U.S. flag

An official website of the United States government

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Cover of Pretreatment Assessment in Adults With Chronic Hepatitis C Virus Infection

Pretreatment Assessment in Adults With Chronic Hepatitis C Virus Infection

Lead Author: , MD; Writing Group: , MD, , MD, , RN, MS, , MD, MPH, and , MD; on behalf of Hepatitis C Virus (HCV) Guideline Committee .

Baltimore (MD): Johns Hopkins University; .

Updates, Authorship, and Related Guidelines

Developer and funding source

New York State Department of Health AIDS Institute (NYSDOH AI)

Intended users

Clinicians in New York State who treat adults with chronic HCV

Development

See Supplement: Guideline Development and Recommendation Ratings

Updates

October 06, 2022

  • Medical History and Physical Examination: Treatment after organ transplantation was added to patient conditions that suggest referral to a specialist. A recommendation was added on use of birth control during HCV treatment in individuals of childbearing capacity.
  • Table 1: Key Elements of Patient History and Physical Examination: Assessing cardiac status is no longer recommended; birth control use during HCV treatment is now recommended.
  • Note: The NYSDOH AI guideline Treatment of Chronic HCV with Direct-Acting Antivirals (July 2017 through October 2020) was replaced with 3 guidelines: 1) Hepatitis C Virus Screening, Testing and Diagnosis in Adults; 2) Pretreatment Assessment in Adults With Chronic Hepatitis C Virus Infection; and 3) Treatment of Chronic Hepatitis C Virus Infection in Adults

Author and writing group conflict of interest disclosures

See Conflict of Interest statement*

Related NYSDOH AI guidelines

Purpose of This Guideline

Date of current publication: October 6, 2022 Lead author: Christine A. Kerr, MD Writing group: Joshua S. Aron, MD; David E. Bernstein, MD; Colleen Flanigan, RN, MS; Christopher J. Hoffmann, MD, MPH; Charles J. Gonzalez, MD Committee: Hepatitis C Virus (HCV) Guideline Committee Date of original publication: October 6, 2022

This guideline on pretreatment assessment of patients with chronic hepatitis C virus (HCV) was developed by the New York State Department of Health AIDS Institute (NYSDOH AI) to guide primary care providers and other practitioners in New York State in all aspects of treating and curing patients with chronic HCV. The guideline aims to achieve the following goals:

  • Provide evidence-based treatment guidelines to New York State clinicians to increase the number of New York State residents with chronic HCV who are treated and cured.
  • Provide guidance to clinicians on key pretreatment assessment criteria to ensure that HCV medications are prescribed safely and correctly and that all patients receive the highest quality of care.
  • Provide evidence-based clinical recommendations to support the goals of the New York State Hepatitis C Elimination Plan (NY Cures HepC).

Medical History and Physical Examination

RECOMMENDATIONS

Medical History and Physical Examination

  • Clinicians should assess all patients with a confirmed diagnosis of chronic HCV infection, defined as a positive HCV surface antibody test result and detectable HCV RNA, for treatment. (A1)
  • Clinicians should refer patients with chronic HCV and decompensated liver disease and patients who are pre- or post-liver transplant to a liver disease specialist. (A3)
  • Clinicians new to treating chronic HCV infection should consult with a liver disease specialist when treating chronic HCV in patients with any of the following conditions (A3):
    • Compensated cirrhosis; concurrent hepatobiliary conditions
    • Extrahepatic manifestations of HCV, including renal, dermatologic, and rheumatologic manifestations
    • Significant renal impairment (CrCl <30 mL/min) or who are undergoing hemodialysis
    • Active HBV infection, defined as a positive HBsAg test result and detectable HBV DNA
    • Ongoing HCV infection after failure of treatment with DAAs
    • Treatment after organ transplantation

Abbreviations: CrCl, creatinine clearance; DAA, direct-acting antiviral; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus.

With few exceptions, nonpregnant patients with confirmed HCV are candidates for treatment [EASL 2020Ghany and Morgan 2020]. Treatment of HCV infection reduces all-cause mortality, regardless of disease stage [Simmons, et al. 2015]. Patients who are not candidates for treatment with DAAs are those with a life expectancy of fewer than 12 months or for whom treatment or liver transplantation would not improve symptoms or prognosis [AASLD/IDSA 2021]. For recommendations for pregnant patients with chronic HCV and those who become pregnant while taking antiviral therapy for chronic HCV, see the NYSDOH AI guideline Treatment of Chronic Hepatitis C Virus Infection in Adults > HCV Testing and Management in Pregnant Adults.

Screening for mental health and substance use disorders and providing treatment or referral as needed is essential but is not a reason to defer treatment. The approach to treating HCV infection in patients with mental health or substance use disorders is the same as for other patients with HCV. Patients with active substance use or mental health disorders can and should be successfully treated, although additional support for adherence, follow-up, and harm reduction may be necessary [Granozzi, et al. 2021Hajarizadeh, et al. 2020Torrens, et al. 2020Gountas, et al. 2018Sackey, et al. 2018Tsui, et al. 2016].

Key elements of medical history and physical examination: Table 1, below, lists components of the patient history and physical examination that apply specifically to pretreatment assessment of patients with chronic HCV.

Table 1: Key Elements of Patient History and Physical Examination
Elements of Patient History Rationale
Previous treatment for HCV infectionPrevious regimen and treatment outcome will guide choice and duration of therapy.
History of hepatic decompensationWarrants referral to a liver disease specialist.
History of renal diseaseFindings may influence choice of regimen.
Medication history and current medications, including over-the-counter and herbal productsCarefully consider potential drug-drug interactions with DAAs. See American Association for the Study of Liver Diseases (AASLD)/Infectious Diseases Society of America (IDSA) or University of Liverpool HEP Drug Interactions.
Pregnancy status and plans
  • HCV treatment may be deferred during pregnancy [a].
  • Clinician could discuss the possibility of clinical trial participation and refer patient as appropriate (see Clinical Trials.gov).
  • Birth control use is recommended during HCV treatment due to limited data on the safety of treatment during pregnancy.
  • For patients who have been exposed to DAA treatment during pregnancy, contact the Treatment in Pregnancy for Hepatitis C Registry.
HIV infection
  • If HIV infection is confirmed, offer the patient ART [b].
  • If the patient is being treated with antiretroviral medications, assess potential drug-drug interactions.
  • HIV infection may influence fibrosis assessment modality, choice of treatment, treatment duration, and monitoring.
History of infection/vaccination status
  • HAV: Obtain HAV antibody test (IgG or total).
  • HBV: Obtain HBsAg, anti-HBs, and anti-HBc (total).
  • Pneumococcal: Administer pneumococcal polysaccharide vaccine [c] to all patients with cirrhosis, which is associated with increased susceptibility to bacterial infections [Jalan, et al. 2014].
  • Influenza: Administer annual influenza vaccine [d].
Elements of Pretreatment Physical Examination Clinical Details
Presence or absence of ankle edema, abdominal veins, jaundice, palmar erythema, gynecomastia, spider telangiectasia, ascites, encephalopathy, and asterixisPresence may suggest cirrhosis or decompensated cirrhosis and may require additional evaluation and management or treatment.
Presence or absence of physical signs related to extrahepatic manifestations of HCV, such as porphyria cutanea tarda, vasculitis, or lichen planusPresence may increase urgency of HCV treatment and may require additional evaluation and treatment needs [e].
Liver size by palpation or auscultation for hepatomegaly or splenomegaly, as well as tenderness or hepatic bruitsSize and tenderness may suggest the severity of liver disease and may require additional evaluation.

