Differences in HCV between Caucasians (C) and African Americans (AA) remain controversial. Previous studies have been limited by size and heterogeneity of the populations studied.

Although HCV is common in the Virginia Department of Corrections (DOC), the spectrum of liver disease in this setting has not been well characterized and offers a unique opportunity to compare the spectrum of liver disease between C and AA in a relatively homogeneous population.

The aim of this study was to describe the biochemical, virologic, and histologic spectrum of HCV in the DOC.

A retrospective analysis of consecutive inmates biopsied for chronic HCV between 10/98 and 7/02 was performed. All patients included were anti-HCV +, had a platelet count > 70,000, an INR < 1.4, and no evidence of hepatic decompensation.

Patients were excluded from analysis if they were HIV +, HBV SAg +, had evidence of other liver disease, or creatinine > 2.0 mg/dl. HCV RNA and genotyping (GT) were obtained at time of biopsy and liver histology assessed by Knodell histologic activity index (HAI) with histologically significant disease defined as total HAI > 4 or any degree of fibrosis and advanced disease as presence of bridging fibrosis (BF) or cirrhosis (Cx).

302 inmates meeting criteria were analyzed. The mean age was 41, 91% were male, and 51% C. The mean ALT was 94 U/l and 49% had a normal ALT at the time of biopsy. HCV RNA was + in all tested and 80% were GT 1.

The total HAI was 7.03: 85% had significant hepatitis and 24% had advanced fibrosis. When stratified by race, AA were more likely GT 1 (94% vs 67%; p<.001) and have lower ALT (79 U/l vs 106 U/l; p=.01) with similar overall HAI (6.99 vs 7.59; p=.09) compared to C.

While AA had slightly lower fibrosis scores, there were no differences in % advanced fibrosis (22 vs 28). Those with mild disease (HAI < 5) had lower ALT values and higher % with normal ALT (70 vs 46; p=.004) compared to those with significant disease.

The sensitivity, specificity, positive and negative predictive values for a normal ALT to predict mild disease were 70%, 53%, 22% and 90% and for an elevated ALT to predict significant histology were 90%, 21%, 53%, and 69%, respectively.

Conclusions: Significant hepatitis is seen in the majority of inmates with HCV and 24% have advanced fibrosis. There were no clinically significant differences between C and AA.

Because ALT had poor accuracy, liver biopsy is essential to identify those with significant or advanced histopathology that might benefit from anti-HCV therapy.

05/28/03

Reference
RK Sterling and others. Comparison of Hepatitis C Virus (HCV)-related Liver Disease Between Caucasians (C) and African Americans (AA): Analysis of HCV in the Virginia Department of Corrections (DOC). Abstract 252 (oral). Abstracts of Digestive Disease Week 2003. May 17-22, 2003. Orlando, FL, USA.

Multiple studies have shown that individuals with severe mental illness are at increased risk for acquiring HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV). In addition, patients with chronic HCV infection are at risk for fulminant hepatitis from acquired infection with hepatitis A virus (HAV) or HBV.

There are limited data on the prevalence of HIV, HAV, and HBV in chronically hospitalized US psychiatric patients without mental retardation who are HCV positive. To address this issue, a comprehensive screening program was started at Oregon State Hospital (Salem, Ore.) beginning in 1999.

The computerized records of all non geriatric adult inpatients at Oregon State Hospital on April 23, 2001, were reviewed to assess physician compliance with screening and the prevalence of infection with HIV, HAV, HBV, and HCV.

Among the 535 patient records reviewed, 94.8% of patients were screened for HCV, of whom 20.3% were HCV positive. Among HCV positive patients, only 1.9% were not screened for HAV and HBV, but 23.3% were not tested for HIV. In the HCV positive group, 35.9% were HAV-positive, 49.5% HBV-positive, and 2.6% HIV-positive.

The authors conclude, “Chronic psychiatric inpatients have high HCV prevalence rates. Hepatitis C-seropositive individuals may be at risk for complications unless vaccinated for HAV and HBV.”

