of maximally tolerable doses of diuretics and repeated thoracentesis are considered to have refractory hepatic hydrothorax. SBEM is a frequent underlying condition. SBEM occurs in up to 13% of patients with hepatic hydrothorax and should be treated by antibiotic therapy. Refractory hydrothorax is observed in 10% of patients with hepatic hydrothorax. These patients should be considered for transjugular intrahepatic portal systemic shunt (TIPS) placement which is the most effective option for refractory hepatic hydrothorax with response rates ranging up to 80% in most studies. Suitable patients with hepatic hydrothorax should be considered as candidates for liver transplantation. TIPS may help to bridge the time to liver transplantation.
Empyema, Pleural↗
Noninvasive assessment of liver steatosis, fibrosis and inflammation in chronic hepatitis C virus infection.
BACKGROUND: Duplex-Doppler ultrasound is a noninvasive method for the assessment of hepatic hemodynamics beyond conventional gray-scale imaging. The clinical value of the method for the grading and staging of chronic hepatitis C virus (HCV) infection and the prediction of hepatic steatosis still has to be determined. This study aimed to compare Duplex-Doppler and ultrasound with the histologic staging and the estimation of hepatic steatosis in chronic HCV infection. PATIENTS AND METHODS: One hundred and nineteen consecutive patients with chronic HCV infection underwent both liver biopsy and ultrasound with Duplex-Doppler. Maximum portal venous blood flow velocity, portal venous flow undulation, hepatic venous flow pattern and spleen size were assessed and compared with histologic findings. Histologic grading and staging was performed according to the modified HAI and hepatic steatosis was estimated. RESULTS: Doppler ultrasound was unable to discriminate between different degrees of fibrosis. Sensitivity/specificity of portal venous flow and undulations for the diagnosis of hepatic cirrhosis was 74.5%/53% and 76.5%/100%. The PPV and NPV of reduced undulations was 100% and 96.2%. Mono- or biphasic hepatic venous flow indicated advanced hepatic steatosis (sensitivity 88.2%, specificity 74.5%, PPV 36.6%, NPV 97.5%). Spleen size was significantly enlarged both in patients with cirrhosis and steatosis. CONCLUSIONS: Although Duplex-Doppler of the portal and hepatic veins is not a substitute for histologic grading and staging, portal vein undulations can predict liver cirrhosis with considerable accuracy. Moreover, triphasic patterns of hepatic venous flow virtually exclude significant fatty liver disease. Additional studies should perform intraindividual follow-up investigations to further define the role of Duplex-Doppler ultrasound in chronic HCV infection.
Aged↗
Response predictors and results of a long-term treatment with lamivudine in patients with chronic hepatitis B.
INTRODUCTION: European data on outcome and follow-up of long-term lamivudine treatment are sparse. Moreover, little is known about predictors for sustained virologic response and for development of drug resistance in patients with lamivudine monotherapy. Patients and methods : 39 patients (17 HBeAg+, 22 HBeAg-) were treated with lamivudine for a median duration of 2.5 years (range: 0.5-4). Outcome to therapy and predictors for response and drug resistance were analyzed retrospectively. RESULTS: None of the patients lost HBsAg. In 14 of 17 initially HBeAg positive patients the HBeAg status was available at the end of treatment. Loss of HBeAg was observed in 8 patients and 7 of these 8 patients seroconverted to anti-HBe. Five of 6 patients with HBeAg seroconversion and a post-treatment follow-up period showed sustained HBeAg seroconversion. In HBeAg negative patients virologic response (serum HBV DNA< or =1 x 10(5) copies/ml) was observed in 12 of 22 patients after a median treatment period of 2.5 years. Post-treatment follow-up data were available in only 2 patients, one of which remained below 1 x 10(5) HBV DNA copies/ml for one year. Resistance emerged in 15 of 36 patients with available serum HBV DNA data after a median treatment period of 2 years. CONCLUSION: The present retrospective study confirms international data for lamivudine treatment in a central European setting. Lamivudine therapy achieved disease control in more than 50 % of patients treated for chronic hepatitis B. Baseline predictors could neither be identified for sustained virologic response nor for the development of drug resistance.
