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World Health Organization Guidelines on Treatment of Hepatitis C Virus Infection: Best Practice Advice From the American College of Physicians

2020; American College of Physicians; Volume: 174; Issue: 1 Linguagem: Inglês

10.7326/m19-3860

1539-3704

George M. Abraham, Adam J. Obley, Linda L. Humphrey, Amir Qaseem,

Hepatitis B Virus Studies

Ideas and OpinionsJanuary 2021World Health Organization Guidelines on Treatment of Hepatitis C Virus Infection: Best Practice Advice From the American College of PhysiciansFREEGeorge M. Abraham, MD, MPH, Adam J. Obley, MD, Linda L. Humphrey, MD, MPH, and Amir Qaseem, MD, PhD, MHA, for the Scientific Medical Policy Committee of the American College of Physicians*George M. Abraham, MD, MPHUniversity of Massachusetts Medical School and Saint Vincent Hospital, Worcester, Massachusetts (G.M.A.), Adam J. Obley, MDPortland Veterans Affairs Medical Center and Oregon Health & Science University, Portland, Oregon (A.J.O., L.L.H.), Linda L. Humphrey, MD, MPHPortland Veterans Affairs Medical Center and Oregon Health & Science University, Portland, Oregon (A.J.O., L.L.H.), and Amir Qaseem, MD, PhD, MHAAmerican College of Physicians, Philadelphia, Pennsylvania (A.Q.), for the Scientific Medical Policy Committee of the American College of Physicians*Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M19-3860 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In the United States, the incidence of hepatitis C virus (HCV) infection is 1.2 per 100 000 persons, the prevalence is 2.4 million cases, and annual mortality is more than 15 000 deaths (1, 2). Eliminating hepatitis will require diagnosis of 90% of those infected followed by treatment of 80% of those diagnosed (3). The World Health Organization (WHO) updated its evidence-based guideline on chronic HCV infection in July 2018 (Table) (3). Although the WHO guideline is primarily targeted toward policymakers in low- and middle-income countries, recommendations are relevant to the United States, where equity and resource allocation issues are also important considerations. We discuss implications of the WHO recommendations for clinicians and patients in the United States.Table. Summary of the 2018 WHO Recommended Treatments for Adults With Chronic HCV Infection, With Estimated Cost of Treatment in the United StatesDiscussionThe WHO recommends offering treatment to all persons older than 12 years who have chronic HCV infection, and it notes 3 major considerations for this "treat all" strategy: the effectiveness and safety of direct-acting antiviral agents (DAAs), the emergence of pangenotypic drug regimens, and reduction in the cost of treatment (3). In current treatment regimens, combination therapy with oral DAAs has replaced interferon and ribavirin. The WHO recommends pangenotypic regimens that simplify pretreatment and on-treatment testing. This differs from guidance from the American Association for the Study of Liver Diseases and Infectious Diseases Society of America (4, 5), which recommends specific DAA treatment regimens based on genotype and more intensive laboratory testing before and during treatment. The WHO recommendations offer U.S. clinicians the opportunity to simplify and reduce the cost of care without compromising care quality.The WHO defines pangenotypic treatment regimens as those achieving a rate of sustained virologic response (SVR) greater than 85% across all major HCV genotypes (3). However, in the United States, the sofosbuvir–daclatasvir regimen has fallen out of favor given inferior response rates in non–head-to-head comparisons with other regimens in registration trials (6). In patients with decompensated cirrhosis (Child–Turcotte–Pugh class C), treatment options are similar to those for other patients with cirrhosis, but response may be lower and risk for adverse effects may be higher. In addition, experts suggest lifelong monitoring for hepatocellular carcinoma for all patients with cirrhosis, even with SVR (4).Successful treatment is defined as an undetectable viral load 12 weeks after completion of therapy (SVR12) (7). Pangenotypic DAA regimens are highly effective, and pooled SVR12 rates generally exceed 85% to 90%. Systematic reviews