LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries.

BACKGROUND: The development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease. METHODS: This study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged ≥ 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is ≥ 8 kPa and/or if ALT levels are ≥1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM ≥ 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program. DISCUSSION: This study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country. TRIAL REGISTRATION: This study is registered on Clinicaltrials.gov ( NCT03789825 ).

Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases.

Cirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non-alcoholic fatty liver disease and alcohol-related liver disease, although chronic hepatitis B and C infections are still major etiological factors in some areas of the world. Recent studies have shown that liver fibrosis can be assessed with relatively high accuracy noninvasively by serological tests, transient elastography, and radiological methods. These modalities may be utilized for screening for liver fibrosis in at-risk populations. Thus far, a limited number of population-based studies using noninvasive tests in different areas of the world indicate that a significant percentage of subjects without known liver disease (around 5% in general populations and a higher rate -18% to 27%-in populations with risk factors for liver disease) have significant undetected liver fibrosis or established cirrhosis. Larger international studies are required to show the harms and benefits before concluding that screening for liver fibrosis should be applied to populations at risk for chronic liver diseases. Screening for liver fibrosis has the potential for changing the current approach from diagnosing chronic liver diseases late when patients have already developed complications of cirrhosis to diagnosing liver fibrosis in asymptomatic subjects providing the opportunity of preventing disease progression.

[Influence of a spontaneous bacterial peritonitis, nosocomial infections and acute-on-chronic liver failure on treatment revenues in patients with decompensated cirrhosis in Germany]. / Einfluss einer spontan bakteriellen Peritonitis, nosokomialer Infektionen und eines akut auf chronischen Leberversagens auf die Behandlungserlöse bei Patienten mit dekompensierter Leberzirrhose in Deutschland.

BACKGROUND: The economic effects of spontaneous bacterial peritonitis (SBP), nosocomial infections (nosInf) and acute-on-chronic liver failure (ACLF) have so far been poorly studied. We analyzed the impact of these complications on treatment revenues in hospitalized patients with decompensated cirrhosis. METHODS: 371 consecutive patients with decompensated liver cirrhosis, who received a paracentesis between 2012 and 2016, were included retrospectively. DRG (diagnosis-related group), "ZE/NUB" (additional charges/new examination/treatment methods), medication costs, length of hospital stay as well as different kinds of specific treatments (e. g., dialysis) were considered. Exclusion criteria included any kind of malignancy, a history of organ transplantation and/or missing accounting data. RESULTS: Total treatment costs (DRG + ZE/NUB) were higher in those with nosInf (€â€Š10,653 vs. €â€Š5,611, p < 0.0001) driven by a longer hospital stay (23 d vs. 12 d, p < 0.0001). Of note, revenues per day were not different (€â€Š473 vs. €â€Š488, p = 0.98) despite a far more complicated treatment with a more frequent need for dialysis (p < 0.0001) and high-complex care (p = 0.0002). Similarly, SBP was associated with higher total revenues (€â€Š10,307 vs. €â€Š6,659, p < 0.0001). However, the far higher effort for the care of SBP patients resulted in lower daily revenues compared to patients without SBP (€â€Š443 vs. €â€Š499, p = 0.18). ACLF increased treatment revenues to €â€Š10,593 vs. €6,369 without ACLF (p < 0.0001). While treatment of ACLF was more complicated, revenue per day was not different to no-ACLF patients (€â€Š483 vs. €â€Š480, p = 0.29). CONCLUSION: SBP, nosInf and/or ACLF lead to a significant increase in the effort, revenue and duration in the treatment of patients with cirrhosis. The lower daily revenue, despite a much more complex therapy, might indicate that these complications are not yet sufficiently considered in the German DRG system.

Second-line and third-line therapy for autoimmune hepatitis: A position statement from the European Reference Network on Hepatological Diseases and the International Autoimmune Hepatitis Group.

