ALT Flares Are Not Necessary for a Significant Response to Therapy with Roferon or Pegasys in Patients with HBeAg positive Chronic Hepatitis B 11-03-03

Daily and Higher Initial Dosing of Consensus Interferon (Infergen) May Be a Worthwhile Alternative to Peginterferon + Ribavirin in Genotype 1 HCV Patients with High HCV RNA 11/07/03

In Patients 65 Years or Older, Chronic HCV Is More Severe and Presents with Lower ALT Levels Than in Younger Patients 11/10/03

Qualitative Tests (QLFTS) Detect Impaired Hepatic Function in a High Proportion of Patients with Chronic HCV and Fibrosis or Cirrhosis and May Predict Risk of Cirrhosis, Splenomegaly and Varices 11/17/03
 

The combination of pegylated interferon alfa and ribavirin is the currently recommended treatment for patients with chronic hepatitis C (CHC) and elevated alanine aminotransferase (ALT) levels.

Recent data with Pegasys (peginterferon alfa-2a/ 40 KD) 180 μg/week and ribavirin have established that the treatment duration for CHC patients with elevated ALT should be based on the HCV genotype: 48 weeks for genotype 1 and 24 weeks for genotype 2/3 patients.
 

However, many patients with chronic hepatitis C (CHC) have persistently normal serum ALT levels. The effectiveness of interferon alfa (IFN-alfa) therapy in these patients is controversial. The US and EU consensus conferences on hepatitis C recommend not to treat normal ALT CHC patients until data from controlled clinical studies become available.
 

The purpose of the current international, multicenter, randomized, controlled study was to determine the efficacy and safety of PEG-IFN alfa-2a in combination with ribavirin administered during 2 different treatment durations in CHC patients with normal ALT.

491 patients were randomized (ratio 3:3:1) into three arms: 212 were treated with PEG-IFN alfa-2a 180 μg/week plus ribavirin 800 mg/day for 24 weeks, 210 received the same combination for 48 wks and 69 patients received no treatment and were monitored for 72 weeks.

All patients were required to have CHC infection documented by positive anti-HCV antibody test and detection of HCV RNA by PCR. Persistently normal ALT activity was defined by at least 3 ALT determinations ≤ the upper limit of normal (ULN), a minimum of 4 weeks apart, with 1 value within the 42-day screening time and 1 value 6 to 18 months before the study onset.

Patients with ALT levels > ULN during the 18 months preceding baseline were excluded from the study. Liver disease consistent with CHC was confirmed by biopsy within 36 months before the study. Cirrhotic patients and patients with other chronic liver disease or co-infected with human immunodeficiency virus were excluded from the trial. Sustained virological response (SVR) was defined as HCV RNA negativity by PCR (<50 IU/mL COBAS AMPLICOR^® HCV Test v. 2.0) at the end of 24 weeks of untreated follow-up.
 

Study Results

Demographic and baseline virologic features were similar in all three groups. Male gender: 42%, 39%, 38%; median age: 44, 44, 41 years, and median weight, 74 kg, 73 kg, 70 kg, respectively. Genotype 1: 68%, 67%, 66 %; and mean viral load: 1.2, 1.1 and 1.3 x 10⁶ IU/mL, respectively.

Overall SVR was 30% and 52% for the 24 and 48 wk treatment groups, respectively, versus 0% for the untreated control group (p <0.0001). For genotype 1, SVR was 13% in the 24 wk treatment group vs 40% in the 48 wk treatment group (p<0.001).

For genotypes 2 and 3, 24 weeks treatment had a SVR of 72% vs 78% in patients treated for 48 weeks (p = ns).

The safety profile was typical of IFN treatment but the incidence of the commonest IFN-related adverse events was lower than in previous studies on abnormal ALT CHC patients. ALT values remained normal or near normal in the vast majority of patients from both treatment and control groups. Median ALT levels decreased from baseline in treatment responders. Mild, transient ALT elevations were observed after end of treatment in relapsers from treatment groups. Only 2 patients, one treated for 24 weeks, and one from the control group, developed ALT flares (>10x ULN).