University of California, San Diego, and San Diego VAMC.

05/28/03

Reference
JM Meyer. Prevalence of Hepatitis A, Hepatitis B, and HIV Among Hepatitis C-Seropositive State Hospital Patients: Results From Oregon State Hospital. Journal of Clinical Psychiatry 64(5): 540-545. May 2003

Senators Kay Bailey Hutchison and Edward Kennedy today filed The Hepatitis C Epidemic Control and Prevention Act (S-1143), announced the National Hepatitis C Advocacy Council (NHCAC). This is the first federal response to the hepatitis C epidemic, the most common blood-borne viral infection in the United States.

An estimated four million Americans are currently infected with the hepatitis C virus (HCV). HCV yearly costs are already at an alarming $15 billion dollars. That figure is expected to skyrocket to $26 billion by 2021.

Hepatitis C threatens the health of millions of Americans. NHCAC has worked to educate federal and state governments about the seriousness and magnitude of the hepatitis C epidemic. Approximately 85 percent of those who contract HCV remain infected for life, and an estimated 15,000 die each year. The annual death toll is expected to triple by 2010. There is currently no vaccine to prevent HCV infection.

The Hepatitis C Epidemic Control and Prevention Act is groundbreaking legislation. It will establish a comprehensive program for HCV public awareness campaigns, screening and counseling, early detection, professional education, and research. The program will be administered by the Department of Health and Human Services. State and local hepatitis C agencies will be supported to implement program activities.

The National Hepatitis C Advocacy Council is comprised of 22 hepatitis C groups from across the United States. NHCAC President Lorren Sandt commented: "This is a major step in achieving a key goal of NHCAC: increasing financial and infrastructure support for the delivery of hepatitis C prevention, education, and patient care services at a level commensurate with the impact of this disease. Chronic hepatitis C is completely preventable with sound public health policy in place."

NHCAC Government Affairs Chairperson Sharon Phillips added: "For the first time, we have a bill that will work for the millions of infected Americans. We congratulate Senators Hutchison and Kennedy for taking action now with S-1143 and providing the resources necessary to address this previously unfunded epidemic."

Cosponsors of this bipartisan bill include Senators Daschle (D-SD), Biden (D-DE), Smith, (R-OR), Johnson, (D-SD), Bingaman (D-NM), Breaux (D-LA), Campbell (R-CO), Clinton (D-NY), Cornyn (R-TX), Dodd (D-CT), Jeffords (I-VT), and Schumer (D-NY). A companion bill will be introduced in the House in the next few weeks.
 
Contacts
   
National Hepatitis C Advocacy Council
Lorren Sandt, 877/737-4372
Andi Thomas, 954/931-8463
Sharon Phillips, 903/235-0408

Source
Business Wire. May 23, 2003

Daily Interferon Plus Ribavirin Is More Effective Than Three Times Weekly Dosing in Genotype 1 HCV Patients But Not in Those with Genotype 2 and 3
 

The current standard of care for treatment of chronic hepatitis C is peginterferon injection once weekly plus ribavirin taken orally twice daily. In the use of standard interferon, 3 times weekly injections (plus oral ribavirin twice daily) are FDA-approved.

The aims of the present study were:

1)  To determine the sustained virologic response to IFN alfa-2b (3 MU TIW) and RBV for 48 weeks in veterans with chronic HCV,

2)  To evaluate whether 3 MU of daily IFN in combination with RBV for 24 weeks is superior to standard combination therapy; and

3)  To determine the impact of HCV therapy on health-related quality of life (HRQOL).

158 IFN naive patients from 11 VA Medical Centers were randomized to receive either 3 MU of IFN alfa-2b QD plus RBV (1000 - 1200 mg/d) for 24 weeks (daily therapy group) or 3 MU of IFN alfa-2b TIW plus RBV (1000 - 1200 mg/d) for 24 weeks (genotype 2 & 3) or 48 weeks (genotype 1) (standard therapy group). HRQOL was measured using the Hepatitis QOL Questionnaire.