Abbreviations: anti-HBc, hepatitis B core antibody; anti-HBs, hepatitis B surface antibody; ART, antiretroviral therapy; DAA, direct-acting antiviral; HAV, hepatitis A virus; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; IgG, immunoglobulin G.

Notes:

a
b

See NYSDOH AI guideline Rapid ART Initiation.

c

As indicated in the Centers for Disease Control and Prevention Adult Immunization Schedule (recommendations for ages 19 years or older).

d

See U.S. Food and Drug Administration Influenza Virus Vaccine Safety & Availability.

e

Mental Health, Substance Use, and Adherence

Mental health: Mental health disorders are not contraindications to treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs). Strategies to overcome mental health-related barriers to successful HCV treatment include counseling, education, and referral to psychiatry and behavioral health services. Patients with mental health disorders may need increased attention to management of adverse effects and coordination of care during HCV treatment. An integrated care model in which mental health care providers provide HCV treatment and risk-reduction counseling has been effective [Sackey, et al. 2018Groessl, et al. 2013]. Few data are currently available regarding the effect of an existing psychiatric diagnosis on patient adherence to any oral HCV treatment regimen.

With interferon-free regimens, depression is no longer a common adverse effect of HCV treatment. However, antidepressant and antipsychotic drug-drug interactions have been reported with DAAs, so monitoring is necessary; see Table 1: Key Elements of Patient History and Physical Examination for resources for identifying drug-drug interactions. Similarly, it is important to be aware of patient use of nonprescription medication. St. John’s wort (Hypericum perforatum), an herbal self-remedy for depression, may decrease the effectiveness of DAA therapy [FDA 2019FDA 2017FDA 2016].

Substance use: A history of or active use of alcohol, tobacco, marijuana, and other substances is not a contraindication to HCV treatment unless the drug or alcohol use significantly interferes with adherence to medications or appointments. Studies have demonstrated that individuals who are receiving substance use treatment can be effectively treated for chronic HCV infection [Coffin, et al. 2019Grebely, et al. 2018Tsui, et al. 2016].

Once a patient’s alcohol consumption habits have been assessed, counseling may help the patient reduce or eliminate alcohol use. It is important for patients with HCV who use alcohol to be made aware of the effects of alcohol on the course of HCV disease. Alcohol use has been associated with increased rates of liver disease progression and hepatocellular carcinoma (HCC) in people with chronic HCV. Moderate alcohol intake is associated with an increased risk of fibrosis progression [Westin, et al. 2002], and light-to-moderate alcohol intake is associated with an increased risk of HCC in patients with compensated cirrhosis [Vandenbulcke, et al. 2016]. There is no consensus on a safe level of alcohol ingestion for people with chronic HCV.

Barriers to adherence: The purpose of the adherence assessment is to optimize support, not to deny access to treatment. After the pretreatment assessment and before treatment initiation, a plan can be developed with the patient to address potential barriers and put support resources in place [Al-Khazraji, et al. 2020]. Support groups and peer programs can promote increased patient engagement.

Key Points
  • The purpose of the adherence assessment is to optimize support, not to deny access to treatment.
  • Though HCV treatment regimens are relatively short, assessing a patient’s readiness for treatment and ability to adhere to a medication regimen and medical care appointments before initiating DAA therapy is essential.
  • After the pretreatment assessment and before treatment initiation, a plan can be developed with the patient to address potential barriers and put support resources in place.

Baseline Laboratory Testing

Hepatitis C virus (HCV) genotype may influence the choice of direct-acting antiviral regimen and treatment duration in patients with chronic HCV; however, given the availability of pangenotypic regimens, genotyping is not required to initiate treatment in treatment-naive patients. Baseline genotyping may also help in understanding treatment options if a sustained viral response is not attained because it may help distinguish reinfection from virologic relapse.

There are 6 common HCV genotypes [Chevaliez and Pawlotsky 2007]. Based on data from 8,140 participants (≥18 years old) in the U.S.-based Chronic Hepatitis Cohort Study, genotype 1 was most common (75.4%), followed by genotypes 2 (12.6%) and 3 (10.2%); genotypes 4 (1.5%) and 6 (0.3%) were less prevalent [Gordon, et al. 2019]. The single participant with genotype 5 was excluded from the study. Distribution varied significantly by geography and demographics; birth decade, race, and study site were independently associated with genotype distribution (P < 0.01).

Additional baseline laboratory testing essential to pre-HCV treatment is listed in Table 2, below.

Table 2: Pretreatment Laboratory Testing
Test Clinical Note
Quantitative HCV RNAConfirms active HCV infection and determines HCV viral load.
Genotype/subtypeGenotype and subtype guide choice of regimen.
Complete blood count
  • Low platelet count (<140,000 platelets/µL) suggests cirrhosis and portal hypertension [Ebell 2003Kaul and Munoz 2000].
  • Anemia may necessitate choice of a regimen that does not contain ribavirin.
Serum electrolytes with creatinine
  • Marked electrolyte abnormalities may suggest decompensated cirrhosis (e.g., hyponatremia).
  • Renal function will influence choice of regimen.
Hepatic function panel
  • Elevated direct bilirubin suggests decompensated cirrhosis.
  • Markedly elevated transaminases may suggest comorbidities.
INRElevated INR suggests decompensated cirrhosis.
Pregnancy test for all individuals of childbearing potentialIf patient is pregnant, suggest treatment deferral [a].
HAV antibodiesObtain HAV antibody test (IgG or total) and administer the full HAV vaccine series in patients not immune to HAV.
HBV antibodies
  • Obtain HBsAg, anti-HBs, and anti-HBc (total) and recommend administration of the HBV vaccine series (0, 1, and 6 months) for HBV-susceptible patients (negative for all serologies).
  • In patients with a positive HBsAg test result, perform HBV DNA testing to assess for active HBV infection.
  • If HBV DNA is detectable, care providers new to HCV treatment should consult a liver disease specialist regarding treatment for HBV and HCV.
HIV test if status is unknownIf HIV infection is confirmed, offer the patient antiretroviral therapy [b].
UrinalysisProtein may suggest extrahepatic manifestation of HCV.
Fibrosis serum markersIf not previously evaluated by biopsy or FibroScan.