“These findings suggest that a large number of hepatitis C patients with normal ALT levels would benefit from Pegasys combination therapy,” said Mitchell L. Shiffman, M.D., chief of the Hepatology Section and medical director of VCU’s Liver Transplant Program, who was a U.S. investigator on the study. “While normally associated with milder liver disease, ALT levels vary from person to person and can fluctuate from month to month. This study provides a great deal more information on how we should treat the 30 percent of chronic hepatitis C patients who have normal ALT levels.”
 

The authors conclude, “The efficacy results are comparable to those obtained in previous trials in CHC patients with elevated ALT (Hadziyannis et al. J Hepatol 2002; 36(S1) pp.3A) and a duration of treatment according to genotype can be recommended following established algorithms.”

10/27/03

Reference
S Zeuzem and others. INTERNATIONAL, MULTICENTER, RANDOMIZED, CONTROLLED STUDY FOR THE TREATMENT OF PATIENTS WITH CHRONIC HEPATITIS C AND PERSISTENTLY NORMAL ALT LEVELS WITH PEGINTERFERON ALFA-2A (40KD) (PEGASYS^®) AND RIBAVIRIN (COPEGUS^®). Abstract 106. Presidential Plenary 1. 54^th AASLD. October 24-28, 2003. Boston, MA.

Untreated Patients with Chronic Hepatitis C (CHC) and Normal ALT Levels Have Distinct Biological and Virological Features and a Majority Report CHC Symptoms Associated with Interferon Treatment
 

A large proportion of patients with chronic hepatitis C (CHC) have alanine aminotransferase (ALT) levels persistently within normal range, but the natural history of these patients is not well defined.
 

The purpose of this study was to characterize the clinical and virological features and the evolution of disease in untreated patients with CHC and normal ALT levels.
 

An international, multicenter study evaluating efficacy and safety of treatment with peginterferon alfa-2a (40KD) (PEGASYS^®) and ribavirin (COPEGUS^®) in normal ALT CHC patients was performed. Patients in the control group were observed untreated for 72 weeks. All patients were required to have CHC infection documented by positive anti-HCV antibody test and detection of HCV RNA by PCR.

Persistently normal ALT was defined by at least 3 determinations ≤ the upper limit of normal (ULN) a minimum of 4 weeks apart, with one value within the 42-day screening period and another between 6 and 18 months before the study onset. Patients with

ALT levels >ULN during the 18 months preceding baseline were excluded from the study. Liver disease consistent with CHC was confirmed by biopsy within 36 months before the study.

Patients with cirrhosis or other chronic liver disease, or those coinfected with human immunodeficiency virus, were also excluded from the trial.
 

Study Results

Sixty-nine patients were randomized to the untreated control group and were monitored for the 72 weeks of the study.

Demographic characteristics were: male gender 38%, mean age 41 years, and mean weight 71 Kg. Mode of infection, iv drug use 35%, transfusion 20%, unknown 32%, other percutaneous exposure 10% and sexual transmission 3%.

Sixty-eight percent (68%) of the patients had HCV genotype 1 infection (38% 1a, and 30% 1b), 19% and 9% of the patients had genotype 2 and 3, respectively, and 3% had genotype 4.

Histological activity (Ishak score): 81% of the patients had a score ≤4 for necroinflammatory changes, 93% had a fibrosis score ≤2; only 5 patients had a fibrosis score of 3. The mean baseline viral load was 1.3 x 10⁶ IU/mL. Viremia levels were stable during the study period with mean values fluctuating between 1.3 and 1.8 x 10³ IU/mL.

No patient spontaneously cleared HCV. ALT values remained within normal limits throughout the trial in 48% of the patients. Occasional ALT elevations of <2 x ULN occurred in 45% of patients, and of <5 x ULN in 6% of patients. One patient had an isolated 12 x ULN ALT flare accompanied by a moderate AST increase.