The proportion of patients with genotype 1 (78.2% vs. 80.0%), number of patients with cirrhosis (10.3% vs. 10.0%), mean HCV viral load (1.8 vs. 2.0 x 10⁶ copies/ml, and proportion of African American patients (26.9% vs. 35.0%) did not differ significantly.

The virologic response rates at the end of treatment in the daily IFN group were higher than in the standard group for all genotypes (46.2% vs. 23.8%, P = 0.003) and for those with genotype 1 (37.7% vs. 12.5%), but did not differ for those with genotype 2 and 3 (76.5% vs. 68.8%).

Similarly, the sustained virologic response rates 24 weeks after treatment in the daily IFN group were higher than in the standard group for all genotypes (30.8% vs. 16.3%) and for those with genotype 1 (19.7% vs. 6.3%), but did not differ for those with genotype 2 and 3 (70.6% vs. 56.3%).

The proportion of patients who completed therapy did not differ between groups (82.1% vs. 80.0%). Both daily and standard therapies were associated with significant improvements in several domains of HRQOL.

Conclusions: The sustained virologic response to IFN alfa-2b 3 MU TIW and RBV in veterans with chronic HCV is lower than the response rates reported in non-veterans.

Daily administration of 3 MU of IFN alfa-2b in combination with RBV for 24 weeks is superior to standard IFN alfa-2b 3 MU TIW and RBV for 48 weeks in veterans with genotype 1.

In contrast, daily therapy was no better than standard therapy for patients with genotype 2 and 3. In our patient population, treatment with combination therapy was associated with significant improvements in HRQOL.

05/28/03

Reference
EJ Bini and others. Efficacy of Daily Interferon in Combination with Ribavirin in Patients with Chronic Hepatitis C: Final Results of A VA Multicenter Study.  Abstract T1219 (poster). Abstracts of Digestive Disease Week 2003. May 17-22, 2003. Orlando, FL, USA.
 

African Americans and Asians with Cirrhosis Have Higher Risk for Liver Cancer
 

The incidence of hepatitis C cirrhosis (HCC) is rising in the US with HCV infection accounting for one-third of the cases. Early detection with screening may offer the best hope for treatment and improved survival.

Identifying high-risk patients is an essential requirement for a cost-effective screening program. No study to date has examined race as a potential risk factor for HCC in a diverse U.S. population with HCV cirrhosis.

In this study, researchers performed a hospital-based, clinic-based case-control study of 507 patients with HCV cirrhosis at 4 study centers using pathology records, ICD-9 diagnosis, and patient visits to the study centers. Hepatitis B carriers and patients with chronic hepatitis B, HIV or other malignancies were not included in this study.

Cases were confirmed by cytology, histology and/or by the presence of focal hypervascular hepatic mass (on biphasic CT, MRI and/or angiogram) and elevated AFP. HCC was ruled out in controls by negative AFP and imaging studies. Multivariate logistic regression was employed to examine associations between HCC and race. Adjustment was made for age, gender, severity of liver disease (MELD score, Child class), moderate-to-heavy alcohol use, and study centers. For all variables, values at diagnosis were obtained for HCC cases and at first negative AFP and x-ray for controls.

The investigators identified 205 HCC cases and 264 controls without HCC. Thirty-eight patients could not be classified as cases or controls based on above criteria and were excluded.

HCC patients were significantly older (median age=59 vs. 52, p < 0.001), more likely to be male (84% vs. 71%, p=0.001), more likely to be Child class C (57% vs. 43%, p=0.001), and had slightly higher MELD score (median MELD=11 versus 10, p=0.05).

There was no significant association between alcohol use or Hispanic race (n=66) and HCC compared with Caucasian (n=274). After adjustment was made for age, gender, MELD score, Child class, moderate-to-heavy alcohol use, and study centers, multivariate OR was 3.0 for African Americans (n=38, p=0.003) and 5.7 for Asians (n=83, p<0.0001) as predictors for HCC.

