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Keywords:

  • acute HCV infection;
  • chronic hepatitis C;
  • EASL;
  • HCV RNA;
  • pegylated-interferon alpha;
  • ribavirin

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology and natural history
  5. Guideline recommendations methodology
  6. Diagnostic tools and staging of HCV liver disease – main recommendations
  7. Results of current therapies and predictors of response summary of evidence
  8. Indications for treatment – main recommendations
  9. Standard of care, dose regimen and monitoring of treatment efficacy
  10. Monitoring of safety and treatment dose reductions – main recommendations
  11. Main recommendation of treatment in patients with severe liver disease and with post-transplant HCV recurrence
  12. Treatment of patients with co-infection and with comorbidities
  13. Treatment of acute hepatitis C
  14. Future perspectives
  15. Conflicts of interest
  16. References

Hepatitis C virus (HCV) is the leading cause of liver transplantation in Europe and is associated with an increased risk of hepatocellular carcinoma (HCC). Because of the chronic nature of the disease, estimates suggest that the burden on healthcare will increase dramatically for this entity. Clinical care of patients with HCV-related liver disease has advanced considerably in the last two decades, thanks to increasing knowledge about the mechanisms of the disease, development of diagnostic procedures, and advances in therapeutic and preventive approaches. HCV RNA testing, HCV genotyping and staging of liver disease are essential for the diagnosis and the management of HCV therapy. Furthermore, the important role of host polymorphisms of the IL28B gene on virological response to treatment with pegylated interferon (PEG-IFN) alpha and ribavirin (RBV) has recently been clearly demonstrated. In relation to treatment, although numerous drugs for HCV are in various stages of preclinical and clinical development, the current standard of care (SoC) is the combination of PEG-IFN-α and RBV for chronic hepatitis C. With SoC, a sustained viral response (SVR) is achieved in approximately 45% of patients infected with HCV genotype 1 and in approximately 80% of patients infected with HCV genotypes 2 and 3. The EASL HCV guidelines recommend treating all naïve patients with compensated disease from HCV without contraindications to treatment and strongly suggest initiating SoC promptly in patients with advanced fibrosis. Further recommendations on monitoring treatment efficacy, treatment duration, dose reduction indications and the role of co-factors are provided.


Abbreviations
SVR

sustained viral response

HCC

hepatocellular carcinoma

ETVR

end-of-treatment viral response

EVR

early virological response

RVR

rapid virological response

HCV

hepatitis C virus

RBV

ribavirin

IFN

interferon

PEG-IFN

pegylated interferon

SoC

standard of care

Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology and natural history
  5. Guideline recommendations methodology
  6. Diagnostic tools and staging of HCV liver disease – main recommendations
  7. Results of current therapies and predictors of response summary of evidence
  8. Indications for treatment – main recommendations
  9. Standard of care, dose regimen and monitoring of treatment efficacy
  10. Monitoring of safety and treatment dose reductions – main recommendations
  11. Main recommendation of treatment in patients with severe liver disease and with post-transplant HCV recurrence
  12. Treatment of patients with co-infection and with comorbidities
  13. Treatment of acute hepatitis C
  14. Future perspectives
  15. Conflicts of interest
  16. References

The European Association of the Study of the Liver (EASL) is the leading liver association in Europe and has promoted research on the liver, facilitated scientific exchange and fostered public awareness of liver disease and its management for many years. The most recent HCV EASL Clinical Practice Guidelines [1] were published mainly to help physicians in the clinical decision-making process by describing optimal management of patients with acute and chronic HCV infections.

These guidelines are based on the extensive knowledge of the management of HCV-related liver diseases and provide the most up-to-date evidence-based recommendations on diagnosis, staging of disease severity, detecting co-factors, monitoring and antiviral therapy.