of studies using interferon-based treatment indicate that achievement of SVR12 reduces illness associated with cirrhosis and extrahepatic manifestations of HCV (3, 7). However, direct evidence that DAA treatment regimens lead to these patient-important outcomes is sparse, indicating an area for future research.The WHO estimates that a treat all approach would prevent 0.57 infections over 20 years for each person treated (3). Although some of the parameters used in the WHO model, such as population growth rate and HCV prevalence, are lower in the United States, the population benefits of treating all patients with HCV are still likely to be meaningful. The WHO notes that DAA regimens are well tolerated and have mild adverse effects but acknowledges that broader use of DAAs could uncover more severe adverse effects. It also cautions about the heightened risk for hepatitis B reactivation during HCV treatment, as well as the possibility that a treat all approach could divert attention and resources from interventions for HCV harm reduction. Drug interactions with DAAs are also important to consider, especially because commonly used drugs, such as proton-pump inhibitors, statins, antidepressants, and antiretroviral therapy, can inactivate some DAAs (3, 6). Most patients support a treat all strategy, but some express concern about adverse effects and costs (3).The WHO recommendations have implications for high-value care. First, wider adoption of pangenotypic regimens in the United States would obviate the need for viral genotyping before treatment is started (except when using glecaprevir–pibrentasvir [GLE–PIB], in which case genotyping is necessary to identify genotype 3, which requires longer treatment). Second, pretreatment testing is required only to distinguish patients with cirrhosis from those without to determine treatment duration, a distinction reliably made with inexpensive, noninvasive tests (8). When clinical circumstances require a more refined assessment of the degree of precirrhotic fibrosis, noninvasive techniques, such as vibration-controlled transient elastography, can be considered in lieu of liver biopsy (4, 9). Third, many patients with uncomplicated HCV infection do not require specialist involvement, and laboratory monitoring can be limited to the beginning and end of treatment. Patients with decompensated cirrhosis, hepatitis B or HIV co-infection, or chronic kidney disease; pregnant women; and those in whom a prior DAA regimen has been unsuccessful should be managed in consultation with a specialist and likely require more careful laboratory monitoring.Although the WHO guidance provides several opportunities to improve hepatitis C care, affordability still poses a barrier to DAA treatment, and price varies globally. Recognizing this, the WHO has developed a calculator (www.hepccalculator.org/hepccalc) that estimates the cost-effectiveness of HCV treatment in 28 countries that it has deemed high-priority by applying its customary willingness-to-pay threshold of 3 times the per capita gross domestic product of the country. The cost of a 4-week DAA regimen in the online model ranges from $15 in Pakistan to $73 944 in Romania. Although the United States is not represented in the WHO cost-effectiveness calculator and the cost of DAA treatment in the United States can vary greatly on the basis of several factors, the average cost of treatment has decreased and may now be less than $15 000 per patient. In comparison, the total lifelong cost of HIV treatment with darunavir, cobicistat, emtricitabine, and tenofovir alafenamide is $1.2 million. In addition, the opportunity to prevent the transmission of HCV must be considered when cost-effectiveness is discussed.Treatment of chronic hepatitis C disease has reached a stage where pangenotypic regimens with shorter durations of therapy (8 to 16 weeks) can achieve virologic cure rates (SVR12) of more than 90% (6). Improving affordability and availability worldwide are important next steps in universal reduction in the prevalence of this disease. Given the simplicity of the testing and treatment regimens, particularly with sofosbuvir–velpatasvir, referral to a subspecialist is not necessary.Best Practice AdviceViral genotyping is unnecessary