Most patients with autoimmune hepatitis respond well to standard immunosuppressive therapy with steroids and azathioprine, and while untreated disease is usually fatal, patients who respond well to therapy have an excellent prognosis. However, insufficient response to standard therapy or intolerable side effects requiring dose adaptions or treatment changes occur in 10-20% of patients. While there is fairly good agreement on second-line treatment options, there is very wide variation in the indication and use of possible third-line therapies. Herein, the European Reference Network on Hepatological Diseases (ERN RARE-LIVER) and the International Autoimmune Hepatitis Group (IAIHG) outline a treatment algorithm for both children and adults that should help to standardise treatment approaches, in order to improve patient care and to enable the comparison of treatment results between scientific publications.

Therapeutic plasma exchange in acute liver failure.

BACKGROUND: Multi-organ dysfunction in acute liver failure (ALF) has been attributed to a systemic inflammatory response directly triggered by the injured liver. High-volume therapeutic plasma exchange (HV-TPE) has been demonstrated in a large randomized controlled trial to improve survival. Here, we investigated if a more cost-/ resource effective low-volume (LV) TPE strategy might have comparable beneficial effects. METHODS: This retrospective study evaluated the effect of LV-TPE on remote organ failure, hemodynamical and biochemical parameters as well as on survival in patients with ALF. Twenty patients treated with LV-TPE in addition to standard medical therapy (SMT) were identified and 1:1 matched to a historical ALF cohort treated with SMT only. Clinical and biochemical parameters were recorded at admission to the intensive care unit and the following 7 days after LV-TPE. RESULTS: Mean arterial pressure increased following first LV-TPE treatments (d0: 68 [61-75] mm Hg vs d7: 88 [79-98] mm Hg, P = .003) and norepinephrine dose was reduced (d0: 0.264 [0.051-0.906] µg/kg/min vs d3: 0 [0-0.024] µg/kg/min, P = .016). Multi-organ dysfunction was significantly diminished following LV-TPE (CLIF-SOFA d0: 17 [13-20] vs d7: 7 [3-11], P = .001). Thirty-day in-hospital survival was 65% in the LV-TPE cohort and 50% in the SMT cohort (Hazard-ratio for TPE: 0.637; 95% CI: 0.238-1.706, P = .369). CONCLUSIONS: Patients treated with LV-TPE showed improved surrogate parameters comparable with the effects reported with HV-TPE. These data need to be interpreted with caution due to their retrospective character. Future controlled studies are highly desirable.

Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are increasingly a cause of cirrhosis and hepatocellular carcinoma globally. This burden is expected to increase as epidemics of obesity, diabetes and metabolic syndrome continue to grow. The goal of this analysis was to use a Markov model to forecast NAFLD disease burden using currently available data. METHODS: A model was used to estimate NAFLD and NASH disease progression in eight countries based on data for adult prevalence of obesity and type 2 diabetes mellitus (DM). Published estimates and expert consensus were used to build and validate the model projections. RESULTS: If obesity and DM level off in the future, we project a modest growth in total NAFLD cases (0-30%), between 2016-2030, with the highest growth in China as a result of urbanization and the lowest growth in Japan as a result of a shrinking population. However, at the same time, NASH prevalence will increase 15-56%, while liver mortality and advanced liver disease will more than double as a result of an aging/increasing population. CONCLUSIONS: NAFLD and NASH represent a large and growing public health problem and efforts to understand this epidemic and to mitigate the disease burden are needed. If obesity and DM continue to increase at current and historical rates, both NAFLD and NASH prevalence are expected to increase. Since both are reversible, public health campaigns to increase awareness and diagnosis, and to promote diet and exercise can help manage the growth in future disease burden. LAY SUMMARY: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis can lead to advanced liver disease. Both conditions are becoming increasingly prevalent as the epidemics of obesity and diabetes continue to increase. A mathematical model was built to understand how the disease burden associated with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis will change over time. Results suggest increasing cases of advanced liver disease and liver-related mortality in the coming years.

[HBV-infections in Germany - health care costs in a real-life-setting]. / HBV-Infektionen in Deutschland ­ Versorgungskosten in einem Real-life-Setting.