Epidemiology and natural history

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology and natural history
  5. Guideline recommendations methodology
  6. Diagnostic tools and staging of HCV liver disease – main recommendations
  7. Results of current therapies and predictors of response summary of evidence
  8. Indications for treatment – main recommendations
  9. Standard of care, dose regimen and monitoring of treatment efficacy
  10. Monitoring of safety and treatment dose reductions – main recommendations
  11. Main recommendation of treatment in patients with severe liver disease and with post-transplant HCV recurrence
  12. Treatment of patients with co-infection and with comorbidities
  13. Treatment of acute hepatitis C
  14. Future perspectives
  15. Conflicts of interest
  16. References

Approximately 130–210 million individuals, i.e. 3% of the world population, are chronically infected with HCV [2, 3]. The prevalence ranges from 0.4% to 3% in Western Europe to 9% in Egypt throughout the country and up to 50% in certain Egyptian rural areas [4], the highest prevalence in the world. In the last 20 years, the principal routes of HCV transmission have changed from blood transfusions and unsafe injections or surgical procedures to intravenous or nasal drug use, and tattooing or acupuncture with unsafe materials.

Virological studies have identified six HCV genotypes [1-6], and a large number of subtypes [5]. Genotype 1 (subtypes 1a and 1b) is the most prevalent genotype worldwide, with a higher prevalence of 1b in Europe and 1a in the US. Genotype 2 is found in clusters in the Mediterranean region, genotype 3 is highly prevalent in European intravenous drug users [6] in whom the prevalence of genotype 4 is also increasing. Finally, genotypes 5 and 6 are less frequent.

Chronic infection is the main expression of HCV infection and is associated with variable degrees of hepatic inflammation and progression of fibrosis, whatever the HCV genotype or viral load. Depending on the presence of co-factors, between 10% and 40% of patients with chronic HCV infection will develop cirrhosis [7]. Death related to the complications of cirrhosis occurs at an incidence of approximately 4% per year, whereas HCC occurs in this population at an estimated incidence of 1–5% per year [8].

Diagnostic tools and staging of HCV liver disease – main recommendations

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology and natural history
  5. Guideline recommendations methodology
  6. Diagnostic tools and staging of HCV liver disease – main recommendations
  7. Results of current therapies and predictors of response summary of evidence
  8. Indications for treatment – main recommendations
  9. Standard of care, dose regimen and monitoring of treatment efficacy
  10. Monitoring of safety and treatment dose reductions – main recommendations
  11. Main recommendation of treatment in patients with severe liver disease and with post-transplant HCV recurrence
  12. Treatment of patients with co-infection and with comorbidities
  13. Treatment of acute hepatitis C
  14. Future perspectives
  15. Conflicts of interest
  16. References

Virological assessment

  • Diagnosis of HCV infection is based on detection of anti-HCV antibodies by EIA and HCV RNA by a sensitive molecular method (A1).
  • For the diagnosis of acute hepatitis C, HCV RNA testing is required as HCV RNA appears before anti-HCV antibodies may be detectable (A2).

The use of real-time polymerase chain reaction (PCR) detects minute quantities of HCV RNA (as few as 10 international units (IU)/ml) and accurately quantifies HCV RNA levels up to approximately 107 IU/ml.

  • HCV RNA detection and quantification should be made by a sensitive assay (lower limit of detection of 50 IU/ml or less), ideally a real-time PCR assay, and HCV RNA levels should be expressed in IU/ml (C1).

The HCV genotype and subtype can be determined via various methods, including direct sequence analysis, reverse hybridization and genotype-specific real-time PCR [9].

  • The HCV genotype must be assessed prior to antiviral treatment initiation and will determine the dose of RBV and treatment decision (A1).
  • With SoC, only the genotype [1-6], not the subtype, needs to be determined (A1).

Assessment of liver fibrosis

Assessment of the severity of liver disease is recommended before beginning therapy.

Liver biopsy, the gold standard and more recently, non-invasive methods, including serological markers and transient elastography, have been extensively evaluated in patients with chronic HCV infection. The accuracy of non-invasive tests of liver fibrosis is good for identifying patients with mild fibrosis and cirrhosis, but is less reliable for discriminating moderate and severe fibrosis [10, 11].