when treating HCV with pangenotypic medications unless planning treatment with GLE–PIB. Invasive testing to establish the degree of fibrosis is not necessary, and inexpensive laboratory tests can reliably identify patients with cirrhosis. Patients aged 18 years or older without cirrhosis should receive sofosbuvir–velpatasvir for 12 weeks or GLE–PIB for 8 weeks (16 weeks in cases with known genotype 3 infection) (3, 10). Those with compensated cirrhosis should be treated with sofosbuvir–velpatasvir for 12 weeks or GLE–PIB for 12 weeks (16 weeks in cases with known genotype 3 infection) (3). Laboratory monitoring can be limited to the beginning and end of the treatment in adults with no or compensated cirrhosis. Patients with decompensated cirrhosis will need closer monitoring. The simplification of treatment and monitoring enables patients with uncomplicated HCV infection to receive treatment in primary care settings.References1. Hofmeister MG, Rosenthal EM, Barker LK, et al. Estimating prevalence of hepatitis C virus infection in the United States, 2013-2016. Hepatology. 2019;69:1020-31. [PMID: 30398671] doi:10.1002/hep.30297 CrossrefMedlineGoogle Scholar 2. 2. Centers for Disease Control and Prevention. Viral hepatitis surveillance report 2018—hepatitis C. May 2018. Accessed at www.cdc.gov/hepatitis/statistics/2018surveillance/HepC.htm on 17 September 2020. Google Scholar3. World Health Organization. Guidelines for the Care and Treatment of Persons Diagnosed With Chronic Hepatitis C Virus Infection. 2018. Accessed at www.who.int/hepatitis/publications/hepatitis-c-guidelines-2018/en on 12 June 2019. Google Scholar4. AASLD-IDSA HCV Guidance Panel. Hepatitis C guidance 2018 update: AASLD-IDSA recommendations for testing, managing, and treating hepatitis C virus infection. Clin Infect Dis. 2018;67:1477-1492. [PMID: 30215672] doi:10.1093/cid/ciy585 CrossrefMedlineGoogle Scholar5. Ghany MG, Morgan TR, et al. Hepatitis C guidance 2019 update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America recommendations for testing, managing, and treating hepatitis C virus infection. Hepatology. 2020;71:686-721. [PMID: 31816111] doi:10.1002/hep.31060 CrossrefMedlineGoogle Scholar6. Abraham GM, Spooner LM. Citius, altius, fortius: the new paradigm in the treatment of chronic hepatitis C disease. Clin Infect Dis. 2018;66:464-474. [PMID: 29020275] doi:10.1093/cid/cix746 CrossrefMedlineGoogle Scholar7. Morgan RL, Baack B, Smith BD, et al. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med. 2013;158:329-37. doi:10.7326/0003-4819-158-5-201303050-00005 LinkGoogle Scholar8. Chou R, Wasson N. Blood tests to diagnose fibrosis or cirrhosis in patients with chronic hepatitis C virus infection: a systematic review. Ann Intern Med. 2013;158:807-20. doi:10.7326/0003-4819-158-11-201306040-00005 LinkGoogle Scholar9. Castéra L, Vergniol J, Foucher J, et al. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005;128:343-50. [PMID: 15685546] CrossrefMedlineGoogle Scholar10. Asselah T, Kowdley KV, Zadeikis N, et al. Efficacy of glecaprevir/pibrentasvir for 8 or 12 weeks in patients with hepatitis C virus genotype 2, 4, 5, or 6 infection without cirrhosis. Clin Gastroenterol Hepatol. 2018;16:417-426. [PMID: 28951228] doi:10.1016/j.cgh.2017.09.027 CrossrefMedlineGoogle Scholar Comments0 CommentsSign In to Submit A Comment Jorge Bezerra, Thomas File Jr., Marc G. Ghany, Timothy Morgan, Kristin Marks, Debika Bhattacharya, David Wyles.AASLD and IDSA3 November 2020 AASLD-IDSA HCV Guidance Rebuttal We have concerns regarding the Ideas and Opinion article by Abraham et. al. on healthcare providers in the United States (U.S.) embracing the 2018 World Health Organization (WHO) recommendations for chronic hepatitis C (CHC) management.(1) While we agree with offering treatment to all persons older than 12 years with CHC, the authors have both 1) misrepresented the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) guidance on management of CHC and 2) provided erroneous information on the management of CHC. Almost a year ago the AASLD/IDSA updated its recommendations to include simplified HCV treatment recommendations for treatment-naive adults with and without cirrhosis using approved pangenotypic regimens.