Background An estimated 500 000 people are infected with hepatitis B in Germany, inducing an enormous burden on infected patients and the health care system. The aim of our study was to estimate the real-life costs of treating hepatitis B and to analyze sociodemographic factors. Methods We conducted a retrospective, non-interventional, single-center study from 07/2009 to 12/2012. Information on health care delivery was extracted from patient records. Besides that, a questionnaire survey regarding sociodemographic parameters and quality of life of HBV-infected patients was performed. Results A total of 117 patients were included in our study and grouped in six different disease stages. The response rate of our survey was 80 %. We determined annual total costs of €â€Š3509. The different groups altered between €â€Š221 and €â€Š5618. The main costs (80 %) were caused by the antiviral therapy. Costs of co-medication and hospitalizations were of minor importance. Laboratory costs were primarily caused by determination of virological parameters. Route of transmission of HBV-infection was unknown in 2/3 of all cases. Restrictions in quality of life due to the HBV-infection were reported by 60 % of the patients. Patients receiving interferon treatment reported highest restrictions. In an extrapolation, we estimated total annual hepatitis B treatment costs of 430 million € in Germany. Conclusion This is the first study estimating real-life treatment costs of hepatitis B infections in Germany. Further research should follow in the context of newly introduced generic antivirals.

Real-world medical costs of antiviral therapy among patients with chronic HCV infection and advanced hepatic fibrosis.

BACKGROUND AND AIMS: Very potent direct acting antivirals for the treatment of chronic hepatitis C virus infection were recently introduced into daily clinical practice. Currently, treatment uptake is hampered by their high costs, eliciting prioritization of treatment. We aimed to evaluate the direct medical costs during interferon (IFN)-based antiviral treatment and the costs per sustained virological response (SVR) among patients with advanced hepatic fibrosis. METHODS: This retrospective cohort study included all consecutive patients with chronic hepatitis C virus infection and biopsy-proven bridging fibrosis or cirrhosis (Ishak 4-6) treated with IFN-based regimens in five hepatology units of tertiary care centers in Europe and Canada. Direct medical costs, expressed in 2013 Euros, during therapy were assessed. The components of care were quantified by three distinct categories: treatment, safety/ monitoring, and complications. Cost per SVR was calculated by dividing the mean cost by the SVR rate. RESULTS: In total, 672 interferon-based treatments administered to 455 patients were included. Total medical costs per patient were averaged to €14 559 (95% confidence interval [CI], €13 323-€15 836). The mean cost per SVR was €38 514 (95% CI, €35 244-€41 892). The costs per SVR were €26 105 (95% CI, €23 068-€29 296) for patients with a normal platelet count and €50 907 (95% CI, €44 151-€59 612) for patients with thrombocytopenia, with the costs per SVR of €74 961 (95% CI, €55 463-€103 541) among those patients with a platelet count below 100 * 109 /L. CONCLUSIONS: Because of the lower SVR rates, the cost per SVR of IFN-based treatment increased when patients with more advanced liver disease were treated. Additional costs of IFN-free therapy could be limited among these patients.

Targeted therapies in metastatic colorectal cancer: a systematic review and assessment of currently available data.

BACKGROUND: Survival of patients with metastatic colorectal cancer (mCRC) has been significantly improved with the introduction of the monoclonal antibodies targeting the vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR). Novel molecular-targeted agents such as aflibercept and regorafenib have recently been approved. The aim of this review is to summarize and assess the effects of molecular agents in mCRC based on the available phase II and III trials, pooled analyses, and meta-analyses/systematic reviews. METHODS: A systematic literature search was conducted using the meta-database of the German Institute of Medical Documentation and Information. Criteria of the Scottish Intercollegiate Guidelines Network were used to assess the quality of the controlled trials and systematic reviews/meta-analyses. RESULTS: Of the 806 retrieved records, 40 publications were included. For bevacizumab, efficacy in combination with fluoropyrimidine-based chemotherapy in first- and subsequent-line settings has been shown. The benefit of continued VEGF targeting has also been demonstrated with aflibercept and regorafenib. Cetuximab is effective with fluoropyrimidine, leucovorin, and irinotecan (FOLFIRI) in first-line settings and as a single agent in last-line settings. Efficacy for panitumumab has been shown with oxaliplatin with fluoropyrimidine in first-line settings, with FOLFIRI in second-line settings, and as monotherapy in last-line settings. Treatment of anti-EGFR antibodies is restricted to patients with tumors that do not harbor mutations in Kirsten rat sarcoma and in neuroblastoma RAS. CONCLUSION: Among various therapeutic options, the future challenge will be a better selection of the population that will benefit the most from specific anti-VEGF or anti- EGFR treatment and a careful consideration of therapy sequence.