  • Identifying patients with cirrhosis is of particular importance, as their prognosis and likelihood to respond to therapy are altered, and they require surveillance for HCC (A1).
  • As liver disease can progress in patients with repeatedly normal ALT levels, disease severity evaluation should be performed regardless of ALT levels (B2).
  • Assessment of the severity of liver fibrosis is important in decision making in patients with chronic hepatitis C (A1).
  • Liver biopsy is still regarded as the reference method to assess the grade of inflammation and the stage of fibrosis (A2).
  • Transient elastography can be used to assess liver fibrosis in patients with chronic hepatitis C (A2).
  • Non-invasive serum makers can be recommended for the detection of significant fibrosis (METAVIR score F2–F4) (A2).

Evaluation of genetic polymorphisms

Several studies in the past year have focused attention on the role of host polymorphisms of the IL28B (interferon lambda 3) gene in the rate of SVR to treatment with PEG-IFN-α in combination with RBV [12-15]. Although the predictive value is low, determination of IL28B polymorphisms seems to be useful in identifying a patient's probability of response to PEG-IFN-α and RBV treatment.

  • Determination of IL28B polymorphisms may assist in evaluating a patient's likelihood of response to treatment with PEG-IFN-α/RBV (B2).

Results of current therapies and predictors of response summary of evidence

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology and natural history
  5. Guideline recommendations methodology
  6. Diagnostic tools and staging of HCV liver disease – main recommendations
  7. Results of current therapies and predictors of response summary of evidence
  8. Indications for treatment – main recommendations
  9. Standard of care, dose regimen and monitoring of treatment efficacy
  10. Monitoring of safety and treatment dose reductions – main recommendations
  11. Main recommendation of treatment in patients with severe liver disease and with post-transplant HCV recurrence
  12. Treatment of patients with co-infection and with comorbidities
  13. Treatment of acute hepatitis C
  14. Future perspectives
  15. Conflicts of interest
  16. References

Naïve patients

  • SVR is achieved in 40–54% of patients infected with HCV genotype 1 treated with PEG-IFN-α/RBV at approved doses for 48 weeks (A1).
  • SVR is achieved in 65–82% of patients infected with HCV genotypes 2 or 3 treated with PEG-IFN-α/RBV at approved doses for 24 weeks (A1).
  • SVR rates are slightly higher in patients infected with HCV genotype 2 than in those with genotype 3 (B2).
  • Strongest baseline predictors of SVR are:
    1. HCV genotype (A1).
    2. Genetic polymorphisms located in chromosome 19 (IL28B), particularly in genotype 1 patients (A1).
    3. Stage of liver fibrosis (A1).

Relapsers and non-responder patients

Patients who achieve an end-of-treatment viral response (undetectable HCV RNA at the end of treatment) but subsequently relapse, and do not achieve an SVR are defined as relapsers. The relapse rate after treatment with PEG-IFN-α and RBV is approximately 15–25%, but varies depending on, when HCV RNA becomes undetectable during therapy. Patients who relapse after treatment with standard IFN-based regimens respond to re-treatment with PEG-IFN-α/RBV in 32–53% of the patients [16].

Non-responders are patients who fail to achieve a decline of 2 log HCV RNA IU/ml after 12 weeks of treatment or who never achieve undetectable HCV RNA during a minimum of 24 weeks of treatment.

Indications for treatment – main recommendations

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology and natural history
  5. Guideline recommendations methodology
  6. Diagnostic tools and staging of HCV liver disease – main recommendations
  7. Results of current therapies and predictors of response summary of evidence
  8. Indications for treatment – main recommendations
  9. Standard of care, dose regimen and monitoring of treatment efficacy
  10. Monitoring of safety and treatment dose reductions – main recommendations
  11. Main recommendation of treatment in patients with severe liver disease and with post-transplant HCV recurrence
  12. Treatment of patients with co-infection and with comorbidities
  13. Treatment of acute hepatitis C
  14. Future perspectives
  15. Conflicts of interest
  16. References
  • All treatment-naïve patients with compensated disease because of HCV should be considered for therapy (A2)
  • Treatment should be initiated promptly in patients with advanced fibrosis (METAVIR score F3–F4), and strongly considered in patients with moderate fibrosis (METAVIR score F2) (B2)

Patients infected with HCV genotype 1 who fail to eradicate HCV after prior therapy with PEG-IFN-α and RBV should not be re-treated with the same drug regimen, because SVR rates are low (9–15% for all genotypes and 4–6% for genotype 1) [17, 18].

