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PubMed2000

Recent advances in prevention and treatment of hepatitis C virus infections.

Hepatitis C virus (HCV) is the leading cause of chronic hepatitis in humans. As members of the flavivirus family, HCVs are a group of small single-stranded, positive-sense RNA viruses. Upon translation of the genome, a polyprotein precursor is synthesized and further processed by both cellular and viral proteases to generate functional viral proteins. Treatment options are currently limited to the administration of alpha-interferon alone or in combination with ribavirin. Unfortunately, these approaches are characterized by relatively poor efficacy and an unfavorable side-effect profile. Therefore, intensive effort is directed at the discovery of novel molecules to treat this disease. These new approaches include the development of prophylactic and therapeutic vaccines, the identification of interferons with improved pharmacokinetic characteristics, and the discovery of novel drugs designed to inhibit the function of three major viral proteins: protease, helicase and polymerase. Finally, the HCV RNA genome itself, particularly the IRES element, is being actively exploited as an antiviral target using antisense molecules and catalytic ribozymes. This review summarizes the most recent findings in each of these areas. Although not intended to be comprehensive, it should serve as a first resource for those individuals who desire updated information in this rapidly changing field.

Animals↗

PubMed1998

The identification and development of antiviral agents for the treatment of chronic hepatitis B virus infection.

Hepatitis B virus (HBV) is the leading cause of chronic hepatitis throughout the world. Notwithstanding the availability of a safe and effective vaccine, the world prevalence of HBV has not declined significantly, thus resulting in the need for a selective antiviral agent. HBV is a small, partially double-stranded DNA virus which replicates through an RNA intermediate. Most efforts to develop anti-HBV agents have been targeted to the viral DNA polymerase which possesses reverse transcriptase activity. Currently, the most promising anti-HBV agents are nucleoside analogs which interfere with viral DNA replication. Although earlier nucleoside analogs such as vidarabine (ara-A) and fialuridine (FIAU) have displayed unacceptable toxicities, newer analogs such as lamivudine (3TC), bis-POM PMEA (GS-840), lobucavir, and BMS-200,475 have demonstrated clinical utility. In particular, the use of lamivudine has generated considerable interest in the development of other L-enantiomeric nucleoside analogs for use against HBV. Here, we provide an overview of HBV structure and replication strategy and discuss the use of cell culture systems, in vitro viral polymerase systems, and animal models to identify and evaluate anti-HBV agents. We also discuss the various classes of nucleoside analogs in terms of structure, mechanism of action, status in clinical development, ability to select for resistant HBV variants, and use in combination therapies. Finally, we present a discussion of novel antiviral approaches, including antisense and gene therapy, and address the various challenges to successful anti-HBV chemotherapeutic intervention.

Animals↗

PubMed1996

Outcome of renal graft recipients with hepatitis C virus infection.

Hepatitis C virus (HCV) is a major cause of posttransplantation chronic liver disease. The aim of this study was to evaluate the prevalence of HCV in renal transplant recipients and to investigate risk and prognostic factors. Of 427 renal transplants carried out between July 1983 and January 1993, we retrospectively studied 66 (15.5%) HBsAg-negative patients with anti-HCV detected by enzyme-linked immunosorbent assay (ELISA) and recombinant immunoblot assay (RIBA). Patient and graft survivals were estimated. Anti-HCV positive patients had more time on hemodialysis and pretransplant blood transfusions (P = 0.0001) than did the seronegative population. In a mean follow-up of 52.3 +/- 27.7 months, 36 patients (54%) had biochemical evidence of liver disease, predominantly with a persistently high pattern of serum alanine aminotransferase (ALT). Pretransplantation ALT elevation was associated (P = 0.004) with chronic liver disease (CLD) in the graft recipient. None of the other variables studied predicted posttransplantation CLD. Liver failure occurred in two (3%) and was the cause of death in one of the patients. Death occurred in eight significantly more aged (P = 0.0001) patients, at 45.5 +/- 28.8 months posttransplant. In 50% of the cases, death was ascribed to sepsis. The biochemical pattern of HCV showed no predictive value for prognosis. The disease had no significant effect on the number of rejections or graft survival. The study revealed lower actuarial survival (P = 0.004) for HCV-positive patients in comparison with the seronegative population.

Adult↗

PubMed2006

Role of obesity, insulin resistance, and steatosis in hepatitis C virus infection.

