Maria Lucia G. Ferraz

Historical epidemiology of hepatitis C virus (HCV) in selected countries

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6 358 000 cases in 2008 and Brazil with 2 106 000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV‐infected populations are critical for addressing HCV‐related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

Strategies to manage hepatitis C virus (HCV) disease burden

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV‐related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3–5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

Noninvasive serum markers in the diagnosis of structural liver damage in chronic hepatitis C virus infection.

Abstract: Aim: Several noninvasive markers are being used to assess the structural liver damage in patients with chronic hepatitis C (CHC). We evaluated the capacity of serum hyaluronic acid (HA), aspartate aminotransferase (AST)/ALT ratio, the AST to platelet ratio index (APRI) and γ‐glutamyltransferase (GGT) levels to predict the intensity of hepatic fibrosis in patients with CHC.

Simple blood tests as noninvasive markers of liver fibrosis in hemodialysis patients with chronic hepatitis C virus infection.

HCV infection is common among patients with end‐stage renal disease (ESRD) on hemodialysis, and it has been considered an independent risk factor for mortality in this setting. Although liver biopsy in ESRD patients with HCV infection is useful before kidney transplantation, it carries a high risk of complications. We sought to assess the diagnostic value of noninvasive markers to stage liver fibrosis in 203 ESRD HCV‐infected patients. Univariate and multivariate analysis were used to identify variables associated with significant fibrosis (METAVIR F2, F3, or F4 stages). Significant liver fibrosis was observed in 48 patients (24%). Logistic regression analysis identified AST and platelet count as independent predictors of significant fibrosis (P < 0.001 and P = 0.001, respectively). The area under the receiver operating characteristic curve of the AST to platelet ratio index (APRI) for predicting significant fibrosis was 0.801. An APRI < 0.40 accurately identified patients with fibrosis stage 0 or 1 in 93% of the cases (NPV = 93%), and all misclassified subjects were F2. A cutoff ≥ 0.95 to confirm significant fibrosis had a PPV of 66%. If biopsy indication was restricted to APRI scores in the intermediate range (≥0.40 and < 0.95), 52% of liver biopsies could have been correctly avoided. Conclusion: Stage of liver fibrosis can be reliably predicted in ESRD HCV‐infected subjects by simple and widely available blood tests such as AST levels and platelet count. These tests might obviate the requirement for a liver biopsy in a significant proportion of those patients. (HEPATOLOGY 2007.)

High prevalence of hepatitis C infection in a Brazilian prison: identification of risk factors for infection

Hepatitis C virus (HCV) causes infectious hepatitis worldwide. It is transmitted mainly by blood products and sharing of intravenous paraphernalia during illicit drug use. High prevalence rates have been described among specific groups considered to be at higher risk for HCV infection, including prison inmates. The objectives of this study were: to determine the HCV seroprevalence among inmates of Casa de Detenção de São Paulo; to identify risk factors for HCV infection; and to compare the seroprevalence of HCV to other blood borne or sexually transmitted diseases. From December, 1993, to January, 1994, a total of 779 inmates were interviewed to collect information on sociodemographic status, sexual behavior, and past experience with illicit drugs. Blood samples were obtained from 756 inmates for serological tests. 310 (41%) blood samples were positive for anti-HCV, 425 (56.2%) were negative, and 21 (2.8%) showed indeterminate results. In this population, we found a seroprevalence of 13.7% for HIV, 3.3% for syphilis (VDRL), and 68.1% for hepatitis B virus previous infection. Four variables were each identified as associated with a positive anti-HCV serologic test: a positive VDRL (OR = 2.63 IC 95% 1.08 to 6.36); a time of current imprisonment longer than 130 months (OR = 2.44 IC 95% 1.04 to 5.71); previous incarceration at Casa de Detenção de São Paulo (OR = 1.73 IC 95% 1.19 to 2.52) and; illicit drug use before admission to the Casa de Detenção de São Paulo (OR = 1.64 IC 95% 1.15 to 2.33). The seroprevalence of HCV antibodies among the study population was high (41%), indeed, one of the highest clusters of HCV infection recorded until now. Four variables were each shown to be associated with HCV infection. The simultaneous presence of these 4 variables is associated with an 82% probability of being anti-HCV positive. Although risk factor analysis indicates most HCV infections occur prior to inprisonment, initiation of control measures to prevent continued transmission after incarceration should be done.