These patients should wait for approval of new combination therapies, which have been shown to result in higher SVR rates of between 30% and 60%, depending upon the type of previous non-response and the stage of liver disease [19].

Standard of care, dose regimen and monitoring of treatment efficacy

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology and natural history
  5. Guideline recommendations methodology
  6. Diagnostic tools and staging of HCV liver disease – main recommendations
  7. Results of current therapies and predictors of response summary of evidence
  8. Indications for treatment – main recommendations
  9. Standard of care, dose regimen and monitoring of treatment efficacy
  10. Monitoring of safety and treatment dose reductions – main recommendations
  11. Main recommendation of treatment in patients with severe liver disease and with post-transplant HCV recurrence
  12. Treatment of patients with co-infection and with comorbidities
  13. Treatment of acute hepatitis C
  14. Future perspectives
  15. Conflicts of interest
  16. References
  • The combination of PEG-IFN-α/RBV is the approved SoC for chronic hepatitis C (A1).
  • Two PEG-IFN-α molecules, PEG-IFN-α2a (180 μg once per week) and PEG-IFN-α2b (1.5 μg/kg once per week), can be used in combination with RBV.
  • RBV should be given at a weight-based dose of 15 mg/kg/day for genotypes 1 and 4–6 (A2) and at a flat dose of 800 mg/day for genotypes 2 and 3 (A2)
  • Patients with genotypes 2 and 3 with baseline factors suggesting low responsiveness (insulin resistance, metabolic syndrome, severe fibrosis or cirrhosis, older age) should receive weight-based RBV at the dose of 15 mg/kg/day (C2).

Monitoring of treatment efficacy is based on the repeated measurement of HCV RNA levels (Fig. 1).

  • During treatment, HCV RNA measurements should be performed at weeks 4, 12 and 24 to help tailor treatment (A2).
  • The end-of-treatment virological response and the SVR 24 weeks after the end of treatment must be assessed (A1).
image

Figure 1. Likelihood of sustained virological response according to timing of viral response.

Download figure to PowerPoint

Shorter treatment (24 week treatment) is indicated in patients with genotype 1 and a low vs. high baseline and undetectable HCV RNA after 4 weeks of treatment.

However, there is no current agreement on the most discriminatory HCV RNA level, which can range from 400,000 to 800,000 IU/ml (5.6–5.9 log10 IU/ml) [20-26].

Patients can be classified into different groups according to their virological outcome (Table 1).

Table 1. Different classes of patients according to virological response
Sustained virological responseUndectable HCV RNA level(<50 IU/ml), 24 weeks after treatment
Rapid virological responseUndectable HCV RNA in a sensitive assay (lower limit of detection ≤ 50 IU/ml) at week 4 of therapy, maintained up to end of treatment
Early virological responseHCV RNA detectable at week 4 but undetectable at week 12, maintained up to end of treatment
Delayed virological responseMore than 2 log10drop but detectable HCV RNA at week 12, HCV RNA undetectable at week 24, maintained up to end of treatment
Null responseLess than 2 log10 IU/ml decrease in HCV RNA level from baseline at 12 weeks of therapy
Partial nonresponseMore than 2 log10 IU/ml decrease in HCV RNA level from baseline at 12 weeks of therapy but detectable HCV RNA at weeks 12 and 24
BreakthroughRe-appearance of HCV RNA at any time during treatment after virological response

Depending on genotype, baseline viral load and timing of virological response, strict adherence to the following recommendations is suggested:

  • Treatment for all HCV genotypes should be stopped at week 12 if the HCV RNA decrease is less than 2 log10 IU/ml and at week 24 if HCV RNA is still detectable (≥50 IU/ml) (B1).
  • In patients with a rapid virological response (RVR) and low baseline viral load (<400,000–800,000 IU/ml), treatment for 24 weeks (genotypes 1 and 4) or 12–16 weeks (genotypes 2/3) can be considered. If negative predictors of response (i.e. advanced fibrosis/cirrhosis, metabolic syndrome, insulin resistance, hepatic steatosis) are present, evidence for equal efficacy of shortened treatment is insufficient (B2).
  • Patients who have an early virological response (EVR), i.e. HCV RNA which is detectable at week 4 but undetectable at week 12 should be treated for 48 weeks regardless of the HCV genotype and baseline viral load (C2).
  • Patients with genotype 1 and a delayed virological response can be treated for 72 weeks (B2). This may also apply to other genotypes.