Hepatitis C, nonalcoholic fatty liver characterized by hepatic steatosis, and obesity inflict significant health and economic burdens on the Western world. Insulin resistance is the key player in these disease processes. Complex interplay between these conditions results in the ultimate phenotype of liver disease. This article focuses on the current understanding of host and viral interactions as well as on consequent clinical implications.

Adipose Tissue, White↗

PubMed2002

Ribavirin dose modification based on renal function is necessary to reduce hemolysis in liver transplant patients with hepatitis C virus infection.

Hepatitis C virus (HCV) is currently the most common etiology for liver transplantation (LTx) in the United States. A significant number of patients develop recurrent HCV after LTx. Although there is no completely satisfactory treatment for recurrent HCV, a combination of interferon-alpha (INF) and ribavirin remains the most widely used. Ribavirin is eliminated through the kidneys and tends to accumulate in the presence of renal dysfunction. The primary side effect of ribavirin is hemolysis. The goal of the present study was to correlate the incidence of hemolysis with renal function in LTx patients with recurrent HCV who were being treated with ribavirin. The incidence of hemolysis and the renal function were examined in 72 liver transplant patients (58 male and 14 female patients) with recurrent HCV receiving INF (3 million units, three times per week) and ribavirin (initial dose of 400 mg twice daily). Patients were grouped according to the decrease in the percentage of hematocrit after the introduction of ribavirin, with their baseline serum creatinine and creatinine clearance calculated using the Cockcroft-Gault formula. The decrease in the percentage of hematocrit after ribavirin treatment was also examined with respect to creatinine clearance as a continuous variable. In addition, for purposes of presentation, patients were analyzed in three groups: creatinine clearance of >/= 70 mL/min (group A), creatinine clearance < 70 mL/min and >/= 40 mL/min (group B), and creatinine clearance < 40 mL/min (group C). Forty-five (62.5%) patients experienced a decrease in hematocrit (Hct) >/=15% after starting INF and ribavirin. The mean serum creatinine was 1.3 +/- 0.5 mg/dL (median, 1.3) in this group, and the mean calculated creatinine clearance was 71 +/- 29 mL/min (median, 66.47). In the 27 patients who did not show a significant decrease (< 15%) in hematocrit, the mean serum creatinine was 1.1 +/- 0.3 mg/dL (median, 1.0) and the mean creatinine clearance was 95 +/- 39 (median, 96) mL/min (P =.018). On continuous variable of calculated creatinine clearance, there was a trend in the decrease in hematocrit after ribavirin treatment compared with pretreatment (P =.09). However, the rate of hemolysis was significantly different in group A (53.7%), group B (70.8%), and group C (100%) (P =.042). Patients on INF and ribavirin therapy who experienced hemolysis had significantly higher serum creatinine levels and lower creatinine clearances compared with those who did not have hemolysis. The incidence of hemolysis was significantly associated with higher serum creatinine and decreased creatinine clearance. Because ribavirin is eliminated by the kidneys, this observation points to the need for adjustments in the dose of this agent in LTx patients, who tend to have some degree of renal dysfunction, to reduce the incidence of hemolysis. Further pharmacokinetic studies of ribavirin in LTx patients with varying degrees of renal function may allow the development of an algorithm for the safer use of ribavirin in HCV-positive LTx patients.

Adult↗

PubMed1994

Susceptibility of nonprimate cell lines to hepatitis A virus infection.

Hepatitis A virus (HAV) has been adapted to grow in primate cell cultures. We investigated replication of HAV in nonprimate cells by inoculating 20 cell lines from different species with the tissue culture-adapted HM175 strain. Slot blot hybridization and immunofluorescence analysis revealed that HAV replicated in GPE, SP 1K, and IB-RS-2 D10 cells of guinea pig, dolphin, and pig origin, respectively. Studies in IB-RS-2 D10 cells were discontinued because cultures were contaminated with classical swine fever virus. A growth curve showed that HAV grew poorly in GPE cells and intermediately in SP 1K cells compared with growth in FRhK-4 cells. Therefore, the cell surface receptor(s) and other host factor(s) required for HAV replication are present in nonprimate as well as primate cells.

Animals↗

PubMed1986

Arthritis, vasculitis, and cryoglobulinemia associated with relapsing hepatitis A virus infection.