Fifty-three patients (77%) reported adverse events during the study, such as fatigue, headache, insomnia, and depression.
 

Conclusions

CHC patients with persistently normal ALT values appear to have distinct biological and virological features.

In comparison to a previous multinational trial performed in patients with elevated ALT levels (Hadziyannis et al. J Hepatol. 2002;36 [suppl 1]:3A), the male to female ratio was inverted, with a female predominance in normal ALT patients, the HCV genotype distribution was different, baseline viremia was lower, and liver disease was mild.

During the 72-week observation period, viremia was stable but no patient cleared HCV RNA.

ALT values remained within the normal or near-normal range in most patients.

A majority of individuals reported CHC symptoms often believed to be associated with IFN treatment.

Transient, generally low-grade ALT elevations were noted in over 50% of control patients.

10/27/03

Reference
M Shiffman and others. (THE MULTINATIONAL PEGASYS^® STUDY). . NATURAL HISTORY OF PATIENTS WITH CHRONIC HEPATITIS C AND PERSISTENTLY NORMAL ALANINE AMINOTRANSFERASE LEVELS: DATA FROM THE MULTINATIONAL PEGASYS^® STUDY (NR 16071). Abstract 568 (poster). 54^th AASLD. October 24-28, 2003. Boston, MA.

Patients with Chronic Hepatitis C and Normal ALT Levels Show Impaired Quality of Life But Significantly Lower Liver Inflammation and Fibrosis Progression Compared to Patients with Elevated ALT
 

A significant proportion of the patients chronically infected with the hepatitis C virus (HCV) have persistently normal serum ALT levels. Previous studies suggested a lower risk for these patients to progress to liver cirrhosis and its sequelae. Comprehensive data on the quality of life in these patients are currently not available.
 

In the present study, 45 patients with chronic hepatitis C and persistently normal aminotransferases, defined by normal serum ALT levels on at least three occasions during a 6 months period, 70 patients with chronic hepatitis C and elevated aminotransferases and 50 healthy subjects without any evidence of a chronic disease were enrolled.

Patients with chronic hepatitis C and persistently normal ALT levels and healthy subjects were matched regarding age and gender. For patients with chronic hepatitis C several biochemical (e. g. ALT, AST, ferritine) and virological tests (e. g. HCV RNA serum concentration, HCV genotype) were performed.

In 27/45 patients with persistently normal ALT levels and in 68/70 patients with elevated ALT levels liver inflammation and fibrosis were histologically evaluated by the HAI scoring system.

Emotional and psychological states were measured by a German adapted and validated “Profile of Mood States scale,” which measures 4 factor scores for depression, fatigue, vigor, and anger.

Furthermore, quality of life was assessed by the “Everyday Life” questionnaire (EDLQ), a German validated questionnaire related to the SF-36 Health Survey. Statistical significance was assessed by Fisher exact test and Mann-Whitney U test.
 

Study Results

In patients with chronic hepatitis C and persistently normal ALT levels duration of infection was significantly longer than in patients with chronic hepatitis C and elevated ALT levels (176.9 vs. 131.2 months; p=.016).

However, the portion of male patients (36% vs. 66%; p=.001) and the number of patients with hepatitis B infection in the past (27 vs. 51%; p=.01) were significantly lower in the group of patients with persistently normal ALT levels.

Liver histology showed significantly less inflammation (3.88 vs. 4.89; p<.02) in patients with persistently normal ALT levels compared with those with elevated ALT levels.

Calculation of the liver fibrosis progression rate per year as the ratio between the liver fibrosis stage and the estimated duration of infection in years revealed a significant lower fibrosis progression rate for patients with persistently normal ALT levels (0.2 vs. 0.5; p=.002).