Efficacy and tolerance of interferon-alpha in the treatment of chronic Hepatitis C in end-stage renal disease patients on hemodialysis

Abstract: Background: Patients with end‐stage renal disease (ESRD) show a high prevalence of hepatitis C, with a negative impact on the survival on hemodialysis and after renal transplantation. We evaluated the efficacy and tolerance of interferon‐α (IFN‐α) in HCV‐infected ESRD patients on dialysis.

Optimized cutoffs improve performance of the aspartate aminotransferase to platelet ratio index for predicting significant liver fibrosis in human immunodeficiency virus/hepatitis C virus co‐infection

Aim: To assess the diagnostic value of modified cutoffs for aspartate aminotransferase to platelet ratio index (APRI) to predict significant liver fibrosis in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) patients.

Iron overload in patients with chronic hepatitis C virus infection: clinical and histological study.

Background:  Recently it has been found that iron is an important element in the natural history of hepatitis C. Serum markers of iron stores are frequently increased in chronic hepatitis C virus (HCV)‐infected carriers but the real impact of the hepatic iron overload is poorly understood. The purpose of the present paper was to determine the prevalence of iron overload and to study the relationship between hepatic iron concentration (HIC) and clinical, biochemical and histological characteristics in chronic HCV‐infected carriers.

Longitudinal Study of a Human Drug-Induced Model of Autoantibody to Cytoplasmic Rods/Rings following HCV Therapy with Ribavirin and Interferon-α

Background A novel pattern in the indirect immunofluorescence antinuclear antibody assay on HEp-2 cells (IIF-HEp-2) characterized by cytoplasmic rods and rings (RR) was reported in HCV patients, but stringent disease specificity studies and longitudinal analysis are lacking. We investigated the clinical significance of anti-RR in an HCV cohort with up to a 12-month treatment follow up. Methodology/Results 597 patients (342 HCV, 55 HCV/HIV, 200 non-HCV) were screened and titered for anti-RR. Serial samples were available from 78 of 176 treated and 27 of 166 untreated patients. Anti-RR was detected in 14.1% of 342 HCV patients, 9.1% of 55 HCV/HIV, 3.4% of 29 Hepatitis B, and none of 171 non-HCV (p<0.0001; HCV versus non-HCV). Anti-RR was present in 38% of 108 patients receiving interferon-α/ribavirin, but none in 26 receiving either interferon-α or ribavirin, or 166 untreated patients (p<0.0001). Other IIF-HEp-2 patterns were more frequently associated with interferon-α treatment alone (52.2%) as compared to interferon-α/ribavirin (25%), ribavirin alone (33.3%), and no therapy (26.5%). Anti-RR frequency was not associated with sex, age, ethnicity, HCV genotype or viral load. Anti-RR occurred only after initiation of treatment, beginning as early as 1 month (6%), but by the sixth month >47% tested positive for anti-RR. The anti-RR titer generally increased with sustained treatment and remained high in 53% of patients. After treatment, anti-RR titer was negative in 41%. Non-responders to HCV therapy were 77% in anti-RR-positive versus 64% in anti-RR-negative patients. Response to treatment was not associated with anti-RR titer or the dynamics of anti-RR reactivity during and after treatment. Conclusions The exquisite association of anti-RR reactivity with combined interferon-α/ribavirin therapy in HCV patients represents a unique model for drug-induced autoantibody generation in humans as demonstrated by the fact that a significant fraction of patients who have anti-RR during therapy becomes anti-RR-negative after completion of therapy.

Steatosis in chronic hepatitis C : Relationship to the virus and host risk factors

Background:  Steatosis occurs frequently in hepatitis C. However, the mechanisms leading to this lesion are still unknown, and the role of steatosis in the progression of the disease remains controversial. The aim of the present paper was to determine the prevalence of steatosis in hepatitis C and its association with hepatitis C virus (HCV) genotype, viral load and the presence of risk factors for steatosis, and to analyze the association between steatosis and the intensity of liver disease.