Abbreviations: anti-HBc, hepatitis B core antibody; anti-HBs, hepatitis B surface antibody; ART, antiretroviral therapy; HAV, hepatitis A virus; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; IgG, immunoglobulin G; INR, international normalized ratio.

Notes:

a
b

See NYSDOH AI guideline Rapid ART Initiation.

Fibrosis Assessment

RECOMMENDATIONS

Fibrosis Assessment

  • Clinicians should assess the degree of fibrosis in patients with chronic HCV infection to aid in determining the need for pretreatment varices and HCC screening, the duration of antiviral treatment, whether the regimen should include RBV, and post-treatment follow-up. (A1)
  • Clinicians should assess patients with chronic HCV for decompensated liver disease (A1) and, if present, refer patients with decompensated cirrhosis to a liver disease specialist. (A3)

Abbreviations: HCC, hepatocellular carcinoma; HCV, hepatitis C virus; RBV, ribavirin.

Fibrosis stage predicts HCV treatment response [Ogawa, et al. 2015]. An assessment of the degree of fibrosis should be performed regardless of alanine aminotransferase (ALT) patterns because significant fibrosis may be present in patients with repeatedly normal ALT [EASL 2020]. In 1 study, approximately 50% of people with HCV born between 1945 and 1965 had severe fibrosis or cirrhosis as measured by Fibrosis-4 (FIB-4) index scoring [Klevens, et al. 2016]. It is particularly important to identify patients with bridging fibrosis or cirrhosis; these findings may influence treatment selection and duration and may dictate post-treatment follow-up, such as the need for ongoing assessment for esophageal varices, hepatic function, and surveillance monitoring for HCC [AASLD/IDSA 2021Bruix and Sherman 2011Garcia-Tsao, et al. 2007]. Patients known to have cirrhosis do not require repeat determination of the degree of fibrosis before treatment.

Fibrosis stage can be assessed using noninvasive modalities, such as transient elastography, aspartate aminotransferase (AST)-to-platelet ratio index (APRI), FIB-4 index, and assays of direct markers of liver fibrosis (see Table 3, below). Noninvasive modalities are well suited for rapid pretreatment assessment of chronic HCV infection in the primary care setting. Indirect serum markers use mathematical algorithms with different variables to predict fibrosis and are easily accessible in the primary care setting. Tests such as the APRI and FIB-4 index (age, AST, ALT, platelet count) appear efficacious in patients with little or no fibrosis and those with cirrhosis. However, these tests have limited ability to discriminate between intermediate stages of fibrosis [Castera, et al. 2014Patel and Shackel 2014Schiavon Lde, et al. 2014]. Several studies have found the FIB-4 index to predict fibrosis more accurately than the APRI [Amorim, et al. 2012Shaikh, et al. 2009].

Liver biopsies are not routinely required but are useful for patients with highly discordant results on noninvasive testing and in patients suspected of having a second etiology for liver disease in addition to HCV infection. Liver biopsy is an important instrument for diagnosing concurrent diseases, such as metabolic nonalcoholic steatohepatitis, hemochromatosis, autoimmune primary biliary cholangitis, and autoimmune hepatitis. Although liver biopsy is safe and has a very low risk of complications, invasive procedures may be difficult to obtain in a timely fashion or unacceptably costly for uninsured patients [Seeff, et al. 2010].

An APRI calculator, FIB-4 index calculator, and other online clinical tools are available at Hepatitis C Online. Assays of direct markers of liver fibrosis measure various combinations of liver matrix components in combination with standard biochemical markers. These assays (FibroSure, FibroTest, FibroMeter, FIBROSpect II, and HepaScore) appear efficacious in patients with little or no fibrosis and those with cirrhosis, but, like the FIB-4 index and APRI, these assays have limited ability to discriminate between intermediate stages of fibrosis [Castera, et al. 2014Patel and Shackel 2014Schiavon Lde, et al. 2014]. These tests will provide an indication of disease progression over time and can be helpful in counseling patients who are considering treatment [Poynard, et al. 2014].

Vibration-controlled transient elastography (VCTE) measures shear wave velocity (expressed in kilopascals) and assesses a larger volume of liver parenchyma than liver biopsy. VCTE is most efficacious in F0 to F1 and F4 fibrosis but may be difficult to interpret in F2 and F3 disease [Loomba, et al. 2023Tapper, et al. 2015Castera, et al. 2014Schiavon Lde, et al. 2014Verveer, et al. 2012]. Although VCTE is approved by the U.S. Food and Drug Administration, it is not yet available in all settings and, although highly accurate, is not as cost-effective as laboratory liver fibrosis determinations [Schmid, et al. 2015]. There may also be limitations for patients with obesity [Lai and Afdhal 2019]. Other technologies, such as acoustic radiation force imaging, portal venous transit time, and magnetic resonance imaging elastography or a combination of modalities, show promise for possible future use; these procedures are not recommended at this time because of their lack of sensitivity and specificity in early fibrosis, high cost, and limited availability [EASL 2020Agbim and Asrani 2019Bohte, et al. 2014].

Table 3: Methods for Staging Fibrosis
Method Procedure Advantages Disadvantages
Indirect serum markersAPRI, FIB-4 [a]
  • Noninvasive
  • Inexpensive
Limited ability to differentiate intermediate stages of fibrosis
Direct markersFibroSure, FibroTest, FibroMeter, FIBROSpect II, and HepaScore
  • Noninvasive
  • Easily accessible
Limited ability to differentiate intermediate stages of fibrosis
VCTEShear wave velocity
  • Noninvasive
  • Assesses large volume of liver parenchyma
  • May be difficult to interpret in F2 and F3 liver disease
  • Limited availability
Liver biopsyPathologic examination
  • Diagnostic standard
  • Diagnoses concurrent liver disease
  • Invasive procedure
  • Costly
  • Sampling error

Abbreviations: APRI, aspartate aminotransferase-to-platelet ratio index; FIB-4, Fibrosis-4; VCTE, vibration-controlled transient elastography.

Note:

a

See Hepatitis C Online for APRI and FIB-4 index calculators.