However, current stage of liver fibrosis was similar in both groups. I

In patients with persistently normal ALT levels the “Profile of Mood States scale” showed a reduction in quality of life in all 4 items compared with the matched control group with significant differences for depression (p=.006) and anger (p=.007).

In the EDLQ significant differences were also found for the items body (p=.04), relationship to partner (p=.01), self-confidence (p=.04), and zest for life (p=.01) between patients with chronic hepatitis C and persistently normal ALT levels and healthy subjects.

No significant differences were observed for any item in POMS or EDLQ between patients with chronic hepatitis C and persistently normal ALT levels and patients with elevated ALT levels and chronic hepatitis C.

Conclusions

Patients with chronic hepatitis C and persistently normal ALT levels show significantly lower liver inflammation and fibrosis progression rate per year compared with patients with elevated ALT levels. Quality of life assessments show a significant impairment of health-related quality of life in patients with chronic hepatitis C compared with healthy controls, however, no differences between chronically HCV-infected patients with persistently normal or elevated aminotransferase levels.

10/27/03

Reference
M von Wagner and others. IMPAIRED QUALITY OF LIFE IN PATIENTS WITH CHRONIC HEPATITIS C AND PERSISTENTLY NORMAL AMINOTRANSFERASE LEVELS. Abstract 606 (poster). 54^th AASLD. October 24-28, 2003. Boston, MA.

ALT Flares Are Not Necessary for a Significant Response to Therapy with Roferon or Pegasys in Patients with HBeAg positive Chronic Hepatitis B

Transaminase (ALT) flares are an inherent aspect of the natural course and progression of chronic hepatitis B (CHB) and are considered to be a reflection of host immune activity against infected hepatocytes.

Furthermore, prominent ALT flares occurring during, or shortly after, interferon treatment of CHB have been associated with HBeAg seroconversion. Nucleoside/nucleotide analogues lead to suppression of viral replication and concomitant reduction of ALT flares. The antiviral activity of interferon also suppresses viral replication but at the same time modulation of the host immune system may provoke cytotoxic elimination of hepatocytes.

The use of Pegasys (peginterferon alfa-2a /40KD) has previously been shown to exert greater antiviral activity than conventional interferon as measured by PCR testing of HBV DNA during therapy (Cooksley et al, J Viral Hep 2003).

The objective here is to explore the incidence of significant ALT flares during the same comparative clinical trial of conventional interferon alfa-2a and peginterferon alfa-2a (40KD) therapy in HBeAg positive CHB, and relate them to the combined viral HBeAg status, HBV DNA and ALT outcomes.

 

A total of 194 adults with HBeAg-positive CHB and screening ALT >2 times the upper limit of normal (ULN), were randomized to treatment with conventional interferon alfa-2a 4.5 MIU, or Pegasys 90 μg, 180 μg, or 270 μg for 24 weeks and then monitored for an additional 24 weeks.

The most discriminating measure of efficacy was made using a combined response, which was determined at the end of the follow up period and required: loss of HBeAg, HBV DNA suppression to <500,000 copies/mL (Roche COBAS AMPLICOR HBV MONITOR Test, sensitivity of 200 copies/mL) and ALT normalization.

Various levels of ALT rises have been used to define a significant flare and the definition used here is a peak ALT in excess of 10 x ULN.

Study Results

ALT flares (>10 x ULN) were seen in 22% of patients receiving conventional interferon alfa-2a, and 27%, 28% and 19% of patients receiving 90,180 and 270 μg Pegasys, respectively. Data on the frequency of on-therapy and follow-up flares in responders and non-responders are summarized below.

Conclusions

Flares were observed in almost a quarter of all patients, but they occurred less frequently in patients who showed a significant therapeutic response (6 patients, 15%) than in those who did not (40 patients, 26%).

This suggests that a marked ALT flare in patients treated with either conventional interferon alfa-2a or Pegasys is not necessary for a significant response to therapy to occur.