Adolescent↗
TH1/TH2 serum cytokine profiles and soluble TNF-receptor response in patients with chronic hepatitis C during recombinant human interleukin-12 (rHuIL-12) treatment.
Interleukin-12 (IL-12) has many antiviral properties both in vitro and in vivo, such as enhancing cytotoxic lymphocyte reaction, promoting Th1-helper cell response and inducing interferon-gamma - (IFN-gamma) production. The present study investigated possible antiviral effects of recombinant human IL-12 in vivo in 11 chronic hepatitis patients treated with rHuIL-12 subcutaneously in 3 different dosages (0.03, 0.1, 0.5 microg/kg) once weekly for a period of 10 weeks. ELISA was employed to determine before onset of therapy the serum concentrations of IL-12, IL-12p40, IFN-gamma, IL-4, IL-10, tumor mecrosis factor-alpha (TNF-alpha), TNFR p55 and p75, as well as on days 3, 5, 8, 10, 12, 15, 17, 22 after onset of therapy and subsequently weekly until the end of the treatment period and at the end of the 12 months' postobservatory period. The HCV-RNS serum concentration was determined by means of an RT-PCR method. Two to three days after the subcutaneous rHuIL-12 injections there was a transient significant rise of n the serum concentrations of IL-12, IL-12p40, IFN-gamma and TNFR p55, followed by a decrease to the original level. The increases of the IL-12 and IFN-gamma serum concentrations were dose-dependent. In patients where there was a decline of the HCV-RNS concentration in the serum we confirmed a trend to higher IL-12 serum concentrations. The serum levels of IL-2, TNF-alpha and IL-10 fluctuated only during the treatment period. The present study showed that a once-a-week injection of rHuIL-12 results in a merely transient rise of the IL-12, IL-12-p40- and IFN-gamma serum concentrations. This may offer an explanation for the unsatisfactory clinical efficiency of the substance.
Adult↗
[Retrospective cohort study of lamivudine therapy in patients with chronic hepatitis B].
BACKGROUND AND AIMS: Lamivudine, a nucleoside analogue with specific antiviral activity against the hepatitis B virus, is now available as an alternative therapeutic option to standard interferon-alpha treatment in chronic hepatitis B. Larger studies with lamivudine treatment in chronic hepatitis B were mainly performed in North America and Asia. Data on treatment responses in European patients are sparse. Therefore, we evaluated the efficacy and safety of lamivudine therapy in Central European patients and compared the data with the results from international trials. PATIENTS AND METHODS: In this retrospective, multicenter, cohort study, 95 patients with chronic hepatitis B (median age: 40.4 years, male: 87 patients, female: 8 patients, HBeAg positive: 47 patients, anti-HBe positive: 48 patients), who were treated with lamivudine (100-300 mg/d per os) between 1997 to 1999, were enrolled. RESULTS: During lamivudine treatment a virologic response with HBeAg to anti-HBe seroconversion was achieved in 22/47 (47%) of the HBeAg positive patients. Pretreatment ALT levels (> threefold the upper limit of normal; p = 0.03) and HBV-DNA serum concentration (< or = 100 pg/ml; p = 0.08) were identified as positive predictors for virologic responses. The virologic response was sustained in six of nine patients who had a follow-up period (median 26 weeks). In anti-HBe positive patients a virologic response with undectable HBV-DNA levels was achieved in 35/48 (73%) patients during lamivudine treatment. Side effects during lamivudine therapy were generally mild and reversible. CONCLUSIONS: In this retrospective cohort study virologic end-of-treatment responses to lamivudine monotherapy in patients with chronic hepatitis B were comparable with yet reported international trials. Thus, lamivudine represents a cost-effective and well tolerable option in addition to IFN-alpha in the treatment of chronic hepatitis B.
Adult↗
Randomized, placebo-controlled, double-blind trial with interferon-alpha with and without amantadine sulphate in primary interferon-alpha nonresponders with chronic hepatitis C.