Cirrhosis Evaluation

RECOMMENDATIONS

Cirrhosis Evaluation

  • Clinicians should determine the severity of cirrhosis (A1) and refer patients with a history of decompensation or decompensated cirrhosis (CTP class B or C) to a liver disease specialist. (A3)
  • Clinicians should refer all patients with HCV-related cirrhosis for an upper endoscopy to screen for the presence of esophageal varices. (A3)
  • Clinicians should screen for HCC with ultrasound, CT, or MRI every 6 months in patients with HCV-related bridging fibrosis or cirrhosis. (A3)

Abbreviations: CTP, Child-Turcotte-Pugh; CT, computerized axial tomography; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; MRI, magnetic resonance imaging.

The Model for End-Stage Liver Disease (MELD) score (MELD calculator) or the CTP score (see Table 4, below) may be used to classify the severity of cirrhosis.

Table 4: Calculating the Child-Turcotte-Pugh (CTP) Score for Severity of Cirrhosis [a]
1 point [b] 2 points [b] 3 points [b]
EncephalopathyNoneStage 1 to 2 (or precipitant-induced)Stage 3 to 4 (or chronic)
AscitesNoneMild/moderate (diuretic-responsive)Severe (diuretic-refractory)
Bilirubin (mg/dL)<2.02.0 to 3.0>3.0
Albumin (g/dL)>3.52.8 to 3.5<2.8
Prothrombin time (sec prolonged) or international normalized ratio (INR)<4.04.0 to 6.0>6.0
<1.71.7 to 2.3>2.3

Notes:

a

Adapted from U.S. Department of Veterans Affairs Viral Hepatitis and Liver Disease: Child-Turcotte-Pugh Calculator.

b

CTP score is obtained by adding the score for each parameter. CTP class:

A = 5 to 6 points (compensated, least severe liver disease)

B = 7 to 9 points (decompensated, moderately severe liver disease)

C = 10 to 15 points (decompensated, most severe liver disease)

Assessment for decompensation in patients with cirrhosis can be accomplished through medical history-taking and initial laboratory testing (see Table 5, below). Decompensation is defined as a MELD score of >15 or the presence of ascites, hepatic encephalopathy, portal hypertensive bleeding, HCC, intractable pruritus, hepatopulmonary syndrome, coagulopathy, or portopulmonary hypertension [Fox and Brown 2012]. Because of the clinical complexity of the condition, patients with a history or presence of decompensated cirrhosis should be referred to a liver disease specialist.

All patients with cirrhosis should undergo an upper endoscopy to screen for the presence of esophageal varices. Patients with HCV-related bridging fibrosis or cirrhosis are at increased risk of developing primary HCC and should undergo surveillance with an ultrasound every 6 months [Shoreibah, et al. 2014Bruix and Sherman 2011]. Alpha-fetoprotein (AFP) testing lacks adequate sensitivity and specificity for effective use in surveillance and diagnosis of HCC. Elevated AFP levels may be seen in HCV infection in the absence of HCC [EASL 2018El-Serag and Mason 1999].

For additional risk stratification and diagnosis information, see the American Association of the Study for Liver Diseases practice guidance on portal hypertensive bleeding in cirrhosis [Garcia-Tsao, et al. 2017].

Table 5: Baseline Evaluation and Follow-Up Screening for Patients With Cirrhosis
Type of Evaluation Rationale
Assess for decompensation; refer to a liver disease specialist if history of or current decompensationDecompensation is defined as the presence (or history) of 1 of the following:
  • CTP class B or C
  • MELD score of >15
  • Ascites
  • Hepatic encephalopathy
  • Portal hypertensive bleeding
  • HCC
  • Intractable pruritus
  • Hepatopulmonary syndrome
  • Portopulmonary hypertension
Abdominal ultrasound to screen for HCCOngoing HCC surveillance should be performed for patients with bridging fibrosis or cirrhosis every 6 to 12 months.
Upper endoscopyRefer to a liver disease specialist to screen for varices.

Abbreviations: CTP, Child-Turcotte-Pugh; HCC, hepatocellular carcinoma; MELD, Model of End-Stage Liver Disease.

Renal, HAV/HBV, Metabolic, and Cardiovascular Status

RECOMMENDATIONS

Renal Status

  • Clinicians should assess CrCl in all patients with HCV. (A1)
  • Clinicians new to HCV treatment should consult a liver disease specialist when treating patients with severe renal impairment (CrCl <30 mL/min). (A3)

HAV and HBV Immunity Status

  • Clinicians should obtain HAV antibody (IgG or total) testing and administer the full HAV vaccine series in patients who are not immune to HAV. (A3)
  • Clinicians should obtain HBsAg, anti-HBs, and anti-HBc test results (total) and should recommend administration of the HBV vaccine series (at 0, 1, and 6 months) for HBV-susceptible patients (negative for all serologies). (A3)
  • In patients with positive HBsAg test results, clinicians should perform HBV DNA testing to assess for active HBV infection. (A1)
  • If HBV DNA is detectable, clinicians new to HCV treatment should consult a clinician experienced in managing both HBV and HCV. (A1)

Abbreviations: anti-HBc, hepatitis B core antibody; anti-HBs, hepatitis B surface antibody; CrCl, creatinine clearance; HAV, hepatitis A virus; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; IgG, immunoglobulin G.

Renal status: A patient’s renal status will influence the choice of direct-acting antiviral (DAA) regimen. Evaluation for renal disease includes assessing HCV-related causes of kidney disease, such as membranoproliferative glomerulonephritis and membranous glomerulonephritis, even if patients have other comorbidities also associated with kidney disease, such as diabetes and hypertension.

HAV and HBV immunity status: Completion of HAV and HBV vaccination is not a pretreatment mandate and is appropriate during or after treatment for chronic HCV infection. Coinfection with HCV and either HAV or HBV may result in additional liver inflammation and pathology; vaccination against HAV and HBV is important for patients with HCV to prevent acute decompensation and the sequelae of chronic superinfection by HBV [Lau and Hewlett 2005]. Approximately 40% to 50% of patients with HCV have no documented immunity against HAV or HBV [Henkle, et al. 2015].

If a patient is susceptible to both HAV and HBV infection, the combined vaccine series should be initiated.

The laboratory assessment and vaccination (as appropriate) for HAV and HBV should be performed as soon as possible, but completion of the vaccine series is not necessary before initiation of HCV treatment.

Vaccination of patients with positive anti-HBc and negative HBsAg and anti-HBs (i.e., isolated anti-HBc) test results is controversial because results are subject to several interpretations. In patients from regions where HBV infection is highly endemic or in patients with risk factors for acquiring HBV, a positive anti-HBc result may represent acute or chronic active HBV or serologic clearance of anti-HBs after a prior infection. In patients who have no risk factors or are from regions where HBV infection rates are low, a positive anti-HBc result may represent a false-positive result. In patients with isolated anti-HBc, HBV DNA testing to assess for active HBV infection is recommended, with subsequent vaccination if results are negative.