High prevalence of hepatitis markers in immigrant populations: a prospective screening approach in a real-world setting.

BACKGROUND: Immigrant populations are believed to be more frequently infected with hepatitis viruses. However, limited unbiased data are available on immigrants outside of academic centres. Therefore, the aim of this study was to perform large-scale screening for hepatitis markers in primary care centres treating mainly individuals with a migrational background in Germany. METHODS: Between November 2010 and January 2012, we prospectively screened 1313 individuals treated by general practitioners at eight primary care centres in North-western Germany. Patients were eligible if they or their parents were not born in Germany. Serological screening for hepatitis B core protein antibodies, hepatitis B surface antigens (HBsAgs), and anti-hepatitis C virus antibodies was performed in each individual. HBsAg-positive and anti-hepatitis C virus-positive patients were further tested for molecular markers of viral replication. RESULTS: The mean age was 49.1±15.8 years. Of the patients, 45.7% were male; 87.3% had migrated to Germany from the Eastern Mediterranean area and 12.0% from Eastern Europe. Of the patients, 32.5% tested positive for hepatitis B core protein antibodies. HBsAgs were found in 3.6% of patients. Overall, hepatitis B virus DNA was detected in 2.2% of patients. Markers for hepatitis C virus infection were found in an almost similar high frequency (1.9%). Individuals with migrational background showed significant deficits in knowledge on general routes of transmission. CONCLUSION: Hepatitis virus infections are indeed significantly more prevalent in immigrant populations as compared with the general German population. These data underline the importance of introducing screening programs in this particular risk group.

Cost-effectiveness of truncated therapy for hepatitis C based on rapid virologic response.

BACKGROUND: Shortened courses of treatment with pegylated interferon alfa and ribavirin for patients with hepatitis C virus infection who experience rapid virologic response can be effective in appropriately selected patients. The cost-effectiveness of truncated therapy is not known. OBJECTIVE: To assess the cost-effectiveness of response-guided therapy versus standard-duration therapy on the basis of best available evidence. METHODS: We developed a decision model for chronic hepatitis C virus infection representing two treatment strategies: 1) standard-duration therapy with pegylated interferon alfa and ribavirin for 48 weeks in patients with genotype 1 or 4 and for 24 weeks in patients with genotype 2 or 3 and 2) truncated therapy (i.e., 50% decrease in treatment duration) in patients with rapid virologic response. Patients for whom truncated therapy failed began standard-duration therapy guided by genotype. We used a Markov model to estimate lifetime costs and quality-adjusted life-years. RESULTS: In the base-case analysis, mean lifetime costs were $46,623 ± $2,483 with standard-duration therapy and $42,354 ± $2,489 with truncated therapy. Mean lifetime quality-adjusted life-years were similar between the groups (17.1 ± 0.7 with standard therapy; 17.2 ± 0.7 with truncated therapy). Across model simulations, the probability of truncated therapy being economically dominant (i.e., both cost saving and more effective) was 78.6%. The results were consistent when we stratified the data by genotype. In one-way sensitivity analyses, the results were sensitive only to changes in treatment efficacy. CONCLUSION: Truncated therapy based on rapid virologic response is likely to be cost saving for treatment-naive patients with chronic hepatitis C virus infection. Cost-effectiveness varied with small changes in relative treatment efficacy.

Multicentric evaluation of model for end-stage liver disease-based allocation and survival after liver transplantation in Germany--limitations of the 'sickest first'-concept.