In primary interferon-alpha (IFN-alpha) nonresponders with chronic hepatitis C, retreatment with IFN-alpha has only limited efficacy with sustained response rates below 10%. Therefore, the aims of the present study were to compare the efficacy and safety of IFN-alpha alone or in combination with amantadine sulphate in nonresponders to previous IFN-alpha monotherapy. Fifty-five IFN-alpha nonresponders with chronic hepatitis C (mean age: 46.6 years) received IFN-alpha 6 MIU thrice weekly for 24 weeks followed by 3 MIU thrice weekly for additional 24 weeks. Amantadine sulphate (n=26) or a matched placebo (n=29) was given orally twice daily for 48 weeks. Because of a low initial response rate at week 12 (13/55 patients) and a high breakthrough rate (8/13 patients) after IFN-alpha dose reduction in week 24, a virological end-of-treatment response with undetectable serum HCV-RNA (< 1000 copies/mL) was achieved in only five patients (IFN-alpha/amantadine sulphate, one patient; IFN-alpha/placebo, four patients). After 24 weeks follow-up a sustained virological response was observed in only two patients receiving IFN-alpha and placebo. Health-related quality-of-life analysis showed a substantial improvement of the Profile of Mood States (POMS) scale concerning the subscales fatigue (P < 0.05) and vigor (P < 0.05) in patients receiving combined IFN-alpha/amantadine sulphate treatment compared with those treated with IFN-alpha alone. IFN-alpha/amantadine sulphate combination therapy was well tolerated without any serious adverse events. In conclusion, retreatment with IFN-alpha and amantadine sulphate does not increase the low sustained virological response rates of IFN-alpha therapy in primary IFN-alpha nonresponders with chronic hepatitis C, but may lead to a sustained improvement of health-related quality-of-life.
Adolescent↗
Comparison of new faecal antigen test with (13)C-urea breath test for detecting Helicobacter pylori infection and monitoring eradication treatment: prospective clinical evaluation.
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Adolescent↗
Efficacy of a short-term ribavirin plus interferon alpha combination therapy followed by interferon alpha alone in previously untreated patients with chronic hepatitis C: a randomized multicenter trial.
BACKGROUND: Combination therapy with interferon alpha (IFNalpha) plus ribavirin has been shown to improve the sustained response rate in patients with chronic hepatitis C but there is little information regarding the lengths of time for this therapeutic regimen. In this study we therefore tried to evaluate whether the analysis of different virological parameters could provide new clues with respect to the early determination of the efficacy of this form of combination therapy. Furthermore, we also examined whether short-term induction combination therapy followed by IFNalpha alone is more effective than monotherapy in mounting an initial as well as a sustained virological response. METHODS: 185 patients with histologically proven chronic hepatitis C (mean age 42 years (range 19-65 years); 110 males, 75 females) were enrolled in the study. The patients were randomly assigned to receive, over the first 12 weeks, either interferon alpha 2a 6 million units (MU) three times weekly plus ribavirin 14 mg/kg per day (n=93) or the same dose of IFNalpha alone (n=92). Patients with a virological response (serum HCV RNA undetectable) after 12 weeks were subsequently treated with 3 MU IFNalpha alone thrice weekly for a further 40 weeks. Otherwise, treatment was discontinued. After the end of treatment, patients were followed up for 24 weeks. RESULTS: Patient characteristics at baseline were not significantly different in the two treatment groups. An initial virological response at week 12 was seen in 61 (66%) patients receiving IFNalpha plus ribavirin and in 44 (48%) being treated with IFNalpha alone (p=0.015) and this improvement in the response rate was mainly restricted to HCV genotype 1-infected patients (58% vs. 38%). In contrast, end-of-treatment (week 52) and sustained virological response rates were similar in both groups (37% vs. 29% and 26% vs. 17% [p=0.1], respectively). Interestingly, patients with HCV genotype 3, however, clearly benefited from short-term combination therapy. Thus, sustained virological response rates in these patients significantly increased from 25% (IFNalpha monotherapy) to 59% (combination therapy) (p=0.05). CONCLUSIONS: Short-term combined therapy for 12 weeks is more effective than the monotherapy with respect to the induction of an initial virological response but this effect applies only to genotype 1-infected patients. However, there is no significant difference between both therapeutic schedules with regard to the induction of sustained response. Although HCV genotype 3-infected patients seem to benefit from this short-term combined therapy, prolonged combined therapy may be necessary in HCV genotype 1-infected patients.
Adult↗
Evaluation of factors controlling glucose tolerance in patients with HCV infection before and after 4 months therapy with interferon-alpha.