HBV reactivation and HBV-related hepatic flares, sometimes fulminant, have been reported both during and after DAA therapy in patients who were not receiving concurrent HBV treatment [Butt, et al. 2018Belperio, et al. 2017Wang, et al. 2017De Monte, et al. 2016Hayashi, et al. 2016Sulkowski, et al. 2016Takayama, et al. 2016Collins, et al. 2015Ende, et al. 2015]. Studies have demonstrated that HCV has a suppressive effect on HBV replication. For more information about the risk of HBV reactivation, see the U.S. Food and Drug Administration Drug Safety Communication.

Key Point
  • For patients with active HBV infection, treatment of both HBV and HCV should be provided in consultation with a clinician experienced in managing both HCV and HBV.

Metabolic status: Obesity does not affect the treatment of HCV with DAAs. Among individuals with HCV, both obesity and hepatic steatosis have been associated with progression of fibrosis, increased risk of advanced liver disease, and hepatocellular carcinoma (HCC) [Minami, et al. 2021Dyal, et al. 2015Goossens and Negro 2014Charlton, et al. 2006Bressler, et al. 2003].

Chronic HCV infection appears to be associated with an increased risk of developing type 2 diabetes mellitus (DM2) in predisposed individuals [Lecube, et al. 2004Mehta, et al. 2003Mehta, et al. 2000]. Insulin resistance (IR) and diabetes are associated with increased liver fibrosis [Patel, et al. 2011Moucari, et al. 2008Petta, et al. 2008], cirrhosis [Gordon, et al. 2015], and HCC [Hung, et al. 2011Donadon, et al. 2009Veldt, et al. 2008Tazawa, et al. 2002] in patients with HCV. Successful treatment of chronic HCV infection may be associated with improved IR, reduced incidence of DM2, and potentially decreased DM2-associated renovascular complications [Hsu, et al. 2014Thompson, et al. 2012Arase, et al. 2009]. No serious drug-drug interactions have been reported with DAA agents and insulin-sensitizing or diabetic medications. However, because of the potential for improved glycemic control, diabetic patients have a higher risk for hypoglycemia during or after treatment with DAAs [Zhou, et al. 2022Andres, et al. 2020Yuan, et al. 2020Li(b), et al. 2019Li(a), et al. 2019] and should be counseled to monitor blood sugars during and after treatment.

Cardiovascular status: Although cardiovascular disease and congestive heart failure may be worsened by possible anemia associated with the use of ribavirin (RBV)-containing regimens, no such concern is noted with DAA regimens that do not contain RBV. However, drug-drug interactions between DAA medications and cardiovascular medications have been reported and may require adjustments or changes before initiation of therapy.

All Recommendations

RECOMMENDATIONS

Medical History and Physical Examination

  • Clinicians should assess all patients with a confirmed diagnosis of chronic HCV infection, defined as a positive HCV surface antibody test result and detectable HCV RNA, for treatment. (A1)
  • Clinicians should refer patients with chronic HCV and decompensated liver disease and patients who are pre- or post-liver transplant to a liver disease specialist. (A3)
  • Clinicians new to treating chronic HCV infection should consult with a liver disease specialist when treating chronic HCV in patients with any of the following conditions (A3):
    • Compensated cirrhosis; concurrent hepatobiliary conditions
    • Extrahepatic manifestations of HCV, including renal, dermatologic, and rheumatologic manifestations
    • Significant renal impairment (CrCl <30 mL/min) or who are undergoing hemodialysis
    • Active HBV infection, defined as a positive HBsAg test result and detectable HBV DNA
    • Ongoing HCV infection after failure of treatment with DAAs
    • Treatment after organ transplantation

Fibrosis Assessment

  • Clinicians should assess the degree of fibrosis in patients with chronic HCV infection to aid in determining the need for pretreatment varices and HCC screening, the duration of antiviral treatment, whether the regimen should include RBV, and post-treatment follow-up. (A1)
  • Clinicians should assess patients with chronic HCV for decompensated liver disease (A1) and, if present, refer patients with decompensated cirrhosis to a liver disease specialist. (A3)

Cirrhosis Evaluation

  • Clinicians should determine the severity of cirrhosis (A1) and refer patients with a history of decompensation or decompensated cirrhosis (CTP class B or C) to a liver disease specialist. (A3)
  • Clinicians should refer all patients with HCV-related cirrhosis for an upper endoscopy to screen for the presence of esophageal varices. (A3)
  • Clinicians should screen for HCC with ultrasound, CT, or MRI every 6 months in patients with HCV-related bridging fibrosis or cirrhosis. (A3)

Renal Status

  • Clinicians should assess CrCl in all patients with HCV. (A1)
  • Clinicians new to HCV treatment should consult a liver disease specialist when treating patients with severe renal impairment (CrCl <30 mL/min). (A3)

HAV and HBV Immunity Status

  • Clinicians should obtain HAV antibody (IgG or total) testing and administer the full HAV vaccine series in patients who are not immune to HAV. (A3)
  • Clinicians should obtain HBsAg, anti-HBs, and anti-HBc test results (total) and should recommend administration of the HBV vaccine series (at 0, 1, and 6 months) for HBV-susceptible patients (negative for all serologies). (A3)
  • In patients with positive HBsAg test results, clinicians should perform HBV DNA testing to assess for active HBV infection. (A1)
  • If HBV DNA is detectable, clinicians new to HCV treatment should consult a clinician experienced in managing both HBV and HCV. (A1)

Abbreviations: anti-HBc, hepatitis B core antibody; anti-HBs, hepatitis B surface antibody; CTP, Child-Turcotte-Pugh; CrCl, creatinine clearance; CT, computerized axial tomography; DAA, direct-acting antiviral; HAV, hepatitis A virus; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; IgG, immunoglobulin G; MRI, magnetic resonance imaging.