It is noteworthy that in the patients not showing a combined response, ALT flares were seen more frequently in those treated with peginterferon alfa-2a (40KD). However, these flares occurred more often during therapy than after therapy.

Further implications of these observations will be explored in large ongoing comparative studies of Pegasys at 180 μg in combination with either placebo or lamivudine vs lamivudine alone.

11/05/03

Reference
WGE Cooksley and others. ALT FLARES IN PATIENTS WITH HBEAG-POSITIVE CHRONIC HEPATITIS B AND TREATED WITH EITHER CONVENTIONAL INTERFERON ALFA-2A OR PEGINTERFERON ALFA-2A (40KD) (PEGASYS^®) ARE NOT NECESSARY FOR A SIGNIFICANT RESPONSE TO THERAPY. Abstract 1189 (poster). 54^th Annual Meeting of the American Association for the Study of Liver Diseases. October 24-28, 2003. Boston, MA.

Daily and Higher Initial Dosing of Consensus Interferon (Infergen) May Be a Worthwhile Alternative to Peginterferon + Ribavirin in Genotype 1 HCV Patients with High HCV RNA

Treatment with pegylated interferon alfa and ribavirin has an efficacy in chronic hepatitis C patients with sustained response rates of about 50%. However, response in genotype 1 patients with high viral load is considerably lower and is not significantly improved by pegylation of interferon.

In the present study, conducted at the University of Tubingen, Germany, the efficacy of consensus interferon (CIFN) daily dosing and induction therapy followed by combination with ribavirin in 200 naive patients with chronic hepatitis C and genotype 1 was evaluated.

All patients had histologically proven hepatitis, elevated ALT values and were viremic, the average weight was 80 kg. Patients were treated with CIFN dosages of 27 or 18 ug QD for 4 weeks, followed by 18 or 9 ug QD for 8 weeks. Treatment was continued with CIFN at 9 ug QD with ribavirin (7.5 or 15 mg/kg/d) for another 36 weeks.
 

Study Results

At 48 weeks therapy an undetectable HCV-RNA was observed in 79 % and 72 % in the CIFN 27/18 and 18/9 ug groups, respectively. Data regarding sustained response rates showed 64% and 58% for CIFN 27/18 and 18/9 ug groups, respectively. Due to side effects CIFN had to be dose reduced in 11% and discontinued in 6% of patients.

Addition of ribavirin potentiated the effect of consensus interferon in a dose-dependent manner as has been shown for other interferons previously.

When viral response rates were related to the initial viral load, in the genotype 1 / low viral load group, SR rates of 71 and 74% were obtained for the CIFN 27/18 and 18/9 ug groups (diff. n.s.). In contrast, genotype 1 / high viral load patients showed SR rates for the CIFN 27/18 and CIFN 18/9 ug groups of 41 and 49% (diff. sig.), respectively. The viral response rates obtained with daily dosing of CIFN were significantly higher than an independently run control arm using CIFN at 9 ug TIW with ribavirin irrespective of the initial viral load.

Four patients (2%) experienced grade III thrombocytopenias, while no grade IV neutropenias or thrombocytopenias were observed. The overall tolerability in the CIFN 18/9 ug QD arm was comparable to standard therapy with pegylated interferon a2b and ribavirin, while the CIFN 27/18/9 ug arm was less tolerable during the high dosing period. However, the withdrawal rates were not significantly affected by the higher dose of CIFN.
 

Conclusions

CIFN daily dosing / induction therapy in combination with ribavirin thus shows significant response rates with the highest response rates in genotype 1 patients seen to-date. The sustained response rates for genotype 1 / high viral load patients are higher than the ones demonstrated in the PEG Interferon and ribavirin registration trials. These data suggest that for difficult-to-treat genotype 1 / high viral load patients CIFN with daily and higher initial dosing may be a worthwhile alternative to standard combination therapy with pegylated interferons.