The authors conclude, “African Americans and Asians with HCV cirrhosis may have 3 and 6 times higher risk for HCC as compared to their Caucasian counterparts - independent of age, gender, severity of liver disease, and alcohol use.

“Genetic study of liver cancer in a racially diverse population should be carried out, and high-risk ethnic patients may be among those with HCV cirrhosis who would benefit the most from HCC screening.“

05/28/03

Reference
H Mindie and others. Racial Differences in Risk for Liver Cancer in Patients with Hepatitis C Cirrhosis: A Multicenter Case-Control Study. Abstract 121 (oral). Abstracts of Digestive Disease Week 2003. May 17-22, 2003. Orlando, FL, USA.

African Americans Failing Treatment with Interferon Monotherapy Are Less Likely to Achieve Sustained Response to Subsequent Retreatments Compared to Caucasians
 

African Americans (AA) are less likely to respond to interferon (IFN)-based therapies than Caucasians (Cau).

The objective of this study was to determine and compare the sustained virological response (SR) rates in AA and Cau who received 3 courses of IFN-based therapy for chronic hepatitis C (CHC). SR was defined as undetectable HCV RNA 6 months after the end-of- treatment.

This was a retrospective study. Patients who received IFN monotherapy and those who were subsequently treated with one or two courses of combination therapy were identified. The SR rate was determined for each consecutive treatment and the results were compared between AA and Cau. Variables affecting treatment outcome, such as genotype and 12-week HCV RNA levels, when available, were analyzed.

234 patients (AA=140; Cau=94) received IFN monotherapy. Race was a significant predictor of SR to monotherapy in patients who completed this treatment, 7 (5%) AA, 9 (10%) Cau.

Genotype was available for 117 AA (type 1=106; type non-1=11) and for 79 Cau (type 1=61; non-1=18). Only 1 (1%) AA with type 1 had a SR compared with 5 (45%) AA with non-1.

Genotype was not a predictor of SR in Cau. One hundred patients (AA=58; Cau=42) received a second treatment with a combination of IFN alpha-2b and modified weight-based ribavirin.

Race again was a significant predictor of SR, 6 (10%) AA, 18 (43%) Cau. Genotype was available for 43 AA (type 1=40; non-1=3) and for 36 Cau (type 1=29; non-1=7).

Genotype was a predictor of SR in both AA and Cau. Three (8%) AA with genotype 1 and 3(100%) AA with non-1 genotype had a SR. Nine (33%) Cau with genotype 1 and 6 (86%) with non-1 genotype had a SR.

Negative PCR for HCV RNA at 12 weeks of treatment was a significant predictor of SR in both AA and Cau. All AA and Cau who achieved SR had undetectable levels of HCV RNA at 12 weeks. Twenty-six patients (18 AA and 8 Cau) received a third course of treatment with pegylated-IFN (PEG-IFN) alpha-2b and ribavirin of varying dose and schedule.

Only 1 Cau achieved SR, 2 patients (1 AA, 1 Cau) had an end-of- treatment response, SR results are pending.

Conclusions: AA have a significantly lower rate of SR to all IFN-based therapies than Cau. Although combination therapy with IFN alpha-2b and ribavirin modestly improves SR rate, retreatment with PEG-IFN and ribavirin of AA failing combination therapy does not appear to be effective.

05/30-03

Reference
I Zalewska. African Americans Failing Treatment with Interferon Monotherapy for Chronic Hepatitis C Are Less Likely to Achieve Sustained Response to Subsequent Retreatments Compared to Caucasians. Abstract T1278 (poster). Abstracts of Digestive Disease Week 2003. May 17-22, 2003. Orlando, FL, USA.

Racial Makeup of Patients Determines Response Rates to HCV Treatments
 

Researchers have noted in their practice that Afro-American patients treated with Interferon/Ribavarin or PEG/Ribavarin combination therapy seem to have sustained clearance of hepatitis C virus at a lower rate than Caucasian patients.