References

  • AASLD/IDSA. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. 2021. https://www​.hcvguidelines.org/ [accessed 2022 Aug 29] [PubMed: 26111063]
  • Agbim U., Asrani S. K. Non-invasive assessment of liver fibrosis and prognosis: an update on serum and elastography markers. Expert Rev Gastroenterol Hepatol. 2019;13(4):361–374. [PubMed: 30791772]
  • Al-Khazraji A., Patel I., Saleh M., et al. Identifying barriers to the treatment of chronic hepatitis C infection. Dig Dis. 2020;38(1):46–52. [PubMed: 31422405]
  • Amorim T. G., Staub G. J., Lazzarotto C., et al. Validation and comparison of simple noninvasive models for the prediction of liver fibrosis in chronic hepatitis C. Ann Hepatol. 2012;11(6):855–861. [PubMed: 23109448]
  • Andres J., Barros M., Arutunian M., et al. Treatment of hepatitis C virus and long-term effect on glycemic control. J Manag Care Spec Pharm. 2020;26(6):775–781. [PMC free article: PMC10390901] [PubMed: 32463777]
  • Arase Y., Suzuki F., Suzuki Y., et al. Sustained virological response reduces incidence of onset of type 2 diabetes in chronic hepatitis C. Hepatology. 2009;49(3):739–744. [PubMed: 19127513]
  • Belperio P. S., Shahoumian T. A., Mole L. A., et al. Evaluation of hepatitis B reactivation among 62,920 veterans treated with oral hepatitis C antivirals. Hepatology. 2017;66(1):27–36. [PubMed: 28240789]
  • Bohte A. E., de Niet A., Jansen L., et al. Non-invasive evaluation of liver fibrosis: a comparison of ultrasound-based transient elastography and MR elastography in patients with viral hepatitis B and C. Eur Radiol. 2014;24(3):638–648. [PubMed: 24158528]
  • Bressler B. L., Guindi M., Tomlinson G., et al. High body mass index is an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C. Hepatology. 2003;38(3):639–644. [PubMed: 12939590]
  • Bruix J., Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020–1022. [PMC free article: PMC3084991] [PubMed: 21374666]
  • Butt A. A., Yan P., Shaikh O. S., et al. Hepatitis B reactivation and outcomes in persons treated with directly acting antiviral agents against hepatitis C virus: results from ERCHIVES. Aliment Pharmacol Ther. 2018;47(3):412–420. [PubMed: 29181838]
  • Castera L., Winnock M., Pambrun E., et al. Comparison of transient elastography (FibroScan), FibroTest, APRI and two algorithms combining these non-invasive tests for liver fibrosis staging in HIV/HCV coinfected patients: ANRS CO13 HEPAVIH and FIBROSTIC Collaboration. HIV Med. 2014;15(1):30–39. [PubMed: 24007567]
  • Charlton M. R., Pockros P. J., Harrison S. A. Impact of obesity on treatment of chronic hepatitis C. Hepatology. 2006;43(6):1177–1186. [PubMed: 16729327]
  • Chevaliez S., Pawlotsky J. M. Hepatitis C virus: virology, diagnosis and management of antiviral therapy. World J Gastroenterol. 2007;13(17):2461–2466. [PMC free article: PMC4146765] [PubMed: 17552030]
  • Coffin P. O., Santos G. M., Behar E., et al. Randomized feasibility trial of directly observed versus unobserved hepatitis C treatment with ledipasvir-sofosbuvir among people who inject drugs. PLoS One. 2019;14(6):e0217471. [PMC free article: PMC6546233] [PubMed: 31158245]
  • Collins J. M., Raphael K. L., Terry C., et al. Hepatitis B virus reactivation during successful treatment of hepatitis C virus with sofosbuvir and simeprevir. Clin Infect Dis. 2015;61(8):1304–1306. [PubMed: 26082511]
  • De Monte A., Courjon J., Anty R., et al. Direct-acting antiviral treatment in adults infected with hepatitis C virus: reactivation of hepatitis B virus coinfection as a further challenge. J Clin Virol. 2016;78:27–30. [PubMed: 26967675]
  • Donadon V., Balbi M., Zanette G. Hyperinsulinemia and risk for hepatocellular carcinoma in patients with chronic liver diseases and type 2 diabetes mellitus. Expert Rev Gastroenterol Hepatol. 2009;3(5):465–467. [PubMed: 19817667]
  • Dyal H. K., Aguilar M., Bhuket T., et al. Concurrent obesity, diabetes, and steatosis increase risk of advanced fibrosis among HCV patients: a systematic review. Dig Dis Sci. 2015;60(9):2813–2824. [PubMed: 26138651]
  • EASL EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69(1):182–236. [PubMed: 29628281]
  • EASL EASL recommendations on treatment of hepatitis C: final update of the series. J Hepatol. 2020;73(5):1170–1218. [PubMed: 32956768]
  • Ebell M. H. Probability of cirrhosis in patients with hepatitis C. Am Fam Physician. 2003;68(9):1831–1833. [PubMed: 14620604]
  • El-Serag H. B., Mason A. C. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med. 1999;340(10):745–750. [PubMed: 10072408]
  • Ende A. R., Kim N. H., Yeh M. M., et al. Fulminant hepatitis B reactivation leading to liver transplantation in a patient with chronic hepatitis C treated with simeprevir and sofosbuvir: a case report. J Med Case Rep. 2015;9:164. [PMC free article: PMC4535371] [PubMed: 26215390]
  • FDA. Epclusa (sofosbuvir and velpatasvir) tablets, for oral use. 2016. https://www​.accessdata​.fda.gov/drugsatfda_docs​/label/2016/208341s000lbl.pdf [accessed 2022 Feb 1]
  • FDA. Vosevi (sofosbuvir, velpatasvir, and voxilaprevir) tablets, for oral use. 2017. https://www​.accessdata​.fda.gov/drugsatfda_docs​/label/2017/209195s000lbl.pdf [accessed 2022 Feb 1]
  • FDA. Harvoni (ledipasvir and sofosbuvir) tablets, for oral use. 2019. https://www​.accessdata​.fda.gov/drugsatfda_docs​/label/2019/212477s000lbl.pdf [accessed 2022 Feb 1]
  • Fox A. N., Brown R. S. Is the patient a candidate for liver transplantation?. Clin Liver Dis. 2012;16(2):435–448. [PubMed: 22541708]
  • Garcia-Tsao G., Abraldes J. G., Berzigotti A., et al. Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, an management: 2016 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2017;65(1):310–335. [PubMed: 27786365]
  • Garcia-Tsao G., Sanyal A. J., Grace N. D., et al. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007;46(3):922–938. [PubMed: 17879356]
  • Ghany M. G., Morgan T. R. 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(2):686–721. [PMC free article: PMC9710295] [PubMed: 31816111]
  • Goossens N., Negro F. The impact of obesity and metabolic syndrome on chronic hepatitis C. Clin Liver Dis. 2014;18(1):147–156. [PubMed: 24274870]