Monitoring of safety and treatment dose reductions – main recommendations

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology and natural history
  5. Guideline recommendations methodology
  6. Diagnostic tools and staging of HCV liver disease – main recommendations
  7. Results of current therapies and predictors of response summary of evidence
  8. Indications for treatment – main recommendations
  9. Standard of care, dose regimen and monitoring of treatment efficacy
  10. Monitoring of safety and treatment dose reductions – main recommendations
  11. Main recommendation of treatment in patients with severe liver disease and with post-transplant HCV recurrence
  12. Treatment of patients with co-infection and with comorbidities
  13. Treatment of acute hepatitis C
  14. Future perspectives
  15. Conflicts of interest
  16. References

At each visit, the patients should be assessed for clinical side effects, such as severe fatigue, depression, irritability, sleeping disorders, skin reactions and dyspnoea. Haematological and biochemical side effects of PEG-IFN-α and RBV include neutropenia, anaemia, thrombocytopenia and ALT flares.

Thyroid stimulating hormone and free thyroxine levels should be measured every 12 weeks while on therapy [27] and patients should be advised about the risk of teratogenicity with RBV and the need for contraception during and 6 months after treatment.

  • The PEG-IFN-α dose should be reduced if the absolute neutrophil count falls below 750/mm3, or the platelet count falls below 50,000/mm3, and stopped if the neutrophil count falls below 500/mm3 or the platelet count falls below 25,000/mm3 or if severe unmanageable depression develops (C2).
  • If neutrophil or platelet counts go up, treatment can be restarted, but at a reduced PEG-IFN-α dose (C2).
  • If haemoglobin < 10 g/dl occurs, the dose of RBV should be adjusted downward by 200 mg at a time (C2), and RBV stopped if haemoglobin falls below 8.5 g/dl.
  • Treatment should be stopped in case of a severe hepatitis flare or severe sepsis (C2).

When using PEG-IFN-α2a, the dose can be reduced from 180 to 135 μg/week and then to 90 μg/week. When using PEG-IFN-α2b, the dose can be reduced from 1.5 to 1.0 μg/kg/week and then to 0.5 μg/kg/week.

However, full adherence to both PEG-IFN-α and RBV is associated with improved SVR rates [27], thus it is recommended that any dose reductions be reviewed and the full dose reinstituted as soon as possible to attain and sustain maximum exposure to each drug [28]. Patients should be informed of the preventive and therapeutic measures to relieve these side effects, for example, using antipyretics, analgesics or antidepressants, and it has been suggested that the use of growth factors may help limit dose reductions.

  • Recombinant erythropoietin can be administered when the haemoglobin level falls below 10 g/dl to avoid RBV dose reduction or discontinuation (C2).
  • There is no evidence that neutropenia during PEG-IFN-α/RBV therapy is associated with more frequent infection episodes (C1), or that the use of granulocyte colony-stimulating factor (G-CSF) reduces the rate of infections and/or improves SVR rates (B1).
  • Patients with a history and/or signs of depression should be seen by a psychiatrist before therapy (C2). Patients who develop depression during therapy should be treated with antidepressants. Preventive antidepressant therapy in selected subjects may reduce the incidence of depression during treatment, without any impact on the SVR (B2).