Hepatitis A virus, unlike hepatitis B virus, has rarely been associated with extrahepatic features. Two patients developed relapsing hepatitis A complicated by arthritis in both cases and cutaneous vasculitis in one. Both patients had cryoglobulinemia, with cryocrit values of 4.3% and 8.6%. Serologic studies showed that the cryoglobulin consisted of polyclonal IgM and IgG. The washed cryoglobulin was analyzed by sucrose density gradient ultracentrifugation under neutral (pH 7.4) and acidic (pH 2.8) conditions. Enzyme-linked immunosorbent assay techniques were used to characterize the native and dissociated cryoglobulin. The cryoglobulin contained acid-dissociable IgG complexes greater than 19S, and high molecular weight rheumatoid factors of both IgG and IgM isotypes that could be dissociated to 7S and 19S forms, respectively. Dissociation of the cryoglobulin augmented 7S anti-hepatitis A virus IgG 2.27-fold, but augmented total 7S IgG only 1.12-fold, suggesting enrichment of antiviral antibody in the cryoglobulin.

Adult↗

PubMed2005

Hepatic steatosis associated with hepatitis C virus infection.

Hepatic steatosis (including microvesicular and macrovesicular fat) is a significant histologic feature associated to the chronic hepatitis C (HCV). The purpose of this paper was to analyze the incidence of hepatocyte steatosis in patients with HCV and the potential role of some the known variables as risk factors possibly involved in the occurrence of steatosis: age, sex, obesity, biological parameters, diabetes mellitus, degree of necroinflammation (NI) and stage of fibrosis. 96 of 125 (76.8%) patients had hepatic steatosis (mild 76%, moderate and severe 24%); in comparison with patients without steatosis, those with HCV and steatosis were more frequently women (males/females: 1/1.9) of older age (49.97 vs. 47.7 years), with a greater ICM (index of corporal mass) (26.55 sqm vs. 23.52 sqm), with raised glycemic values (13 of the 14 patients with HCV and diabetes mellitus had steatosis), an average value of serum ALT significantly raised (95.38 U/l vs. 78.96 U/l), and an average score of NI activity significantly higher (9.39 vs. 6.75).

Adult↗

PubMed1995

Antiviral therapy for chronic hepatitis C viral infection.

Hepatitis C affects at least 200 million people worldwide. It can be followed by chronic hepatitis, cirrhosis, and primary liver cancer. Outcome assessments in controlled trials of antiviral therapy are based on serum transaminase values, serum HCV-RNA determinations, and liver biopsy scores. Patients most likely to respond to antiviral treatment are relatively young, have low serum HCV-RNA and transaminase levels, and do not have cirrhosis. Patients whose disease is caused by genotype 1b HCV isolates are unlikely to respond. Interferon alfa (3 million units [MU] three times a week for 6 months) is associated with a 50% response rate and a 50% relapse rate--an overall response rate of 25%. Increasing the duration of therapy may increase the sustained response rate. Ribavirin, given orally, may be used for patients who fail to respond to or relapse after interferon therapy. Its side effects are few. Treatment results in a fall in transaminase levels and some decrease in hepatic inflammation, but serum HCV RNA (viral titer) is unaltered. Combinations of interferon with ribavirin are giving promising results with increased sustained, complete responses.

Antiviral Agents↗

PubMed1997

Rheumatologic and autoimmune manifestations in patients with chronic hepatitis C virus infection.

Hepatitis C virus (HCV) has been associated with several autoimmune and rheumatologic disorders. The aim of this study was to determine the incidence of these abnormalities in patients with chronic HCV. We studied 56 patients, 29 of whom (52%) had biochemical abnormalities that suggested immunological disorders. Cryoglobulinemia was detected in nine patients (22%), antinuclear antibodies in eleven (20%), rheumatoid factor in seven (19.27%) and hypocomplementemia in fourteen (29.16%). The most common clinical manifestations were: arthralgias (52%), myalgias (16%), xerostomia (28.5%) and xerophthalmia (14%). These results indicate the existence of a relationship between HCV and rheumatologic disorders. We conclude that HCV may play a role in the pathogenesis of these autoimmune phenomena, but more studies are required to define the extent of this role.

Adult↗

PubMed2006

The natural history of hepatitis C virus (HCV) infection.