BACKGROUND: Epidemiological data suggest that chronic hepatitis C virus (HCV) infection may contribute to the development of diabetes mellitus. Therapy of HCV infection with recombinant interferon-alpha (r-IFN-alpha) can also impair of glucose metabolism. METHODS: To investigate the impact of HCV infection and the therapy with r-IFN-alpha on glucose metabolism we measured insulin sensitivity, glucose effectiveness, and first and second phase insulin secretion, using the minimal modelling analysis of frequently sampled intravenous glucose tolerance tests in 13 nondiabetic patients with HCV-induced liver disease before and after therapy with r-INF-alpha (6 x 106 U, subcutaneously, three times a week over 4 months). Liver biopsy was performed to evaluate and score liver fibrosis as a marker of HCV-induced cell injury. RESULTS: Insulin sensitivity (r = - 0.59, P < 0.05) and first phase insulin secretion (r = - 0.66, P < 0.03) were negatively related to the fibrosis score. Insulin sensitivity rose from 1.96 (SEM 0.37, n = 8) to 5.69 (SEM 0.99, n = 8) 10-4 min-1 per microU mL-1 (P < 0.01) in responders and from 2.51 (SEM 0.61, n = 5) to 6.95 (SEM 1.99, n = 5) in nonresponders after 4 months r-INF-alpha therapy. Fasting free fatty acids decreased significantly to about 50% (P < 0.01) in patients with and without therapy response after 4 months, whereas first phase insulin secretion did not change. CONCLUSIONS: HCV-induced liver injury is related to the deterioration of insulin sensitivity and first phase insulin response, thus impairing glucose homeostasis in these HCV-infected patients. The administration of r-INF-alpha three times a week over 4 months is not associated with an impairment of glucose homeostasis.
Blood Glucose↗
Detection of residual hepatitis C virus RNA by transcription-mediated amplification in patients with complete virologic response according to polymerase chain reaction-based assays.
A considerable proportion of patients with chronic hepatitis C who achieve a virologic end-of-treatment response relapse after discontinuation of therapy. It is conceivable that polymerase chain reaction (PCR)-based assays with a lower detection limit of 100 to 1, 000 hepatitic C virus (HCV) RNA copies/mL are still too insensitive to detect residual viremia. End-of-treatment serum samples of 47 patients with a virologic relapse according to results of qualitative PCR assays (Amplicor HCV; Roche Molecular Systems, Mannheim, Germany) were tested by transcription-mediated amplification (TMA), an isothermal, autocatalytic target amplification method that has the potential to detect less than 50 HCV RNA copies/mL. Virologic sustained responders (n = 59) and nonresponders (n = 49) served as controls. In end-of-treatment serum samples of virologic sustained responders and nonresponders an almost complete concordance between PCR and TMA results was observed (98%). However, HCV RNA was detectable by TMA in end-of-treatment serum samples from 16 of 25 relapse patients (64%) who were HCV-RNA-negative according to Amplicor HCV version 1.0 (lower detection limit 1,000 copies/mL) and in 8 of 22 patients (36%) who were HCV-RNA-negative according to Amplicor HCV version 2.0 (lower detection limit 100 copies/mL). End-of-treatment alanine transaminase (ALT) levels of sustained virologic responders and TMA-negative relapsers were similar, whereas a trend toward higher ALT values was observed in TMA-positive relapsers compared with sustained virologic responders (P = 0.09). In conclusion, HCV RNA can be detected at the end of treatment by TMA in a considerable proportion of patients who were classified as virologic end-of-treatment responders with a subsequent virologic relapse according to PCR-based methods.
Adult↗
Randomized, double-blind, placebo-controlled trial of interferon alfa2a with and without amantadine as initial treatment for chronic hepatitis C.