(2) This simplified approach provides clear guidance on eligibility and testing before, during, and after treatment. This simplified approach should expand the number of healthcare professionals who treat CHC and increase the number of persons treated. This would align with the National Academies of Science, Engineering, and Medicine strategy to reduce cases of CHC by 90% by 2030.(3) Although sofosbuvir-daclatasvir is available in other countries, this combination was never approved in the U.S. and daclatasvir was withdrawn from the U.S. market in June 2019. This is the reason daclatasvir was removed from the AASLD-IDSA guidance. More importantly, the ACP Opinion document provides erroneous recommendations on HCV genotype testing prior to treatment as well as treatment duration with glecaprevir/pibrentasvir (G/P). We wish to correct these errors. Pre-treatment testing for HCV genotype is not required for treatment-naïve patients, regardless of cirrhosis status, when prescribing G/P. All treatment naïve patients can receive 8 weeks of G/P, including those with genotype 3 infection.(4) Further, sixteen weeks of treatment with G/P is only recommended for persons with genotype 3 infection who were previously treated with interferon-based therapy. Since the availability of highly potent DAAs, this represents a small fraction of patients. Additionally, the Table lists the duration of G/P for previously untreated patients with compensated cirrhosis as 12 weeks. The FDA-approval is 8 weeks for this population. HCV treatment can be provided by a range of health care professionals without compromising efficacy or safety. We therefore enthusiastically support a simplified approach to HCV treatment to facilitate increased treatment uptake. However, the mistakes in the Opinion piece will lead to errors by U.S. healthcare providers managing patients with CHC. We strongly recommend that these errors be corrected as soon as possible. Jorge Bezerra, MD, FAASLD, President AASLD Thomas File, Jr. MD, FISDA, President IDSA Marc G. Ghany, MD, MHDc, Timothy Morgan, MD, Co-Chairs AASLD, HCV guidance committee, David Wyles, MD, Kristen Marks, MD, Debika Bhattacharya, MD, Co-Chairs IDSA HCV guidance committee All authors contributed equally to the drafting and editing of this document. References: Abraham GM, Obley AJ, Humphrey LL, Qaseem A. World Health Organization Guidelines on Treatment of Hepatitis C Virus Infection: Best Practice Advice From the American College of Physicians. Ann Intern Med 2020. Ghany MG, Morgan TR, Panel A-IHCG. Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Hepatology 2020;71:686-721. Buckley GJ, Strom BL. A National Strategy for the Elimination of Viral Hepatitis Emphasizes Prevention, Screening, and Universal Treatment of Hepatitis C. Ann Intern Med 2017;166:895-896. https://www.rxabbvie.com/pdf/mavyret_pi.pdf 2019;Last accessed October 16th, 2020. Flamm S, Reddy KR, Zadeikis N, et al. Efficacy and Pharmacokinetics of Glecaprevir and Pibrentasvir With Concurrent Use of Acid-Reducing Agents in Patients With Chronic HCV Infection. Clin Gastroenterol Hepatol 2019; 17:527-535.e6. George M. Abraham, MD, MPH, Linda L. Humphrey, MD, MPH, Adam J. Obley, MD, & Amir Qaseem, MD, PhD, MHA, for the American College of Physician's Scientific Medical Policy CommitteeAmerican College of Physicians1 December 2020 Authors' response We thank Drs. Bezerra, Bhattacharya File, Ghany, Marks, Morgan, and Wyles for their comments. The purpose of this article was to discuss the World Health Organization's (WHO) recommendations on treatment of chronic hepatitis C (HCV); the goal was not to critique the American Association for the Study of Liver Diseases-Infectious Diseases Society of America (AASLD/IDSA) guideline (1). Since writing our paper, the AASLD/IDSA have updated their guideline with a simplified algorithm, which focuses on treatment-naïve patients only. We believe that the simplified and converging treatment guidelines from WHO and AASLD/IDSA will help promote broader access to treatment. The WHO guidance (2) does not differentiate between treatment-naïve and treatment-experienced populations and recommends a treat all strategy using pangenotypic regimens. Perhaps this key underlying difference accounts for the seeming discrepancies