Hepatitis C virus (HCV) is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma, as well as the most common indication for liver transplantation in many countries. Although the incidence of hepatitis C infection has dramatically decreased during the past decade, the worldwide reservoir of chronically infected persons is estimated at 170 million, or 3% of the global population. There is much controversy surrounding the natural history of hepatitis C infection. The rate of chronic HCV infection is affected by a person's age, gender, race, and viral immune response. Approximately 75%-85% of HCV-infected persons will progress to chronic HCV infection, and are at risk for the development of extrahepatic manifestations, compensated and decompensated cirrhosis, and hepatocellular carcinoma (HCC). The rate of progression to cirrhosis is highly variable, and is influenced by several factors, including the amount of alcohol consumption, age of initial HCV infection, degree of inflammation and fibrosis on liver biopsy, HIV and HBV coinfection, and comordid conditions. An estimated 10%-15% of HCV-infected persons will advance to cirrhosis within the first 20 years. Persons with cirrhosis are at increased risk of developing HCC. An understanding of the natural history of hepatitis C is essential to effectively manage, treat, and counsel individuals with HCV infection.

Journal Article↗

PubMed2002

Prevention of de novo hepatitis B infection in liver allograft recipients with previous hepatitis B infection or hepatitis B vaccination.

OBJECTIVES: To assess de novo hepatitis B virus (HBV) transmission from liver donors with HBV serum markers (HBM) to their recipients and the need for HBV vaccination before liver transplantation. METHODS: A total of 108 orthotopic liver transplantations for nonviral disease and the risk of developing de novo hepatitis B based on HBMs before transplantation have been studied. Of the 108 patients, 94 met the study criteria and were divided into two groups: 27 who had HBMs before transplantation (from past infection or by previous vaccination) and 67 who had no HBM. Development of de novo hepatitis B was determined by analytical, serological, and histological parameters. RESULTS: No case (0%) of de novo hepatitis B was detected in the pretransplantation HBM group, whereas there were 10 cases (14.5%) in the other group (p < 0.005). CONCLUSIONS: The presence of pretransplantation HBM in liver transplant recipients protects these patients against the development of de novo hepatitis B. This is especially important considering that there is a high prevalence of donors with positive hepatitis B core antibody (especially in some countries), and that these donors transmit HBV infection to recipients without HBM in a significant number of cases. Thus, vaccination against HBV in patients who are candidates for liver transplantation is fundamental to avoid cases of de novo hepatitis B.

Adult↗

PubMed1993

Occurrence of hepatitis delta virus infection in hepatitis B virus-infected patients with different serum patterns of preS gene-encoded proteins.

The occurrence of delta superinfection among viremic and nonviremic HbsAg-positive carriers with different serum patterns and levels of preS1 and preS2 antigens was investigated. PreS1 and preS2 antigens in serum, as well as their levels, were found to be independent of hepatitis B virus (HBV) replicative activity. Serological evidence of hepatitis delta virus (HDV) superinfection was found in 34 out of 233 (14.6%) HBsAg-positive carriers; all these 34 patients resulted positive for antibody to hepatitis B 'e' antigen, and 33 of them were negative for circulating HBV-DNA. Delta superinfection occurred only among HBsAg-positive carriers whose sera were reactive for both preS1 and preS2 antigens (30 out of 142; 21.1%) or at least for preS1 alone (4 out of 63; 6.3%), but not among the patients with undetectable levels of both these antigens. Serum levels of both preS1 (p < 0.005) and preS2 (p < 0.001) antigens were found to be significantly higher in delta-positive HBsAg-positive carriers than in patients with HBV infection uncomplicated by HDV. In addition to confirm previous observations that the detection of both preS antigens in HBsAg-positive sera is independent of HBV replication, these findings clearly show that HDV infection requires not only the presence of HBsAg, but also the presence of preS peptides, and seem to suggest a low susceptibility of HBsAg-positive carriers with low or undetectable synthesis and secretion of HBV surface proteins to delta superinfection.

Adult↗

PubMed1986

Detection of hepatitis B virus infection in hepatitis B surface antigen-negative hemodialysis patients by monoclonal radioimmunoassays.