Main recommendation of treatment in patients with severe liver disease and with post-transplant HCV recurrence

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology and natural history
  5. Guideline recommendations methodology
  6. Diagnostic tools and staging of HCV liver disease – main recommendations
  7. Results of current therapies and predictors of response summary of evidence
  8. Indications for treatment – main recommendations
  9. Standard of care, dose regimen and monitoring of treatment efficacy
  10. Monitoring of safety and treatment dose reductions – main recommendations
  11. Main recommendation of treatment in patients with severe liver disease and with post-transplant HCV recurrence
  12. Treatment of patients with co-infection and with comorbidities
  13. Treatment of acute hepatitis C
  14. Future perspectives
  15. Conflicts of interest
  16. References
  • Patients with compensated cirrhosis should be treated, in the absence of contraindications, to prevent short to mid-term complications (A1).
  • Assiduous monitoring and management of side effects, especially those linked to portal hypertension and hypersplenism, is required. Growth factors are particularly useful in this group (C2).
  • Patients with cirrhosis should undergo regular surveillance for HCC, irrespective of SVR (B1).
  • Patients awaiting transplantation, antiviral therapy, when feasible, prevents graft re-infection if an SVR is achieved (B1). Many patients have contraindications to treatment and the results of therapy are generally poor in this group of individuals with very advanced liver disease (B1).
  • Antiviral therapy is indicated in patients with conserved liver function (Child–Pugh A) in whom the indication for transplantation is HCC (B2).
  • In patients with Child–Pugh B cirrhosis, antiviral therapy is offered on an individual basis in experienced centres, preferentially in patients with predictors of good response (C2). Norfloxacin prophylaxis should be given if ascites is present (C2).
  • Patients with Child–Pugh C cirrhosis should not be treated with the current antiviral regimen, because of a high risk of life-threatening complications (C1).
  • Patients with post-transplant recurrence of HCV infection should initiate therapy once chronic hepatitis is established and is histologically proven (B2). Significant fibrosis or portal hypertension 1 year after transplantation predicts rapid disease progression and graft loss and indicates urgent antiviral treatment (B2).

Treatment of patients with co-infection and with comorbidities

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology and natural history
  5. Guideline recommendations methodology
  6. Diagnostic tools and staging of HCV liver disease – main recommendations
  7. Results of current therapies and predictors of response summary of evidence
  8. Indications for treatment – main recommendations
  9. Standard of care, dose regimen and monitoring of treatment efficacy
  10. Monitoring of safety and treatment dose reductions – main recommendations
  11. Main recommendation of treatment in patients with severe liver disease and with post-transplant HCV recurrence
  12. Treatment of patients with co-infection and with comorbidities
  13. Treatment of acute hepatitis C
  14. Future perspectives
  15. Conflicts of interest
  16. References

HIV

Progression of liver disease is accelerated in patients with HIV–HCV co-infection, in particular those with a low CD4-positive cell count and impaired immune function. For this reason, early antiretroviral therapy should be considered in patients with HIV–HCV co-infection [29]. Rates of SVR are generally lower than in monoinfected patients, in proportion to the HCV genotype [30], thus

  • Longer treatment duration (72 weeks for genotype 1 and 48 weeks for genotypes 2 and 3) may be needed (B2).

HBV

In patients with HBV co-infection, the replicative status of both HBV and HCV should be determined, and hepatitis delta virus infection excluded.

  • Patients should be treated with PEG-IFN-α/RBV, following the same rules as monoinfected patients (B2).
  • If HBV replicates at significant levels before, during or after HCV clearance, concurrent HBV nucleoside/nucleotide analogue therapy is indicated (C2).

Haemoglobinopathies

Thalassaemia major is the most frequent haemoglobinopathy associated with chronic hepatitis C. In the few published clinical trials, these patients had a higher incidence of anaemia and iron accumulation with a standard combination of PEG-IFN-α and RBV. Therefore, although they can be treated with standard combination therapy, these complications should be carefully managed with growth factors, blood transfusions and iron chelation therapy when needed [31].

Haemodialysis patients

Haemodialysis patients have been treated with PEG-IFN-α monotherapy at the usual doses [32] as RBV is cleared by the kidneys.

Furthermore, as PEG-IFN-α2a is cleared through the liver and PEG-IFN-α2b primarily through the kidneys, there could be a theoretical accumulation of PEG-IFN-α2b in haemodialysis patients, which could either cause more side effects or an increased efficacy [33, 34].