  • Gordon S. C., Lamerato L. E., Rupp L. B., et al. Prevalence of cirrhosis in hepatitis C patients in the Chronic Hepatitis Cohort Study (CHeCS): a retrospective and prospective observational study. Am J Gastroenterol. 2015;110(8):1169–77; quiz 1178. [PMC free article: PMC5731242] [PubMed: 26215529]
  • Gordon S. C., Trudeau S., Li J., et al. Race, age, and geography impact hepatitis C genotype distribution in the United States. J Clin Gastroenterol. 2019;53(1):40–50. [PMC free article: PMC5776051] [PubMed: 28737649]
  • Gountas I., Sypsa V., Blach S., et al. HCV elimination among people who inject drugs. Modelling pre- and post-WHO elimination era. PLoS One. 2018;13(8):e0202109. [PMC free article: PMC6095544] [PubMed: 30114207]
  • Granozzi B., Guardigni V., Badia L., et al. Out-of-hospital treatment of hepatitis C increases retention in care among people who inject drugs and homeless persons: an observational study. J Clin Med. 2021;10(21):4955. [PMC free article: PMC8584608] [PubMed: 34768474]
  • Grebely J., Dalgard O., Conway B., et al. Sofosbuvir and velpatasvir for hepatitis C virus infection in people with recent injection drug use (SIMPLIFY): an open-label, single-arm, phase 4, multicentre trial. Lancet Gastroenterol Hepatol. 2018;3(3):153–161. [PubMed: 29310928]
  • Groessl E. J., Sklar M., Cheung R. C., et al. Increasing antiviral treatment through integrated hepatitis C care: a randomized multicenter trial. Contemp Clin Trials. 2013;35(2):97–107. [PubMed: 23669414]
  • Hajarizadeh B., Cunningham E. B., Valerio H., et al. Hepatitis C reinfection after successful antiviral treatment among people who inject drugs: a meta-analysis. J Hepatol. 2020;72(4):643–657. [PubMed: 31785345]
  • Hayashi K., Ishigami M., Ishizu Y., et al. A case of acute hepatitis B in a chronic hepatitis C patient after daclatasvir and asunaprevir combination therapy: hepatitis B virus reactivation or acute self-limited hepatitis?. Clin J Gastroenterol. 2016;9(4):252–256. [PubMed: 27329484]
  • Henkle E., Lu M., Rupp L. B., et al. Hepatitis A and B immunity and vaccination in chronic hepatitis B and C patients in a large United States cohort. Clin Infect Dis. 2015;60(4):514–522. [PubMed: 25371489]
  • Hsu Y. C., Wu C. Y., Lane H. Y., et al. Determinants of hepatocellular carcinoma in cirrhotic patients treated with nucleos(t)ide analogues for chronic hepatitis B. J Antimicrob Chemother. 2014;69(7):1920–1927. [PubMed: 24576950]
  • Hung C. H., Lee C. M., Wang J. H., et al. Impact of diabetes mellitus on incidence of hepatocellular carcinoma in chronic hepatitis C patients treated with interferon-based antiviral therapy. Int J Cancer. 2011;128(10):2344–2352. [PubMed: 20669224]
  • Jalan R., Fernandez J., Wiest R., et al. Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013. J Hepatol. 2014;60(6):1310–1324. [PubMed: 24530646]
  • Kaul V. V., Munoz S. J. Coagulopathy of liver disease. Curr Treat Options Gastroenterol. 2000;3(6):433–438. [PubMed: 11096602]
  • Klevens R. M., Canary L., Huang X., et al. The burden of hepatitis C infection-related liver fibrosis in the United States. Clin Infect Dis. 2016;63(8):1049–1055. [PubMed: 27506688]
  • Lai M., Afdhal N. H. Liver fibrosis determination. Gastroenterol Clin North Am. 2019;48(2):281–289. [PubMed: 31046975]
  • Lau D. T., Hewlett A. T. Screening for hepatitis A and B antibodies in patients with chronic liver disease. Am J Med. 2005;118 Suppl 10A:28s–33s. [PubMed: 16271538]
  • Lecube A., Hernandez C., Genesca J., et al. High prevalence of glucose abnormalities in patients with hepatitis C virus infection: a multivariate analysis considering the liver injury. Diabetes Care. 2004;27(5):1171–1175. [PubMed: 15111540]
  • Li(a) J., Gordon S. C., Rupp L. B., et al. Sustained virological response does not improve long-term glycaemic control in patients with type 2 diabetes and chronic hepatitis C. Liver Int. 2019;39(6):1027–1032. [PMC free article: PMC6628708] [PubMed: 30570808]
  • Li(b) J., Gordon S. C., Rupp L. B., et al. Sustained virological response to hepatitis C treatment decreases the incidence of complications associated with type 2 diabetes. Aliment Pharmacol Ther. 2019;49(5):599–608. [PMC free article: PMC6599612] [PubMed: 30650468]
  • Loomba R., Huang D. Q., Sanyal A. J., et al. Liver stiffness thresholds to predict disease progression and clinical outcomes in bridging fibrosis and cirrhosis. Gut. 2023;72(3):581–589. [PMC free article: PMC9905707] [PubMed: 36750244]
  • Mehta S. H., Brancati F. L., Strathdee S. A., et al. Hepatitis C virus infection and incident type 2 diabetes. Hepatology. 2003;38(1):50–56. [PubMed: 12829986]
  • Mehta S. H., Brancati F. L., Sulkowski M. S., et al. Prevalence of type 2 diabetes mellitus among persons with hepatitis C virus infection in the United States. Ann Intern Med. 2000;133(8):592–599. [PubMed: 11033586]
  • Minami T., Tateishi R., Fujiwara N., et al. Impact of obesity and heavy alcohol consumption on hepatocellular carcinoma development after HCV eradication with antivirals. Liver Cancer. 2021;10(4):309–319. [PMC free article: PMC8339497] [PubMed: 34414119]
  • Moucari R., Asselah T., Cazals-Hatem D., et al. Insulin resistance in chronic hepatitis C: association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis. Gastroenterology. 2008;134(2):416–423. [PubMed: 18164296]
  • Ogawa E., Furusyo N., Shimizu M., et al. Non-invasive fibrosis assessment predicts sustained virological response to telaprevir with pegylated interferon and ribavirin for chronic hepatitis C. Antivir Ther. 2015;20(2):185–192. [PubMed: 24941012]
  • Patel K., Shackel N. A. Current status of fibrosis markers. Curr Opin Gastroenterol. 2014;30(3):253–259. [PubMed: 24671009]
  • Patel K., Thompson A. J., Chuang W. L., et al. Insulin resistance is independently associated with significant hepatic fibrosis in Asian chronic hepatitis C genotype 2 or 3 patients. J Gastroenterol Hepatol. 2011;26(7):1182–1188. [PubMed: 21410752]
  • Petta S., Camma C., Di Marco V., et al. Insulin resistance and diabetes increase fibrosis in the liver of patients with genotype 1 HCV infection. Am J Gastroenterol. 2008;103(5):1136–1144. [PubMed: 18477344]
  • Poynard T., Vergniol J., Ngo Y., et al. Staging chronic hepatitis C in seven categories using fibrosis biomarker (FibroTest) and transient elastography (FibroScan(R)). J Hepatol. 2014;60(4):706–714. [PubMed: 24291240]