Although the antiviral effects of amantadine sulphate (1-aminoadamantan sulphate) have not been characterized for the hepatitis C virus (HCV), previous pilot studies have suggested promising results in patients with chronic hepatitis C. The aim of the present study was to compare the efficacy, safety, and health-related quality of life (HRQOL) of interferon alfa (IFN-alpha) alone or in combination with oral amantadine for treatment of chronic hepatitis C. One hundred nineteen previously untreated patients with chronic hepatitis C were randomly allocated to treatment with IFN-alpha2a at a dose of 6 megaunits 3 times a week subcutaneously for 24 weeks, followed by 3 megaunits thrice weekly for an additional 24 weeks plus amantadine sulphate administered orally 100 mg twice a day for 48 weeks or the same IFN regimen plus a matched placebo. The primary endpoint was undectable serum HCV RNA (<1,000 copies/mL) at week 24 after treatment. At the end of treatment and the 24-week follow-up period serum HCV RNA was undetectable in 20 (34%) and 6 (10%) of the 59 patients treated with the combination IFN-alpha plus amantadine and in 20 (33%) and 13 (22%) of the 60 patients treated with IFN-alpha alone, respectively (P = n.s.). Discontinuation of therapy for adverse events was similar in both treatment groups. Although treatment with IFN-alpha worsened HRQOL, combination with amantadine showed a substantial trend to improve fatigue and vigor. In conclusion, combination therapy IFN-alpha plus amantadine is as effective as IFN-alpha monotherapy in previously untreated patients with chronic hepatitis C.
Adolescent↗
Retreatment with interferon-alpha and ribavirin in primary interferon-alpha non-responders with chronic hepatitis C.
BACKGROUND/AIMS: Combination therapy with interferon-alpha (IFN-alpha) plus ribavirin is more efficacious than IFN-alpha monotherapy in previously untreated patients with chronic hepatitis C and patients with IFN-alpha relapse. Only limited data are available in IFN-alpha non-responders. In a multicenter trial we therefore evaluated the efficacy of combination therapy in IFN-alpha-resistant chronic hepatitis C. METHODS: Eighty-two patients (mean age 46.8 years, 54 males, 28 females) with chronic hepatitis C were treated with IFN-alpha-2a (3 x 6 MIU/week) and ribavirin (14 mg/kg daily) for 12 weeks. Thereafter, treatment was continued only in virological responders (undetectable serum HCV RNA at week 12) with an IFN-alpha dose of 3 x 3 MIU/week and without ribavirin for a further 9 months. The primary study endpoint was an undetectable HCV RNA by RT-PCR at the end of the 24-week follow-up period. RESULTS: After 12 weeks of combination therapy, an initial virological response was observed in 29 of 82 (35.4%) patients. Due to a high breakthrough rate after IFN-alpha dose reduction and ribavirin discontinuation, an end-of-treatment response was only achieved in 12 of 82 (14.6%) patients. After the follow-up period, a sustained virological response was observed in 8 of 82 (9.8%) patients. Infection with HCV genotype 3 was the only pretreatment parameter, which could predict a sustained response (HCV-1, 5%; HCV-3, 57.1%; p < 0.001). CONCLUSIONS: Despite a high initial response rate of 35.4%, sustained viral clearance was achieved only in 9.8% of the retreated primary IFN-alpha non-responders. Higher IFN-alpha induction and maintenance dose, as well as prolonged ribavirin treatment may possibly increase the virological response rates in non-responders, particularly in those infected by HCV-1.
Adolescent↗
Severity of HCV-induced liver damage alters glucose homeostasis in noncirrhotic patients with chronic HCV infection.
BACKGROUND/AIMS: To investigate the link between hepatitis C infection and glucose intolerance, we measured insulin sensitivity, glucose effectiveness and beta-cell secretion in noncirrhotic HCV-infected patients with normal glucose tolerance according to WHO criteria as assessed by oral glucose tolerance tests. METHODS: Glucose, insulin and C-peptide data from frequently sampled intravenous glucose tolerance tests were analyzed using the minimal modeling technique for glucose and C-peptide to determine insulin sensitivity, glucose effectiveness, first and second phase insulin secretion in noncirrhotic HCV-infected patients (n = 10) and in healthy control subjects (n = 10). Histological activity index (HAI) as well as the extent of fibrosis were evaluated by scoring liver biopsies. RESULTS: Insulin sensitivity (2.72 +/- 1.63 vs. 6.84 +/- 1. 20 10(-4) min(-1) per microU/ml, p < 0.01) and glucose effectiveness (2.29 +/- 0.45 vs. 2.89 +/- 0.39 10(-2) min(-1), p < 0.05) ere significantly lower in patients with HCV-induced liver disease. Insulin sensitivity was negatively related to serum alanine aminotransferase (r = -0.47, p < 0.05) and aspartate aminotransferase concentrations (r = -0.65, p < 0.05). Multiple linear regression analysis revealed a strong relation of insulin sensitivity with fibrosis score and HAI (r = -0.82, p < 0.02 for both). Second phase insulin secretion was significantly enhanced in HCV-infected patients (14.30 +/- 2.04 vs. 8.29 +/- 1.65 min(-1), p < 0.05). CONCLUSIONS: HCV-infected patients with normal glucose tolerance are insulin and glucose resistant. The impairment of glucose tolerance appears to be closely related with the severity of HCV-induced liver damage.