11/07/03

Reference
S Kaiser and others. DAILY DOSING REGIMEN OF CONSENSUS INTERFERON AND RIBAVIRIN FOR TREATMENT-NAIVE PATIENTS WITH CHRONIC HEPATITIS C AND GENOTYPE 1. Abstract 304 (poster). 54^th Annual Meeting of the American Association for the Study of Liver Diseases. October 24-28, 2003. Boston, MA.

In Patients 65 Years or Older, Chronic HCV Is More Severe and Presents with Lower ALT Levels Than in Younger Patients
 

Unfortunately, there are scant data available on hepatitis C in elderly patients, most of whom became infected from contaminated blood or blood products prior to the development of the HCV antibody test.

The aim of the current study was to compare patients 65 years or older (GE65) with those less than 65 (LT65) in terms of the demographic and clinical features of hepatitis C, the severity of hepatic injury, the efficacy and safety of antiviral therapy and the usefulness of biochemical markers [FibroTest-ActiTest (AT-FT)].
 

Two groups of patients were analyzed: group 1, a prospective cohort including all HCV patients from our institution (n=4,182); and group 2, all consecutive patients who had had FT-AT performed in France between September 2002 and May 2003 (n=8,540).
 

Study Results

A total of 2,410 GE65 were included, 881 from group 1 and 1,529 from group 2.

In group 1, the duration of infection and age at infection were higher in GE65 than in LT65 (26 vs 20 and 50 vs 24 years, respectively, p< 0.001). Infection with genotype 1 and history of transfusion were more frequent in GE65 than in LT65 (78% vs 57% and 51% vs 29%, respectively, p<0.001).

Fibrosis stage at liver biopsy was higher in GE65 than in LT65, regardless of the duration of infection. Among the 2,169 patients who underwent liver biopsy, bridging fibrosis (F2F3F4) was more frequent in GE65 than in LT65 (76% vs 46%, respectively, p<0.001).

In multivariate analysis, factors associated with F2F3F4 were age at biopsy and age at infection.

The initial manifestation of HCV infection was most often a complication (jaundice, bleeding, ascites, liver cancer) in GE65 as compared to LT65 (14% vs 4%, p<0.001).

In multivariate analysis, 3 factors were associated with complications: age at diagnosis, alcohol consumption >50g/day and coinfection with HIV.

A total of 170 (19%) GE65 had received interferon and/or ribavirin (patients > 80 years, n=4); treatment was well tolerated (interruption of treatment: 20%; decrease of dose: 7%).

In 20 GE65 treated by PEG Interferon-Ribavirin, a sustained virologic response was obtained in 45% of cases.

In group 2, the prevalence of F2F3F4 estimated by FT was 73% in GE65 (1,121 of 1,529) vs 35% in LT65 (2,419 of 7,011; Armitage trend p<0.001).

The prevalence of moderate or severe necrosis (AT) was also higher, 39% vs 14%, respectively (p<0.001).

Cirrhosis was detected in 70% (94/148) of patients older than 80 yrs, 36% of patients between 65-80 and 14% of LT65 (p<0.001).

Despite the dramatic increase in fibrosis and necrosis prevalences in GE65, the prevalence of elevated ALT (greater than 50 IU/L) was similar between GE65 (53%) and LT65 (52%).

Among patients with F2F3F4, non-elevated ALT was observed in 41% of patients older than 80 years, 39% of those between 65-80 and 31% in LT65 (p<0.001); despite non-elevated ALT, cirrhosis was present in 36%, 30% and 27%, respectively (p=0.03).
 

The authors conclude, “In patients 65 years or older, chronic hepatitis C is more severe and presents with lower ALT levels than in younger patients. Treatment is effective and well tolerated. Biochemical markers such as FibroTest-ActiTest seem particularly useful as a non-invasive alternative to liver biopsy in this population.