  • Sackey B., Shults J. G., Moore T. A., et al. Evaluating psychiatric outcomes associated with direct-acting antiviral treatment in veterans with hepatitis C infection. Ment Health Clin. 2018;8(3):116–121. [PMC free article: PMC6007636] [PubMed: 29955556]
  • Schiavon Lde L., Narciso-Schiavon J. L., de Carvalho-Filho R. J. Non-invasive diagnosis of liver fibrosis in chronic hepatitis C. World J Gastroenterol. 2014;20(11):2854–2866. [PMC free article: PMC3961992] [PubMed: 24659877]
  • Schmid P., Bregenzer A., Huber M., et al. Progression of liver fibrosis in HIV/HCV co-infection: a comparison between non-invasive assessment methods and liver biopsy. PLoS One. 2015;10(9):e0138838. [PMC free article: PMC4587859] [PubMed: 26418061]
  • Seeff L. B., Everson G. T., Morgan T. R., et al. Complication rate of percutaneous liver biopsies among persons with advanced chronic liver disease in the HALT-C trial. Clin Gastroenterol Hepatol. 2010;8(10):877–883. [PMC free article: PMC3771318] [PubMed: 20362695]
  • Shaikh S., Memon M. S., Ghani H., et al. Validation of three non-invasive markers in assessing the severity of liver fibrosis in chronic hepatitis C. J Coll Physicians Surg Pak. 2009;19(8):478–482. [PubMed: 19651008]
  • Shoreibah M. G., Bloomer J. R., McGuire B. M., et al. Surveillance for hepatocellular carcinoma: evidence, guidelines and utilization. Am J Med Sci. 2014;347(5):415–419. [PubMed: 24759379]
  • Simmons B., Saleem J., Heath K., et al. Long-term treatment outcomes of patients infected with hepatitis C virus: a systematic review and meta-analysis of the survival benefit of achieving a sustained virological response. Clin Infect Dis. 2015;61(5):730–740. [PMC free article: PMC4530725] [PubMed: 25987643]
  • Sulkowski M. S., Chuang W. L., Kao J. H., et al. No evidence of reactivation of hepatitis B virus among patients treated with ledipasvir-sofosbuvir for hepatitis C virus infection. Clin Infect Dis. 2016;63(9):1202–1204. [PMC free article: PMC6276897] [PubMed: 27486112]
  • Takayama H., Sato T., Ikeda F., et al. Reactivation of hepatitis B virus during interferon-free therapy with daclatasvir and asunaprevir in patient with hepatitis B virus/hepatitis C virus co-infection. Hepatol Res. 2016;46(5):489–491. [PubMed: 26297529]
  • Tapper E. B., Castera L., Afdhal N. H. FibroScan (vibration-controlled transient elastography): where does it stand in the United States practice. Clin Gastroenterol Hepatol. 2015;13(1):27–36. [PubMed: 24909907]
  • Tazawa J., Maeda M., Nakagawa M., et al. Diabetes mellitus may be associated with hepatocarcinogenesis in patients with chronic hepatitis C. Dig Dis Sci. 2002;47(4):710–715. [PubMed: 11991597]
  • Thompson A. J., Patel K., Chuang W. L., et al. Viral clearance is associated with improved insulin resistance in genotype 1 chronic hepatitis C but not genotype 2/3. Gut. 2012;61(1):128–134. [PMC free article: PMC3766841] [PubMed: 21873466]
  • Torrens M., Soyemi T., Bowman D., et al. Beyond clinical outcomes: the social and healthcare system implications of hepatitis C treatment. BMC Infect Dis. 2020;20(1):702. [PMC free article: PMC7517680] [PubMed: 32972393]
  • Tsui J. I., Williams E. C., Green P. K., et al. Alcohol use and hepatitis C virus treatment outcomes among patients receiving direct antiviral agents. Drug Alcohol Depend. 2016;169:101–109. [PMC free article: PMC6534140] [PubMed: 27810652]
  • Vandenbulcke H., Moreno C., Colle I., et al. Alcohol intake increases the risk of HCC in hepatitis C virus-related compensated cirrhosis: a prospective study. J Hepatol. 2016;65(3):543–551. [PubMed: 27180899]
  • Veldt B. J., Chen W., Heathcote E. J., et al. Increased risk of hepatocellular carcinoma among patients with hepatitis C cirrhosis and diabetes mellitus. Hepatology. 2008;47(6):1856–1862. [PubMed: 18506898]
  • Verveer C., Zondervan P. E., ten Kate F. J., et al. Evaluation of transient elastography for fibrosis assessment compared with large biopsies in chronic hepatitis B and C. Liver Int. 2012;32(4):622–628. [PubMed: 22098684]
  • Wang C., Ji D., Chen J., et al. Hepatitis due to reactivation of hepatitis B virus in endemic areas among patients with hepatitis C treated with direct-acting antiviral agents. Clin Gastroenterol Hepatol. 2017;15(1):132–136. [PubMed: 27392759]
  • Westin J., Lagging L. M., Spak F., et al. Moderate alcohol intake increases fibrosis progression in untreated patients with hepatitis C virus infection. J Viral Hepat. 2002;9(3):235–241. [PubMed: 12010513]
  • Yuan M., Zhou J., Du L., et al. Hepatitis C virus clearance with glucose improvement and factors affecting the glucose control in chronic hepatitis C patients. Sci Rep. 2020;10(1):1976. [PMC free article: PMC7005176] [PubMed: 32029793]
  • Zhou Y., Xie W., Zheng C., et al. Hypoglycemia associated with direct-acting anti-hepatitis C virus drugs: an epidemiologic surveillance study of the FDA adverse event reporting system (FAERS). Clin Endocrinol (Oxf). 2022;96(5):690–697. [PubMed: 34913180]

Footnotes

Conflict of Interest: There are no author or writing group conflict of interest disclosures.

Created: October 2022; Last Update: October 2022.

Copyright © Johns Hopkins University Clinical Guidelines Program 2000-2024. The Clinical Guidelines Program, a collaborative effort of the NYSDOH AI and the Johns Hopkins University School of Medicine, Division of Infectious Diseases, encourages the use, reproduction, and distribution of original documents and related graphics from this program website accompanied by a full citation of source that includes: Author(s). Committee. Title. Date of publication. Full URL. Date accessed. Links to pages on this Clinical Guidelines Program website are also encouraged and may be created without seeking permission. Requests to adapt material, i.e., to change or alter in any way material from this website for inclusion in another publication, should be sent to aiguidelines@jhmi.edu. Please include detailed information about the intended use and desired adaptations.

This book is licensed under the terms of the Attribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND 3.0).

Bookshelf ID: NBK598240PMID: 38091455

Views

Related information

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...