Adult↗
Perihepatic lymph nodes as a marker of antiviral response in patients with chronic hepatitis C infection.
OBJECTIVE: In patients with chronic hepatitis C, the sonographically determined total perihepatic lymph node volume reflects liver histology and viremia. The aim of this prospective study was to assess whether the response to antiviral therapy is reflected by changes in the total perihepatic lymph node volume. SUBJECTS AND METHODS: In 59 patients with chronic hepatitis C infection. the total perihepatic lymph node volume was assessed using sonography before the initiation of antiviral treatment, at the end of treatment, and at the end of a 6-month follow-up period. Hepatitis C viremia was assessed by reverse transcription-polymerase chain reaction assay at the same time points. Liver biopsy was performed in all patients before therapy and in 40 of the 59 patients 6 months after therapy. RESULTS: At the end of follow-up, the total perihepatic lymph node volume was significantly smaller in the 15 patients with a sustained virologic response than in the 44 patients who failed to respond to treatment (0.5+/-0.3 ml versus 2.0+/-1.2 ml; p<0.0001). In the group of sustained virologic responders, the decline of the perihepatic lymph node volume was associated with an improvement in liver histology. CONCLUSION: Total perihepatic lymph node volume changes according to the antiviral response and leads to progressive normalization of the perihepatic lymph node volume in sustained virologic responders. A decrease in the perihepatic lymph node volume is associated with an improvement in liver histology.
Adult↗
Antiviral effect of human recombinant interleukin-12 in patients infected with hepatitis C virus.
The heterogeneity of hepatitis C virus (HCV) is due to the continuous and high replication rate, the low fidelity of the RNA-dependent RNA polymerase, and the immune surveillance of the host. Interleukin-12 (IL-12) plays a central role in mounting an effective cellular immune response directed towards elimination of intracellular pathogens. The effect of IL-12 on hepatitis C viremia and the HCV quasispecies population is unknown. In this study, 12 patients (9 males, 3 females; mean age: 44 +/- 11 years), all virological non-responders to previous IFN-alpha treatment, received recombinant human IL-12 s.c. once weekly for 10 weeks stratified to three dose schedules (0.03 microg/kg, 0.1 microg/kg, and 0.5 microg/kg body weight, respectively). Fourteen IFN-alpha non-responders and 14 untreated patients served as age- and sex-matched controls. Serum HCV RNA concentrations and HCV quasispecies distribution were measured serially by quantitative reverse transcription - polymerase chain reaction and single strand conformation polymorphism analysis of the hypervariable region of the second envelope gene, respectively. Serum ALT and median HCV RNA levels before treatment (52.7 +/- 21.7 U/L; 2.6 x 10(6) copies/mL) showed no significant changes during IL-12 treatment (57.3 +/- 58.8 U/L and 3.2 x 10(6) copies/mL, 50.3 +/- 46.2 U/L and 3.1 x 10(6) copies/mL, and 46.8 +/- 35.3 U/L and 3.9 x 10(6) copies/mL at weeks 1, 4, and 10, respectively). Similar results were observed in 14 IFN-alpha non-responders and 14 untreated patients. However, changes in HCV quasispecies occurred in 10/12 (83%) and 9/14 (64%) patients treated with interleukin-12 and interferon-alpha, respectively, but only in 3/14 (21%) untreated subjects (P < 0.003 and P < 0.03). These results imply that interleukin-12 exerts only limited antiviral activity against certain HCV quasispecies in vivo.
Adult↗