Since the introduction of model for end-stage liver disease (MELD) in 2006, post-orthotopic liver transplantation (OLT) survival in Germany has declined. The aim of this study was to evaluate risk factors and prognostic scores for outcome. All adult OLT recipients in seven German transplant centers after MELD implementation (December 2006-December 2007) were included. Recipient data were analyzed for their influence on 1-year outcome. A total of 462 patients (mean calculated MELD = 20.5, follow-up: 1 year) were transplanted for alcoholic cirrhosis (33.1%), hepatocellular carcinoma (26.6%), Hepatitis-C (17.1%), Hepatitis-B (9.5%), primary sclerosing cholangitis (5.6%) and late graft-failure after first OLT before December 2006 (8.7%). 1-year patient survival was 75.8% (graft survival 71.2%) correlating with MELD parameters and serum choline esterase. MELD score >30 [odds ratio (OR) = 4.17, confidence interval: 2.57-6.78, 12-month survival = 52.6%, c-statistic = 0.669], hyponatremia (OR = 2.07), and pre-OLT hemodialysis (OR = 2.35) were the main death risk factors. In alcoholic cirrhosis (n = 153, mean MELD = 21.1) and hepatocellular carcinoma (n = 123, mean MELD = 13.5), serum bilirubin and the survival after liver transplantation score were independent outcome parameters, respectively. MELD >30 currently represents a major risk factor for outcome. Risk factors differ in individual patient subgroups. In the current German practice of organ allocation to sicker patients, outcome prediction should be considered to prevent results below acceptable standards.

Epidemiology, pathogenesis and management of hepatitis D: update and challenges ahead.

Hepatitis D is caused by infection with the hepatitis D virus (HDV) and is considered to be the most severe form of viral hepatitis in humans. Hepatitis D occurs only in individuals positive for the HBV surface antigen (HBsAg) as HDV is a defective RNA viroid that requires HBsAg for transmission. At least eight different HDV genotypes have been described and each has a characteristic geographic distribution and a distinct clinical course. HDV and HBV coinfection can be associated with complex and dynamic viral dominance patterns. Chronic HDV infection leads to more severe liver disease than HBV monoinfection and is associated with accelerated fibrosis progression, earlier hepatic decompensation and an increased risk for the development of hepatocellular carcinoma. So far, only IFN-alpha treatment has proven antiviral activity against HDV in humans and has been linked to improved long-term outcomes. Studies conducted in the past 2 years on the use of PEG-IFN-alpha show that a sustained virologic response to therapy, measured in terms of undetectable serum HDV RNA levels, can be achieved in about one quarter of patients with hepatitis D. Novel alternative treatment options including prenylation inhibitors are awaiting clinical development for use in hepatitis D.

Economic evaluation of early monotherapy versus delayed monotherapy or combination therapy in patients with acute hepatitis C in Germany.

BACKGROUND: Antiviral treatment of acute hepatitis C virus (HCV) almost doubles the chance of sustained virological response (SVR) compared with that achievable by treating chronic HCV. AIM: To conduct a health economic evaluation comparing early and delayed therapies for acute HCV in Germany. METHODS: One hundred and thirty-three patients with acute HCV were evaluated in two early monotherapy (EMT) studies and 60 in a delayed therapy study. Efficacy was determined by SVR. In the EMT studies, patients were treated with either standard or pegylated interferon for 24 weeks. In the delayed therapy study, patients with persisting infection were treated with interferon monotherapy or combination therapy with ribavirin for a median of 36 weeks. We conducted a cost-effectiveness analysis based on the study results and a linear simulation model based on current treatment recommendations. RESULTS: The SVR rate for the sex-adjusted on-treatment analysis between early and delayed therapies was not significantly different (92.7 vs. 90.9%; P = 0.7). Medication costs accounted for more than 90% in both treatment options. Direct medical costs of early therapy (euro7064/patient) were euro321 lower than those of delayed therapy (P = 0.8). The incremental cost-effectiveness ratio was -178 euro/SVR(%) (confidence interval: -224 to 360 euro/SVR(%)). Average modeled direct medical costs of delayed combination therapy were from euro6745 to euro8299 per patient (from approximately 7% less up to 15% higher than EMT). Spontaneous viral clearance and therapy duration were the most sensitive variables. CONCLUSION: There was no significant efficacy and cost difference between therapy alternatives in base cases. However, in the majority of scenarios in the sensitivity analyses, EMT was a more cost-effective option in acute HCV therapy.

