Prevalence of Chronic Renal Insufficiency is Increased in Patients with Chronic Hepatitis C

Sorin Petre, Vijayan Balan, Jose Hernandez, Marek Mazur, Raymond Heilman, Mankanwal Sachdev, Hugo Vargas., Thomas Byrne, M. Edwyn Harrison, David Douglas, Marianne Rosati, Jane Hart, Jorge Rakela



The prevalence of chronic hepatitis C (CHC) in patients with predialysis chronic renal failure has been estimated to be 20%. However the prevalence of chronic renal insufficiency (CRI) in patients with CHC remains unknown. Renal insufficiency in CHC patients may lead to a higher incidence of complications of HCV treatment and may prevent optimal treatment.



The aim of this study is to determine the prevalence of CRI in patients with CHC and to describe the severity of the kidney impairment as defined by the National Kidney Foundation and Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines.



Review of consecutive CHC patients seen at least once in our clinic from July 2000 to August 2003. Creatinine clearance was calculated using Cockroft-Gault formula and patients were categorized according to severity of kidney dysfunction as follows: stage 1 - GFR (glomerular filtration rate -expressed in ml/min/1.73m2)- > 90 and proteinuria; stage 2 - GFR between 60 and 80; stage 3 - GFR 30-59; stage 4 - GFR 15-29; stage 5 - GFR < 15 or on hemodialysis or peritoneodialysis. Hepatic chemistries, CBC and liver synthetic function markers were recorded for each patient.



831 patients were evaluated during the study period. Of these 522 patients had data to determine creatinine clearance and 170/531 (32%) were found to have renal impairment. The degree of CRI was as follows: stage 1 -(5%); stage 2 - (33%; stage 3 - 30/170 (17.64%); stage 4 - 2/170 (1.17%); and stage 5 - 38/170 (22.35 %). The prevalence of cirrhosis was similar in all groups (normal 14%, stage 1-67%, stage 2-5%, stage 3-33%, stage 4-0%, stage 5-7% p=NS. Serum hemoglobin, AST and albumin were significantly lower in patients with stage 5 disease. Other laboratory tests were similar in all groups. The etiology of CRI in 38 patients with end stage kidney disease were: 3 - cryoglobulinemia, 5 - glomerulonephritis, 23 - diabetes and/or hypertension, 3 - reflux nephropathy, 3 - polycystic kidney disease and 1- mixed connective tissue disease.



The prevalence of CRI in our large series of chronic hepatitis C patients is 30-49. The presence of cirrhosis was not associated with the degree of CRI in our series. In CHC patients, serum creatinine alone cannot reliably identify those with CRI. Hepatitis C patients should be more rigorously be screened for renal insufficiency due to the high prevalence of kidney impairment which may lead to a higher incidence of complications of hepatitis C treatment.


Prevalence of Hepatitis C Infection in Veterans: Results of VA Cooperative Study #488

Jason A. Dominitz, Edward J. Boyko, Thomas D. Koepsell, Patrick J. Heagerty, Charles Maynard, Jennifer L. Sporleder, VA Cooperative Study #488 Investigators



Several studies have suggested that the prevalence of hepatitis C virus (HCV) infection is higher in veterans than in the general population, possibly related to military exposures.



To estimate the prevalence of anti-HCV antibody and to determine the risk factors for infection among randomly selected users of Veterans Health Administration (VA) medical centers.


Using a population-based, two-staged cluster sample and cross-sectional design, veterans were selected at random from 20 randomly selected VA medical centers with 200 Vietnam Era Veterans. 1288 of 3863 veterans who had used one of the 20 VA facilities participated. Non-participants either refused (n=1139), could not be contacted despite extensive efforts (n=1325), died (n=73) or could not have blood drawn (n=38). Adjustment for non-participation bias was performed using demographic and clinical data in VA databases. HCV serostatus was determined by EIA with RIBA confirmation.


The prevalence of anti-HCV antibody among serology participants was 4.0 per 100 (95% confidence interval (CI) 2.6-5.5). The estimated prevalence in the full population of VA users was 5.4 per 100 (95% CI 3.3-7.5) after adjustment for sociodemographic and clinical characteristics known to differ between participants and non-participants. Significant predictors of HCV included demographic factors (age, marital status, lower income); period of military service, prior diagnoses (drug and alcohol use, cirrhosis, mental illness, prior diagnosis of hepatitis C or B); health care utilization (greater clinic visit and hospitalization frequency, liver biopsy, liver transplantation, hemodialysis, prior testing for hepatitis C or HIV, air injection vaccination); and lifestyle factors (drug use, tattoos, body piercing, high risk sexual behavior, incarceration for more than 48 hours, and homelessness). Using logistic regression to adjust for injection drug use and non-participation, the odds of seropositivity were increased with prior testing for HCV and HIV, tattoos, and incarceration for 48 or more hours. 63% of all subjects and 100% of those seropositive for HCV reported blood transfusions, intravenous drug use, drug snorting, tattoos, incarceration, or >15 sexual partners.



The prevalence of HCV in this population exceeds the estimate from the general United States population, likely reflecting more exposure to HCV risk factors among veterans that use VA facilities. Infections in this population are associated with risk factors found in non-veteran populations.