in genotyping and treatment durations for glecaprevir/pibrentasvir (GLE-PIB) in treatment-naïve or treatment-experienced patients. We appreciate the opportunity to clarify that we agree that viral genotyping is generally not necessary when using pangenotypic regimens and we also reiterate that there is no need for invasive testing. Direct-acting antivirals are well tolerated and laboratory monitoring can be limited to the beginning and end of treatment in adults with no or compensated cirrhosis, as recommended by the WHO. As far as the duration of treatment using GLE-PIB is concerned, the WHO recommends using GLE-PIB for 8 weeks in patients without cirrhosis and 12 weeks in patients with compensated cirrhosis, regardless of genotype. However, the duration is 16 weeks in patients with genotype 3 infection who have previously received interferon and/or ribavirin, as noted in our table. It is in this specific clinical scenario, that physicians planning to use the GLE-PIB combination, will find genotyping helpful in clinical decision-making. After the publication of the WHO guideline, both the US Food & Drug Administration and AASLD/IDSA reduced their recommended duration for treatment-naïve patients with compensated cirrhosis from 12 to 8 weeks in 2019 (3, 4). However, the WHO guideline has not been updated and clinicians should be aware of this discrepancy. It is important to note that the FDA still recommends 12-16 weeks of GLE-PIB in treatment-experienced patients with compensated cirrhosis, and as previously noted, the WHO guideline does not differentiate treatment-naïve and treatment-experienced. We have updated our table to reflect the 2019 durations recommended by the AASLD/IDSA and to clarify the differences between treatment experiences (see below). We disagree that we erroneously reported on sofosbuvir-daclatasvir: we specifically state that its use has been discontinued in the US and we do not discuss this combination in our best practice advice. We are encouraged that there is agreement and enthusiasm for a simplified approach to the treatment of chronic HCV with the ultimate goal of reducing the prevalence, transmission and complications of Hepatitis C. Updated Table. Summary of the 2018 WHO Recommended Treatments for Adults With Chronic HCV Infection, With Estimated Cost of Treatment in the United States Pangenotypic DAAs* Treatment Duration, wk Drug Price per Patient in the United States, $† Total Cost of Treating All Patients With Chronic HCV Infection in the United States, $‡ 2019 AASLD/IDSA Recommendations** Adults without cirrhosis SOF–VEL 12 10 917 26.05 billion Yes, for genotypes 1–6†† SOF–DCV§ 12 || || NoGLE–PIB¶ 8 10 196 24.3 billion Treatment-naïve: 8 wk for genotypes 1–6Treatment-experienced (P/R): 8 wk for genotypes 1,2,4–6 (16 wk for genotype 3) Adults with compensated cirrhosis SOF–VEL 12 10 917 26.05 billion Yes, for genotypes 1–6SOF–DCV§ 24 || || NoGLE–PIB¶ 12 13 029 31.1 billion Treatment-naïve: 8 wk for genotypes 1–6 Treatment-experienced (P/R): 12 wk for genotypes 1,2,4–6 (16 wk for genotype 3) AASLD/IDSA = American Association for the Study of Liver Disease/Infectious Diseases Society of America; DAA = direct-acting antiviral agent; DCV = daclatasvir; GLE–PIB = glecaprevir–pibrentasvir; P/R = peginterfon/ribavirin; SOF = sofosbuvir; VEL = velpatasvir; WHO = World Health Organization. * Defined as those leading to a sustained virologic response rate >85% across all 6 major HCV genotypes.† Individual patient drug cost data were obtained from https://healthcarebluebook.com (accessed 19 March 2020). ‡ Based on U.S. prevalence of 2.4 million cases (1).§ 12 wk may be considered for compensated cirrhosis in countries where genotype 3 distribution is known and prevalence is <5%. As of 2019, many major insurance plans no longer cover GLE–PIB/(www.goodrx.com/mavyret).|| As of 2019, DCV is discontinued in the United States. Source: www.drugs.com/history/daklinza.html (accessed 19 March 2020).