In this study, the investigators sought to determine the viral clearance rate of Hepatitis C virus in patients with chronic hepatitis C treated with Interferon/Ribavirin or PEG/Ribavirin combination based on racial makeup.

This study is a retrospective review of 287 patients with documented hepatitis C (PCR positive) who were treated with Interferon/Ribavirin or PEG/Ribavirin combination therapy. There were 170 Caucasians, 32 Hispanic and 85 Afro-American patients. The percentage of patients with sustained clearance of the virus for six months post-treatment was calculated for each racial group.

7% of Afro-American patients cleared the virus. 28% of Hispanic patients cleared the virus. 42% of Caucasian patients cleared the virus. The difference in clearance rates of the virus between Afro-Americans and Caucasians was highly significant with the p < 0.0001.

The difference in clearance rates between Caucasians and Hispanics was significant with p < 0.04.

The difference in clearance rates between Afro-Americans and Hispanics was significant with p < 0.02.

Conclusion: Afro-American patients with chronic hepatitis C showed a significantly lower sustained clearance rate to Interferon/Ribavirin or PEG/Ribavirin combination therapy than Caucasian or Hispanic patients.

05/30/03

Reference
BJ Levitt and others. Differential Response Rates to Clearance of Hepatitis C Virus in Chronic Hepatitis C, Based on Racial Makeup of Patients Treated With Interferon/Ribavirin (I/R) or Peg/Ribavirin (Peg/R) Combination. Abstract T1286 (poster). Abstracts of Digestive Disease Week 2003. May 17-22, 2003. Orlando, FL, USA.

A Trial of Peginterferon Alfa in Active Ulcerative Colitis
 

Uncontrolled pilot studies of interferon-alfa suggest a high remission rate in the treatment of active ulcerative colitis. The aim of this study was to evaluate safety and the role in induction of remission of pegylated interferon-alpha (PegIFN) in patients with active ulcerative colitis by a multicenter placebo-controlled trial.

Patients with a CAI > 6 were randomized to receive either placebo, 0.5 microgram/kg or 1.0 microgram/kg body weight pegylated interferon-alfa (PEG-Intron) once weekly during a twelve week treatment period. Patients receiving either mesalazine (48/60), steroids (20/60) and/or azathioprine (8/60) in stable dosages were included. Clinical remission was defined as a CAI < 6.

Sixty patients entered the study (20 placebo, 19 in the 0.5 microgram/ kg and 21 at the 1.0 microgram/kg group PegIFN). The clinical remission rate at week +12 of treatment was highest at the 0.5 microgram/kg group (11/19; 58 %), whereas remission rates were similar in placebo-treated patients (40%) and in the 1.0 microgram/kg group of PegIFN (38%).

The drop-out rate altogether was 45% with the highest rate in placebo-treated (11/20, lack of efficacy) and in the 1.0 microgram/kg group (8/21, adverse events). Side effects were not observed in the 0.5 microgram/kg group of PegIFN. Clinical improvement at week +12 was accompanied by endoscopic remission in more than 60% of the patients.

The authors conclude, “ A low dose of Peg IFN is safe in patients with ulcerative colitis and showed tendency towards efficacy. Larger trials are needed to establish its potential role in the treatment of this disorder.”

05/30/03

Reference
H Tilg and others. A Randomized Placebo-Controlled Trial of Pegylated Interferon Alpha in Active Ulcerative Colitis. Abstract 472 (oral). Abstracts of Digestive Disease Week 2003. May 17-22, 2003. Orlando, FL, USA.

The Impact of Diabetes on Chronic Hepatitis C
 

Data from the NHANES III trial has suggested that type 2 diabetes (DM) is more prevalent in patients with chronic hepatitis C (Ann Intern Med 2000;133:592-9). In this study, researchers sought to describe clinical features of patients with chronic hepatitis C (CHC) and DM and to determine the impact of DM on the natural history of CHC and its treatment.