In addition the investigator, Jason A. Dominitz, stated that the VA system should start to prepare for the increasing burden of care since HCV positive patients will progress on to more serious disease progression over time.


Hepatitis C Infection and Hepatic Steatosis: Fibrosis is not Forged in the Flame of Fat

Ponni Perumalswami, David Kleiner, Glen A. Lutchman, Theo Heller, Bahman Bozorg, Yoon Park, T. Jake Liang, Marc Ghany, Jay Hoofnagle



Fibrosis progression is the best predictor of long-term outcome in CHC. Hepatic steatosis is a frequent histologic finding in CHC and was recently reported to be an independent factor associated with progression of hepatic fibrosis. However this finding is controversial. Longitudinal studies of untreated patients may help resolve the issue.



To evaluate the clinical correlates of hepatic steatosis and to determine whether hepatic steatosis is associated with fibrosis progression in a large cohort of untreated CHC pts with paired liver biopsies (LBx).



A computer NIH database was searched from 1980 to 2003 for all pts with a diagnosis of CHC and an adequate LBx. Pts.charts were reviewed and the following clinical information was recorded: age at biopsy, sex, race, weight, height, BMI, LFT's, cholesterol, triglycerides (TG), ETOH use, presence of DM and viral genotype. Pts with HIV and other chronic liver diseases were excluded. All LBx were read under code by a single hepatopathologist using the Knodell HAI scale to score necroinflammation and Ishak scale for fibrosis. Hepatic steatosis was graded as none, <5%, 5-25%, 25-50%, 50-75% and 75-100%. These were grouped as none, mild (<25%) and moderate to severe (>25%). ANOVA controlling for degree of fibrosis was used to analyze correlations with steatosis. Multivariate regression analysis was used to identify factors associated with steatosis and fibrosis progression.



720 pts were identified of whom 494 pts met study criteria. Mean age at biopsy was 44+/- 9.8 years, 60% were male, 80% Caucasian and 50% had genotype 1. Mean HAI and Ishak scores were 8.3 and 2.3 respectively. Age, sex, weight, BMI, ALKP, ALT, AST, TG, HAI and Ishak score were significantly associated with steatosis but not DM and ETOH. In multivariate analysis, only age, BMI and ALT were associated with steatosis. To assess whether steatosis affected progression of fibrosis, we analyzed 140 pts. with paired Lbx without intervening therapy. Mean duration between biopsies was 44.4 months. Older age at biopsy, periportal inflammation, Ishak score, and ALT were independently associated with fibrosis progression. There was no correlation between change in steatosis grade and change in fibrosis score between biopsies (p=.75).



Hepatic steatosis in CHC appears to be associated with altered metabolic indices. Although hepatic steatosis is associated with hepatic fibrosis it does not predict fibrosis progression in pts with CHC.

Metabolic Syndrome and Microalbuminuria in Individuals with Hepatitis C

Suthat Liangpunsakul, Raj Vuppalanchi, Naga Chalasani


Background & Aims

While the strong association between hepatitis C and type 2-diabetes and insulin resistance is established, it is unclear if individuals with hepatitis C have higher prevalence of metabolic syndrome. Microalbuminuria is associated with diabetes, insulin resistance and metabolic syndrome, and predicts progressive renal disease as well as cardiovascular morbidity and mortality. As individuals with hepatitis C have higher prevalence of diabetes and insulin resistance, it is possible that they may have higher prevalence of microalbuminuria. However, this hypothesis has not been tested. Therefore, we conducted a large population-based case-control study by using a representative sample of the general population of the United States through the NHANES III to test the hypothesis that non-diabetic persons with HCV have an increased risk of metabolic syndrome and microalbuminuria.



Study cohort consisted of 15,336 US adults who had hepatitis C antibody measured as part of NHANES III. The presence of the metabolic syndrome was determined by the ATP III criteria. Individuals with urine albumin levels between 30 to 300 g per mg creatinine were considered to have microalbuminuria. The prevalence of metabolic syndrome and microalbuminuria were compared between individuals with HCV and controls. Hepatitis C group consisted of individuals with a detectable anti-HCV antibody in the absence of significant alcohol consumption, hepatitis B or iron overload. The control group consisted of age, gender, race and BMI-matched individuals with normal ALT (≤ 40 U/L) and no evidence for HCV, HBV, iron overload or significant alcohol consumption. Univariate and multivariate analyses were conducted to explore the association between metabolic syndrome, microalbuminuria, and hepatitis C infection.



The study cohort consisted of 362 subjects with HCV and 995 matched controls. As expected, the prevalence of diabetes and insulin resistance was significantly higher in hepatitis C than the controls. Compared to the controls, individuals in the HCV group had a significantly higher prevalence of microalbuminuria but not metabolic syndrome. HCV was an independent risk factor for microalbuminuria. In the multivariate analysis, older age and being African-American were independently associated with microalbuminuria in HCV.



Hepatitis C is independently associated with microalbuminuria but not the metabolic syndrome. African-Americans with hepatitis C are at significantly higher risk to have microalbuminuria. More research is needed to examine the significance of these findings.