Clinical effectiveness and cost effectiveness of tailoring chronic hepatitis C treatment with peginterferon alpha-2b plus ribavirin to HCV genotype and early viral response: a decision analysis based on German guidelines.

BACKGROUND: Recently developed German guidelines for antiviral treatment in patients with chronic hepatitis C recommend basing drug dosage, intended treatment duration and early stopping rules on the genotype of the hepatitis C virus and early viral responses to treatment. OBJECTIVES: To evaluate effectiveness and cost effectiveness of different antiviral treatment strategies including the German guidelines, for chronic hepatitis C. METHODS: A validated lifetime Markov model was used to project life expectancy, QALYs and lifetime costs for the following strategies: (i) no antiviral therapy (NoAVT); (ii) interferon-alpha-2b plus ribavirin for 48 weeks (IFN + R); (iii) peginterferon-alpha-2b plus weight-based ribavirin for 48 weeks (PEG + R); (iv) peginterferon-alpha-2b plus ribavirin according to German guidelines with genotype-dependent treatment duration, dosage and 12-week viral response evaluation (GUIDE). Clinical and resource utilization data were derived from a clinical trial, the published literature and a survey of German hepatologists. Incremental cost-effectiveness ratios (ICERs) were calculated adopting the German societal perspective. Costs (in euro, year 2005 values) and health outcomes were discounted at 3% annually. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. RESULTS: Compared with NoAVT, PEG + R increased undiscounted life expectancy by 5.0 life-years (5.2 QALYs) and GUIDE increased undiscounted life expectancy by 4.9 years (5.1 QALYs). Compared with PEG + R, GUIDE saved 13% of hepatitis C virus-related lifetime costs per patient. GUIDE dominated IFN + R. Compared with NoAVT, discounted ICERs were euro1500 per QALY for GUIDE and euro3200 per QALY for PEG + R. CONCLUSION: Administering GUIDE should allow tailoring treatment efficiently to genotype, bodyweight and early viral response in patients with chronic hepatitis C, and appears cost effective compared with other well accepted medical interventions.

Adherence to combination therapy: influence on sustained virologic response and economic impact.

The health care burden of hepatitis C virus (HCV) infection is projected to continue to increase over the next two decades, so improving the efficacy of anti-HCV therapy has the potential to significantly affect health care utilization associated with the disease. Adherence to standard combination therapy and maintaining the doses of interferon (IFN) or peginterferon (PEG-IFN) and ribavirin (RBV) are now recognized as critical to maximizing a sustained virologic response (SVR) rate, particularly in patients infected with genotype 1 and patients who demonstrate an early virologic response. Early identification and management of the treatment-related side effects that are most likely to result in dose reductions or discontinuation might also play a role in successful adherence to therapy and achieving an SVR, as side effects are the primary reason for nonadherance. Educating patients, their family members, and their caregivers about the expectations of treatment, side effects, and the importance of maintaining doses and completing therapy is essential to optimizing adherence. Although patient quality of life (QOL) may decrease during treatment, patients achieving an SVR experience an improved QOL. Cohort economic modeling studies and available data from recent controlled trials suggest that PEG-IFN/RBV therapy increases life expectancy and is cost effective compared with standard IFN/RBV, and that the use of treatment management algorithms based on early virologic testing can substantially reduce antiviral drug costs and further improve the cost effectiveness of therapy, as can increased adherence to PEG-IFN/RBV therapy. Further research will be needed to develop optimum and cost-effective treatment strategies for the general HCV-infected population, particularly patients with comorbidities.