¶ WHO recommends treating persons with genotype 3 infection who have previously received interferon and/or ribavirin for 16 wk. As of 2019, many major insurance plans no longer cover GLE-PIB (www.goodrx.com/mavyret)**For treatment-naïve and treatment-experienced (peginterfeon/ribavirin) patients, unless otherwise specified. See AASLD/IDSA guideline for full recommendations (4) †† For GT 3 patients without Y93H References1. Abraham GM, Obley AJ, Humphrey LL, Qaseem A. World Health Organization Guidelines on Treatment of Hepatitis C Virus Infection: Best Practice Advice From the American College of Physicians. Ann Intern Med 2020.2. World Health Organization. Guidelines for the Care and Treatment of Persons Diagnosed With Chronic Hepatitis C Virus Infection. 2018. Accessed at www.who.int/hepatitis/publications/hepatitis-c-guidelines-2018/en on 12 June 2019.3. Mavyret [package insert]. North Chicago, IL: AbbVie, Inc.; 2020.4. AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Author, Article, and Disclosure InformationAffiliations: University of Massachusetts Medical School and Saint Vincent Hospital, Worcester, Massachusetts (G.M.A.)Portland Veterans Affairs Medical Center and Oregon Health & Science University, Portland, Oregon (A.J.O., L.L.H.)American College of Physicians, Philadelphia, Pennsylvania (A.Q.)Financial Support: Financial support for the development of this commentary comes exclusively from the ACP operating budget.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-3860. The authors and Scientific Medical Policy Committee declared all financial and intellectual disclosures of interest, and potential conflicts were discussed and managed. No committee members were recused from participation because of a conflict of interest. A record of disclosures of interest is kept for each Scientific Medical Policy Committee meeting and conference call and can be viewed at www.acponline.org/clinical-information/high-value-care.Corresponding Author: Amir Qaseem, MD, PhD, MHA, American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106; e-mail, [email protected]org.Current Author Addresses: Dr. Abraham: 123 Summer Street, Suite 370, North Worcester, MA 01608.Dr. Obley: 3030 SW Moody Avenue, Suite 250, Portland, OR 97201.Dr. Humphrey: 3710 SW U.S. Veterans Hospital Road, Portland, OR 97201.Dr. Qaseem: 190 N. Independence Mall West, Philadelphia, PA 19106.Author Contributions: Conception and design: G.M. Abraham, A.J. Obley, A. Qaseem.Analysis and interpretation of the data: A.J. Obley, L.L. Humphrey, A. Qaseem.Drafting of the article: G.M. Abraham, A.J. Obley, A. Qaseem.Critical revision of the article for important intellectual content: G.M. Abraham, A.J. Obley, L.L. Humphrey, A. Qaseem.Final approval of the article: G.M. Abraham, A.J. Obley, L.L. Humphrey, A. Qaseem.Administrative, technical, or logistic support: A. Qaseem.This article was published at Annals.org on 6 October 2020.* This paper, authored by George M. Abraham, MD, MPH; Adam J. Obley, MD; Linda L. Humphrey, MD, MPH; and Amir Qaseem, MD, PhD, MHA, was developed for the Scientific Medical Policy Committee of the American College of Physicians. Individuals who served on the Scientific Medical Policy Committee from initiation of the project until its approval were Linda L. Humphrey, MD, MPH† (Chair); Robert M. Centor, MD† (Vice Chair); Elie Akl, MD, MPH, PhD†; Mary Ann Forciea, MD†; Ray Haeme†‡; Peter G. Hamilton, MBBCh†; Gregory A. Hood, MD†; Janet A. Jokela, MD, MPH†; Devan L. Kansagara, MD, MCR†; Mark A. Levine, MD†; James R. Mason, MD†; Maura Marcucci, MD, MSc†; and Adam J. Obley, MD†. Approved by the ACP Board of Regents on 3 November 2019.† Author (participated in discussion and voting).‡ Nonphysician public representative. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe tolerability of sofosbuvir/velpatasvir for 12 weeks in patients treated in the ASTRAL 1, 2 and 3 studies: A pooled safety analysisHealthcare resource utilization in Hepatitis C-infected patients completing eight versus twelve weeks of treatment: A retrospective cohort studyClinical Approach to Treatment of Viral InfectionsEditorial commentary on the Indian Journal of Gastroenterology November-December 2020 January 2021Volume 174, Issue 1Page: 98-100KeywordsCirrhosisConflicts of interestDisclosureGenotypingGlobal healthInfectious hepatitisLiver fibrosisResearch laboratoriesSystemic vascular resistanceTreatment guidelines ePublished: 6 October 2020 Issue Published: January 2021 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...