There are very few recommendations for non-hepatic solid organ transplant recipients:

  • Patients with HCV and end stage renal disease scheduled for kidney transplantation should undergo antiviral therapy prior to kidney transplantation because of the increased risk of acute transplant rejection (B2).

Alcohol and drug abuse patients

Chronic alcohol consumption in patients with chronic hepatitis C is associated with an accelerated progression of fibrosis, a higher frequency of cirrhosis and a higher incidence of HCC [35].

Moreover, it is generally accepted that patients should be drug-free or on stable substitution therapy for at least 6–12 months.

Treatment of acute hepatitis C

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology and natural history
  5. Guideline recommendations methodology
  6. Diagnostic tools and staging of HCV liver disease – main recommendations
  7. Results of current therapies and predictors of response summary of evidence
  8. Indications for treatment – main recommendations
  9. Standard of care, dose regimen and monitoring of treatment efficacy
  10. Monitoring of safety and treatment dose reductions – main recommendations
  11. Main recommendation of treatment in patients with severe liver disease and with post-transplant HCV recurrence
  12. Treatment of patients with co-infection and with comorbidities
  13. Treatment of acute hepatitis C
  14. Future perspectives
  15. Conflicts of interest
  16. References

Patients with acute hepatitis C should be considered for antiviral therapy to prevent the progression to chronic hepatitis C. High SVR rates (up to 90% or even higher) have been reported with PEG-IFN-α monotherapy in a series of mostly symptomatic patients, regardless of the HCV genotype.

Combination therapy with RBV does not increase the SVR rate in this setting but may be considered in patients in whom the differential diagnosis of acute vs. chronic hepatitis remains uncertain [4, 36-41].

  • PEG-IFN-α monotherapy (PEG-IFN-α2a, 180 μg/week or PEG-IFN-α2b, 1.5 μg/kg/week, for 24 weeks) is recommended in patients with acute hepatitis C and obtains viral eradication in > 90% of patients (B2).
  • Patients failing to respond should be re-treated according to the SoC for chronic hepatitis C (C2).

Future perspectives

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology and natural history
  5. Guideline recommendations methodology
  6. Diagnostic tools and staging of HCV liver disease – main recommendations
  7. Results of current therapies and predictors of response summary of evidence
  8. Indications for treatment – main recommendations
  9. Standard of care, dose regimen and monitoring of treatment efficacy
  10. Monitoring of safety and treatment dose reductions – main recommendations
  11. Main recommendation of treatment in patients with severe liver disease and with post-transplant HCV recurrence
  12. Treatment of patients with co-infection and with comorbidities
  13. Treatment of acute hepatitis C
  14. Future perspectives
  15. Conflicts of interest
  16. References

Important progress has been made in the development of new treatments, in particular, new specific inhibitors or direct antiviral agents that are active against hepatitis C.

Numerous studies have been conducted mostly in patients infected by HCV genotype 1 [42] showing an increase in the SVR rate of 27–31% in treatment-naïve patients. Previous relapse patients show very high SVR rates of 75%–86%, while response rates are lower for partial responders (>2 log decline in HCV RNA at 12 weeks of prior therapy) (50–60%) and previous non-responder patients (33%, data only for telaprevir) [43].

Thus, the EASL HCV guidelines will be updated when these combinations are approved. In patients infected with HCV genotypes other than 1, the current guidelines still apply.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology and natural history
  5. Guideline recommendations methodology
  6. Diagnostic tools and staging of HCV liver disease – main recommendations
  7. Results of current therapies and predictors of response summary of evidence
  8. Indications for treatment – main recommendations
  9. Standard of care, dose regimen and monitoring of treatment efficacy
  10. Monitoring of safety and treatment dose reductions – main recommendations
  11. Main recommendation of treatment in patients with severe liver disease and with post-transplant HCV recurrence
  12. Treatment of patients with co-infection and with comorbidities
  13. Treatment of acute hepatitis C
  14. Future perspectives
  15. Conflicts of interest
  16. References