The researchers performed a retrospective case control study of 60 patients with CHC and DM and 60 controls with HCV alone who were matched for age, gender, race, genotype, and treatment status. Comparisons were made of BMI, liver histology, fibrosis progression rates, and response to antiviral therapy. We also assessed the effect of antiviral therapy on DM management.

Although there were more overweight patients (BMI > or = 25) in the CHC and DM group (83% vs. 53%, p=0.02), the average BMI was similar in the 2 groups (28.3 vs. 26.1, p= 0.09). Forty-nine of the diabetics and 53 controls had liver biopsy. Patients with CHC and DM were more likely to have advanced fibrosis on liver biopsy (Metavir stage 3&4) than controls (61% vs. 28%, p= 0.04).

Steatosis was also more common in the CHC and DM group when compared with controls (65% vs. 40%, p=0.8) although this difference was not statistically significant. The severity of steatosis was similar in both groups. Of the 79 patients with a known estimated duration of infection, CHC and DM patients had significantly higher overall fibrosis progression rates than controls. Even in the absence of steatosis, patients with CHC and DM had higher fibrosis progression rates than patients without DM.

CHC and DM patients had lower overall SVR rates to CHC treatment than controls, although this difference disappeared when response rates to PEGIFN/RBV were looked at alone (33% vs. 31%).

While on CHC treatment, 37% (13/35) of CHC and DM patients required changes in their DM management. These changes included new diagnosis of DM (n=3), the addition of a new oral hypoglycemic agent (OHA; n=3), an increase in OHA or insulin dose (n=5), and change from OHA to insulin while on therapy (n=2).

The authors concluded the following:

(1)      Patients with CHC and DM are heavier than those without DM;

(2)      Patients with DM have more steatosis and significantly more fibrosis on liver biopsy when compared with controls;

(3)      Patients with DM have significantly higher fibrosis progression rates even in the absence of steatosis;

(4)      Changes in DM management while on CHC treatment are common;

(5)      Further studies on this population are warranted.

05/30/03

Reference
F Ahmed and others. Impact of Diabetes on Chronic Hepatitis C. Abstract M1416 (poster). Abstracts of Digestive Disease Week 2003. May 17-22, 2003. Orlando, FL, USA

A Cryocrit Cutoff of 2% Best Predicts Outcome After Liver Transplantation for Hepatitis C
 

The rapid recurrence of severe hepatitis C viral (HCV) hepatitis after liver transplantation remains a major problem. Currently, there are no known predictors of rapid recurrence of HCV disease.

Because of the poor outcome observed in patients with cryoglobulinemia (cryo), we have evaluated the effect of cryo on graft survival, severe activity, and severe fibrosis after transplantation and have looked at various cutoffs for defining a cryocrit as positive.

Using their longitudinal database, researchers analyzed survival for all recipients of liver transplants for cirrhosis due to HCV (1991 onward) based on the presence or absence of cryo.

All liver transplant biopsies were analyzed (in a blinded fashion) and activity and fibrosis were graded using the Ludwigs scale. Severe activity was defined as moderate (or worse activity, including fibrosing cholestatic hepatitis) and severe fibrosis was defined as bridging fibrosis or cirrhosis.

Graft survival, and survival until the onset of severe activity and fibrosis were determined using Kaplan Meier estimates. Survival analysis was performed for the entire population and after excluding patients who died or lost their grafts for reasons other than recurrent HCV.

The log rank test was used to compare survival and Cox multivariate analysis was used to determine relative risks (RR).

Results are noted in the table below:

Conclusions: Liver transplant recipients with cryoglobulinemia are at greater risk for graft loss, severe early activity, and severe early fibrosis. Using a cryocrit cutoff of 2% increases the apparent deleterious effect of cryoglobulinemia and provides the strongest indication of those at increased risk.

05/30/03

Reference
SC Rayhill and others. A Cryocrit Cutoff of 2% Best Predicts Outcome After Liver Transplantation for Hepatitis C. Abstract 52 (poster). Abstracts of Digestive Disease Week 2003. May 17-22, 2003. Orlando, FL, USA.