 

11/10/03

Reference
D Thabut and others. HEPATITIS C IN 2,410 PATIENTS 65 YEARS OR OLDER. A SEVERE AND NEGLECTED CURABLE DISEASE? ABSTRACT 549 (POSTER). 54^th Annual Meeting of the American Association for the Study of Liver Diseases. October 24-28, 2003. Boston, MA.
 

Qualitative Tests (QLFTS) Detect Impaired Hepatic Function in a High Proportion of Patients with Chronic HCV and Fibrosis or Cirrhosis and May Predict Risk of Cirrhosis, Splenomegaly and Varices
 

Conventional clinical blood tests (bilirubin, albumin, prothrombin, platelets) are insensitive measures of hepatic function and do not adequately define risk for cirrhosis and portal hypertensive complications, such as varices. Liver biopsy may be inaccurate due to sampling variability.

Quantitative Tests (QLFTs) measure the liver’s ability to metabolize or extract test compounds, may identify patients with impaired hepatic function at earlier stages of disease, and possibly define risk for cirrhosis, splenomegaly, and varices.

Specific Study Aims:

1. Use 7 QLFTs to define hepatic impairment in patients with chronic hepatitis C and bridging fibrosis or compensated cirrhosis enrolled in the Hepatitis Antiviral Long-Term Treatment to Prevent Cirrhosis Trial (HALT C).
2. Compare test results between those with or without biopsy-proven cirrhosis, splenomegaly on ultrasonography, and varices at endoscopy.

Patients: The mean age of the 248 enrolled patients was 49.9 + 7.3 yr and 75% were male. Mean BMI was 29.6 + 5.3, 40% had cirrhosis, 60% had bridging fibrosis, 93% were infected with HCV genotype 1, and mean serum HCV RNA was 4.39 + 4.66 x 10⁶ copies/ml. 30% had platelet count < 140,000 /ul, 25% had albumin < 3.5 g/dl, 25% had INR > 1.1, 10% had bilirubin > 1.2 mg/dl, and 25% had AST:ALT > 1.

Analytical Methods: ¹³C-methionine (MBT), caffeine (Caf), antipyrine (AP), and 2,2,4,4-²H-cholate (CA) were taken orally and 24-¹³C-cholate, galactose (Gal), and lidocaine were administered intravenously. These compounds or their metabolites were measured from timed serial samples of blood, saliva, and breath using standard techniques.

Elimination rate (k_elim), volume of distribution (V_d), clearance (Cl), elimination capacity (Elim), and shunt were calculated from measured analytes. Perfused hepatic mass (PHM) was determined from SPECT liver scan. Mean test results were compared by T statistic and area under the receiver operator curve (ROC) by C statistic. Table results are ordered by T statistic for association with cirrhosis

PHM had the highest area under ROC with cirrhosis (C statistic .87), splenomegaly (C statistic .75), and varices (C statistic .832) and correlated best with platelet count, bilirubin, prothrombin time, and albumin.

Conclusions

QLFTs uncover hepatic impairment in a high proportion of fibrotic patients with chronic hepatitis C, and some tests, particularly CA Cl_oral, PHM, and CA_shunt, identify patients with chronic hepatitis C with cirrhosis, splenomegaly or varices.

Long-term followup, as planned in the HALT C trial, will determine whether hepatic impairment as defined by QLFTs predicts risk for clinical deterioration.

This study was supported by contracts from NIDDK and gifts from Metabolic Solutions and Roche Pharmaceuticals.

11/17/03

Reference
GT Everson and others. QUANTITATIVE TESTS (QLFTS) DETECT IMPAIRED HEPATIC FUNCTION IN A HIGH PROPORTION OF CHRONIC HEPATITIS C PATIENTS WITH FIBROSIS OR COMPENSATED CIRRHOSIS AND MAY PREDICT RISK OF CIRRHOSIS, SPLENOMEGALY, AND VARICES. Abstract 309 (poster). 54^th Annual Meeting of the American Association for the Study of Liver Diseases. October 24-28, 2003. Boston, MA.