We studied 375 chronic hemodialysis patients for evidence of hepatitis B virus infection using first- and second-generation monoclonal radioimmunoassays. These assays employ high-affinity monoclonal antibodies produced against antigenic determinants that reside on hepatitis B surface antigen. Such assays have a lower limit of detection for hepatitis B surface antigen-associated determinants in serum of approximately 55 and 15 pg/ml, respectively. We found that 14 of 375 chronic hemodialysis patients were positive for hepatitis B surface antigen by both polyclonal and monoclonal radioimmunoassay. However, an additional 17, some of whom had chronic hepatitis and hepatocellular carcinoma, were identified as harboring hepatitis B virus infection only by the monoclonal radioimmunoassays. Thus the monoclonal radioimmunoassays improved the hepatitis B virus detection rate by 120% (3.7% vs. 8.3%). More importantly, 6 of the 17 monoclonal radioimmunoassay-reactive patients had no serologic evidence of recent or past hepatitis B virus exposure as shown by the absence of antibodies to the hepatitis B core and surface antigens in the blood. We conclude that there are hemodialysis patients with hepatitis B virus infection undetectable by conventional polyclonal radioimmunoassays.

Adult↗

PubMed1999

[Long-term consequences of co-infection by hepatitis G virus in hepatitis c virus infected kidney transplant patients].

The objectives of this retrospective study were to determine the prevalence of hepatitis G virus (HGV) infection in hepatitis C virus positive (HCV+ve) renal transplant (RT) patients and to evaluate the impact of HGV both on liver function tests, liver histology tests and renal parameters such as the prevalence of acute rejection and renal function. Seventy-one HCV+ve renal transplant patients with a functioning graft for whom a post renal transplant liver biopsy was available, were included. Serum HGV RNA was assessed by reverse transcription polymerase chain reaction before, at the time of, and after renal transplantation. A total of 21 (30%) of the HCV+ve RT patients had a positive HGV RNA (Group 1); seventeen of these patients (81%) were already HGV RNA+ve when the most recent renal transplantation was performed. The other 4 patients became HGV RNA+ve following renal transplantation. The mean duration of HGV infection was at least 119 +/- 64 months (18-240). Patients in group 1 did not statistically differ from the 50 HGV RNA-ve/HCV+ve RT patients (Group 2) according to sex ratio; time on dialysis; number of blood transfusions; HLA matching; the duration of HCV infection; duration and type of immunosuppression or levels of liver enzymes i.e. aspartate aminotransferase, alanine aminotransferase and gamma glutamyl transpeptidase; serum HCV RNA concentration; or frequency of genotype 1b. However, Group 1 patients were statistically younger (41 +/- 10 y compared to 47 +/- 10 y; p = 0.016) than Group 2 patients. Liver histology showed a significantly lower degree of fibrosis in Group 1 (0.4 +/- 0.5) than in Group 2 (1 +/- 1.2; p = 0.02); two patients from Group 2 but none of Group 1 had overt cirrhosis. Conversely, the extent of hepatic inflammation and hepatocellular necrosis was not statistically different between the two groups. The number of patients who experienced at least one acute rejection episode was significantly higher in Group 1 (76.2%) than in Group 2 (46%; p = 0.02), although the difference was no longer significant in the multivariate analysis. In conclusion, this study shows that: i) HGV infection was often present when the patients seroconverted for HCV; ii) HGV RNA+ve/HCV+ve RT patients experience acute rejection more frequently than HGV RNA-ve/HCV+ve RT patients; iii) HGV infection seems to have no detrimental effect upon liver enzymes or liver histology in HCV+ve RT patients.

Adult↗

PubMed2003

Geographic characterization of hepatitis virus infections, genotyping of hepatitis B virus, and p53 mutation in hepatocellular carcinoma analyzed by in situ detection of viral genomes from carcinoma tissues: comparison among six different countries.

We investigated the relationship of infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) to p53 mutation in hepatocellular carcinomas (HCC) from six countries, including Japan, China, Korea, Vietnam, Spain, and the Unites States. For this purpose, we used formalin-fixed, paraffin-embedded liver tissues obtained from 449 patients with HCC to detect the viral and p53 genes by polymerase chain reaction (PCR). HBV was the most prevalent in Korea (69.1%), China (66.1%), Vietnam (60.5%), and Spain (38.6%). In contrast, HCV was the most prevalent in Japan (59.8%) and in the United States (41.5%). Type C of HBV was the most common genotype (78.6%) encountered in HCC in these countries. Importantly, among 125 intrahepatic HBV DNA-positive patients, 44 (35.2%) were serologically negative for HBsAg (occult hepatitis B). Based on PCR, immunohistochemical, serological, and clinical findings, 4.8% of HCC patients were diagnosed with non-B, non-C. A point mutation at exon 7 of p53 was detected in 20 of the 239 HCC samples examined, including those from 9 Chinese, 5 American, 2 Japanese, 2 Korean, and 2 Spanish patients, respectively. Interestingly, a point mutation with an amino acid substitution at codon 251 (Ile-->Asn) was detected frequently in 11 of 20 (55%) cases. A specific mutation induced by Aflatoxin B1 at codon 249 was seen in two patients, both Chinese. Our results suggest that genotype C of HBV may play an important role in hepatocarcinogenesis in different geographic regions, and that in situ detection of HBV genomes could be important for clarifying the agent(s) of unknown etiology related to HCC.

Asia↗

PubMed2006

Hepatitis A virus infection suppresses hepatitis C virus replication and may lead to clearance of HCV.

BACKGROUND/AIMS: The significance of hepatitis A virus (HAV) super-infection in patients with chronic hepatitis C had been a matter of debate. While some studies suggested an incidence of fulminant hepatitis A of up to 35%, this could not be confirmed by others. METHODS: We identified 17 anti-HCV-positive patients with acute hepatitis A from a cohort of 3170 anti-HCV-positive patients recruited at a single center over a period of 12 years. RESULTS: Importantly, none of the anti-HCV-positive patients had a fulminant course of hepatitis A. HCV-RNA was detected by PCR in 84% of the anti-HCV-positive/anti-HAV-IgM-negative patients but only in 65% of anti-HCV-positive patients with acute hepatitis A (p=0.03), indicating suppression of HCV replication during hepatitis A. Previous HAV infection had no effect on HCV replication. After recovery from hepatitis A, an increased HCV replication could be demonstrated for 6 out of 9 patients with serial quantitative HCV-RNA values available while 2 patients remained HCV-RNA negative after clearance of HAV throughout follow-up of at least 2 years. CONCLUSIONS: HAV super-infection is associated with decreased HCV-RNA replication which may lead to recovery from HCV in some individuals. Fulminant hepatitis A is not frequent in patients with chronic hepatitis C recruited at a tertiary referral center.

Acute Disease↗

PubMed2007

The cost-effectiveness of two strategies for vaccinating US veterans with hepatitis C virus infection against hepatitis A and hepatitis B viruses.

OBJECTIVES: Although hepatitis A and B vaccinations are recommended for patients with chronic hepatitis C virus (HCV), the ideal vaccination strategy has not been determined. Our objective was to model the cost-effectiveness of two strategies for vaccinating patients with HCV infection against hepatitis A (HAV) and hepatitis B (HBV) viruses. The strategies evaluated were: universal vaccination with the combined HAV and HBV vaccine, and selective vaccination based on immunity determined by blood testing. METHODS: A decision tree model was constructed to compare the cost-effectiveness of the two vaccination strategies from the New Mexico Veterans Affairs Health Care System (NMVAHCS) perspective. A retrospective review of all HCV patients (2517 subjects) at the NMVAHCS was performed to extract prevalence of immunity to HAV and HBV, and prevalence of decompensated liver disease. Literature review was performed to obtain other probabilities for the model. Only direct medical costs were considered; the effectiveness measure was the number of patients immune to both HAV and HBV. Sensitivity analyses were performed to test robustness of the results to changes in input variables. All costs were in 2004 US dollars. RESULTS: The selective strategy was less costly but less effective, with a cost-effectiveness ratio of 105 dollars per patient immune to HAV and HBV. The universal strategy was more effective but more expensive with a cost-effectiveness ratio of 112 dollars per patient immune to HAV and HBV. Compared with the selective strategy, universal strategy was associated with an incremental cost-effectiveness (ICE) ratio of 154 dollars per additional patient immune to HAV and HBV. The universal strategy would become more cost-effective if 1) the cost of combined vaccine was reduced to less than 30.75 dollars (9.7% reduction), 2) the cost of HBV vaccine increased to greater than 34.50 dollars (25% increase), 3) the cost of blood tests for immunity increased to more than 25.25 dollars (23% increase), or (4) the prevalence of anti-HBs decreased to less than 24%. CONCLUSIONS: The selective vaccination strategy for HAV and HBV in our sample of patients with HCV is more cost-effective. However, the universal strategy is more effective and its ICE is minimal, thus it may be worth the additional cost.

Computer Simulation↗